The use of adjuvant chemotherapy combined with concurrent chemoradiotherapy enhances survival rates in cases of locally advanced nasopharyngeal carcinoma.

This study aimed to evaluate the impact of adjuvant chemotherapy on survival rates, adverse events, and quality of life (QOL) in patients with locally advanced nasopharyngeal carcinoma (NPC). A retrospective cohort study was conducted, including patients with firstly histologically confirmed non-metastatic stage III-IVB NPC between February 2018 and February 2020, and with continuous follow-up data available, were chosen from the medical records of the affiliated hospital of Qingdao University and Zibo Central Hospital. There were 395 patients receiving concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (adjuvant chemotherapy group) and 428 patients receiving CCRT alone (control group). The two groups were compared for treatment response, adverse events, and QOL scores. Besides, Kaplan-Meier plots, and multivariate COX analysis were conducted. The adjuvant chemotherapy group demonstrated a significantly higher overall survival and disease-free survival compared to the control group. The use of adjuvant chemotherapy was significantly correlated with improved overall survival and disease-free survival. Adjuvant chemotherapy was associated with reduced local recurrence and distant metastasis rates. However, higher rates of adverse events were observed in the adjuvant chemotherapy group. QOL scores for physical functioning, emotional functioning, and overall quality of life were higher in the adjuvant chemotherapy group. The findings of this study indicate that adjuvant chemotherapy in locally advanced NPC is associated with improved treatment response, extended overall and disease-free survivals, and better QOL, despite higher rates of adverse events.

Clinical­imaging­radiomic nomogram based on unenhanced CT effectively predicts adrenal metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas.

The aim of the present study was to develop and evaluate a clinical-imaging-radiomic nomogram based on pre-enhanced computed tomography (CT) for pre-operative differentiation lipid-poor adenomas (LPAs) from metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas (AIs). A total of 196 consecutive patients with lung cancer, who underwent initial chest or abdominal pre-enhanced CT scan with small hyperattenuating AIs, were included. The patients were randomly divided into a training cohort with 71 cases of LPAs and 66 cases of metastases, and a testing cohort with 31 cases of LPAs and 28 cases of metastases. Plain CT radiological and clinical features were evaluated, including sex, age, size, pre-enhanced CT value (CTpre), shape, homogeneity and border. A total of 1,316 radiomic features were extracted from the plain CT images of the AIs, and the significant features selected by the least absolute shrinkage and selection operator were used to establish a Radscore. Subsequently, a clinical-imaging-radiomic model was developed by multivariable logistic regression incorporating the Radscore with significant clinical and imaging features. This model was then presented as a nomogram. The performance of the nomogram was assessed by calibration curves and decision curve analysis (DCA). A total of 4 significant radiomic features were incorporated in the Radscore, which yielded notable area under the receiver operating characteristic curves (AUCs) of 0.920 in the training dataset and 0.888 in the testing dataset. The clinical-imaging-radiomic nomogram incorporating the Radscore, CTpre, sex and age revealed favourable differential diagnostic performance (AUC: Training, 0.968; testing, 0.915) and favourable calibration curves. The nomogram was revealed to be more useful than the Radscore and the clinical-imaging model in clinical practice by DCA. The clinical-imaging-radiomics nomogram based on initial plain CT images by integrating the Radscore and clinical-imaging factors provided a potential tool to effectively differentiate LPAs from metastases in patients with lung cancer with small hyperattenuating AIs.

Impact of summer hypoxia on macrobenthic communities in a semi-enclosed bay: A long-term observation in the North Yellow sea of China.

The O2 content of the global ocean has been declining progressively over the past decades, mainly because of human activities and global warming. Despite this situation, the responses of macrobenthos under hypoxic conditions remain poorly understood. In this study, we conducted a long-term observation (2015-2022) to investigate the intricate impact of summer hypoxia on macrobenthic communities in a semi-enclosed bay of the North Yellow Sea. Comparative analyses revealed higher macrobenthos abundance (1956.8 ± 1507.5 ind./m2 vs. 871.8 ± 636.9 ind./m2) and biomass (8.2 ± 4.1 g/m2 vs. 5.6 ± 3.2 g/m2) at hypoxic sites compared to normoxic sites during hypoxic years. Notably, polychaete species demonstrated remarkable adaptability, dominating hypoxic sites, and shaping community structure. The decline in biodiversity underscored the vulnerability and diminished resilience of macrobenthic communities to hypoxic stressors. Stable isotope analysis provided valuable insights into food web structures. The average trophic level of macrobenthos measured 2.84 ± 0.70 at hypoxic sites, contrasting with the higher value of 3.14 ± 0.74 observed at normoxic sites, indicating the absence of predators at high trophic levels under hypoxic conditions. Moreover, trophic interactions were significantly altered, resulting in a simplified and more vulnerable macrobenthic trophic structure. The findings underscored the importance of comprehensive research to understand the complex responses of macrobenthic communities to hypoxia, thereby informing future conservation efforts in impacted ecosystems.

Fourier Transform Infrared (FT-IR) Spectroscopy and Simple Algorithm Analysis for Rapid and Non-Destructive Assessment of Cotton Fiber Maturity and Crystallinity for Plant Mapping.

Information on boll distribution within a cotton plant is critical to evaluate the adaptation and response of cotton plants to environmental and biotic stress in cotton production. Cotton researchers have applied available conventional fiber measurements, such as the high volume instrument (HVI) and advanced fiber information system (AFIS), to map the location and the timing of boll development and distribution within plants and further to determine within-plant variability of cotton fiber properties. Both HVI and AFIS require numerous cotton bolls combined for the measurement. As an alternative approach, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy was proposed to measure fiber maturity (MIR) and crystallinity (CIIR) of a sample as little as 0.5 mg lint. Extending fiber maturity and crystallinity measurement into a single boll for node-by-node mapping, FT-IR method might be advantageous due to less sampling amount compared with HVI and AFIS methods. Results showed that FT-IR technique enabled the evaluation of fiber MIR and CIIR at a boll level, which resulted in average MIR and CIIR values highly correlated with HVI micronaire (MIC) and AFIS maturity ratio (M). Hence, FT-IR technique possesses a good potential for a rapid and non-destructive node-by-node mapping of cotton boll maturity and crystallinity distribution.

A Cotyledon-based Virus-Induced Gene Silencing (Cotyledon-VIGS) approach to study specialized metabolism in medicinal plants.

BACKGROUND: Virus-induced gene silencing (VIGS) is widely used in plant functional genomics. However, the efficiency of VIGS in young plantlets varies across plant species. Additionally, VIGS is not optimized for many plant species, especially medicinal plants that produce valuable specialized metabolites. RESULTS: We evaluated the efficacy of five-day-old, etiolated seedlings of Catharanthus roseus (periwinkle) for VIGS. The seedlings were vacuum-infiltrated with Agrobacterium tumefaciens GV3101 cells carrying the tobacco rattle virus (TRV) vectors. The protoporphyrin IX magnesium chelatase subunit H (ChlH) gene, a key gene in chlorophyll biosynthesis, was used as the target for VIGS, and we observed yellow cotyledons 6 days after infiltration. As expected, the expression of CrChlH and the chlorophyll contents of the cotyledons were significantly decreased after VIGS. To validate the cotyledon based-VIGS method, we silenced the genes encoding several transcriptional regulators of the terpenoid indole alkaloid (TIA) biosynthesis in C. roseus, including two activators (CrGATA1 and CrMYC2) and two repressors (CrGBF1 and CrGBF2). Silencing CrGATA1 led to downregulation of the vindoline pathway genes (T3O, T3R, and DAT) and decreased vindoline contents in cotyledons. Silencing CrMYC2, followed by elicitation with methyl jasmonate (MeJA), resulted in the downregulation of ORCA2 and ORCA3. We also co-infiltrated C. roseus seedlings with TRV vectors that silence both CrGBF1 and CrGBF2 and overexpress CrMYC2, aiming to simultaneous silencing two repressors while overexpressing an activator. The simultaneous manipulation of repressors and activator resulted in significant upregulation of the TIA pathway genes. To demonstrate the broad application of the cotyledon-based VIGS method, we optimized the method for two other valuable medicinal plants, Glycyrrhiza inflata (licorice) and Artemisia annua (sweet wormwood). When TRV vectors carrying the fragments of the ChlH genes were infiltrated into the seedlings of these plants, we observed yellow cotyledons with decreased chlorophyll contents. CONCLUSIONS: The widely applicable cotyledon-based VIGS method is faster, more efficient, and easily accessible to additional treatments than the traditional VIGS method. It can be combined with transient gene overexpression to achieve simultaneous up- and down-regulation of desired genes in non-model plants. This method provides a powerful tool for functional genomics of medicinal plants, facilitating the discovery and production of valuable therapeutic compounds.

cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.

Cancer is a complex disease resulting from abnormal cell growth that is induced by a number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells and angiogenesis, plays a critical role in tumor progression. Cyclic adenosine monophosphate (cAMP) is a second messenger that has pleiotropic effects on the TME. The downstream effectors of cAMP include cAMP-dependent protein kinase (PKA), exchange protein activated by cAMP (EPAC) and ion channels. While cAMP can activate PKA or EPAC and promote cancer cell growth, it can also inhibit cell proliferation and survival in context- and cancer type-dependent manner. Tumor-associated stromal cells, such as CAF and immune cells, can release cytokines and growth factors that either stimulate or inhibit cAMP production within the TME. Recent studies have shown that targeting cAMP signaling in the TME has therapeutic benefits in cancer. Small-molecule agents that inhibit adenylate cyclase and PKA have been shown to inhibit tumor growth. In addition, cAMP-elevating agents, such as forskolin, can not only induce cancer cell death, but also directly inhibit cell proliferation in some cancer types. In this review, we summarize current understanding of cAMP signaling in cancer biology and immunology and discuss the basis for its context-dependent dual role in oncogenesis. Understanding the precise mechanisms by which cAMP and the TME interact in cancer will be critical for the development of effective therapies. Future studies aimed at investigating the cAMP-cancer axis and its regulation in the TME may provide new insights into the underlying mechanisms of tumorigenesis and lead to the development of novel therapeutic strategies.

The pollution characteristics and risk assessment of microplastics in mollusks collected from the Bohai Sea.

Microplastics (MPs) pollution in the marine environment has become a global problem. In this study, a number of 21 mollusk species (n = 2006) with different feeding habits were collected from 11 sites along the Bohai Sea for MPs uptake analysis. The MPs in mollusk samples were isolated and identified by micro-Fourier Transform Infrared Spectroscopy (µ-FTIR), and an assessment of the health risks of MPs ingested by mollusk consumption is also conducted. Approximately 91.9 % of the individuals among all the collected species inhaled MPs, and there was an average abundance of 3.30 ± 2.04 items·individual-1 or 1.04 ± 0.74 items·g-1 of wet weight. The shape of MPs was mainly fiber, and a total number of 8 polymers were detected, of which rayon had the highest detection rate (58.3 %). The highest abundance, uptake rate and polymer composition of MPs was observed in creeping types, suggesting that they might ingest these MPs from their food. The gastropod Siphonalia subdilatata contains the highest levels of MPs, which may increase the risk of human exposure if consumed whole without removing the digestive gland. The polymer risk level of MPs in these mollusks was Level III (H = 299), presenting harmful MPs such as polyvinyl chloride. In terms of human exposure risk, the average risk of human exposure to MPs through consumption of Bohai mollusks is estimated to be 3399 items·(capita·year)-1 (424-9349 items·(capita·year)-1). Overall, this study provides a basis for the ecological and health Risk assessment of MPs in mollusks collected from the coastline of China.

Attenuated Total Reflection Fourier Transform Infrared Spectroscopy with Soft Independent Modeling of Class Analogy-Principal Component Analysis for Classifying Cotton Fiber Maturity Phenotypes of Cotton Population Composed of Various Genotypes.

Maturity is a major fiber trait that affects the processing and performance of cotton fiber. Rapid and accurate identification of fiber maturity phenotypes and genotypes is of importance to breeders. Previous studies showed that either conventional fiber measurements or attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) analysis discriminated the immature fiber (im) phenotype from the wild type (WT) mature fiber phenotype in a segregating F2 population from a cross between two upland cotton lines differing in fiber maturity. However, both conventional fiber property measurement methods and FT-IR analyses with current algorithms could not detect the subtle differences among the WT fibers composed of two different genotypes, WT homozygosity (WT-homo) and WT heterozygosity (WT-hetero). This research explored the FT-IR method, in combination with soft independent modeling of class analogy of principal component analysis (SIMCA-PCA), for the discrimination of WT fiber phenotypes consisting of two different genotypes (WT-homo and WT-hetero). The new approach enabled the detection of IR spectral intensity differences between WT-homo and WT-hetero fibers. Successful classification originated from a distinctive spectral difference in the low-wavenumber region (<700 cm-1) between WT-hetero fibers and WT-homo fibers. This observation emphasized that ATR FT-IR with a SIMCA-PCA approach would be a sensitive tool for classifying the WT fibers demonstrating minor phenotypic differences. The improved sensitivity of the infrared method may provide a way of dissecting genotype-phenotype interactions of cotton fibers rapidly and efficiently.

Source identification and risk assessment of trace metals in surface sediment of China Sea by combining APCA-MLR receptor model and lead isotope analysis.

This study aimed to investigate the distribution, pollution, risk and sources of trace metals in sediments along China Sea. Clear spatial variations were found for Cr, Mn, Co, Ni, Cu, Zn, Se, Mo, Ag, Cd, and Pb, whereas As did not show spatial variation. East China Sea (ECS) contained the highest concentrations of Mn, Co, Ni, Cu, Zn, South China Sea (SCS) shallow sea contained the highest concentrations of Zn, Se, Mo, Ag, Cd, and Pb, whereas coral reefs contained the lowest concentrations of trace metals. Spatial variations could be explained by economic development characteristics along China Sea. As, Se and Cd exhibited low to moderate pollution in China Sea sediment, yet pollution for Cu, Zn, Ni, and Ag appeared in some regions. Sediment in ECS had moderate ecological risks and other regions at low ecological risks. The absolute principle component score-multiple linear regression (APCS-MLR) and Pb stable isotope indicated that 43-74% of trace metals (Ni, Cu, Zn, As, Se, Cd, and Pb) were derived from anthropogenic sources like traffic emission, agricultural activities, industrial source. No pollution and ecological risk were observed in coral reefs, yet 39-71% (Pb) was derived from anthropogenic activities such as motor vessels.

Application of environmental DNA metabarcoding and quantitative PCR to detect blooming jellyfish in a temperate bay of northern China.

Frequently occurring jellyfish blooms have severe impacts on the socioeconomics of coastal areas, which stress the importance of early detection and assessments of blooming jellyfish taxa. Environmental DNA (eDNA) techniques (quantitative PCR and eDNA metabarcoding) have the advantage of high sensitivity and are an emerging powerful tool for investigations of target species. However, a comprehensive analysis of the biodiversity and biomass of jellyfish taxa in the target area by combining the two eDNA techniques is still lacking. Here, we developed eDNA metabarcoding and quantitative PCR for the detection and assessment of jellyfish taxa in the temperate Yantai Sishili Bay (YSB) and estimated the spatial distribution of Aurelia coerulea. Species-specific quantitative PCR assays targeting the mitochondrial cytochrome c oxidase subunit I gene of A. coerulea were developed. Additionally, eDNA metabarcoding based on the mitochondrial 16S rDNA sequences identified six jellyfish species in YSB. Moreover, our results indicate that A. coerulea aggregations were more likely to occur in the inner part of the bay than in the outer part, and they gathered in the bottom layer of seawater rather than in the surface layer. Our results demonstrate the potential of two eDNA techniques in jellyfish biomass investigation and jellyfish taxa detection. These eDNA techniques may contribute to the discovery of jellyfish aggregation so as to achieve early warning of large-scale jellyfish blooms in coastal areas.

Light regulation of the biosynthesis of phenolics, terpenoids, and alkaloids in plants.

Biosynthesis of specialized metabolites (SM), including phenolics, terpenoids, and alkaloids, is stimulated by many environmental factors including light. In recent years, significant progress has been made in understanding the regulatory mechanisms involved in light-stimulated SM biosynthesis at the transcriptional, posttranscriptional, and posttranslational levels of regulation. While several excellent recent reviews have primarily focused on the impacts of general environmental factors, including light, on biosynthesis of an individual class of SM, here we highlight the regulation of three major SM biosynthesis pathways by light-responsive gene expression, microRNA regulation, and posttranslational modification of regulatory proteins. In addition, we present our future perspectives on this topic.

Sustainable Cementitious Materials for Civil and Transportation Engineering.

The current Special Issue entitled "Sustainable Cementitious Materials for Civil and Transportation Engineering" aims to discuss current research on the preparation, characterization, and application of sustainable cementitious materials for civil and transportation engineering, with a special focus on the development of low-carbon construction materials [...].

18F-FDG-PET/CT-based machine learning model evaluates indeterminate adrenal nodules in patients with extra-adrenal malignancies.

BACKGROUND: To assess the value of an 18F-FDG-positron emission tomography/computed tomography (PET/CT)-based machine learning model for distinguishing between adrenal benign nodules (ABNs) and adrenal metastases (AMs) in patients with indeterminate adrenal nodules and extra-adrenal malignancies. METHODS: A total of 303 patients who underwent 18F-FDG-PET/CT with indeterminate adrenal nodules and extra-adrenal malignancies from March 2015 to June 2021 were included in this retrospective study (training dataset (n = 182): AMs (n = 97), ABNs (n = 85); testing dataset (n = 121): AMs (n = 68), ABNs (n = 55)). The clinical and PET/CT imaging features of the two groups were analyzed. The predictive model and simplified scoring system for distinguishing between AMs and ABNs were built based on clinical and PET/CT risk factors using multivariable logistic regression in the training cohort. The performances of the predictive model and simplified scoring system in both the training and testing cohorts were evaluated by the areas under the receiver operating characteristic curves (AUCs) and calibration curves. The comparison of AUCs was evaluated by the DeLong test. RESULTS: The predictive model included four risk factors: sex, the ratio of the maximum standardized uptake value (SUVmax) of adrenal lesions to the mean liver standardized uptake value, the value on unenhanced CT (CTU), and the clinical stage of extra-adrenal malignancies. The model achieved an AUC of 0.936 with a specificity, sensitivity and accuracy of 0.918, 0.835, and 0.874 in the training dataset, respectively, while it yielded an AUC of 0.931 with a specificity, sensitivity, and accuracy of 1.00, 0.735, and 0.851 in the testing dataset, respectively. The simplified scoring system had comparable diagnostic value to the predictive model in both the training (AUC 0.938, sensitivity: 0.825, specificity 0.953, accuracy 0.885; P = 0.5733) and testing (AUC 0.931, sensitivity 0.735, specificity 1.000, accuracy 0.851; P = 1.00) datasets. CONCLUSIONS: Our study showed the potential ability of a machine learning model and a simplified scoring system based on clinical and 18F-FDG-PET/CT imaging features to predict AMs in patients with indeterminate adrenal nodules and extra-adrenal malignancies. The simplified scoring system is simple, convenient, and easy to popularize.

A combination of fluorine-induced effect and co-sensitization for highly efficient and stable dye-sensitized solar cells.

Developing dyes with high open-circuit photovoltage (Voc) is a vital strategy to improve the power conversion efficiency (PCE) of co-sensitized solar cells (co-DSSCs). Herein, three organic fluorine-containing dyes [YY-ThP(3F), YY-ThP(2F), and YY-ThP(26F)] are designed and synthesized for investigating the fluorine-induced effect on photophysical and photovoltaic performances. Consequently, this effect can significantly broaden the UV-vis absorption spectra of dyes but fail to improve the light-harvesting capability of DSSCs. Strikingly, YY-ThP(3F), featuring 3-position fluorine substitution to cyanoacrylic acid, yields a relatively high Voc compared to the corresponding fluorine-free dye (YY-ThP). Furthermore, the co-sensitization of YY-ThP+YY-ThP(3F) achieves a remarkably high PCE and long-term stability. This work implies that the combination of judicious molecular engineering and co-sensitization is a promising strategy for highly efficient and stable DSSCs.

Partial desensitization of MYC2 transcription factor alters the interaction with jasmonate signaling components and affects specialized metabolism.

The activity of bHLH transcription factor MYC2, a key regulator in jasmonate signaling and plant specialized metabolism, is sensitive to repression by JASMONATE-ZIM-domain (JAZ) proteins and co-activation by the mediator subunit MED25. The substitution of a conserved aspartic acid (D) to asparagine (N) in the JAZ-interacting domain (JID) of Arabidopsis MYC2 affects interaction with JAZ, although the mechanism remained unclear. The effects of the conserved residue MYC2D128 on interaction with MED25 have not been investigated. Using tobacco as a model, we generated all possible substitutions of aspartic acid 128 (D128) in NtMYC2a. NtMYC2aD128N partially desensitized the repression by JAZ proteins, while strongly interacting with MED25, resulting in increased expression of nicotine pathway genes and nicotine accumulation in tobacco hairy roots overexpressing NtMYC2aD128N compared to those overexpressing NtMYC2a. The proline substitution, NtMYC2aD128P, negatively affected transactivation and abolished the interaction with JAZ proteins and MED25. Structural modeling and simulation suggest that the overall stability of the JID binding pocket is a predominant cause for the observed effects of substitutions at D128. The D128N substitution has an overall stabilizing effect on the binding pocket, which is destabilized by D128P. Our study offers an innovative tool to increase the production of plant natural products.

Transcriptome analysis reveals genes connected to temperature adaptation in juvenile antarctic krill Euphausia superba.

BACKGROUND: The Antarctic krill, Euphausia superba (E. superba), is a key organism in the Antarctic marine ecosystem and has been widely studied. However, there is a lack of transcriptome data focusing on temperature responses. METHODS: In this study, we performed transcriptome sequencing of E. superba samples exposed to three different temperatures: -1.19 °C (low temperature, LT), - 0.37 °C (medium temperature, MT), and 3 °C (high temperature, HT). RESULTS: Illumina sequencing generated 772,109,224 clean reads from the three temperature groups. In total, 1,623, 142, and 842 genes were differentially expressed in MT versus LT, HT versus LT, and HT versus MT, respectively. Moreover, Kyoto Encyclopedia of Genes and Genomes analysis revealed that these differentially expressed genes were mainly involved in the Hippo signaling pathway, MAPK signaling pathway, and Toll-like receptor signaling pathway. Quantitative reverse-transcription PCR revealed that ESG037073 expression was significantly upregulated in the MT group compared with the LT group, and ESG037998 expression was significantly higher in the HT group than in the LT group. CONCLUSIONS: This is the first transcriptome analysis of E. superba exposed to three different temperatures. Our results provide valuable resources for further studies on the molecular mechanisms underlying temperature adaptation in E. superba.

Exosomal circ-AHCY promotes glioblastoma cell growth via Wnt/ß-catenin signaling pathway.

BACKGROUND: Glioblastoma (GBM) is the most aggressive brain tumor. Reportedly, circular RNAs (circRNAs) participate in regulation of the development and progression of diverse cancers, including GBM. METHODS: Dysregulated circRNAs in GBM tissues were screened out from GEO database. The expression of candidate circRNAs in GBM cells was measured by qRT-PCR. Loss-of function assays, including colony formation assay, EdU assay, TUNEL assay, and flow cytometry analysis were conducted to determine the effects of circ-AHCY knockdown on GBM cell proliferation and apoptosis. Animal study was further used to prove the inhibitory effect of circ-AHCY silencing on GMB cell growth. Mechanistic experiments like luciferase reporter, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays were performed to unveil the downstream molecular mechanism of circ-AHCY. Nanosight Nanoparticle Tracking Analysis (NTA) and PKH67 staining were applied to identify the existence of exosomes. RESULTS: Circ-AHCY was confirmed to be highly expressed in GBM cells. Circ-AHCY silencing suppressed GBM cell proliferation both in vitro and in vivo. Mechanistically, circ-AHCY activates Wnt/ß-catenin signaling pathway by sequestering miR-1294 to up-regulate MYC which activated CTNNB1 transcription. It was also found that circ-AHCY recruited EIF4A3 to stabilize TCF4 mRNA. Enhanced levels of TCF4 and ß-catenin contributed to the stability of TCF4/ß-catenin complex. In turn, TCF4/ß-catenin complex strengthened the transcriptional activity of circ-AHCY. Exosomal circ-AHCY derived from GBM cells induced abnormal proliferation of normal human astrocytes (NHAs). CONCLUSION: Exosomal circ-AHCY forms a positive feedback loop with Wnt/ß-catenin signaling pathway to promote GBM cell growth.

TMEM59 ablation leads to loss of olfactory sensory neurons and impairs olfactory functions via interaction with inflammation.

The olfactory epithelium undergoes constant neurogenesis throughout life in mammals. Several factors including key signaling pathways and inflammatory microenvironment regulate the maintenance and regeneration of the olfactory epithelium. In this study, we identify TMEM59 (also known as DCF1) as a critical regulator to the epithelial maintenance and regeneration. Single-cell RNA-Seq data show downregulation of TMEM59 in multiple epithelial cell lineages with aging. Ablation of TMEM59 leads to apparent alteration at the transcriptional level, including genes associated with olfactory transduction and inflammatory/immune response. These differentially expressed genes are key components belonging to several signaling pathways, such as NF-κB, chemokine, etc. TMEM59 deletion impairs olfactory functions, attenuates proliferation, causes loss of both mature and immature olfactory sensory neurons, and promotes infiltration of inflammatory cells, macrophages, microglia cells and neutrophils into the olfactory epithelium and lamina propria. TMEM59 deletion deteriorates regeneration of the olfactory epithelium after injury, with significant reduction in the number of proliferative cells, immature and mature sensory neurons, accompanied by the increasing number of inflammatory cells and macrophages. Anti-inflammation by dexamethasone recovers neuronal generation and olfactory functions in the TMEM59-KO animals, suggesting the correlation between TMEM59 and inflammation in regulating the epithelial maintenance. Collectively, TMEM59 regulates olfactory functions, as well as neuronal generation in the olfactory epithelium via interaction with inflammation, suggesting a potential role in therapy against olfactory dysfunction associated with inflamm-aging.