Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of ß-catenin.

BACKGROUND: Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for patients with PTC. The Cadherin family plays a pivotal role in tumor metastasis; however, the involvement of Cadherin 4 (CDH4) in the metastatic cascade remains elusive. METHODS: The expression and subcellular localization of CDH4 were determined through immunohistochemistry, immunofluorescence, and western blot analyses. The impact of CDH4 on cell migration, invasion, angiogenesis, and metastasis was assessed using transwell assays, tube formation assays, and animal experiments. Immunoprecipitation assay and mass spectrometry were employed to examine protein associations. The influence of CDH4 on the subcellular expression of ß-catenin and active ß-catenin was investigated via western blotting and immunofluorescence. Protein stability and ubiquitination assay were employed to verify the impact of CDH4 on ß-catenin degradation. Rescue experiments were performed to ensure the significance of CDH4 in regulating nuclear ß-catenin signaling. RESULTS: CDH4 was found to be significantly overexpressed in PTC tissues and predominantly localized in the cytoplasm. Furthermore, the overexpression of CDH4 in tumor tissues is associated with lymph node metastasis in PTC patients. Cytosolic CDH4 promoted the migration, invasion, and lung metastasis of PTC cells and stimulated the angiogenesis and tumorigenesis of PTC; however, this effect could be reversed by Tegavivint, an antagonist of ß-catenin. Mechanistically, cytosolic CDH4 disrupted the interaction between ß-catenin and ß-TrCP1, consequently impeding the ubiquitination process of ß-catenin and activating the nuclear ß-catenin signaling. CONCLUSIONS: CDH4 induces PTC angiogenesis and metastasis via the inhibition of ß-TrCP1-dependent ubiquitination of ß-Catenin.

Assessment of Endocrine Disruptor Exposure in Hospital Professionals Using Hair and Urine Analyses: An Awareness Campaign.

BACKGROUND: In 2021, French public authorities initiated the fourth National Environmental Health Plan to prevent environment-related health risks. This plan primarily focuses on the sensitization of health professionals and health care institutions. Endocrine disruptors (EDs) are environmental factors associated with several adverse health effects, such as reproductive disorders, obesity, and cancer. This study aimed to conduct an awareness campaign among professionals at a general hospital center on the risks related to EDs. METHODS: Hospital professionals were directly involved in this study, and urine and hair samples were collected to determine bisphenol and paraben exposure levels. Analyses were performed using validated liquid chromatography-tandem mass spectrometry methods, enabling the simultaneous determination of bisphenols and parabens. A questionnaire on lifestyle habits was distributed to assess its relationship with the exposure profiles. Nineteen professionals were recruited for the study. RESULTS: Bisphenol A was detected in 95% of the urine samples, and the chlorinated derivatives of bisphenol A were between 16% and 63%. parabens showed detection frequencies between 37% and 100%, and methylparaben was quantified at an average concentration of 0.45 ± 0.46 ng/mL. In hair samples, bisphenols A, F, and S were detected at 95%-100%, chlorinated derivatives of bisphenol A were detected at 37%-68%, and parabens were detected at 100%. CONCLUSIONS: This awareness campaign may encourage health care institutions to adopt a policy of reducing endocrine disruptor exposure among their patients and professionals, who could be educated regarding the risks associated with EDs. Conducting a multicenter study to refine the results herein and establish a dynamic to prevent endocrine disruptor and environmental risks in health care systems would be valuable.

Cinchophen induces RPA1 related DNA damage and apoptosis to impair ENS development of zebrafish.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have become contaminants widely distributed in the environment due to improper disposal and discharge. Previous study has found several components might involve in impairing enteric nervous system (ENS) development of zebrafish, including NSAIDs cinchophen. Deficient ENS development in fetal could lead to Hirschsprung disease (HSCR), a congenital neurocristopathy characterized by absence of enteric neurons in hindgut. However, the intrinsic mechanism of neurotoxicity of cinchophen is unclear. We confirmed that cinchophen could impair ENS development of zebrafish and transcriptome sequencing revealed that disfunction of Replication protein A1 (RPA1), which is involved in DNA replication and repairment, might be relevant to the neurotoxicity effects induced by cinchophen. Based on previous data of single cell RNA sequencing (scRNA-seq) of zebrafish gut cells, we observed that rpa1 mainly expressed in proliferating, differentiating ENS cells and neural crest progenitors. Interestingly, cinchophen induced apoptosis and impaired proliferation. Furthermore, cinchophen caused DNA damage and abnormal activation of ataxia telangiectasia mutated/ Rad3 related (ATM/ATR) and checkpoint kinase 2 (CHK2). Finally, molecular docking indicated cinchophen could bind and antagonize RPA1 more effectively. Our study might provide a better understanding and draw more attention to the role of environmental factors in the pathogenesis of HSCR. And the mechanism of cinchophen neurotoxicity would give theoretical guidance for clinical pharmacy.

Microbial perspective on restoration of degraded urban soil using ornamental plants.

The urban soil where abandoned buildings are demolished is barren and structurally poor, and this degraded soil requires restoration. Ornamental plants enhance the urban environment, increase biodiversity, and affect soil physicochemical properties, microbial diversity; however, their effects remain unclear. Thus, in this study, a mixed-planting meadow consisting of 14 perennial ornamental flower species, including Iris tectorum, Iris lacteal, and Patrinia scabiosaefolia, etc. Was planted at a demolition site with sewage-contaminated soil in Beijing. Simultaneously, a single-planting lawn of I. tectorum was established in a nearby park. We aimed to examine soil physicochemical properties, sequence soil bacterial 16S rRNA and fungal ITS amplicons, and analyze soil microbial diversity and community structure at both sites at five time points in the year after planting, To explore the effect of herbaceous ornamental plants on degraded urban soil, we used FAPROTAX and FUNGuild to predict bacterial and fungal functions, the bin-based null model to evaluate the soil microbial community, and random matrix theory to construct soil microbial molecular networks. The mixed-planting meadow produced a visually appealing landscape and dynamic seasonal enrichment, significantly increasing soil total nitrogen (TN) and organic matter (SOM) contents by 1.99 and 1.21 times, respectively. TN had a positive correlation with soil microbial α diversity and community structure. Dominant phyla at both sites included Proteobacteria, Actinobacteria, and Ascomycota. Although soil microorganisms were primarily influenced by stochastic processes, stochasticity was notably higher in the mixed-planting meadow than in the single-planting lawn. The mixed-planting meadow significantly increased the relative abundance of beneficial microorganisms, improving nitrification and aerobic ammonium oxidation of soil bacteria, as well as symbiotroph of fungi. No significant changes were observed in the single-planting lawn. The mixed-planting meadow established a complex soil microbial molecular network, enhancing the correlation between bacteria and fungi and increasing the number of key microorganisms. Our findings suggest the potential of mixed-planting meadow in restoring degraded urban soils by influencing the soil microbial community and enhancing the ecological service function. Our study provides theoretical support for applying mixed-planting meadow communities to improve the soil environment of urban green spaces.

Active Sites on the CuCo Catalyst in Higher Alcohol Synthesis from Syngas: A Review.

Higher alcohol synthesis through the Fischer-Tropsch (F-T) process was considered a promising route for the efficient utilization of fossil resources could be achieved. The CuCo catalysts were proven to be efficient candidates and attracted much interest. Great efforts have been made to investigate the active sites and mechanisms of CuCo catalysts. However, the industrialized application of CuCo catalysts in this process was still hindered. The poor stability of this catalyst was one of the main reasons. This short review summarized the recent development of active sites on the CuCo catalysts for higher alcohol synthesis, including CuCo alloy particles, CuCo core-shell particles, and unsaturated particles. The complex active sites and their continual changes during the reaction led to the poor stability of the catalysts. The effect of active sites on catalytic performance was discussed. Furthermore, the key factors in fabricating stable CuCo catalysts were proposed. Finally, reasonable proposals were proposed for designing efficient and stable CuCo catalysts in higher alcohol synthesis.

Abnormally elevated expression of ACTA2 of circular smooth muscle leads to hyperactive contraction in aganglionic segments of HSCR.

BACKGROUND: Actin Alpha 2 (ACTA2) is expressed in intestinal smooth muscle cells (iSMCs) and is associated with contractility. Hirschsprung disease (HSCR), one of the most common digested tract malformations, shows peristaltic dysfunction and spasm smooth muscles. The arrangement of the circular and longitudinal smooth muscle (SM) of the aganglionic segments is disorganized. Does ACTA2, as a marker of iSMCs, exhibit abnormal expression in aganglionic segments? Does the ACTA2 expression level affect the contraction function of iSMCs? What are the spatiotemporal expression trends of ACTA2 during different developmental stages of the colon? METHODS: Immunohistochemical staining was used to detect the expression of ACTA2 in iSMCs of children with HSCR and Ednrb-/- mice, and the small interfering RNAs (siRNAs) knockdown technique was employed to investigate how Acta2 affected the systolic function of iSMCs. Additionally, Ednrb-/- mice were used to explore the changes in the expression level of iSMCs ACTA2 at different developmental stages. RESULTS: The expression of ACTA2 is higher in circular SM in the aganglionic segments of HSCR patients and Ednrb-/- mice than in normal control children and mice. Down regulation of Acta2 weakens the contraction ability of intestinal smooth muscle cells. Abnormally elevated expression of ACTA2 of circular smooth muscle occurs since embryonic day 15.5 (E15.5d) in aganglionic segments of Ednrb-/- mice. CONCLUSIONS: Abnormally elevated expression of ACTA2 in the circular SM leads to hyperactive contraction, which may cause the spasm of aganglionic segments in HSCR.

Inflammatory Myofibroblastic Tumor of the Sigmoid Colon in an Infant: A Case Report and Literature Review.

Inflammatory myofibroblastic tumor (IMT) infrequently involves the sigmoid colon, and has not previously been described in an infant sigmoid colon.An inflammatory myofibroblastic tumor arose from the sigmoid colon of an 11-month-old boy, confirmed by anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA) and desmin immunohistochemical staining. The patient recovered well after complete resection of the tumor.Sigmoid IMT can occur in infancy. This eighth case is the youngest so far. The child did well after surgical resection.

Down-Regulation of Double C2 Domain Alpha Promotes the Formation of Hyperplastic Nerve Fibers in Aganglionic Segments of Hirschsprung's Disease.

Hirschsprung's disease (HSCR) is a common developmental anomaly of the gastrointestinal tract in children. The most significant characteristics of aganglionic segments in HSCR are hyperplastic extrinsic nerve fibers and the absence of endogenous ganglion plexus. Double C2 domain alpha (DOC2A) is mainly located in the nucleus and is involved in Ca2+-dependent neurotransmitter release. The loss function of DOC2A influences postsynaptic protein synthesis, dendrite morphology, postsynaptic receptor density and synaptic plasticity. It is still unknown why hyperplastic extrinsic nerve fibers grow into aganglionic segments in HSCR. We detected the expression of DOC2A in HSCR aganglionic segment colons and established three DOC2A-knockdown models in the Neuro-2a cell line, neural spheres and zebrafish separately. First, we detected the protein and mRNA expression of DOC2A and found that DOC2A was negatively correlated with AChE+ grades. Second, in the Neuro-2a cell lines, we found that the amount of neurite outgrowth and mean area per cell were significantly increased, which suggested that the inhibition of DOC2A promotes nerve fiber formation and the neuron's polarity. In the neural spheres, we found that the DOC2A knockdown was manifested by a more obvious connection of nerve fibers in neural spheres. Then, we knocked down Doc2a in zebrafish and found that the down-regulation of Doc2a accelerates the formation of hyperplastic nerve fibers in aganglionic segments in zebrafish. Finally, we detected the expression of MUNC13-2 (UNC13B), which was obviously up-regulated in Grade3/4 (lower DOC2A expression) compared with Grade1/2 (higher DOC2A expression) in the circular muscle layer and longitudinal muscle layer. The expression of UNC13B was up-regulated with the knocking down of DOC2A, and there were protein interactions between DOC2A and UNC13B. The down-regulation of DOC2A may be an important factor leading to hyperplastic nerve fibers in aganglionic segments of HSCR. UNC13B seems to be a downstream molecule to DOC2A, which may participate in the spasm of aganglionic segments of HSCR patient colons.

Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. METHODS: The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). RESULTS: Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. CONCLUSIONS: This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.

[The effect of oxytocin on fear responses: bidirectional regulation or methodological issues?]

One of the core symptoms in anxiety disorders is dysregulated fear response. It is crucial for psychologists and neuroscientists to understand how fear responses are enhanced and inhibited. Although oxytocin (OXT) was initially conceived as a prosocial molecule and mammalian neuropeptide that enhances cooperation and trust, later studies showed that it produces modulatory influence on fear responses. Therefore, OXT is now regarded as a promising pharmacological agent to boost treatment response in anxiety disorders. However, the effect of OXT on fear responses have been somewhat complex, and there are some contradictions among animal experiments and human studies. In this article, we summarize recent studies that employed animal models, brain region-specific manipulations and preclinical studies to explore the role of OXT in the acquisition and processing of fear response. We also discuss the methodological differences among these studies and review the potential factors that may contribute to the complicated effect of OXT on fear response. This review will help to promote the potential clinical application of OXT.

Lower-Molecular-Weight Chitosan-Treated Polyethyleneimine: a Practical Strategy For Gene Delivery to Mesenchymal Stem Cells.

BACKGROUND/AIMS: Genetic modification of mesenchymal stem cells (MSCs) is an essential requirement for their use as a delivery vehicle. To achieve higher transfection efficiency and better reproducibility than previously synthesized chitosan (100 kDa)-polyethylenimine (PEI; 1200 Da), we synthesized a low molecular weight PEI (1200 Da)-grafted chitosan (50 kDa) (CP). METHODS: Safety of CP/DNA or PEI (25 kDa)/DNA was evaluated by an MTT assay using A549 cells or MSCs and a zebrafish embryo model. Effects of CP/DNA on the characteristics of MSCs were evaluated using flow cytometry. Additionally, a pGL3 plasmid was used to investigate the transfection efficiency of PEI (25 kDa), chitosan (100 kDa)-PEI (1200 Da), and CP with different N/P mass ratios on A549 cells and MSCs. Furthermore, CP/pGL3 was used to investigate the effect of serum on transfection, and intracellular transport was assessed by observing the intracellular location of DNA using laser scanning confocal microscopy. In addition, the effect of endocytosis on transfection efficiency was evaluated using A549 cells pre-treated with different inhibitors. Investigations related to analysis of transfection efficiency were all performed using the BCA protein assay to standardize the data. Furthermore, TGF-ß1-and CXCR4-expressing plasmids were applied to evaluate the gene transfer efficiency of CP, including its effects on the osteogenic differentiation and migratory ability of MSCs. RESULTS: The safety evaluation demonstrated that CP/DNA had significantly lower toxicity than PEI (25 kDa)/DNA. Additionally, DNA entered MSCs transfected by CP without changing their properties, while the examination of intracellular transport demonstrated that CP/pGL3 was internalized rapidly into MSCs. Furthermore, studies of the internalization mechanism showed that CP/pGL3 complexes entered the cells through caveolae-mediated endocytosis, thereby suggesting that the CP coating helped DNA enter A549 cells without the requirement for receptors. Compared to PEI (25 kDa), the interference of serum on transfection was reduced significantly with the use of CP in both A549 cells and MSCs. To evaluate the effects of gene delivery using the constructed CP complex and the possibility of obtaining gene-engineered MSCs, TGF-ß1- and CXCR4-expressing plasmids were successfully delivered into MSCs, confirming their ability to induce osteogenesis and change the migratory ability of MSCs, respectively. CONCLUSION: These results demonstrated that CP could be used to deliver genes into MSCs and could potentially be used in gene therapy based on MSCs.

Exploring causal association between malnutrition, nutrients intake and inflammatory bowel disease: a Mendelian randomization analysis.

Background: Malnutrition has emerged as main side effects of inflammatory bowel disease (IBD) which might also affect the prognosis of IBD. However, whether these associations are causal remains unclear. We aimed to identify the causality of IBD on malnutrition and explore the causal relationship of malnutrition and nutrients intake on IBD by using Mendelian randomization (MR). Methods: Single nucleotide polymorphisms associated with IBD, malnutrition and nutrients intake were obtained from previous researches of genome-wide association studies (GWAS) (p < 0.00000005). MR analysis was conducted to evaluate the causality with different methods based on OR and their 95% CIs. Meanwhile, heterogeneity, pleiotropy and MR-PRESSO were used for instrumental variables evaluation. Results: The results of MR analysis revealed that IBD, both Crohn disease (CD) and ulcerative colitis (UC), could directly impact the incidence of malnutrition (p-value <0.01). CD is directly related to nutrients such as sugar, fat, VA, VC, VD and zinc, while UC is correlated with carbohydrate, fat, VB12, VC, VD, VE, iron, zinc and magnesium. However, our results suggested that malnutrition could not affect the risk of IBD directly (p > 0.05). Further analysis showed similar results that nutrients intake had no direct effect on IBD, neither CD or UC. Conclusion: Our results indicated that IBD increases the risk of malnutrition, however, malnutrition and nutrients intake might not directly affect the progression of IBD.

TGM2-Mediated Autophagy Contributes to the Radio-Resistance of Non-Small Cell Lung Cancer Stem-like Cells.

Objectives: Cancer cells with 'stemness' are generally resistant to chemoradiotherapy. This study aims to compare the differences in radiation sensitivity of A549 and CD44+A549 stem-like cells to X-rays and carbon ion radiation (C-ions), and to find a target that can kill cancer stem-like cells (CSCs) of non-small cell lung cancer (NSCLC). Methods: The study used two cell lines (A549 and CD44+A549). The tumorigenicity of cells was tested with animal experiments. The cells were irradiated with X-rays and C-ions. Cell viability was detected using the CCK-8 and EdU assay. A liquid chromatograph-mass spectrometer (LC-MS) helped detect metabolic differences. Protein and mRNA expression were detected using a Western blot, reverse transcription-quantitative (RT-qPCR), and PCR array. The autophagic activity was monitored with a CYTO-ID® Autophagy Detection Kit 2.0. Immunofluorescence and co-immunoprecipitation helped to observe the localization and interaction relationships. Results: First, we verified the radio-resistance of CD44+A549 stem-like cells. LC-MS indicated the difference in autophagy between the two cells, followed by establishing a correlation between the radio-resistance and autophagy. Subsequently, the PCR array proved that TGM2 is significantly upregulated in CD44+A549 stem-like cells. Moreover, the TGM2 knockdown by small interfering RNA could decrease the radio-resistance of CD44+A549 cells. Bioinformatic analyses and experiments showed that TGM2 is correlated with the expression of CD44 and LC3B. Additionally, TGM2 could directly interact with LC3B. Conclusions: We established the CD44-TGM2-LC3 axis: CD44 mediates radio-resistance of CD44+A549 stem-like cells through TGM2 regulation of autophagy. Our study may provide new biomarkers and strategies to alleviate the radio-resistance of CSCs in NSCLC.

Multiomics reveals microbial metabolites as key actors in intestinal fibrosis in Crohn's disease.

Intestinal fibrosis is the primary cause of disability in patients with Crohn's disease (CD), yet effective therapeutic strategies are currently lacking. Here, we report a multiomics analysis of gut microbiota and fecal/blood metabolites of 278 CD patients and 28 healthy controls, identifying characteristic alterations in gut microbiota (e.g., Lachnospiraceae, Ruminococcaceae, Muribaculaceae, Saccharimonadales) and metabolites (e.g., L-aspartic acid, glutamine, ethylmethylacetic acid) in moderate-severe intestinal fibrosis. By integrating multiomics data with magnetic resonance enterography features, putative links between microbial metabolites and intestinal fibrosis-associated morphological alterations were established. These potential associations were mediated by specific combinations of amino acids (e.g., L-aspartic acid), primary bile acids, and glutamine. Finally, we provided causal evidence that L-aspartic acid aggravated intestinal fibrosis both in vitro and in vivo. Overall, we offer a biologically plausible explanation for the hypothesis that gut microbiota and its metabolites promote intestinal fibrosis in CD while also identifying potential targets for therapeutic trials.

Mesenchymal Stem Cells Attenuates Hirschsprung diseases - Associated Enterocolitis by Reducing M1 Macrophages Infiltration via COX-2 Dependent Mechanism.

OBJECTIVE AND DESIGN: Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. MATERIAL OR SUBJECTS: Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. RESULTS: Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. CONCLUSIONS: MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC.

Identification of signaling pathways that specify a subset of migrating enteric neural crest cells at the wavefront in mouse embryos.

During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung's disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.

Remote sensing identification of urban water pollution source types using hyperspectral data.

Owing to accelerated urbanisation, increased pollutants have degraded urban water quality. Timely identification and control of pollution sources enable relevant departments to effectively perform water treatment and restoration. To achieve this goal, a remote sensing identification method for urban water pollution sources applicable to unmanned aerial vehicle (UAV) hyperspectral images was established. First, seven fluorescent components were obtained through three-dimensional excitation-emission matrix fluorescence spectroscopy of dissolved organic matter (DOM) combined with parallel factor analysis. Based on the hierarchical cluster analysis of the seven fluorescence components and three spectral indices, four pollution source (PS) types were determined, namely, domestic sewage, terrestrial input, agricultural and algal, and industrial wastewater sources. Second, several water colour and optical parameters, including the absorption coefficient of chromophoric DOM at 254 nm, humification index, chlorophyll-a concentration, and hue angle, were utilised to develop an identification method with a recognition accuracy exceeding 70% for the four PSs that is suitable for UAV hyperspectral data. This study demonstrated the potential of identifying PSs by combining the fluorescence characteristics of DOM with the optical properties of water, thus expanding the application of remote sensing technologies and providing more comprehensive and reliable information for urban water quality management.

Cumulative and potential synergistic effects of seven different bisphenols on human granulosa cells in vitro?

Bisphenol (BP) structural analogues of BPA are widely used. Previous studies showed similar effects of BPA and BPS on reproduction in several species including human. We hypothesised that the similar effects of several bisphenols (BPs) could accumulate in granulosa cells (GCs) and affects steroidogenesis. This study investigated the effects of seven BP analogues and their equimolar cocktail on human granulosa cells (hGC) and assessed BPA, BPS, BPF and BPAF level exposures in the follicular fluid of 277 women undergoing Assisted Reproductive Technology. The hGCs were recovered after women oocyte punctures and treated with the seven BP analogues (BPS, BPA, BPAF, BPF, BPAP, BPE and BPB) or their equimolar cocktail of 7 × 1.43 or 7 × 7.14 µM for each of the seven BPs, the sum of BPs reaching 10 ("∑BPs 10 µM"), or 50 µM ("∑BPs 50 µM"), respectively. Oestradiol and progesterone secretion, cell proliferation, viability and expression of steroidogenic enzymes were investigated. Progesterone secretion was decreased by 6 BPs 10 µM and the cocktail "∑BPs 10 µM", (-17.8 to -41.3%) and by all seven BPs 50 µM and "∑BPs 50 µM" (-21.8 to -84.2%). Oestradiol secretion was decreased only by 50 µM BPAF and BPAP (-37.8% and -44%, respectively), with corresponding decreases in CYP17A1 and CYP19A1 gene expression. Cellular proliferation was decreased after treatment with 50 µM BPAF (-32.2%), BPAP (-29%), BPB (-24%) and the equimolar cocktail "∑BPs 50 µM" (-33.1%). BPB (50 µM) and the cocktail "∑BPs 50 µM" increased HSD3B2 mRNA expression. At least one BP was detected in 64 of 277 (23.1%) women follicular fluids. Similar effects of the seven BPs or their cocktail were observed on progesterone secretion and/or on cell proliferation, suggesting cumulative effects of BPs. Our results highlight the urge to consider all BPs simultaneously and to further investigate the potential additive or synergistic effects of several BPs.

A hybrid remote sensing approach for estimating chemical oxygen demand concentration in optically complex waters: A case study in inland lake waters in eastern China.

Chemical oxygen demand concentration (CCOD) is widely used to indicate the degree of organic pollution of lakes, reservoirs and rivers. Mastering the spatiotemporal distribution of CCOD is imperative for understanding the variation mechanism and controlling of organic pollution in water. In this study, a hybrid approach suitable for Sentinel 3A/Ocean and Land Colour Instrument (OLCI) data was developed to estimate CCOD in inland optically complex waters embedding the interaction between CCOD and the absorption coefficients of optically active constituents (OACs). Based on in-situ sampling in different waters, the independent validations of the proposed model performed satisfactorily in Lake Taihu (MAPE = 23.52 %, RMSE = 0.95 mg/L, and R2 = 0.81), Lake Qiandaohu (MAPE = 21.63 %, RMSE = 0.50 mg/L and R2 = 0.69), and Yangtze River (MAPE = 29.34 %, RMSE = 0.83 mg/L, and R2 = 0.64). In addition, the approach not only showed significant superiority compared with previous algorithms, but also was suitable for other common satellite sensors equipped same or similar bands. The hybrid approach was applied to OLCI images to retrieve CCOD of Lake Taihu from 2016 to 2020 and reveals substantial interannual and seasonal variations. The above results indicate that the proposed approach is effective and stable for studying spatiotemporal dynamic of CCOD in optically complex waters, and that satellite-derived products can provide reliable information for lake water quality management.

Identification and validation of the common pathogenesis and hub biomarkers in Hirschsprung disease complicated with Crohn's disease.

Background: Although increasing evidence has supported that Hirschsprung disease (HSCR) is the risk factor for children developing Crohn's disease (CD), the common mechanism of its co-occurrence remains unknown. The purpose of this study is to further explore the underlying mechanism and biomarkers for the co-occurrence of HSCR and CD. Methods: The Gene Expression Omnibus (GEO) database was used to obtain gene expression profiles for CD (GSE95095) and HSCR (GSE98502). Following the identification of the shared differentially expressed genes (DEGs) of CD and HSCR, functional annotation, protein-protein interaction (PPI) network creation, and module assembly were performed to discover hub genes. RT-qPCR was performed to validate the expression of the hub genes in HSCR samples. The receiver operating characteristic (ROC) curve was utilized to assess the accuracy of the hub genes as biomarkers in predicting CD in both the training dataset and test dataset. Results: A total of 103 common DEGs (50 downregulated genes and 53 upregulated genes) were chosen for further investigation. The importance of chemokines and cytokines in these two disorders is highlighted by functional analysis. MCODE plug identified three important modules, which functionally enriched the immune system process. Finally, nine hub genes were identified using cytoHubba, including IL1B, IL10, CXCL10, ICAM1, EGR1, FCGR3A, S100A12, S100A9, and FPR1. The nine hub genes were mainly enriched in immune- and inflammation-related pathways. External data profiles and RT-qPCR confirmed the expression of the nine hub genes in HSCR and CD. ROC analysis revealed that the nine hub genes had a strong diagnostic value. Conclusion: Our study reveals the common pathogenesis of HSCR and CD. These hub genes and diagnostic models may provide novel insight for the diagnosis and treatment of HSCR complicated with CD.