Corrigendum: LncRNA-AC02278.4 is a novel prognostic biomarker that promotes tumor growth and metastasis in lung adenocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.860961.].

Shifts in periphyton research themes over the past three decades.

It has been well documented that periphyton communities play a key role in primary productivity, nutrient cycling, and food web interactions. However, a worldwide overview of research on the key themes, current situation, and major trends within the field is lacking. In this study, we applied the machine learning technique (latent Dirichlet allocation, LDA) to analyze the abstracts of 6690 publications related to periphyton from 1991 to 2020 based on the Web of Science database. The relative frequency of classical and basic research on periphyton related to colonization, biomass, growth rate, and habitats has been clearly decreasing. The increasing trends of research on periphyton are embodied in the periphyton function in freshwater ecosystems (e.g., application as ecological indicators, function in the removal of nutrients, and application in paleolimnology), the research at macroscales (e.g., spatial-temporal variation, and functional and taxonomic diversity), and the anthropogenic themes (e.g., climate warming, response to multiple stressors, and land use type). The keyword and title analysis showed that the periphyton studies are concentrated mainly on diatom aspects, especially with respect to streams relative to lakes. The thematic space based on non-metric multidimensional scaling (NMDS) showed that the classical themes such as growth rate, colonization, and environmental factors (e.g., multiple stressors and climate warming) were most linked to other research themes. We proposed that future trends in the periphyton should focus on the function of periphyton in lakes and their response to multiple environmental pressures with the increasingly extensive eutrophication in lakes and the increasingly significant change in the climate.

NCAPG2 Is a Novel Prognostic Biomarker and Promotes Cancer Stem Cell Maintenance in Low-Grade Glioma.

Gliomas account for 75% of all primary malignant brain tumors in adults and are associated with high mortality. Mounting evidence has shown that NCAPG2 is differentially expressed in various cancers. However, the prognostic value and immune functions of NCAPG2 in low-grade glioma (LGG) remain unresolved. In the present study, we revealed that NCAPG2 was up-regulated in LGG, and its higher expression was associated with adverse clinical outcomes and poor clinical characteristics, including WHO grade, IDH mutation, 1p/19q codeletion, and primary therapy outcome. The results of the Cox regression analysis revealed that NCAPG2 was an independent factor for the prognosis of low-grade glioma. Meanwhile, we also established a nomogram based on NCAPG2 to predict the 1-, 3-, or 5-year survival in LGG patients. Furthermore, we found that Copy number variation (CNV) and DNA hypomethylation results in its overexpression in LGG. In addition, functional annotation confirmed that NCAPG2 was mainly involved in the immune regulation and WNT signaling pathways. Finally, we determined that increased expression of NCAPG2 was correlated with infiltration levels of various immune cells and immune checkpoint in LGG. Importantly, we found that NCAPG2 was highly expressed in glioma stem cells lines and knockdown of NCAPG2 significantly inhibited the self-renewal ability of GSC. This is the first study to identify NCAPG2 as a new potential prognostic biomarker and characterize the functional roles of NCAPG2 in the progression of LGG, and provides a novel potential diagnostic and therapeutic biomarker for LGG in the future.

Over-Expression of Long Non-Coding RNA-AC099850.3 Correlates With Tumor Progression and Poor Prognosis in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been implicated in the initiation and progression of various cancers. LncRNA-AC099850.3 is a novel lncRNA that is abnormally expressed in diverse cancer types including LUAD. However, the clinical significance, prognostic value, diagnostic value, immune role, and potential biological function of AC099850.3 LUAD remain elusive. In this study, we found that AC099850.3 was highly expressed in LUAD and associated with an advanced tumor stage, poor prognosis, and immune infiltration. Receiver operating curve analysis revealed the significant diagnostic ability of AC099850.3 (AUC=0.888). Functionally, the knockdown of AC099850.3 restrained LUAD cell proliferation and migration in vitro. Finally, we constructed a competitive endogenous RNAs (ceRNA) network that included hsa-miR-101-3p and 4 mRNAs (ESPL1, AURKB, BUB3, and FAM83D) specific to AC099850.3 in LUAD. Kaplan-Meier survival analysis showed that a lower expression of miR-101-3p and a higher expression of ESPL1, AURKB, BUB3, and FAM83D, were associated with adverse clinical outcomes in patients with LUAD. This finding provided a comprehensive view of the AC099850.3-mediated ceRNA network in LUAD, thereby highlighting its potential role in the diagnosis and prognosis of LUAD.

Long Non-Coding RNA AP000695.2 Acts as a Novel Prognostic Biomarker and Regulates the Cell Growth and Migration of Lung Adenocarcinoma.

Long non-coding RNAs (lncRNAs) are tumor-associated biological molecules and have been found to be implicated in the progression of lung adenocarcinoma (LUAD). LncRNA-AP000695.2 (ENSG00000248538) is a long non-coding RNA (lncRNA) that is widely increased in many tumor types including lung adenocarcinoma (LUAD). However, the aberrant expression profile, clinical significance, and biological function of AP000695.2 in human lung adenocarcinoma (LUAD) need to be further investigated. This study mines key prognostic AP000695.2 and elucidates its potential role and molecular mechanism in regulating the proliferation and metastasis of LUAD. Here, we discovered that AP000695.2 was significantly upregulated in lung adenocarcinoma tissues compared with healthy adjacent lung tissue and higher in LUAD cell lines than in normal human bronchial epithelial cell lines. A higher expression of AP000695.2 was positively correlated with aggressive clinicopathological characteristics, and AP000695.2 served as an independent prognostic indicator for the overall survival, disease-free survival, and progression-free survival in patients with LUAD. Receiver operating curve (ROC) analysis revealed the significant diagnostic ability of AP000695.2 (AUC = 0.838). Our in vivo data confirmed that AP000695.2 promotes the proliferation, migration, and invasion of LUAD cells. GSEA results suggested that AP000695.2 co-expressed genes were mainly enriched in immune-related biological processes such as JAK-STAT signaling pathway and toll-like receptor signaling pathway. Single-sample GSEA analysis showed that AP000695.2 is correlated with tumor-infiltrating immune cells in lung adenocarcinoma. Our findings confirmed that AP000695.2 was involved in the progression of lung adenocarcinoma, providing a novel prognostic indicator and promising diagnostic biomarker in the future.

LncRNA-AL035458.2/hsa-miR-181a-5p Axis-Mediated High Expression of NCAPG2 Correlates With Tumor Immune Infiltration and Non-Small Cell Lung Cancer Progression.

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. NCAPG2 (non-SMC condensin II complex subunit G2) has been shown to be upregulated in various human cancers. Nevertheless, the underlying biological function and potential mechanisms of NCAPG2 driving the progression of LUAD remain unclear. In this study, we investigated the role of NCAPG2 in LUAD and found that the expression of NCAPG2 in LUAD tissues was significantly higher than that of NCAPG2 expression in adjacent normal tissues. Kaplan-Meier survival analysis showed that patients with higher NCAPG2 expression correlated with unfavorable clinical outcomes. Receiver operating characteristic (ROC) curve analysis showed that the AUC value of NCAPG2 was 0.914. Correlation analysis showed that NCAPG2 expression was associated with immune infiltration in LUAD. Finally, we found that AL139385.1 was upregulated in LUAD cancer tissues and cell lines. Knockdown of NCAPG2 inhibited cell proliferation, cell migration, and cell invasion of LUAD in vitro. More importantly, we established the AL035458.2/hsa-miR-181a-5p axis as the most likely upstream ncRNA-related pathway of NCAPG2 in LUAD. In conclusion, our data demonstrated that ncRNA-mediated high expression of NCAPG2 was correlated with progression and immune infiltration, and could serve as a prognostic biomarker for LUAD.

Long Non-Coding RNA AL139385.1 as a Novel Prognostic Biomarker in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. LncRNA-AL139385.1 (ENSG00000275880) is a novel lncRNA that is abnormally expressed in various cancer types including LUAD. However, the underlying biological function and potential mechanisms of AL139385.1 driving the progression of LUAD remain unclear. In this study, we investigated the role of AL139385.1 in LUAD and found that DNA hypomethylation was positively correlated with AL139385.1 expression in LUAD. Moreover, we uncover that the expression of AL139385.1 in LUAD tissues was significantly higher than that of AL139385.1 expression in adjacent normal tissues. Kaplan-Meier survival analysis showed that patients with higher AL139385.1 expression correlated with adverse overall survival and progression-free survival. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) value of AL139385.1 was 0.808. Correlation analysis showed that AL139385.1 expression was associated with immune infiltration in LUAD. We also found that AL139385.1 was upregulated in LUAD cancer tissues and cell lines. Knockdown of AL139385.1 significantly inhibited cell proliferation and migration abilities of LUAD. Finally, we constructed a ceRNA network that includes hsa-miR-532-5p and four mRNAs (GALNT3, CYCS, EIF5A, and ITGB4) specific to AL139385.1 in LUAD. Subsequent Kaplan-Meier survival analysis suggested that polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), cytochrome c, somatic (CYCS), eukaryotic translation initiation factor 5A (EIF5A), and integrin subunit beta 4 (ITGB4), were potential prognostic biomarkers for patients with LUAD. In conclusion, this finding provides possible mechanisms underlying the abnormal upregulation of AL139385.1 as well as a comprehensive view of the AL139385.1-mediated competing endogenous RNAs (ceRNA) network in LUAD, thereby highlighting its potential role in diagnosis and therapy.

Identification and Validation of lncRNA-AC087588.2 in Lung Adenocarcinoma: A Novel Prognostic and Diagnostic Indicator.

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have been implicated in the initiation and progression of various cancers. LncRNA-AC087588.2 (ENSG00000274976) is a novel lncRNA that is abnormally expressed in diverse cancer types, including LUAD. However, the clinical significance, prognostic value, diagnostic value, immune role, and the potential biological function of AC087588.2 LUAD remain elusive. In this study, we found that AC087588.2 was upregulated and associated with a poor prognosis in LUAD. In addition, univariate and multivariate Cox regression analysis indicated that AC087588.2 could be an independent prognostic factor for LUAD. Functionally, the knockdown of AC087588.2 restrained LUAD cell proliferation and migration in vitro. Finally, we constructed a ceRNA network that included hsa-miR-30a-5p and four mRNAs (ANLN, POLR3G, EHBP1, and ERO1A) specific to AC087588.2 in LUAD. The Kaplan-Meier survival analysis showed that lower expression of hsa-miR-30a-5p and higher expression of ANLN, POLR3G, EHBP1, and ERO1A were associated with adverse clinical outcomes in patients with LUAD. This finding provided a comprehensive view of the AC087588.2-mediated ceRNA network in LUAD, thereby highlighting its potential role in the diagnosis and prognosis of LUAD.

LncRNA-AC02278.4 Is a Novel Prognostic Biomarker That Promotes Tumor Growth and Metastasis in Lung Adenocarcinoma.

LncRNA-AC02278.4 (ENSG00000248538) is a long non-coding RNA (lncRNA) found to be highly expressed in multiple human cancers including lung adenocarcinoma (LUAD). However, the underlying biological function and potential mechanisms of AC02278.4 driving the progression of LUAD remain unclear. In this study, we investigated the role of AC02278.4 in LUAD and found that AC02278.4 expression was significantly increased in datasets extracted from The Cancer Genome Atlas. Increased expression of lncRNA-AC02278.4 was correlated with advanced clinical parameters. Receiver operating characteristic (ROC) curve analysis revealed the significant diagnostic ability of AC02278.4 [area under the ROC curve (AUC) = 0.882]. In addition, gene set enrichment analysis (GSEA) enrichment showed that AC02278.4 expression was correlated with immune response-related signaling pathways. Finally, we determined that AC02278.4 regulated cell proliferation and migration of LUAD in vitro. Our clinical sample results also confirmed that AC02278.4 was highly expressed in LUAD and correlated with adverse clinical outcomes. In conclusion, our data demonstrated that AC02278.4 was correlated with progression and immune infiltration and could serve as a prognostic biomarker for LUAD.

Next-generation sequencing identifies HOXA6 as a novel oncogenic gene in low grade glioma.

BACKGROUND: Low grade glioma is one of the most common lethal cancers in the human nervous system. Emerging evidence has demonstrated that homeobox A cluster (HOXA) gene family plays a critical role in the transcriptional regulation as well as cancer initiation and progression. However, the expression, biological functions and upstream regulatory mechanism of 11 HOXAs in low grade glioma are not yet clear. METHODS: In this study, we utilized various public databases and bioinformatics analyzed, including TCGA, CGGA, Rembrandt, HPA, LinkedOmics, cBioPortal, TISDIB, single-sample GSEA (ssGSEA), TIMER, LnCeVar, LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating, characteristic (ROC) analyses, GDSC and CTRP databases to analyzed the mRNA and protein expression profiles, gene mutation, clinical features, diagnosis, prognosis, signaling pathway, TMB, immune subtype, immune cell infiltration, immune modulator, ceRNA network and drug sensitivity of 11 HOXAs. Growth curve and transwell assays were utilized to study the biological characteristics of HOXA6 in LGG progression. RESULTS: In the present study, we found that 11 HOXAs (HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA3) were consistently up-regulated in LGG tissues and GBM tissues. Up-regulated of the HOXAs expression were significantly correlated with higher tumor stage, IDH mutation status, 1p/19q co-deletion, histological type and primary therapy outcome. Survival analyses showed that higher expression of HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA13 were correlated with shorter overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) in LGG patients. Univariate and multivariate analyses revealed that HOXA1, HOXA6 expression and tumor grade, age, primary therapy outcome and age were independent factors affecting the prognosis of LGG patients. ROC curve analysis of HOXAs showed that HOXAs had a high accuracy (AUC > 0.80) in predicting LGG. Furthermore, gene functional enrichment analysis indicated that HOXAs mainly involved in the inflammatory response and immune regulation signaling pathway. CNV and DNA methylation significantly affect the expression of HOXAs. Finally, we uncover that HOXAs expression are highly correlated with immune cells infiltrate, immune modulator and drug sensitivity. We also uncover that the HOXAs related ceRNA network in LGG. More importantly, we found that HOXA6 was highly expressed in LGG cells lines and significantly affected their proliferation and migration abilities. CONCLUSIONS: In conclusion, our data demonstrated that HOXA was correlated with progression and immune infiltration, and could serve as a prognostic biomarker for LGG.

Diatom assemblage responses to multiple environmental stressors in a deep brackish plateau lake, SW China.

Eutrophication, climate change, water level fall, fish introduction, and salinity have been widely recorded to impact lake ecosystems around the world. However, the combined responding pattern in the lake ecosystem to the above multiple environmental stressors is not well understood. Here, we present diatom assemblage and geochemical indicators (total organic carbon (TOC), total nitrogen (TN), and total phosphorous (TP)) in lake sediment to investigate the long-term trends in the aquatic ecosystem in response to multiple environmental stressors in Lake Chenghai, a deep brackish lake located on Yunnan-Guizhou Plateau, SW China, during the past 80 years. We identified 8 genera and 15 species of diatom reaching a relative abundance of ≥ 2% in at least one sample, with the dominant taxa such as Cyclotella rhomboideo-elliptica and Aulacoseira alpigena through the sediment core. There was a clear shift in the diatom community from oligotrophic species of C. rhomboideo-elliptica to eutrophic species such as Cyclotella meneghiniana and Cyclostephanos dubius becoming dominant since ca. 1998 CE. In addition, the changes in the fish introduction, water level, temperature, and salinity also resulted in the variation in abundance of planktonic and benthic diatoms. The increase in the abundance of diatoms of C. rhomboideo-elliptica since ca. 1986 CE may be related to the decline in water level and increasing fish production. For one thing, the decline in water level reduces the concentrations of benthic diatoms but increases the relative biomass of planktonic diatoms. For another, the increasing fish production results in the decrease in the zooplankton biomass, thus reducing the predation pressure on planktonic algae. Besides, some specific species such as C. meneghiniana may respond to the increased nutrient release and increased salinity since ca. 1998 CE. Combined, our findings demonstrate that trophic level is the main driver of diatom assemblage changes, and other environmental variables including water level, fish introduction, and climate warming also contribute to diatom community variation in this brackish plateau lake during the last 80 years.

Progress in the interaction of dissolved organic matter and microbes (1991-2020): a bibliometric review.

Dissolved organic matter (DOM) and microbes are key in the planetary carbon cycle, and research on them can lead to a better understanding of the global carbon cycle and an improved ability to cope with environmental challenges. Several papers have reviewed one or several aspects of the interaction of DOM and microbes, but no overall review has been performed. Here, we bibliometrically analyzed all publications from the Web of Science on DOM and microbes (1991-2020). The results showed that studies on DOM and microbes grew exponentially during this period; the USA contributed the most to the total publications, and China has had the fastest increasing rate since 2010. Moreover, we used the Latent Dirichlet Allocation model to identify topics and determine their (cold or hot) trends by analyzing the abstracts of 9851 publications related to DOM and microbes. A total of 96 topics were extracted, and these topics that are related to the source, composition, and removal path of DOM and the temporal-spatial patterns of DOM and microbes consistently rose from 1991 to 2020. Most studies have used accurate and rapid methods combined with microbiological genetic approaches to study the interaction of DOM and microbes in terrestrial and aquatic ecosystems. The results also showed that the impacts of climate change and land use on the interaction of DOM and microbes, and topics related to human health have received considerable attention. In the future, the interaction mechanism of DOM and microbes and its response to environmental change should be further elucidated.

Keqinzhangia aquatica gen. et sp. nov. and Pseudocoronospora hainanense gen. et sp. nov., isolated from freshwater in southern China.

During an investigation of the diversity of aquatic hyphomycetes from southern China, two interesting isolates were collected. These two isolates were cultured and sequenced, and a BLAST search of their LSU sequences against data in GenBank revealed that the closest related taxa were in the genus Microthyrium. Phylogenetic analyses, based on the combined sequence data from the internal transcribed spacer (ITS) and large nuclear subunit ribosomal DNA (LSU), revealed that our isolates belong to the Microthyriaceae. Combined morphological characters allowed us to describe our isolates as two new genera and species in Microthyriaceae, named as: Keqinzhangia aquatica and Pseudocoronospora hainanense. The full descriptions, illustrations, and a phylogenetic tree showing the position of the two new genera were provided in this paper.

Two new asexual genera and six new asexual species in the family Microthyriaceae (Dothideomycetes, Ascomycota) from China.

The family Microthyriaceae is represented by relatively few mycelial cultures and DNA sequences; as a result, the taxonomy and classification of this group of organisms remain poorly understood. During the investigation of the diversity of aquatic hyphomycetes from southern China, several isolates were collected. These isolates were cultured and sequenced and a BLAST search of its LSU sequences against data in GenBank revealed that the closest related taxa are in the genus Microthyrium. Phylogenetic analyses, based on the combined sequence data from the internal transcribed spacers (ITS) and the large subunit (LSU), revealed that these isolates represent eight new taxa in Microthyriaceae, including two new genera, Antidactylaria gen. nov. and Isthmomyces gen. nov. and six new species, Antidactylariaminifimbriata sp. nov., Isthmomycesoxysporus sp. nov., I.dissimilis sp. nov., I.macrosporus sp. nov., Triscelophorusanisopterioideus sp. nov. and T.sinensis sp. nov. These new taxa are described, illustrated for their morphologies and compared with similar taxa. In addition, two new combinations are proposed in this family.

Anacraspedodidymum submersum sp. nov. (Chaetosphaeriaceae, Chaetosphaeriales), a new species of freshwater hyphomycetes from southwest China.

During a mycological survey of freshwater hyphomycetes on submerged leaves in southwest China, a new species, Anacraspedodidymum submersum, was isolated. The new species A. submersum is characterized by having monophialidic conidiogenous cells with funnel shaped collarettes and globose or subglobose, aseptate and hyaline conidia. Morphologically, A. submersum is somewhat similar to A. aquaticum and A. hyalosporum in conidiophores and conidiogenous cells, but can be easily distinguished by its subglobose to globose and smaller conidia. Phylogenetic analysis of combined ITS and LSU sequences show that the new species of Anacraspedodidymum clustered together with the genus Thozetella in Chaetosphaeriaceae. A full description, illustrations and a phylogenetic tree showing the position of A. submersum are provided herein.

Conceptual mechanical design of antagonistic variable stiffness joint based on equivalent quadratic torsion spring.

The variable stiffness joint is a kind of flexible actuator with variable stiffness characteristics suitable for physical human-robot interaction applications. In the existing variable stiffness joints, the antagonistic variable stiffness joint has the advantages of simple implementation of variable stiffness mechanism and easy modular design of the nonlinear elastic element. The variable stiffness characteristics of antagonistic variable stiffness joints are realized by the antagonistic actuation of two nonlinear springs. A novel design scheme of the equivalent nonlinear torsion spring with compact structure, large angular displacement range, and desired stiffness characteristics is presented in this article. The design calculation for the equivalent quadratic torsion spring is given as an example, and the actuation characteristics of the antagonistic variable stiffness joint based on the equivalent quadratic torsion spring are illustrated. Based on the design idea of constructing the antagonistic variable stiffness joint with compact structure and high compliance, as well as the different design requirements of the joints at different positions of the multi-degrees of freedom robot arm, nine types of mechanical schemes of antagonistic variable stiffness joint with the open design concept are proposed in this article. Finally, the conceptual joint configuration schemes of the robot arm based on the antagonistic variable stiffness joint show the application scheme of the designed antagonistic variable stiffness joint in the multi-degrees of freedom robot.

Phalangispora sinensis sp. nov. from Yunnan, China and two new members of Wiesneriomycetaceae.

Phalangispora sinensis, an aquatic hyphomycete collected from south-western PR China, is described as a new species. This new species is characterized by having multicellular branched conidia composed of a curved main axis and one or two laterals, with the laterals arising from the third or fourth cell of the base of the main axis. Combined analyses of the LSU, SSU, RPB2 and TEF1 gene sequence data revealed that Phalangispora and another aquatic hyphomycete genus, Setosynnema, belonged to Wiesneriomycetaceae, Tubeufiales, Dothideomycetes, Ascomycota.