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Purpose: Wilms' tumor (WT), also known as nephroblastoma, is the predominant form of primary malignant renal cancer. The unfavorable prognoses linked to anaplastic nephroblastoma and recurrent nephroblastoma emphasize the crucial requirement for the exploration of innovative treatment modalities for WT., Methods: Our study conducted one-way Cox regression and Kaplan-Meier analyses using TARGET-WT nephroblastoma data to identify differentially expressed genes in nephroblastoma and evaluate their prognostic relevance. Utilizing the Connectivity Map database, ZSTK474 emerged as a viable therapeutic option for WT. The effect of ZSTK474 on WT and related underlying mechanisms were further investigated through in vitro and in vivo investigations., Results: The in vivo experiment results indicated that ZSTK474 effectively inhibited subcutaneous tumor growth in WT mice. CCK-8 assays revealed two nephroblastoma cell lines exhibited half-inhibitory concentrations of 2μM and 2.51μM for ZSTK474, respectively. ZSTK474 was shown to inhibit the migration and invasion capabilities of WT cells in both Transwell and wound healing assays. Flow cytometry apoptosis and TUNEL assays demonstrated that ZSTK474 induced apoptosis in WT cells. Cell cycle analysis revealed that ZSTK474 led to the induction of G0/G1 phase arrest. Sequencing of ZSTK474-treated WiT49 cells suggested that the impact of ZSTK474 on WT might be mediated by the PI3K/Akt pathway, specifically by inhibiting PIK3R3. Knock-down of PIK3R3 confirmed that ZSTK474 downregulated PIK3R3, reducing Akt phosphorylation, cyclin D and CDK4 levels and elevating P21 expression in nephroblastoma cells. However, current research has limitations, including a lack of understanding of the long-term effects and potential resistance mechanisms of new therapies., Conclusion: This research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Unsaturated lipids with carbon-carbon double bonds (C═C) have been implicated in the pathogenesis of various diseases. While mass spectrometry imaging (MSI) has been employed to map the distribution of lipid isomers in tissue sections, the identification of lipid C═C positional isomers at the single-cell level using MSI poses a significant challenge. In this study, we developed a novel approach utilizing ToF-SIMS in conjunction with the Paternò-Büchi (P-B) photochemical reaction to characterize the C═C localization in unsaturated lipid isomers at the single-cell level. The P-B reaction was employed to produce adduct products, which were subsequently subjected to collision-induced dissociation by the primary ion beam of ToF-SIMS to generate characteristic ion pairs indicative of the presence of C═C bonds. Utilizing this approach, lipid isomers in brain and skeletal tissues from mice, as well as different cell lines, were visualized at single-cell resolution. Furthermore, distinct variations in the composition of FA 18:1 isomers across different microregions and cell types were revealed. Our P-B ToF-SIMS approach enables the accurate identification and characterization of complex lipid structures with remarkable spatial resolution and can be helpful in understanding the physiological role of these C═C positional isomers.

Hepatocellular carcinoma (HCC) is still one of the leading causes of tumor-related deaths. Accumulating evidence indicates that immunogenic cell death (ICD) could occur in tumor cells. However, ICD-related studies are limited in HCC. This study collected HCC RNA sequencing data from the Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R software was used to analyze the expression of ICD in HCC and to screen essential genes with prognostic value. qRT-PCR and WB determined the mRNA and protein expressions of hub gene. Cell viability assay, Clonal formation assay, and Live/dead staining assay were employed to determine the gene functions. After cross-analysis of differentially expressed genes (DEGs) and ICD-related genes (ICDRGs), 7 differentially expressed ICDRGs were identified in HCC. Of them, HSP90AA1, with the most excellent prognostic value in HCC, was selected, whose expression was also validated in public cohorts, cell lines, and clinical tissue samples. High HSP90AA1 expression indicated an inferior prognosis of HCC, and HSP90AA1 knockdown significantly suppressed cell viability and chemotherapy resistance of HCC. ICD-related gene HSP90AA1 was an unfavorable factor for HCC, and high HSP90AA1 expression contributed to tumor cell survival and chemotherapy resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Polygala tenuifolia , commonly known as Yuanzhi (YZ) in Chinese, has been shown to possess anti-insomnia properties. However, the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear. Herein, we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging (MSI)-based spatial resolved metabolomics. According to the results, 17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain, which might be the major components contributing to the sedative-hypnotic effects. Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction, serotonergic synapse, dopaminergic synapse, and dopaminergic synapse, among other pathways. LC-MS/MS-based targeted metabolomics and Western blot (WB) revealed that tryptophan-serotonin-melatonin (Trp-5-HT-Mel) and tyrosine-norepinephrine-adrenaline (Tyr-Ne-Ad) are the key regulated pathways. Dopa decarboxylase (DDC) upregulation and phenylethanolamine N -methyltransferase (PNMT) downregulation further confirmed these pathways. Furthermore, MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland (PG), and Ad in the brainstem, including the middle brain (MB), pons (PN), and hypothalamus (HY). In summary, this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine, YZ., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Authors.)

Evaluating toxicity and decoding the underlying mechanisms of active compounds are crucial for drug development. In this study, we present an innovative, integrated approach that combines air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and spatial metabolomics to comprehensively investigate the nephrotoxicity and underlying mechanisms of nitidine chloride (NC), a promising anti-tumor drug candidate. Our quantitive AFADESI-MSI analysis unveiled the region specific of accumulation of NC in the kidney, particularly within the inner cortex (IC) region, following single and repeated dose of NC. High spatial resolution ToF-SIMS analysis further allowed us to precisely map the localization of NC within the renal tubule. Employing spatial metabolomics based on AFADESI-MSI, we identified over 70 discriminating endogenous metabolites associated with chronic NC exposure. These findings suggest the renal tubule as the primary target of NC toxicity and implicate renal transporters (organic cation transporters, multidrug and toxin extrusion, and organic cation transporter 2 (OCT2)), metabolic enzymes (protein arginine N -methyltransferase (PRMT) and nitric oxide synthase), mitochondria, oxidative stress, and inflammation in NC-induced nephrotoxicity. This study offers novel insights into NC-induced renal damage, representing a crucial step towards devising strategies to mitigate renal damage caused by this compound., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Purpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC)., Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators., Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators., Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC., Competing Interests: The authors claimed that they have no competing interests in this work., (© 2024 Fan et al.)

Spatial-temporal optical vortices (STOVs) have recently become the focus of newly structured optical fields. In this paper, their propagation on a 2D curved surface named the constant Gaussian curvature surface (CGCS) is studied. Using the matrix optics approach, we provide the analytical solution of the STOV propagation under the paraxial approximation on the CGCS with positive curvature. One method of creating timers is made possible by the spatiotemporal distribution direction of STOV light intensity, which swings like a pendulum throughout the evolution, in contrast to propagation on a flat surface. This swing, however, stops when the curved surface's curvature radius matches the light's Rayleigh distance. Besides, the transverse orbital angular momentum of STOV is deduced, and we find that the intrinsic and extrinsic OAM periodically exchange, but the total transverse OAM is always zero during the propagation on CGCS. It aids in controlling the transverse extrinsic orbital angular momentum of STOV in nontrivial space.

Introduction: Accumulating evidence demonstrates that aberrant methylation of enhancers is crucial in gene expression profiles across several cancers. However, the latent effect of differently expressed enhancers between INSS stage 4S and 4 neuroblastoma (NB) remains elusive., Methods: We utilized the transcriptome and methylation data of stage 4S and 4 NB patients to perform Enhancer Linking by Methylation/Expression Relationships (ELMER) analysis, discovering a differently expressed motif within 67 enhancers between stage 4S and 4 NB. Harnessing the 67 motif genes, we established the INSS stage related signature (ISRS) by amalgamating 12 and 10 distinct machine learning (ML) algorithms across 113 and 101 ML combinations to precisely diagnose stage 4 NB among all NB patients and to predict the prognosis of NB patients. Based on risk scores calculated by prognostic ISRS, patients were categorized into high and low-risk groups according to median risk score. We conducted comprehensive comparisons between two risk groups, in terms of clinical applications, immune microenvironment, somatic mutations, immunotherapy, chemotherapy and single-cell analysis. Ultimately, we empirically validated the differential expressions of two ISRS model genes, CAMTA2 and FOXD1, through immunochemistry staining., Results: Through leave-one-out cross-validation, in both feature selection and model construction, we selected the random forest algorithm to diagnose stage 4 NB, and Enet algorithm to develop prognostic ISRS, due to their highest average C-index across five NB cohorts. After validations, the ISRS demonstrated a stable predictive capability, outperforming the previously published NB signatures and several clinic variables. We stratified NB patients into high and low-risk group based on median risk score, which showed the low-risk group with a superior survival outcome, an abundant immune infiltration, a decreased mutation landscape, and an enhanced sensitivity to immunotherapy. Single-cell analysis between two risk groups reveals biologically cellular variations underlying ISRS. Finally, we verified the significantly higher protein levels of CAMTA2 and FOXD1 in stage 4S NB, as well as their protective prognosis value in NB., Conclusion: Based on multi-omics data and ML algorithms, we successfully developed the ISRS to enable accurate diagnosis and prognostic stratification in NB, which shed light on molecular mechanisms of spontaneous regression and clinical utilization of ISRS., (© 2024. The Author(s).)

A tunable dual-band terahertz sensor based on graphene is proposed. The sensor consists of a metal bottom layer, a middle dielectric layer, and single-layer graphene patterned with four strips on the top. The numerical simulations results show that the proposed sensor exhibits two significant absorption peaks at 2.58 THz and 6.07 THz. The corresponding absorption rates are as high as nearly 100% and 98%, respectively. The corresponding quality factor (Q) value is 11.8 at 2.58 THz and 29.6 at 6.07 THz. By adjusting the external electric field or chemical doping of graphene, the positions of the dual-frequency resonance peak can be dynamically tuned. The excitation of plasma resonance in graphene can illustrate the mechanism of the sensor. To verify the practical application of the device, the terahertz response of different kinds and different thicknesses of the analyte is investigated and analyzed. A phenomenon of obvious frequency shifts of the two resonance peaks can be observed. Therefore, the proposed sensor has great potential applications in terahertz fields, such as material characterization, medical diagnosis, and environmental monitoring., Competing Interests: The authors declare no conflicts of interest.

Background: Some reports have indicated a high expression level of ASB3 in various cancers, but its role in hepatocellular carcinoma (HCC) remains elusive., Methods: ASB3 levels and clinical features were obtained from the TCGA database. Meanwhile, the expression levels of ASB3 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Imunohistochemistry (IHC). ASB3-related downstream molecular analysis was carried out with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Pathways linked to ASB3 expression were identified by means of gene set enrichment analysis (GSEA). Single-sample GSEA (ssGSEA) aided in conducting a correlation analysis of ASB3 with immune infiltration. Functional experiments were performed in HepG2 cells by using the small interfering RNA., Results: ASB3 expression was remarkably higher in HCC tissues. Its remarkable precision in forecasting cancer suggests that ASB3 might serve as an unidentified diagnostic and prognostic indicator of HCC. Higher ASB3 expression led to worse overall survival (OS), particularly in various clinical subgroups of HCC. GO/KEGG analysis indicated that critical biological activities, such as the activation of complement systems and humoral immune response, could potentially underlie the progression of HCC. Furthermore, GSEA demonstrated enrichment of certain pathways, including the MAPK, IL17, and fibrinolysis pathways, in samples with elevated ASB3 levels. ASB3 exhibited a substantial association with T helper cells, dendritic cells (DCs), and central memory T (Tcm) cell infiltration level. Cell function experiments confirmed elevated ASB3 levels in HCC cell lines as opposed to hepatic epithelial cell lines. Moreover, the ability of HCC cells to proliferate and invade was remarkably reduced by ASB3 knockdown., Conclusion: Summarize briefly, we found that ASB3 can be a promising biomarker in HCC., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Comprehensive analysis of ASB3 as a prognostic biomarker in hepatocellular carcinoma”., (Copyright © 2023. Published by Elsevier Inc.)

Background: Long-term extensive use of glucocorticoids will lead to hormonal necrosis of the femoral head, and osteoblasts play an important role in the prevention of osteonecrosis. However, there is no complete cure for necrosis of the femoral head. Mesenchymal stem cell- (MSCs-) derived exosomes are widely used for the repair of various tissue lesions. Therefore, the aim of this study was to investigate the mechanism of dexamethasone- (DEX-) induced osteoblast apoptosis and the therapeutic effect of human umbilical cord MSC- (hucMSC-) derived exosome mimetic vesicles (EMVs) on osteoblast-induced apoptosis by DEX., Methods: The viability and apoptosis of primary MC3T3-E1 cells were determined by the Cell Counting Kit-8 (CCK-8), FITC-Annexin V/PI staining and immunoblot. The intracellular levels of reactive oxygen species (ROS) after DEX treatment were measured by 2', 7' -dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In this study, hucMSC-EMVs and N -acetyl-l-cysteine (NAC) were used as therapeutic measures. The expression of B-cell lymphoma 2-associated X, Bcl 2, HO-1, and nuclear factor erythroid-derived 2-like 2 and MAPK- signaling pathway in osteogenic cell MC3T3-E1 cells treated with Dex was analyzed by the immunoblotting., Results: DEX significantly induced osteoblasts MC3T3-E1 apoptosis and ROS accumulation. MAPK-signaling pathway was activated in MC3T3-E1 after DEX treatment. hucMSC-EMVs intervention significantly downregulated DEX-induced MAPK-signaling pathway activation and ROS accumulation. In addition, hucMSC-EMVs can reduce the apoptosis levels in osteoblast MC3T3-E1 cells induced by DEX., Conclusions: Our study confirmed that hucMSC-EMVs regulates MAPK-signaling pathway and ROS levels to inhibit DEX-induced osteoblast apoptosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Hongxu Lu et al.)

Ruthenium(II) polypyridyl complexes have drawn growing attention due to their photophysical properties and anticancer activity. Herein we report four ruthenium(II) polypyridyl complexes [(N^N) 2 Ru II (L)] 2+ (1-4, L = 4-anilinoquinazoline derivatives, N^N = bidentate ligands with bis-nitrogen donors) as multi-functional anticancer agents. The epidermal growth factor receptor (EGFR) is overexpressed in a broad range of cancer cells and related to many kinds of malignance. EGFR inhibitors, such as gefitinib and erlotinib, have been approved as clinical anticancer drugs. The EGFR-inhibiting 4-anilinoquinazoline ligands greatly enhanced the in vitro anticancer activity of these ruthenium(II) polypyridyl complexes against a series of human cancer cell lines compared to [Ru(bpy) 2 (phen)], but interestingly, these complexes were actually not potent EGFR inhibitors. Further mechanism studies revealed that upon irradiation with visible light, complexes 3 and 4 generated a high level of singlet oxygen ( 1 O 2 ), and their in vitro anticancer activities against human non-small-cell lung (A549), cervical (HeLa) and squamous (A431) cancer cells were significantly improved. Specifically, complex 3 displayed potent phototoxicity upon irradiation with blue light, of which the photo-toxicity indexes (PIs) against HeLa and A431 cells were 11 and 8.3, respectively. These complexes exhibited strong fluorescence emission at ca. 600 nm upon excitation at about 450 nm. A subcellular distribution study by fluorescence microscopy imaging and secondary ion mass spectrometry imaging (ToF-SIMS) demonstrated that complex 3 mainly localized at the cytoplasm and complex 4 mainly localized in the nuclei of cells. Competitive binding with ctDNA showed that complex 4 was more favorable to bind to the DNA minor groove than complex 3. These differences support that complex 3 possibly exerts its anticancer activities majorly by photo-induced 1 O 2 generation and complex 4 by binding to DNA.

A multicarrier light source based on a recirculating frequency shift loop (RFSL) driven by a parity-time (PT)-symmetric optoelectronic oscillator (OEO) is proposed and experimentally demonstrated. The impact of the side-mode suppression ratio (SMSR) of the radio frequency (RF) signal on the multicarrier is studied for the first time, to our knowledge. The RFSL driven by PT-symmetric OEO significantly optimizes the phase noise and flatness of the multicarrier, facilitating the system miniaturization. In the experiment, a 10.019 GHz RF signal with a SMSR of 42 dB is generated with -98.63 d B c / H z measured phase noise at 10 kHz offset frequency (actual phase noise should be lower than -122.87 d B c / H z ). Up to 120 subcarriers with 2.32 dB flatness are obtained successfully, covering the overall bandwidth of approximately 1.2 THz.

Bladder outlet obstruction (BOO) can cause serious complications including kidney damage; nevertheless, there are currently no animal models for studying BOO-induced kidney damage. Mesenchymal stem cells (MSCs) are widely used in therapeutic studies of renal fibrosis. However, MSC-derived exosomes show improved safety profile and more controllable characteristics compared with those of MSCs. Herein, we established a kidney injury mouse model of partial bladder outlet obstruction (PBOO) and evaluated the effects of human umbilical cord MSC-derived exosomes (hucMSC-Exos) on PBOO-induced reflux kidney injury in this model. Exosomes were isolated from a hucMSC-conditioned medium, purified by ultracentrifugation, and examined. Living image was performed to indicate the distribution of hucMSC-Exos. The PBOO-treated mice interacted with PBS (phosphate-buffered saline) or hucMSC-Exos. Morphologic changes and expression of interstitial-fibrosis-related, cell proliferation and Wnt/β-catenin signaling-pathway indices were evaluated. At 7 days after induction of PBOO, structural destruction of renal tubules was observed. Expression of the interstitial markers and the cellular-proliferation index increased significantly in the PBOO group compared with the control group. The isolated exosomes were 30-150 nm in diameter, showing a round shape and bilayer membrane structure with CD63, TSG101, Alix expressed, enriched in the kidney of the PBOO group. Administering hucMSC-Exos to post-PBOO mice reversed renal injury and suppressed expression of Wnt/β-catenin signaling pathway-related proteins. hucMSC-Exos inhibited PBOO-induced kidney injury and cellular proliferation and suppressed the Wnt/β-catenin signaling pathway. Our findings will spur the development of novel hucMSC-Exo-mediated therapies for treating patients with renal fibrosis., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Malignant rhabdoid tumor of the kidney (MRTK) has an inferior prognosis and is insensitive to radiotherapy and chemotherapy. Search for novel, potent medicinal agents is urgent. Herein, data on the gene expression and clinical characteristics of malignant rhabdoid tumors (MRT) were retrieved from the TARGET database. Prognosis-related genes were identified by differential analysis and one-way cox regression analysis, and prognosis-related signalling pathways were identified by enrichment analysis. The prognosis-related genes were imported into the Connectivity Map database for query, and BKM120 was predicted and screened as a potential therapeutic agent for MRTK. A combination of high-throughput RNA sequencing and Western blot verified that the PI3K/Akt signaling pathway is associated with MRTK prognosis and is overactivated in MRTK. Our results outlined that BKM120 inhibited the proliferation, migration, and invasion ability of G401 cells and induced apoptosis and cell cycle G0/G1 phase arrest. In vivo, BKM120 inhibited tumor growth and had no significant toxic side effects. Western blot and immunofluorescence results confirmed that BKM120 could reduce the expression of PI3K and p-AKT, critical proteins of the PI3K/Akt signaling pathway. BKM120 inhibits MRTK by inhibiting PI3K/Akt signalling pathway to induce apoptosis and cell cycle G0/G1 phase arrest, which is anticipated to give the clinical treatment of MRTK a new direction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

We investigate the role of external magnetic fields and linearly polarized pump light, especially when their directions are parallel or vertical, on the propagation of the fractional vector vortex beams (FVVBs) through a polarized atomic system. Herein, the different configurations of external magnetic fields lead to various optically polarized selective transmissions of FVVBs with different fractional topological charge α caused by the polarized atoms, which is theoretically demonstrated by the atomic density matrix visualization analysis and experimentally explored by Cesium atom vapor. Meanwhile, we find that the FVVBs-atom interaction is a vectorial process due to the different optical vector polarized states. In this interaction process, the atomic optically polarized selection property provides potential for the realization of the magnetic compass based on warm atoms. For the FVVBs, due to the rotational asymmetry of the intensity distribution, we can observe some transmitted light spots with unequal energy. Compared with the integer vector vortex beam, it is possible to obtain a more precise magnetic field direction by fitting the different "petal" spots of the FVVBs.

In this paper, we propose a novel, to the best of our knowledge, method to our knowledge for generating and accurately measuring Nyquist pulse sequences with an ultra-low duty cycle of only 0.037, which breaks the limitations caused by the noise and bandwidth of the optical sampling oscilloscope (OSO) by using a narrow-bandwidth real-time oscilloscope (OSC) and an electrical spectrum analyzer (ESA). By this method, it is found that the bias point drift of the dual parallel Mach-Zehnder modulator (DPMZM) is the main cause of the distortion of the waveform. In addition, we increase the repetition rate of Nyquist pulse sequences by a factor of 16 by multiplexing the unmodulated Nyquist pulse sequences.

Introduction: Neuroblastoma (NB) is one of the most common extracranial solid malignant tumors in children. The 5-year survival rate of high-risk or refractory NB is less than 50%. Therefore, developing new effective therapeutics for NB remains an urgent challenge. Materials and Methods: Based on the NB dataset TARGET-NBL in the TCGA database, the prognosis-related genes were analyzed using univariate cox regression ( p < 0.01). The protein network interaction of prognostic genes was analyzed using STRING to obtain 150 hub genes with HR > 1 and 150 hub genes with HR < 1. The Connectivity Map database was used to predict a therapeutic drug: BI-D1870, a ribosomal S6 kinase inhibitor. The inhibitory effect of BI-D1870 on NB was investigated through in vivo and in vitro experiments, and its inhibitory mechanism was explored. Results: Both the in vivo and in vitro experiments showed that BI-D1870 could inhibit tumor proliferation and induce tumor apoptosis. Furthermore, we proved that BI-D1870 caused G2/M phase arrest and mitosis damage in cells. RNA-seq of cells showed that BI-D1870 may inhibit the growth of NB by inhibiting the PI3K-Akt-mTOR axis. Western blot and immunofluorescence testing showed that BI-D1870 inhibited the PI3K-Akt-mTORC1 signal pathway to regulate the phosphorylation of RPS6 and 4E BP1 proteins, inhibit protein translation, and inhibit microtubule formation, thus preventing mitotic proliferation and inducing apoptosis. Conclusions: This study provides strong support that BI-D1870 may be a potential adjuvant therapy for NB.

Background: Ribonucleotide reductase regulatory subunit M2 (RRM2) has been reported to be an oncogene in some malignant tumors, such as lung adenocarcinoma, oral squamous cell carcinoma, glioblastoma, and breast cancer. However, the clinical significance of RRM2 in hepatocellular carcinoma has been less studied. The aim of this study was to assess the importance of RRM2 in hepatocellular carcinoma (HCC) based on the Cancer Genome Atlas (TCGA) database., Methods: The RRM2 expression levels and clinical features were downloaded from the TCGA database. Immunohistochemistry results between tumor tissues and normal tissues were downloaded from the Proteinatlas database. Meanwhile, the expression levels of RRM2 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Western Blotting. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein-interactions (PPI) network were constructed to analyze RRM2-related downstream molecules. In addition, RRM2 expression-related pathways performed by gene set enrichment analysis (GSEA). Association analysis of RRM2 gene expression and immune infiltration was performed by single-sample GSEA (ssGSEA)., Results: The RRM2 expression level in tumor tissues was higher than normal tissues ( P < 0.001). The elevated expression of RRM2 in HCC was significantly correlated with T stage ( P < 0.05), pathologic stage ( P < 0.05), tumor status ( P < 0.05), histologic grade ( P< 0.001), and AFP ( P < 0.001). HCC with higher RRM2 expression was positively associated with worse OS (overall survival), PFS (progression-free survival), and DSS (disease-specific survival). In the univariate analysis, the expression of RRM2, T stage, M stage, pathologic stage, and tumor status were negatively correlated with OS ( P < 0.05). Further analysis using multivariate Cox regression showed that tumor status ( P< 0.01) and RRM2 expression ( P< 0.05) were independent prognostic factors of OS in HCC. GO/KEGG analysis showed that the critical biological process (chromosome condensation and p53 signaling pathway) might be the possible function mechanism in promoting HCC. Moreover, GSEA showed that several pathways were enriched in RRM2 high-expression samples, including PD-1 signaling, cell cycle, P27 pathway, and T cell receptor signaling pathway. RRM2 was significantly correlated with the infiltration level of CD8 T cells, Cytotoxic cells, DCs, Neutrophils, NK cells, and T helper cells ( P < 0.05)., Conclusion: Over-expression of RRM2 predict adverse prognosis and is correlated with immune infiltrates in HCC. RRM2 may be a significant molecular biomarker for HCC diagnosis and prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qin, Xie, Qian, Ma, Zhang, Wei, Wang, Fan, Zhu, Qian, Yin, Zhu and Tan.)

With the aid of the newly developed 'Sunway' heterogeneous-architecture supercomputer, which has world-leading HPC (high-performance computer) capability, a series of high-resolution coupled Earth system models (SW-HRESMs) with up to 5 km of atmosphere and 3 km of ocean have been developed. These models can meet the needs of multiscale interaction studies with different computational costs. Here we describe the progress of SW-HRESMs development, with an overview of the major advancements made by the international Earth science community in HR-ESMs. We also show the preliminary results of SW-HRESMs with regard to capturing major weather-climate extremes in the atmosphere and ocean, stressing the importance of permitted clouds and ocean submesoscale eddies in modeling tropical cyclones and eddy-mean flow interactions, and paving the way for further model development to resolve finer scales with even higher resolution and more realistic physics. Finally, in addition to increasing model resolution, the development procedure for a non-hydrostatic cloud and ocean submesoscale resolved ESM is discussed, laying out the major scientific directions of such a huge modeling advancement., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Composition analysis in wine is gaining increasing attention because it can provide information about the wine quality, source, and nutrition. In this work, in situ liquid secondary ion mass spectrometry (SIMS) was applied to 14 representative wines, including six wines manufactured by a manufacturer in Washington State, United States, four Cabernet Sauvignon wines, and four Chardonnay wines from other different manufacturers and locations. In situ liquid SIMS has the unique advantage of simultaneously examining both organic and inorganic compositions from liquid samples. Principal component analysis (PCA) of SIMS spectra showed that red and white wines can be clearly differentiated according to their aromatic and oxygen-contained organic species. Furthermore, the identities of different wines, especially the same variety of wines, can be enforced with a combination of both organic and inorganic species. Meanwhile, in situ liquid SIMS is sample-friendly, so liquid samples can be directly analyzed without any prior sample dilution or separation. Taken together, we demonstrate the great potential of in situ liquid SIMS in applications related to the molecular investigation of various liquid samples in food science., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cheng, Zhou, Nelson, Ahmadullah, Piao, Wang, Guo, Wang, Lai and Zhu.)

Understanding the renal region-specific metabolic alteration in different animal models of diabetic nephropathy (DN) is critical for uncovering the underlying mechanisms and for developing effective treatments. In the present study, spatially resolved metabolomics based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to compare the local metabolic changes in the kidneys of HFD/STZ-induced diabetic rats and db/db mice. As a result, a total of 67 and 59 discriminating metabolites were identified and visualized in the kidneys of the HFD/STZ-induced diabetic rats and db/db mice, respectively. The result showed that there were significant region-specific changes in the glycolysis, TCA cycle, lipid metabolism, carnitine metabolism, choline metabolism, and purine metabolism in both DN models. However, the regional levels of the ten metabolites, including glucose, AMP, eicosenoic acid, eicosapentaenoic acid, Phosphatidylserine (36:1), Phosphatidylserine (36:4), Phosphatidylethanolamine (34:1), Phosphatidylethanolamine (36:4), Phosphatidylcholine (34:2), Phosphatidylinositol (38:5) were changed in reversed directions, indicating significant differences in the local metabolic phenotypes of these two commonly used DN animal models. This study provides comprehensive and in-depth analysis of the differences in the tissue and molecular pathological features in diabetic kidney injury in HFD/STZ-induced diabetic rats and db/db mice.

In this paper, we present an analysis of the amplitude variations of the opto-magnetic resonance absorption signals obtained in a single-beam magnetometer driven by radially or azimuthally polarized light (RPL/APL). It is shown that optically polarized atoms driven by cylindrical vector beams obtained only the alignment of atomic multipole moments but not the orientation, which is in good agreement with our simulation and experimental results. In comparison with the plane polarized pump light fields, cylindrical vector beams with much more complete electric vector polarization distribution in the transverse plane, make it unlikely to create the "emptying state " (no-atom populated) among the ground-state Zeeman sublevels for any possible orientation of the applied static magnetic field. These characteristics of the RPL/APL lead to generally smaller atomic population difference and lower response intensity of the transmitted signal. The tensor decomposition of atomic polarized states and the evolution of atomic multipole moments with the sweeping radio frequency (RF) field offer the way to show the magnetic orientation sensitivity of the radially or azimuthally polarized probe light, which possess similar profiles as that of the linearly polarized light, only with a constant phase lag of about π/2 and obvious amplitude differences.

NFIC is a potent transcriptional factor involved in many physiological and pathological processes, including tumorigenesis. However, the role of NFIC1, the longest isoform of NFIC, in the progression of triple negative breast cancer (TNBC) remains elusive. Our study demonstrates that overexpression of NFIC1 inhibits the migration and invasion of TNBC MDA-MB-231 cells. NFIC1 regulates the expression of S100A2, and knockdown of S100A2 reverses the inhibitive effects of NFIC1 on the migration and invasion of MDA-MB-231 cells. Furthermore, knockdown of S100A2 activates the MEK/ERK signaling transduction pathway that is inhibited by NFIC1 overexperssion. Treatment with MEK/ERK pathway inhibitor, U0126, abolishes the effects of S100A2 knockdown. In addition, overexpression of NFIC1 in MDA-MB-231 cells increases the expression of epithelial markers and decreases the expression of mesenchymal markers, and these effects could also be reversed by knockdown of S100A2. Collectively, these results demonstrate that NFIC1 inhibits the Epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells by regulating S100A2 expression, which suppress the activation of MEK/ERK pathway. Therefore, our study confirms the role of NFIC1 as a tumor repressor in TNBC, and reveals the molecular mechanism through which NFIC1 inhibits the migration and invasion of MDA-MB-231 cells., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fatty aldehydes (FALs) are involved in various biological processes, and their abnormal metabolism is related to the occurrence and development of neurological diseases. Because of their low ionization efficiency, methods for in situ detection and mass spectrometry imaging (MSI) analysis of FALs remain underreported. On-tissue chemical tagging of hardly ionizable target analytes with easily ionized moieties can improve ionization efficiency and detection sensitivity in MSI experiments. In this study, an on-tissue chemical derivatization-air-flow-assisted desorption electrospray ionization-MSI method was developed to visualize FALs in the rat brain. The method showed high sensitivity and specificity, allowing the use of in situ high-resolution MS 3 to identify FALs. The methodology was applied to investigate the region-specific distribution of FALs in the brains of control and diabetic encephalopathy (DE) rats. In DE rats, FALs were found to be significantly enriched in various brain regions, especially in the cerebral cortex, hippocampus, and amygdala. Thus, increased FAL levels and oxidative stress occurred in a region-dependent manner, which may contribute to cognitive function deficits in DE. In summary, we provide a novel method for the in situ detection of FALs in biological tissues as well as new insights into the potential pathogenesis of DE.

A polarization-insensitive broadband terahertz absorber with a sandwich structure of metal−dielectric-graphene is designed and simulated. The graphene is patterned as an array of graphene square blocks with circular apertures. The results of the simulations and theoretical analysis show that the absorption exceeds 99% from 0.93 to 1.65 THz while 90% from 0.80 to 1.87 THz, and a broad relative bandwidth of 80.2% is achieved. The absorption performance is passively enhanced by altering physical dimensions of the graphene pattern and actively adjusted by changing the chemical potential of graphene. When the chemical potential increases from 0.1 eV to 0.7 eV, the corresponding terahertz absorption increases from 59.1% to 99%. The mechanism of absorption is disclosed by analyzing the impedance matching theory and distribution of electric-field intensity. In addition, different polarization modes and incident angles are also studied. The proposed absorber has the superiorities of broad relative bandwidth, high absorption rate, polarization insensitivity, and a wide incident angle, which offers some potential applications in the field of terahertz technology such as imaging, detection, and cloaking.

NFIC1, the longest isoform of NFIC, is essential for the regulation on spatiotemporal expression of drug-metabolizing genes in liver. However, the role of NFIC1 in breast cancer is not clear. Here we showed that increased expression of NFIC1 suppressed the migration and invasion of MCF-7 cells. NFIC1 overexpression increased the expression of IFNB1, IFNL1, IFNL2 and IFNL3, and the activation of interferon-mediated Jak-STAT pathway was enhanced by NFIC1 overexpression. Treatment with Jak-STAT pathway inhibitors, Filgotinib or Ruxolitinib, reversed the suppressive effects of NFIC1 overexpression on migration and invasion of MCF-7 cells. In addition, we found that MX1 and MX2, two target genes of Jak-STAT pathway, mediated the migration and invasion of MCF-7 cells. These results demonstrated that NFIC1 inhibited the migration and invasion in MCF-7 cells through interferon-mediated activation of Jak-STAT pathway, indicating that Jak-STAT pathway might be a potential therapeutic target for preventing breast cancer metastasis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bacterial outer membrane vesicles (OMVs) are spherical microbubbles that contain biological content and are produced by gram-negative bacteria. The use of OMVs as adjuvants for cancer immunotherapy or as drug carriers for targeted therapies has attracted the interest of many scholars. However, it is unclear whether OMVs can exert direct antitumor effects and whether OMVs can inhibit pediatric tumors. Here, we explore the potential of Escherichia coli -derived OMVs to directly suppress neuroblastoma. Our results demonstrate the antitumor effects of OMVs in vitro and in vivo , and no serious adverse reactions were observed. OMV uptake into the cytoplasm and nucleus directly decreases cell stemness, DNA damage, apoptosis and cell cycle arrest, which may be the mechanisms by which OMVs suppress tumors. Our results demonstrate the potential of bacterial OMVs to be used as antitumor adjuvant therapies, increasing the number of candidates for the development of cancer therapies in the future. More relevant studies are urgently needed to demonstrate the efficacy and safety of OMVs.

Background: CSCs play an important role in tumor development. Some studies have demonstrated that piRNAs participate in the progression of various cancers. However, the detailed function of piRNAs in CSCs requires further investigation. This study aimed to investigate the significance of novel piRNA MW557525, one of the top five up-regulated piRNAs screened by gene chip and it has been verified by RT-q-PCR that it is indeed the most obvious up-regulated expression in Piwil2-iCSCs., Methods and Results: Differentially expressed piRNAs in Piwil2-iCSCs were screened by gene chip. Target genes were predicted by the miRanda algorithm and subjected to GO and KEGG analysis. One of the differential piRNAs, novel piRNA MW557525, was transfected and its target gene NOP56 was silenced in Piwil2-iCSCs, respectively. RT-qPCR, western blot (WB) and dual luciferase reporter assay were used to investigate the interaction of piRNA MW557525 and NOP56. We identified the effect of piRNA MW557525 and NOP56 knockdown on cell proliferation, migration, invasion, and apoptosis via CCK-8, transwell assay, and flow cytometry. The expressions of CD24, CD133, KLF4, and SOX2 were detected via WB. The results showed that piRNA MW557525 was negatively correlated with NOP56, and it promoted the proliferation, migration, invasion, and inhibited apoptosis in Piwil2-iCSCs, and it also promoted the expressions of CD24, CD133, KLF4, and SOX2, while NOP56 showed the opposite effect., Conclusions: These findings suggested that novel piRNA MW557525 might be a novel therapeutic target in Piwil2-iCSCs., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

In an atomic fountain, atoms in motion can be spatially separated into discrete Zeeman sub-states by magnetically induced Stern-Gerlach effect. With resonant light pulses acting as a shutter, specific states are selected for subsequent experiments. Such separation-selection process in atomic optics is the analogue of a spatial filter in physical optics which selects and purifies the modes of light. This technique is demonstrated by injecting a pulsed current in a circular coil around a vertical atomic fountain, separating the pre-cooled Rubidium atoms by a distance of centimeters in between, and filtering each single sub-state with block pulses. The filtered atoms after the process is highly purified in the desired sub-state. The apparatus of the atomic spatial filter is adaptable in atomic optics and can be integrated into the high-vacuum chamber of an atomic fountain.

In the era of Corona Virus Disease 2019 (COVID-19), inappropriate indoor ventilation may turn out to be the culprit of microbial contamination in enclosed spaces and deteriorate the environment. To collaboratively improve the thermal comfort, air quality and virus spread control effect, it was essential to have an overall understanding of different ventilation modes. Hence, this study reviewed the latest scientific literature on indoor ventilation modes and manuals of various countries, identified characteristics of different ventilation modes and evaluated effects in different application occasions, wherefore to further propose their main limitations and solutions in the epidemic era. For thermal comfort, various non-uniform ventilation modes could decrease the floor-to-ceiling temperature difference, draft rate or PPD by 60%, 80% or 33% respectively, or increase the PMV by 45%. Unsteady ventilation modes (including intermittent ventilation and pulsating ventilation) could lower PPD values by 12%-37.8%. While for air quality and virus spread control, non-uniform ventilation modes could lower the mean age of air or contaminants concentration by 28.3%-47% or 15%-47% respectively, increase the air change efficiency, contaminant removal effectiveness or protection efficiency by 6.6%-10.4%, 22.6% or 14%-50% respectively. Unsteady ventilation mode (pulsating ventilation) could reduce the peak pollutant concentration and exposure time to undesirable concentrations by 31% and 48% respectively. Non-uniform modes and unsteady modes presented better performance in thermal comfort, air quality and virus spread control, whereas relevant performance evaluation indexes were still imperfect and the application scenarios were also limited., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

Airy beams have provided exciting inspiration in the field of optical communication, particle manipulation, and imaging. We investigate the propagation properties of the exponential truncation Airy beams (ETABs) on constant Gaussian curvature surfaces (CGCSs) in this paper. The analytical expression of the electric field of ETABs propagating on the CGCSs is derived. It shows that the equivalent periodical accelerations of the trajectories of ETABs on the curved surface are always larger than the constant one on the flat surface because the CGCSs have a strong focusing ability. For the same reason, the non-diffraction propagation of ETABs is found when the focusing ability of the CGCSs is strong enough. Moreover, we investigate the self-healing length of ETABs on CGCSs and explore that the ability of self-healing is related to the geometry of CGCSs besides the width of the block and the size of the beam. The self-healing length gets larger with the increase of radius of CGCSs and finally consists with that on the flat surface. These propagation characteristics are different from those in the flat space and are useful for the future applications of ETABs in particle manipulation on waveguides, light-sheet fluorescence microscopy, curved nanophotonics, and so on.

Calommata signata, a burrowing spider, represents a special type of predation mode in spiders, and its utilization of toxins is different from that of web-weaving spiders and wandering spiders. The existing researches on spider toxins are mainly focused on the web-weaving and wandering spiders, but little attention on that of the burrowing spiders. Through transcriptome sequencing of C. signata venom gland and the remaining part as the counterpart tissue, 25 putative neurotoxin precursors were identified. These most neurotoxins were novel because their low similarities with the known sequences except for that of over 50% similarities in four neuropeptide toxins. The 25 neuropeptide toxins were divided into five families according to the constitution of cysteines for the possible disulfide bonds and the similarities of the deduced amino acid sequences. Besides neuropeptide toxins, other potential toxins in the venom gland were also analyzed. Unlike web-weaving spiders and wandering spiders, only a few neurotoxin genes were significantly expressed in the venom gland of C. signata. In the non-peptide toxin genes, only CsTryp&#95;SPc-1, CsPA2-1, CsVa5-2 and four PDI genes were abundantly expressed in the venom gland. The present study provided an improved understanding on the spider toxin diversity and useful information for the exploitation of spider toxins., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The angular momentum (AM) of light has important implications for many fields of optics research, such as optics communication, quantum information and laser-scan microscopy. Thus, in this paper, we intend to investigate the average AM of the vortex ultrashort pulsed beam (VUPB), which is generated and widely applied in the field of high-intensity and ultrafast regimes. According to the vector potential, we firstly derive the electromagnetic field of the VUPB, then analyze the spatial intensity, the phase profile and the polarization state of the beam. We explore that the total AM per photon of VUPB is not n ℏ value when the beam waist w 0 is of wavelength or sub-wavelength order, since the polarization of VUPB is changed from linear to circular polarization with the decrease of beam waist, which introduces the conversion of the orbital AM to the spin AM. Moreover, based on the conservation of the total AM, the minimum waist of VUPB can be obtained, which is dependent on the pulse duration time α and topological charge n. Finally, the average AM of the fractional VUPB expressed by the superposition of the integer VUPB with different weights, is analyzed, which is not equal to the AM of fractional CW beam μ - sin (2μπ)/2π (μ is the fractional topological charge), but is associated with the beam waist w 0 and α. Therefore, we think that the AM of VUPB can be controlled by adjusting the α and w 0 .

The Rindler space-time describing a series of accelerating observers is Ricci flat, but it still has novel optical effects. In the case of Wenzel, Kramers, and Brillouin (WKB) approximation, we derive the light paths in the Rindler frame based on the covariant wave equation and geodesic equations. Then, we use ABCD matrix optics method to explore the propagation characteristics of Rindler frame, thus link three different optical transformation scenes (geometry, gravity, and vacuum refractive index) together. Moreover, the propagation characteristics of hollow beam in Rindler space-time are described analytically. In the longitudinal direction, we demonstrate the shift and stretch effects of the dark spot of a beam, while the transverse spot size is proved to be convergence in the accelerated system, and the wavefront curvature can tend a constant twice the acceleration at the far field. Those characteristics are quite different from the ones in the flat space-time. Based on these calculations, we simply demonstrate the position uncertain relationship between the transverse beam size and the momentum, which surprisingly coincides with the derivation of quantization. We hope that we can provide one simple method to analyze the beam propagation in the accelerated frame.

Modafinil is a mild psychostimulant-like drug enhancing wakefulness, improving attention and developing performance in various cognitive tasks, but its mechanism of action is not completely understood. This is the first combination of amperometry, electrochemical cytometry and mass spectrometry to interrogate the mechanism of action of a drug, here modafinil, at cellular and sub-cellular level. We employed single-cell amperometry (SCA) and intracellular vesicle impact electrochemical cytometry (IVIEC) to investigate the alterations in exocytotic release and vesicular catecholamine storage following modafinil treatment. The SCA results reveal that modafinil slows down the exocytosis process so that, the number of catecholamines released per exocytotic event is enhanced in the modafinil-treated cells. Also, IVIEC results offer an upregulation effect of modafinil on the vesicular catecholamine storage. Mass spectrometry imaging by time-of-flight secondary ion mass spectrometry (ToF-SIMS) illustrates that treatment with modafinil reduces the cylindrical-shaped phosphatidylcholine at the cellular membrane, while the high curvature lipids with conical structures such as phosphatidylethanolamine and phosphatidylinositol are elevated after modafinil treatment. Combining the results obtained by SCA, IVIEC and ToF-SIMS suggests that modafinil-treated cells release a larger portion of their vesicular content at least in part by changing the lipid composition of the cell membrane, suggesting regulation of cognition., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2021.)

We demonstrate the generation of a type of square-shaped pulse in a passively mode-locked erbium-doped fiber laser based on the nonlinear optical loop mirror technique. Through adjusting the pump power and polarization state, square-shaped pulses are generated. Furthermore, we investigate the pulse profile in relation to the optical spectrum. By filtering out short-wavelength spectrum components gradually, pulse shaping is achieved, and the top of the square-shaped pulse becomes flat. Subsequently, by filtering out long-wavelength spectrum components, a type of h-shaped pulse is obtained and the formation reason is also investigated.

Starting from the wave equation with a non-zero space curvature, a generalized coordinate-independent expression for the evolution of a light beam on a curved space is derived. By defining the propagation axes, the expression reduces to integrable Green functions without an inevitable singular point. With a Gaussian incident field, the stationary status and refocusing effect of the light field on different shapes of curved surfaces are discussed. Different from a constant diffusion behavior in a flat space, the field experiences a periodical diffraction and refocusing spontaneously with no additional optical elements. To be more specific, we noticed that the laser field on a curved surface experiences a fractional Fourier transform, with a propagation angle to be the transform order. We hope our theoretical results can provide some references for the practical application in a curved surface space.

Cisplatin is an extremely successful anticancer drug, and is commonly thought to target DNA. However, the way in which cisplatin-induced DNA lesions regulate interactions between transcription factors/cofactors and genomic DNA remains unclear. Herein, we developed a dual-modal microscopy imaging strategy to investigate, in situ , the formation of ternary binding complexes of the transcription cofactor HMGB1 and transcription factor Smad3 with cisplatin crosslinked DNA in single cells. We utilized confocal microscopy imaging to map EYFP-fused HMGB1 and fluorescent dye-stained DNA in single cells, followed by the visualization of cisplatin using high spatial resolution (200-350 nm) time of flight secondary ion mass spectrometry (ToF-SIMS) imaging of the same cells. The superposition of the fluorescence and the mass spectrometry (MS) signals indicate the formation of HMGB1-Pt-DNA ternary complexes in the cells. More significantly, for the first time, similar integrated imaging revealed that the cisplatin lesions at Smad-binding elements, for example GGC(GC)/(CG) and AGAC, disrupted the interactions of Smad3 with DNA, which was evidenced by the remarkable reduction in the expression of Smad-specific luciferase reporters subjected to cisplatin treatment. This finding suggests that Smad3 and its related signalling pathway are most likely involved in the intracellular response to cisplatin induced DNA damage., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Skeletal muscle tissue is composed of various muscle cell types which differ in physiological functions. Changes in cell type composition of skeletal muscle are associated with the development of metabolic diseases. Skeletal muscle cell types are currently distinguished by immunofluorescence (IF) staining based on myosin heavy chain (MHC) isoform difference. However, it remains a challenge to provide metabolic fingerprints of different muscle cell types by IF staining. Therefore, in this study, we proposed a method to examine metabolite distribution within different cell types by time-of-flight secondary ion mass spectrometry (TOF-SIMS) with high spatial resolution. Skeletal muscle samples from C57/BL6 mice were obtained by slicing. Cell types in TOF-SIMS images were labelled corresponding to IF images from the same region of serially cut sections. Mass spectra corresponding to individual muscle cells were extracted to compare metabolic fingerprints among cell types. Skeletal muscle cells were classified into two clusters based on the mass spectra of individual cells. Unsaturated diacylglycerol (DG) and fatty acid (FA) species were found to be distributed in a cell-type dependent manner. Moreover, relative quantification showed that the content of unsaturated DGs, oleic acid and linoleic acid was higher in type I and type IIA cells than in type IIB cells. TOF-SIMS in combination with IF enables us to directly visualize metabolite distribution in different cell types, to find potential biomarkers for cell type classification. TOF-SIMS imaging coupled with IF staining has been proved to be a promising tool for metabolic fingerprinting of different skeletal muscle cell types.

Ultrafast linear frequency modulated continuous-wave (FMCW) lasers are a special category of CW lasers. The linear FMCW laser is the light source for many sensing applications, especially for light detection and ranging (LiDAR). However, systems for the generation of high quality linear FMCW light are limited and diverse in terms of technical approaches and mechanisms. Due to a lack of characterization methods for linear FMCW lasers, it is difficult to compare and judge the generation systems in the same category. We propose a novel scheme for measuring the mapping relationship between instantaneous frequency and time of a FMCW laser based on a modified coherent optical spectrum analyzer (COSA) and digital signal processing (DSP) method. Our method has the potential to measure the instantaneous frequency of a FMCW laser at an unlimited sweep rate. In this paper, we demonstrate how to use this new method to precisely measure a FMCW laser at a large fast sweep rate of 5000 THz/s by both simulation and experiments. We find experimentally that the uncertainty of this method is less than 100 kHz and can be improved further if a frequency feedback servo system is introduced to stabilize the local CW laser.

Platinum(II) terpyridine complexes has attracted increasing attention as they have displayed great potential as antitumor agents due to their high intercalation affinity with nucleic acids. Epidermal growth factor receptor (EGFR) is often overexpressed in various tumor cells, leading to uncontrolled growth of tumor, and is regarded as an important target for developing novel antitumor drugs. Herein, we report four platinum(II) terpyridine complexes bearing EGFR inhibiting 4-anilinoquinazoline derivatives as potent multi-targeting antiproliferation agents against a series of cancer cells. EGFR inhibition assay revealed that these complexes are highly potent EGFR inhibitors. But competitive DNA binding assay and docking simulations also suggested that these complexes exhibited multiple modes of DNA interaction, especially great affinity toward DNA minor groove. Finally, cellular uptake and distribution measurements by inductively coupled plasma mass spectrometry (ICP-MS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) demonstrated that both nucleus DNA and membrane proteins are important targets for their anticancer mechanisms. The complexes herein can therefore be regarded as promising multi-targeting anticancer agents., (Copyright © 2020 Li, Xu, Zhao, Zheng, Zeng, Luo, Wang, Wu, Du and Wang.)

A core-shell hybrid of ZnO and nitrogen-doped carbon (ZnO@C:N) is designed as a long-cycling anode for LIBs. The ZnO@C:N hybrid has a high initial capacity of 1116 mA h g-1 and a reversible capacity of 608 mA h g-1 after 500 cycles at 0.1 A g-1. The unique core-shell structure, high conductivity due to nitrogen doping, and uniform solid electrolyte interphase (SEI) film formed in the electrode are revealed to result in the remarkable electrochemical performances of the ZnO@C:N electrodes.

In most papers about the fractional vortex continuous beams (FVCBs), the relationship between the total vortex strength S α and the propagation distance is not analyzed since the vortex structure is not stable in the near field. In this paper, we theoretically study the fractional vortex ultrashort pulsed beams (FVUPBs) possessing non-integer topological charges α at arbitrary plane and find that the vortex structure is propagation-distance-dependent. Both the intensity and phase distributions are calculated to analyze the vortex structure. To evaluate the propagation properties of FVUPBs, we focus on the total vortex strength (TVS) of FVUPBs to investigate the number of vortex, and demonstrate that the birth of a vortex is at α = m + ɛ, where m is an integer, ɛ is a changing fraction depending on the pulse durations, peak wavelengths and propagation distances. Furthermore, we discover that the FVUPBs carry decreasing TVS along the propagation axis in free space. This special vortex structure for FVUPBs appears due to the mixture weight of vortex pulsed beam with different integer topological charges (TCs) n. However, the total orbital angular momentum is invariant during propagation. The above phenomenon presented in our paper are totally particular and intriguing compared with the FVCBs.

FeSe2-carbon nanotube (FeSe2-CNT) hybrid microspheres are investigated as anode materials for lithium ion batteries (LIBs), exhibiting a high specific capacity of 571.2 mA h g-1 at 0.5 A g-1 with excellent rate performance and cycling stability. The FeSe2-CNT hybrid LIBs could withstand the high-voltage pulse of triboelectric nanogenerators (TENGs) and be charged by TENGs directly for harvesting energy with high stability.

Background: Laparoscopic hepatectomy (LH) has been reported as a safe and efficacious treatment for hepatocellular carcinoma (HCC) patients. However, in cirrhosis patients, LH may be more complex and challenging. So, the short- and long-term outcomes should be well evaluated between LH and open hepatectomy (OH) in HCC patients with cirrhosis. Objectives: To compare the short- and long-term outcomes of LH with OH in HCC patients with cirrhosis. Materials and Methods: The PubMed, EMBASE, and Web of Science were systematically searched to identify the clinical trials published until July 2018 on the comparison of LH and OH in HCC patients with cirrhosis. The statistical analysis was conducted by the Review Manager 5.3 (Cochrane Collaboration, Oxford, United Kingdom). Short-term outcomes included blood loss, operation time, blood transfusion, postoperative complications, mortality, postoperative hospital stay, tumor size, and surgical margin. Long-term outcomes included 1-, 3-, 5-year overall survival (OS) and 1-, 3-, 5-year disease-free survival (DFS). Results: Seventeen studies with 2004 patients were included in this meta-analysis. For short-term outcomes, LH suggested less blood loss, lower blood transfusion rates, reduced occurrence of postoperative complications, wider surgical margin, shorter postoperative hospital stay, and declined rate of mortality (all P  < .05). However, there was no significant difference in operation time ( P  = .67) between the two groups, whereas tumor size was larger in OH ( P  = .004). As to long-term outcomes, 1-, 3-, 5-year OS and 1-year DFS were higher in LH group (all P  < .05). Nevertheless, there were no significant differences in 3- and 5-year DFS ( P  = .23 and .83, respectively). Conclusions: For the HCC patients with cirrhosis, current evidence suggests that LH shows not only better outcomes in short term, but also a comparable and even improved long-term prognosis.

The cold atom absolute gravimeters are intrinsically sensitive to its orientation due to the Coriolis effect, which should be understood clearly and compensated for field applications. The sensitivity on the orientation for a free-fall atom gravimeter is investigated in this paper. The apparatus is simplified and improved a lot such that fast adjustment and measurement could be carried out within 20 minutes. From the experimental results, it is found that the orientation angle has a dominant influence on the absolute gravity measurement, especially when the horizontal velocity of atoms is non-negligible. Besides, the magnitude and direction of average horizontal velocity of the detected atoms are obtained in this experiment. In particular, the direction of East-West has been measured by the atom gravimeter itself, such that gravity bias arising from Coriolis effect is estimated precisely.

Hybrids of iridium-cobalt phosphates (IrCo-Pi) were prepared via a facile co-electrodeposition approach and employed as an electrocatalyst for the oxygen evolution reaction (OER). IrCo-Pi with an optimized Ir-to-Co ratio (RIr-to-Co) exhibited an intrinsic activity toward the OER superior to the two well-known catalysts: cobalt phosphate (Co-Pi) and iridium phosphate (Ir-Pi).

We observe the transient evolution of the laser pumped magnetic resonance in a paraffin-coated rubidium vapor cell and analyze the phenomena numerically by using the four-level density matrix. With the increased radio frequency (RF) sweep rate, the traditional Lorentz signal turns to an asymmetric shape at low sweep rate and starts to oscillate at a high sweep rate. The transient oscillation's features, including frequency and the decay time, are studied by suddenly turning on the RF field to the resonance Larmor precession frequency under the different RF field and light field parameters. The experimental result reveals the transient signals' strong dependence on the RF field power and light power. Especially, the transient oscillation frequency primarily depends on the RF field's power and whatever power the laser light is. When the laser power is lower, the transient oscillation frequency is proportional to the RF field's amplitude. These transient evolution signals are also confirmed with the numerical calculations based on the density-matrix equation of motion.

Accurate evaluation of morphological and physiological traits is critical for selection of wheat ( Triticum aestivum L.) cultivars exhibiting high yield, which is stable over different growing conditions. In order to use selection index based on high yield, high grain quality and drought tolerance in wheat, a set of 145 CIMMYT Wheat Physiological Germplasm Screening Nursery lines and seven local spring wheat varieties were phenotyped and evaluated for physiological and yield traits under two irrigation regimes during the 2011 and 2012 growing seasons in Xinjiang, China. The results showed that drought-stress significantly increased canopy temperature but reduced grain yield, grain weight per spike, normalized difference vegetation index at the flowering and grain filling stages, chlorophyll content at the grain filling stage, grain plumpness, grain number per spike, thousand-grain weight, and plant height. Grain weight per spike, plant height and grain plumpness explained 61.8% of the total phenotypic variation in grain yield under no-stress conditions, where they were the three principal factors most closely related to grain yield. Under drought-stress conditions, canopy temperature at the grain filling stage, plant height and grain plumpness were the three principal factors affecting grain yield, and contributed 44.8% of the total phenotypic variation in grain yield. Finally, ten genotypes, including three local varieties, 'Xinchun 11', 'Xinchun 23' and 'Xinchun 29', with appropriate plant height and high and stable yield under both no-stress and drought-stress conditions over the two years of trials, were identified and can be recommended as core parents for spring wheat drought tolerance breeding in Xinjiang, China.