Research on Online Monitoring Technology and Filtration Process of Inclusions in Aluminum Melt.

Online monitoring and real-time feedback on inclusions in molten metal are essential for metal quality control. However, existing methods for detecting aluminum melt inclusions face challenges, including interference, prolonged processing times, and latency. This paper presents the design and development of an online monitoring system for molten metal inclusions. Initially, the system facilitates real-time adjustment of signal acquisition parameters through a multiplexer. Subsequently, it employs a detection algorithm capable of swiftly extracting pulse peaks, with this task integrated into our proprietary host computer software to ensure timely detection and data visualization. Ultimately, we developed a monitoring device integrated with this online monitoring system, enabling the online monitoring of the aluminum alloy filtration process. Our findings indicate that the system can accurately measure the size and concentration of inclusions during the filtration process in real time, offering enhanced detection speed and stability compared to the industrial LiMCA CM (liquid metal cleanliness analyzer continuous monitoring) standard. Furthermore, our evaluation of the filtration process demonstrates that the effectiveness of filtration significantly improves with the increase in inclusion sizes, and the synergistic effect of combining CFF (ceramic foam filter) and MCF (metallics cartridge filter) filtration methods exceeds the performance of the CFF method alone. This system thus provides valuable technical support for optimizing filtration processes and controlling inclusion quality.

An Online Monitoring System for In Situ and Real-Time Analyzing of Inclusions within the Molten Metal.

Traditional methods for assessing the cleanliness of liquid metal are characterized by prolonged detection times, delays, and susceptibility to variations in sampling conditions. To address these limitations, an online cleanliness-analyzing system grounded in the method of the electrical sensing zone has been developed. This system facilitates real-time, in situ, and quantitative analysis of inclusion size and amount in liquid metal. Comprising pneumatic, embedded, and host computer modules, the system supports the continuous, online evaluation of metal cleanliness across various metallurgical processes in high-temperature environments. Tests conducted with gallium liquid at 90 °C and aluminum melt at 800 °C have validated the system's ability to precisely and quantitatively detect inclusions in molten metal in real time. The detection procedure is stable and reliable, offering immediate data feedback that effectively captures fluctuations in inclusion amount, thereby meeting the metallurgical industry's demand for real-time analyzing and control of inclusion cleanliness in liquid metal. Additionally, the system was used to analyze inclusion size distribution during the hot-dip galvanizing process. At a zinc melt temperature of 500 °C, it achieved a detection limit of 21 µm, simultaneously providing real-time data on the size and amount distribution of inclusions. This represents a novel strategy for the online monitoring and quality control of zinc slag throughout the hot-dip galvanizing process.

Exploring the performance of protected areas in alleviating future human pressure.

Protected areas (PAs) are effective in mitigating human pressures, yet their future pressure alleviating effects remain unclear. In this study, we employed the ConvLSTM model to forecast the future human footprint and analyzed human pressure trends using Theil-Sen median and Mann-Kendall tests. We further evaluated the mitigating effects of PAs within their buffer zones (1-10 km) and the contributions of different IUCN categories of PAs to mitigating human pressure using linear regression models. The results indicate that by 2035, the average human pressure value is expected to increase by 11%, with trends exhibiting a polarized pattern. Furthermore, PAs also effectively mitigate human pressure within their 1 km buffer zones. Different categories of PAs vary in their effectiveness in mitigating human pressure, and stricter conservation areas are not always the most effective. This study can offer insights for evaluating the effectiveness of PAs in reducing human pressure and advocate for their targeted management in urban areas.

Bioinformatics-Based Screening of Key LncRNAs for Modulating the Transcriptome Associated with Glaucoma in Human Trabecular Meshwork Cells.

OBJECTIVE: The morphology and functions of the human trabecular meshwork (HTM) are dysregulated in glaucoma, and the molecular mechanisms of this dysregulation remain unknown. According to an established in vitro model, whose function was to study the regulatory networks sustaining the response of HTM cells to the increased substrate stiffness, we systematically analyzed the expression pattern of long noncoding RNAs (lncRNAs), the important regulatory RNAs in cells. METHODS: Bioinformatics analysis was performed to identify the dysregulated lncRNAs in response to increased substrate stiffness using transcriptome sequencing data (RNA-seq). Then we interfered with the expression of several dysregulated lncRNAs in HTM cells to explore their molecular targets. The cross-linking immunoprecipitation and sequencing method (CLIP-seq) was used to identify enhancer of zeste homolog 2 (EZH2)-targeted RNAs in HTM cells. The chromatin IP and sequencing method (ChIP-seq) was used to identify the targets of EZH2 and histone H3 at lysine 27 (H3K27me3). RESULTS: The response of thousands of dysregulated lncRNAs to increased substrate stiffness was identified through RNA-seq. Functional prediction of these lncRNAs revealed that they potentially regulated key biological processes, including extracellular matrix (ECM) organization. By interfering with the expression of lncRNA SHNG8, ZFHX4-AS1, and RP11-552M11.4, the results demonstrated that those lncRNAs extensively regulated the expression levels of ECM-associated genes. Moreover, we found that EZH2 expression was significantly decreased at high substrate stiffness. Using CLIP-seq to identify EZH2-targeted RNAs in HTM cells, we found that SNHG8 was bound by EZH2. According to the CLIP-seq data of EZH2, we found that EZH2 binding sites were observed in the transcripts of SNHG8-regulated genes, but not in the ChIP-seq results of EZH2 and H3K27me3. CONCLUSION: Our results suggest that SNHG8 and EZH2 may cooperate to regulate the expression of a subset of genes by influencing their RNA abundance, explaining how they support HTM cell morphology and high density. This study contributes to the understanding of the alteration of HTM during the progression of glaucoma by identifying functional lncRNAs, especially SNHG8, and suggests novel therapeutic targets to treat glaucoma.

Identification of a cisplatin resistant-based prognostic immune related gene signature in MIBC.

Cisplatin resistance plays a significant role in the dismal prognosis and progression of muscle-invasive bladder cancer (MIBC). However, the strategies to predict prognosis and cisplatin resistance are inefficient, and it remains unclear whether cisplatin resistance is associated with tumor immunity. In this study, we integrated the transcriptional data from cisplatin-resistant cell lines and a TCGA-MIBC cohort to establish cisplatin-resistance-related cluster classification and a cisplatin-resistance-related gene risk score (CRRGRS). Kaplan-Meier survival curves showed that compared with those in low CRRGRS group, MIBC patients belonging to high CRRGRS group had worse prognosis in TCGA-MIBC cohort and external GEO cohorts. Meanwhile, CRRGRS was able to help forecast chemotherapy and immunotherapy response of MIBC patients in the TGCA cohort and IMvigor210 cohort. Moreover, compared with the low CRRGRS group, the high CRRGS group possessed a relatively immunosuppressive "cold tumor" phenotype with a higher tumor immune dysfunction and exclusion (TIDE) score, ESTIMATE score, stromal score and immune score and a lower immunophenoscore (IPS) score. The upregulated expression levels of immune checkpoint genes, including PD-1, PD-L1 and CTLA4, in the high CRRGRS group also further indicated that a relative immunosuppressive tumor microenvironment may exist in MIBC patients belonging to high CRRGRS group. In addition, we integrated CRRGRS and clinical characteristics with prognostic value to develop a nomogram, which could help forecast overall survival of MIBC patients. Furthermore, DIAPH3 was identified as a regulator of proliferation and cisplatin resistance in MIBC. The expression of DIAPH3 was increased in cisplatin-resistant cell lines and chemotherapy-unsensitive people. Further mechanism exploration revealed that DIAPH3 facilitated tumor proliferation and cisplatin resistance by regulating the NF-kB and epithelial-mesenchymal transition (EMT) pathways. In conclusion, the comprehensive investigations of CRRGRS increased the understanding of cisplatin resistance and provided promising insights to restrain tumor growth and overcome chemoresistance by targeting DIAPH3.

A Biomimetic Synthetic Strategy Can Provide Keratan Sulfate I and II Oligosaccharides with Diverse Fucosylation and Sulfation Patterns.

Keratan sulfate (KS) is a proteoglycan that is widely expressed in the extracellular matrix of various tissue types, where it performs multiple biological functions. KS is the least understood proteoglycan, which in part is due to a lack of panels of well-defined KS oligosaccharides that are needed for structure-binding studies, as analytical standards, to examine substrate specificities of keratinases, and for drug development. Here, we report a biomimetic approach that makes it possible to install, in a regioselective manner, sulfates and fucosides on oligo-N-acetyllactosamine (LacNAc) chains to provide any structural element of KS by using specific enzyme modules. It is based on the observation that α1,3-fucosides, α2,6-sialosides and C-6 sulfation of galactose (Gal6S) are mutually exclusive and cannot occur on the same LacNAc moiety. As a result, the pattern of sulfation on galactosides can be controlled by installing α1,3-fucosides or α2,6-sialosides to temporarily block certain LacNAc moieties from sulfation by keratan sulfate galactose 6-sulfotransferase (CHST1). The patterns of α1,3-fucosylation and α2,6-sialylation can be controlled by exploiting the mutual exclusivity of these modifications, which in turn controls the sites of sulfation by CHST1. Late-stage treatment with a fucosidase or sialidase to remove blocking fucosides or sialosides provides selectively sulfated KS oligosaccharides. These treatments also unmasked specific galactosides for further modification by CHST1. To showcase the potential of the enzymatic strategy, we have prepared a range of poly-LacNAc derivatives having different patterns of fucosylation and sulfation and several N-glycans decorated by specific arrangements of sulfates.

Comprehensive analysis of zinc and ring finger 3 in prognostic value and pan-cancer immunity.

Zinc and ring finger 3 (ZNRF3) is a negative suppressor of Wnt signal and newly identified as an important regulator in tumorigenesis and development. However, the pan-cancer analysis of ZNRF3 has not been reported. We found that ZNRF3 was significantly decreased in six tumors including CESC, KIRP, KIRC, SKCM, OV, and ACC, but increased in twelve tumors, namely LGG, ESCA, STES, COAD, STAD, LUSC, LIHC, THCA, READ, PAAD, TGCT, and LAML. Clinical outcomes of cancer patients were closely related to ZNRF3 expression in ESCA, GBM, KIRC, LUAD, STAD, UCEC, LGG, and SARC. The highest genetic alteration frequency of ZNRF3 occurred in ACC. Abnormal expression of ZNRF3 could be attributed to the differences of copy number variation (CNV) and DNA methylation as well as ZNRF3-interacting proteins. Besides, ZNRF3 were strongly associated with tumor heterogeneity, tumor stemness, immune score, stromal score and ESTIMATE score in certain cancers. In terms of immune cell infiltration, ZNRF3 was positively correlated to infiltration of cancer-associated fibroblasts in CESC, HNSC, OV, PAAD, PRAD, and THYM, but negatively associated with infiltration of CD8 T cells in HNSC, KIRC, KIRP and THYM. Moreover, ZNRF3 expression was correlated with most immune checkpoint genes in SARC, LUSC, LUAD, PRAD, THCA, UVM, TGCT, and OV, and associated with overwhelming majority of immunoregulatory genes in almost all cancers. Most RNA modification genes were also remarkably related to ZNRF3 level in KIRP, LUAD, LUSC, THYM, UVM, PRAD, and UCEC, indicating that ZNRF3 might have an important effect on cancer epigenetic regulation. Finally, we verified the expression and role of ZNRF3 in clinical specimens and cell lines of renal cancer and liver cancer. This study provides a comprehensive pan-cancer analysis of ZNRF3 and reveals the complexity of its carcinogenic effect.

Full-length single-molecule protein fingerprinting.

Proteins are the primary functional actors of the cell. While proteoform diversity is known to be highly biologically relevant, current protein analysis methods are of limited use for distinguishing proteoforms. Mass spectrometric methods, in particular, often provide only ambiguous information on post-translational modification sites, and sequences of co-existing modifications may not be resolved. Here we demonstrate fluorescence resonance energy transfer (FRET)-based single-molecule protein fingerprinting to map the location of individual amino acids and post-translational modifications within single full-length protein molecules. Our data show that both intrinsically disordered proteins and folded globular proteins can be fingerprinted with a subnanometer resolution, achieved by probing the amino acids one by one using single-molecule FRET via DNA exchange. This capability was demonstrated through the analysis of alpha-synuclein, an intrinsically disordered protein, by accurately quantifying isoforms in mixtures using a machine learning classifier, and by determining the locations of two O-GlcNAc moieties. Furthermore, we demonstrate fingerprinting of the globular proteins Bcl-2-like protein 1, procalcitonin and S100A9. We anticipate that our ability to perform proteoform identification with the ultimate sensitivity may unlock exciting new venues in proteomics research and biomarker-based diagnosis.

Drought Stress Inhibits Starch Accumulation in Taro (Colocasia esculenta L. Schott).

BACKGROUND: Colocasia esculenta L. Schott is a main traditional root crop in China, serving as an important vegetable and staple food. Drought stress plays vital role on the growth and development of taro corm. METHODS: Two different varieties of taro in Jiangsu were selected: Xiangsha taro and Longxiang taro. The accumulation characteristics, morphological structure, and physicochemical properties of taro corm starch were studied by microscopic observation, particle size analysis, and X-ray diffractometer (XRD) analysis. Transcriptome analyses were used to identify the related genes of taro corm under drought stress. RESULTS: During the growth of taro, the number of amyloplasts showed an obvious increasing trend and shifted from being dispersed throughout the cells to being gathered on one side of the cells, and morphological observations showed that smaller granular distribution gradually changed to a larger lumpy distribution. The particle size of Longxiang taro is smaller than that of Xiangsha taro. Under drought stress conditions, the occurrence of starch grains and corm size were inhibited in Xiangsha taro. Transcriptome sequencing of drought-stressed taro corms showed that the enzymes related to starch synthesis were differentially expressed. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of drought-stressed taro corms showed that drought affected hormone signal transduction, material metabolism, drought stress tolerance, plant growth and development, and stress resistance, which triggered the plant drought adaptive response. CONCLUSIONS: Drought stress inhibits starch accumulation in taro.

The mitochondrial genome and life history of Tomostethus sinofraxini (Hymenoptera: Tenthredinidae), an emerging pest of Fraxinus chinensis.

Tomostethus sinofraxini Wang & Wei (a new name is proposed for Tomostethus fraxini Niu & Wei, 2022: Tomostethus sinofraxini Wang & Wei, nom. nov.), an emerging sawfly pest of the Chinese ash, Fraxinus chinensis, is now endemic to Beijing, Tianjin, Hebei, and Shandong provinces. Given the severity of its infestation and the speed of its range expansion, we studied the phylogenetic relationship of T. sinofraxini with other sawfly species and its life history to be better informed for the management strategies. The nearly complete T. sinofraxini mitogenome is 16,169 bp in length and encodes 2 ribosomal RNAs (rrnL and rrnS), 22 transfer RNAs (tRNAs), and 13 protein-coding genes. The nucleotide composition is biased toward adenine and thymine (A + T = 81.7%). In comparison to the architecture of the ancestral insect mitogenome, 2 transposition events occur on the IQM tRNA cluster, rearranging it from IQM to MQI. Our phylogenetic analysis suggests that T. sinofraxini belongs to a group composed of paraphyletic subfamilies Blennocampinae and Heterarthrinae. In addition, to document its life history, we observed T. sinofraxini development at 2 geographical locations in Beijing, China, with different altitudes. At Jiulong Mountain, with a higher altitude and a lower average temperature, the developmental time of egg, larval, and adult stages was 19%-31% longer than that observed at the Chinese Academy of Forestry. A basic understanding of biological traits and molecular signatures is the critical first step to develop an integrated pest management framework for this emerging pest of the Chinese ash.

Chemo-Enzymatic Synthesis of Isomeric I-branched Polylactosamines Using Traceless Blocking Groups.

Poly-N-acetyl lactosamines (polyLacNAc) are common structural motifs of N- and O-linked glycan, glycosphingolipids and human milk oligosaccharides. They can be branched by the addition of ß1,6-linked N-acetyl-glucosamine (GlcNAc) moieties to internal galactoside (Gal) residues by the I-branching enzyme beta-1,6-N-acetylglucosaminyltransferase 2 (GCNT2). I-branching has been implicated in many biological processes and is also associated with various diseases such as cancer progression. Currently, there is a lack of methods that can install, in a regioselective manner, I-branches and allows the preparation of isomeric poly-LacNAc derivatives. Here, we described a chemo-enzymatic strategy that addresses this deficiency and is based on the enzymatic assembly of an oligo-LacNAc chain that at specific positions is modified by a GlcNTFA moiety. Replacement of the trifluoroacetyl (TFA) moiety by tert-butyloxycarbonyl (Boc) gives compounds in which the galactoside at the proximal site is blocked from modification by GCNT2. After elaboration of the antennae, the Boc group can be removed, and the resulting amine acetylated to give natural I-branched structures. It is also shown that fucosides can function as a traceless blocking group that can provide complementary I-branched structures from a single precursor. The methodology made it possible to synthesize a library of polyLacNAc chains having various topologies.

A novel DNA methylation signature revealed GDF6 and RCC1 as potential prognostic biomarkers correlated with cell proliferation in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) accounts for the majority (80%-90%) of renal cell carcinoma (RCC) patients at the time of diagnosis, and approximately 15% of ccRCC patients will develop distant metastasis or recurrence during their lifetime. Increasing number of studies have revealed that the aberrant DNA methylations is closely correlated with the tumorigenesis in ccRCC. RESULTS: In this study, we utilized a LASSO (least absolute shrinkage and selection operator) model to identify a combination of 13 probes-based DNA methylation signature that associated with the progression-free survival (PFS) of ccRCC patients. First, differentially methylated regions (CpGs) related to PFS and phenotypes were identified. Next, prognostic DNA methylation probes were selected from the differentially methylated probes (DMPs) and calculated risk scores to stratify patients with ccRCC. The performance of this signature was validated in an independent testing set using various analyses, including Kaplan-Meier analysis for PFS and receiver operating characteristic (ROC) curve analysis. Based on our 13-DNA methylation probes signature, ccRCC patients were successfully stratified into high- and low-risk groups. Combining DNA methylation signature with clinical variables such as T stage, M stage and tumor grade could further improve the accuracy of prediction. Moreover, we highlight two molecular biomarkers (RCC1 and GDF6) corresponding to our probes. Invitro experiments showed that knockdown of RCC1 or GDF6 in ccRCC cell lines reduced cell proliferation, which indicated that both biomarkers are associated with tumorigenesis. CONCLUSIONS: The 13-probes-based DNA methylation signature has the potential to serve as an independent tool for survival outcome improvement and treatment strategy selection for ccRCC patients. In addition, our findings suggest that RCC1 and GDF6 may serve as promising markers for ccRCC.

Exploiting Substrate Specificities of 6-O-Sulfotransferases to Enzymatically Synthesize Keratan Sulfate Oligosaccharides.

Keratan sulfate (KS) is a glycosaminoglycan that is widely expressed in the extracellular matrix of various tissue types, where it is involved in many biological processes. Herein, we describe a chemo-enzymatic approach to preparing well-defined KS oligosaccharides by exploiting the known and newly discovered substrate specificities of relevant sulfotransferases. The premise of the approach is that recombinant GlcNAc-6-O-sulfotransferases (CHST2) only sulfate terminal GlcNAc moieties to give GlcNAc6S that can be galactosylated by B4GalT4. Furthermore, CHST1 can modify the internal galactosides of a poly-LacNAc chain; however, it was found that a GlcNAc6S residue greatly increases the reactivity of CHST1 of a neighboring and internal galactoside. The presence of a 2,3-linked sialoside further modulates the site of modification by CHST1, and a galactoside flanked by 2,3-Neu5Ac and GlcNAc6S is preferentially sulfated over the other Gal residues. The substrate specificities of CHST1 and 2 were exploited to prepare a panel of KS oligosaccharides, including selectively sulfated N-glycans. The compounds and several other reference derivatives were used to construct a microarray that was probed for binding by several plant lectins, Siglec proteins, and hemagglutinins of influenza viruses. It was found that not only the sulfation pattern but also the presentation of epitopes as part of an O- or N-glycan determines binding properties.

RCC1 functions as a tumor facilitator in clear cell renal cell carcinoma by dysregulating cell cycle, apoptosis, and EZH2 stability.

BACKGROUND: RCC1 functions as a pivotal guanine nucleotide exchange factor and was reported to be involved in mitosis, the assembly of the nuclear envelope, nucleocytoplasmic transport in cell physiological processes. Recent studies reported that RCC1 could regulate immunological pathways and promote the growth of some malignant solid tumors. However, the prognostic value and exact function of RCC1 remain unknown in patients with clear cell renal cell carcinoma (cRCC). METHODS: The UALCAN and KM plotter portals were used to analyze the expression profile and related tumor prognosis of RCC1 in ccRCC using data from TCGA. The expression profile of RCC1 was also confirmed in clinical samples using qRT-PCR, western blotting, and immunohistochemistry. The role of RCC1 on ccRCC cells in vitro was confirmed by a series of functional assays. Animal experiments were performed to verify the suppressive effect of RCC1 knockdown on tumor growth in vivo. The correlation of RCC1 expression with that of EZH2 was explored in clinical samples using IHC. The interaction between RCC1 and EZH2 was further verified using a CO-IP assay and a protein stability assay. RESULTS: RCC1 was upregulated in ccRCC tissues compared with normal tissues in TCGA dataset and paired clinical samples. RCC1 promoted ccRCC progression by accelerating the cell cycle and suppressing apoptosis. In addition, RCC1 could bind EZH2 and regulate its expression at the posttranscriptional level. RCC1 and EZH2 expression showed a strong correlation in clinical samples. Further investigation proved that RCC1 regulated EZH2 protein stability through the ubiquitin-proteasome pathway. CONCLUSIONS: RCC1 could be a potential therapeutic target in ccRCC. The RCC1/EZH2 axis takes part in the development of ccRCC.

Association of Non-Invasive Markers with Significant Fibrosis in Patients with Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

Purpose: The identification of significant fibrosis is critical for predicting the prognosis of non-alcoholic fatty liver disease (NAFLD). This study aimed to compare the predictive value of chitinase-3-like protein 1 (CHl3L1) and other non-invasive biomarkers, as well as to establish a novel non-invasive diagnostic model for assessing the risk of significant fibrosis in NAFLD. Patients and Methods: A total of 71 patients with confirmed NAFLD based on liver biopsy were included in this study. Serum CHI3L1 levels and other non-invasive fibrosis assessment measures were determined. The aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 Index (FIB-4) were calculated to assess the diagnostic superiority of serum CHI3L1 compared to other non-invasive fibrosis assessment measures. Multivariate logistic regression analysis was conducted to identify relevant variables for constructing a diagnostic model. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of each index, including the area under ROC curve (AUC), sensitivity, and specificity. A nomogram was established based on the logistic regression model. Results: Serum CHI3LI levels were found to be higher in NAFLD patients with significant fibrosis compared to those without significant fibrosis. Multivariate logistic regression analysis revealed that aspartate aminotransferase (AST), type IV collagen (IV-C), CHI3L1, and liver stiffness measurement (LSM) were identified as potential independent risk factors associated with significant fibrosis in patients. The AUC of CHI3L1 for diagnosing significant liver fibrosis was 0.716 (0.596,0.836), with the optimal cut-off point of 125.315. The nomogram incorporating CHI3LI, AST, IV-C, and LSM further improved the potential predictive value, with an AUC for diagnosing significant fibrosis of 0.864 (0.766,0.962). This was superior to IV-C, CHI3L1, LSM, and APRI (all p < 0.05). Conclusion: The diagnostic model constructed by CHI3L1 combined with the existing non-invasive markers AST, IV-C, and LSM can help assess the risk of significant liver fibrosis in NAFLD.

A pancancer analysis of the oncogenic role of ZNRF2 in human tumours.

Finding effective treatments for cancer requires a thorough understanding of how it develops and progresses. Recent research has revealed the crucial role that Zinc and ring finger 2 (ZNRF2) play in the progression of non-small cell lung cancer (NSCLC) by controlling cell growth and death. However, a comprehensive analysis of ZNRF2's role in cancer as a whole has yet to be conducted. Our study sought to investigate the impact of ZNRF2 on diverse human tumours, as well as the molecular pathways involved, using databases such as TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) and the Human Protein Atlas (HPA), as well as several bioinformatic tools. Our findings indicate that ZNRF2 is generally expressed at higher levels in tumours than in normal tissues, and in some cancers, its levels correlate positively with disease stage, potentially predicting a poor prognosis for patients. We also discovered genetic changes in ZNRF2 among cancer patients, as well as its relationship with cancer-related fibroblasts, endothelial cells and immune cell infiltration. Additionally, we explored potential molecular mechanisms of ZNRF2 in tumours, finding that it increases in hepatocellular carcinoma (HCC) tissues and that inhibiting its expression through ZNRF2 siRNA can limit HepG2 cell proliferation. Overall, our study provides a comprehensive overview of ZNRF2's oncogenic roles across various cancers.

Seasonal variations of mass absorption efficiency of elemental carbon in PM2.5 in urban Guangzhou of South China.

This study investigates seasonal variations of mass absorption efficiency of elemental carbon (MAEEC) and possible influencing factors in urban Guangzhou of South China. Mass concentrations of elemental carbon (EC) and organic carbon (OC) in PM2.5 and aerosol absorption coefficient (bap) at multi-wavelengths were simultaneously measured in four seasons of 2018-2019 at hourly resolution by a semi-continuous carbon analyzer and an aethalometer. Seasonal average mass concentrations of EC were in the range of 1.36-1.70 µgC/m3 with a lower value in summer than in the other seasons, while those of OC were in the range of 4.70-6.49 µgC/m3 with the lowest value in summer and the highest in autumn. Vehicle exhaust from local traffic was identified to be the predominant source of carbonaceous aerosols. The average aerosol absorption Ångström exponents (AAE) were lower than 1.2 in four seasons, indicating EC and bap were closely related with vehicle exhaust. Seasonal MAEEC at 550 nm was 11.0, 8.5, 10.4 and 11.3 m2/g in spring, summer, autumn, and winter, respectively. High MAEEC was related with the high mass ratio of non-carbonaceous aerosols to EC and high ambient relative humidity.

Metasurface-enabled polarization-independent LCoS spatial light modulator for 4K resolution and beyond.

With the distinct advantages of high resolution, small pixel size, and multi-level pure phase modulation, liquid crystal on silicon (LCoS) devices afford precise and reconfigurable spatial light modulation that enables versatile applications ranging from micro-displays to optical communications. However, LCoS devices suffer from a long-standing problem of polarization-dependent response in that they only perform phase modulation on one linear polarization of light, and polarization-independent phase modulation-essential for most applications-have had to use complicated polarization-diversity optics. We propose and demonstrate, for the first time, an LCoS device that directly achieves high-performance polarization-independent phase modulation at telecommunication wavelengths with 4K resolution and beyond by embedding a polarization-rotating metasurface between the LCoS backplane and the liquid crystal phase-modulating layer. We verify the device with a number of typical polarization-independent application functions including beam steering, holographical display, and in a key optical switching element - wavelength selective switch (WSS), demonstrating the significant benefits in terms of both configuration simplification and performance improvement.

POLD1 as a Prognostic Biomarker Correlated with Cell Proliferation and Immune Infiltration in Clear Cell Renal Cell Carcinoma.

DNA polymerase delta 1 catalytic subunit (POLD1) plays a vital role in genomic copy with high fidelity and DNA damage repair processes. However, the prognostic value of POLD1 and its relationship with tumor immunity in clear cell renal cell carcinoma (ccRCC) remains to be further explored. Transcriptional data sets and clinical information were obtained from the TCGA, ICGC, and GEO databases. Differentially expressed genes (DEGs) were derived from the comparison between the low and high POLD1 expression groups in the TCGA-KIRC cohort. KEGG and gene ontology (GO) analyses were performed for those DEGs to explore the potential influence of POLD1 on the biological behaviors of ccRCC. The prognostic clinical value and mutational characteristics of patients were described and analyzed according to the POLD1 expression levels. TIMER and TISIDB databases were utilized to comprehensively investigate the potential relevance between the POLD1 levels and the status of the immune cells, as well as the tumor infiltration of immune cells. In addition, RT-qPCR, Western blot, immunohistochemistry and several functional and animal experiments were performed for clinical, in vitro and in vivo validation. POLD1 was highly expressed in a variety of tumors including ccRCC, and further verified in a validation cohort of 60 ccRCC samples and in vitro cell line experiments. POLD1 expression levels in the ccRCC samples were associated with various clinical characteristics including pathologic tumor stage and histologic grade. ccRCC patients with high POLD1 expression have poor clinical outcomes and exhibit a higher rate of somatic mutations than those with low POLD1 expression. Cox regression analysis also showed that POLD1 could act as a potential independent prognostic biomarker. The DEGs associated with POLD1 were significantly enriched in the immunity-related pathways. Moreover, further immune infiltration analysis indicated that high POLD1 expression was associated with high NK CD56bright cells, Treg cells, and myeloid-derived suppressor cells' (MDSCs) infiltration scores, as well as their marker gene sets of immune cell status. Meanwhile, POLD1 exhibited resistance to various drugs when highly expressed. Finally, the knockdown of POLD1 inhibited the proliferation and migration, and promoted the apoptosis of ccRCC cells in vitro and in vivo, as well as influenced the activation of oncogenic signaling. Our current study demonstrated that POLD1 is a potential prognostic biomarker for ccRCC patients. It might create a tumor immunosuppressive microenvironment and inhibit the susceptibility to ferroptosis leading to a poor prognosis.

Galectin-1 Regulates RNA Expression and Alternative Splicing of Angiogenic Genes in HUVECs.

BACKGROUND: Angiogenesis is essential for tissue development, and therefore its dysregulation can cause various diseases, including cerebrovascular disease. Galectin-1, encoded by the lectin galactoside-binding soluble-1 gene (LGALS1), has critical roles in the regulation of angiogenesis, but the underlying mechanisms need further clarification. METHODS: LGALS1 was silenced in human umbilical vein endothelial cells (HUVECs) and whole transcriptome sequencing (RNA-seq) was then performed to investigate potential targets for galectin-1. Galectin-1-interacting RNA data was also integrated to explore how galectin-1 might regulate gene expression and alternative splicing (AS). RESULTS: A total of 1451 differentially expressed genes (DEGs) were found to be regulated by silencing LGALS1 (siLGALS1), comprising 604 up- and 847 down-regulated DEGs. Down-regulated DEGs were primarily enriched in angiogenesis and inflammatory response pathways, and included CCL2, GJA5, CALCRL, ACKR3, HEY1, AQP1, CD34, ECM1, RAMP2, and SELP. These were validated by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) experiments. siLGALS1 was also used to analyze dysregulated AS profiles, such as the promotion of exon skipping (ES) and intron retention, and inhibition of cassette exon events. Interestingly, regulated AS genes (RASGs) were found to be enriched in focal adhesion and in the angiogenesis-associated vascular endothelial growth factor (VEGF) signaling pathway. Furthermore, based on our previously published RNA interactome data for galectin-1, hundreds of RASGs were found to be bound by galectin-1, including those enriched in the angiogenesis pathway. CONCLUSIONS: Our results demonstrate that galectin-1 can regulate angiogenesis-related genes at transcriptional and post-transcriptional levels, probably by binding to the transcripts. These findings expand our understanding of the functions of galectin-1 and the molecular mechanisms that underlie angiogenesis. They also indicate that galectin-1 could serve as a therapeutic target for future anti-angiogenic treatments.