Clinicopathological features and prognostic analysis of HER2 low and fibrotic focus in HER2-negative breast cancer.

OBJECTIVE: The aim of this study is to evaluate the clinicopathological features and prognostic significance of HER2 low, fibrotic focus (FF), and tumor-infiltrating lymphocytes (TILs) in patients with HER2-negative breast cancer. METHODS: We retrospectively reviewed the data of 293 patients with HER2-negative, stage I-II, invasive breast cancer of non-specific types. The HER2-negative cases were classified into HER2 low and HER2 0. Digital analysis of hematoxylin-eosin stained whole slide images was used to evaluate the FF expression. TILs were also evaluated using the Whole Slide Image. Furthermore, the association between HER2 low, FF, and TILs as well as their prognostic significance were analyzed. RESULTS: The study cohort included 178 cases (60.8%) with HER2 low and 115 cases (39.2%) with HER2 0. Older age, lower Nottingham histological grade (NHG), estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, and hormone receptor (HR) positivity were all associated with HER2 low. FF was correlated with older age, intermediate and low NHG, vascular invasion, HR positivity, HER2 low status, high Ki67 expression, and low TILs. Univariate survival analysis showed that FF was significantly associated with shorter progression-free survival (PFS). Stratified analysis indicated that in the HR-negative and HR-positive groups, HER2 status and TILs did not affect PFS. DFS was longer in patients without FF compared to those with FF in the HR-positive (hazard ratio [HR] = 0.313) and HER2 low (HR = 0.272) groups. DFS was also significantly longer in patients without FF compared to those with FF in the HR-negative (HR = 0.069) and HER2 0 groups (HR = 0.129). CONCLUSION: The results indicated that the HER2 low status and the TILs expression did not impact prognosis. However, patients with FF exhibited distinct biological characteristics and prognostic significance, particularly in the HR-negative and HER2 0 groups. This provides a rationale for accurate diagnosis and treatment of HER2-negative breast cancer.

The Role of Artificial Intelligence in Accurate Interpretation of HER2 Immunohistochemical Scores 0 and 1+ in Breast Cancer.

The new human epidermal growth factor receptor (HER)2-targeting antibody-drug conjugate offers the opportunity to treat patients with HER2-low breast cancer. Distinguishing HER2 immunohistochemical (IHC) scores of 0 and 1+ is not only critical but also challenging owing to HER2 heterogeneity and variability of observers. In this study, we aimed to increase the interpretation accuracy and consistency of HER2 IHC 0 and 1+ evaluation through assistance from an artificial intelligence (AI) algorithm. In addition, we examined the value of our AI algorithm in evaluating HER2 IHC scores in tumors with heterogeneity. AI-assisted interpretation consisted of AI algorithms and an augmenting reality module with a microscope. Fifteen pathologists (5 junior, 5 midlevel, and 5 senior) participated in this multi-institutional 2-round ring study that included 246 infiltrating duct carcinoma cases that were not otherwise specified. In round 1, pathologists analyzed 246 HER2 IHC slides by microscope without AI assistance. After a 2-week washout period, the pathologists read the same slides with AI algorithm assistance and rendered the definitive results by adjusting to the AI algorithm. The accuracy of interpretation accuracy with AI assistance (0.93 vs 0.80), thereby the evaluation precision of HER2 0 and the recall of HER2 1+. In addition, the AI algorithm improved the total consistency (intraclass correlation coefficient = 0.542-0.812), especially in HER2 1+ cases. In cases with heterogeneity, accuracy improved significantly (0.68 to 0.89) and to a similar level as in cases without heterogeneity (accuracy, 0.97). Both accuracy and consistency improved more for junior pathologists than those for the midlevel and senior pathologists. To the best of our knowledge, this is the first study to show that the accuracy and consistency of HER2 IHC 0 and 1+ evaluation and the accuracy of HER2 IHC evaluation in breast cancers with heterogeneity can be significantly improved using AI-assisted interpretation.

Improved Alkaline Seawater Splitting of NiS Nanosheets by Iron Doping.

Seawater electrolysis driven by renewable electricity is deemed a promising and sustainable strategy for green hydrogen production, but it is still formidably challenging. Here, we report an iron-doped NiS nanosheet array on Ni foam (Fe-NiS/NF) as a high-performance and stable seawater splitting electrocatalyst. Such Fe-NiS/NF catalyst needs overpotentials of only 420 and 270 mV at 1000 mA cm-2 for the oxygen evolution reaction and hydrogen evolution reaction in alkaline seawater, respectively. Furthermore, its two-electrode electrolyzer needs a cell voltage of 1.88 V for 1000 mA cm-2 with 50 h of long-term electrochemical durability in alkaline seawater. Additionally, in situ electrochemical Raman and infrared spectroscopy were employed to detect the reconstitution process of NiOOH and the generation of oxygen intermediates under reaction conditions.

Reduced expression of microRNA-432-5p by DNA methyltransferase 3B leads to development of colorectal cancer through upregulation of CCND2.

BACKGROUND: The tumor suppressive function of microRNA-432-5p (miR-432-5p) has been reported in several human malignances. This study aimed to probe the expression profile and role of miR-432-5p in colorectal cancer (CRC) and the molecular mechanism. METHODS: Differentially expressed miRNAs between CRC and healthy samples were screened using a miRNA expression dataset GSE136020. The related molecules were identified by integrated bioinformatic analyses. A murine model of primary CRC was established and xenograft tumors were induced in mice. Altered expression of DNMT3B, miR-432-5p and cyclin D2 (CCND2) were introduced in CRC cells to determine their roles in the development of CRC. RESULTS: miR-432-5p was downregulated in CRC according to the GSE136020 dataset. CCND2 mRNA was confirmed as a target of miR-432-5p. miR-432-5p was downregulated, whereas CCND2 was abundantly expressed in CRC tissues and cells. DNA methyltransferase 3B (DNMT3B) induced DNA methylation at the CpG island of miR-432-5p to inhibit its expression. miR-432-5p mimic significantly suppressed tumorigenesis of primary CRC in mice. Downregulation of DNMT3B weakened viability, invasiveness, blocked the cell cycle progression of CRC cells in vitro, and inhibited xenograft tumor growth and metastasis in nude mice. However, additional downregulation of miR-432-5p or upregulation of CCND2 restored the malignant behaviors of CRC cells. CONCLUSION: This study showed that DNMT3B induced DNA methylation and downregulation of miR-432-5p to promote development of CRC by upregulating CCND2.

[Mechanism of protective effect of resveratrol on poor ovarian response in mice].

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.

Qualitative and Quantitative Analysis of Five Indoles or Indazole Amide Synthetic Cannabinoids in Suspected E-Cigarette Oil by GC-MS.

OBJECTIVES: To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples. METHODS: The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode. RESULTS: The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%. CONCLUSIONS: The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.

Circ_0006948 Contributes to Cell Growth, Migration, Invasion and Epithelial-Mesenchymal Transition in Esophageal Carcinoma.

BACKGROUND: Circular RNAs (circRNAs) can act as promoters or inhibitors in cancer progression. Has_circ_0006948 (circ_0006948) was reported to aggravate the malignant behaviors of esophageal carcinoma (EC). AIMS: This study focused on investigating the molecular mechanism of circ_0006948 in EC progression. METHODS: The quantitative real-time polymerase chain reaction was performed to detect the expression of circ_0006948, microRNA-4262 (miR-4262) and fibronectin type III domain containing 3B (FNDC3B). Cell growth analysis was conducted by Cell Counting Kit-8 and colony formation assays. Cell migration and invasion were assessed by transwell assay. Epithelial-mesenchymal transition (EMT)-associated proteins and FNDC3B protein expression were assayed using western blot. Dual-luciferase reporter and RNA pull-down assays were performed to validate the target combination. Xenograft tumor assay was used for investigating the role of circ_0006948 in vivo. RESULTS: Circ_0006948 was upregulated in EC tissues and cells. Downregulating the expression of circ_0006948 or FNDC3B repressed cell growth, migration, invasion and EMT in EC cells. Target analysis indicated that miR-4262 was a target for circ_0006948 and FNDC3B was a downstream gene for miR-4262. Moreover, circ_0006948 could affect the expression of FNDC3B via sponging miR-4262. The effects of si-circ_0006948#1 on EC cells were partly restored by miR-4262 inhibition or FNDC3B overexpression. In addition, circ_0006948 also facilitated EC tumorigenesis in vivo by targeting the miR-4262/FNDC3B axis. CONCLUSION: Taken together, circ_0006948 functioned as an oncogenic factor in EC by the miR-4262-mediated FNDC3B expression regulation.

Can lymphovascular invasion be predicted by contrast-enhanced CT imaging features in patients with esophageal squamous cell carcinoma? A preliminary retrospective study.

BACKGROUND: To investigate the value of contrast-enhanced CT (CECT)-derived imaging features in predicting lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC) patients. METHODS: One hundred and ninety-seven patients with postoperative pathologically confirmed esophageal squamous cell carcinoma treated in our hospital between January 2017 and January 2019 were enrolled in our study, including fifty-nine patients with LVI and one hundred and thirty-eight patients without LVI. The CECT-derived imaging features of all patients were analyzed. The CECT-derived imaging features were divided into quantitative features and qualitative features. The quantitative features consisted of the CT attenuation value of the tumor (CTVTumor), the CT attenuation value of the normal esophageal wall (CTVNormal), the CT attenuation value ratio of the tumor-to-normal esophageal wall (TNR), the CT attenuation value difference between the tumor and normal esophageal wall (ΔTN), the maximum thickness of the tumor measured by CECT (Thickness), the maximum length of the tumor measured by CECT (Length), and the gross tumor volume measured by CECT (GTV). The qualitative features consisted of an enhancement pattern, tumor margin, enlarged blood supply or drainage vessels to the tumor (EVFDT), and tumor necrosis. For the clinicopathological characteristics and CECT-derived imaging feature analysis, the chi-squared test was used for categorical variables, the Mann-Whitney U test was used for continuous variables with a nonnormal distribution, and the independent sample t-test was used for the continuous variables with a normal distribution. The trend test was used for ordinal variables. The association between LVI status and CECT-derived imaging features was analyzed by univariable logistic analysis, followed by multivariable logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: The CTVTumor, TNR, ΔTN, Thickness, Length, and GTV in the group with LVI were higher than those in the group without LVI (P < 0.05). A higher proportion of patients with heterogeneous enhancement pattern, irregular tumor margin, EVFDT, and tumor necrosis were present in the group with LVI (P < 0.05). As revealed by the univariable logistic analysis, the CECT-derived imaging features, including CTVTumor, TNR, ΔTN and enhancement pattern, Thickness, Length, GTV, tumor margin, EVFDT, and tumor necrosis were associated with LVI status (P < 0.05). Only the TNR (OR 8.655; 95% CI 2.125-37.776), Thickness (OR 6.531; 95% CI 2.410-20.608), and tumor margin (OR 4.384; 95% CI 2.004-9.717) were independent risk factors for LVI in the multivariable logistic regression analysis. The ROC curve analysis incorporating the above three CECT-derived imaging features showed that the area under the curve obtained by the multivariable logistic regression model was 0.820 (95% CI 0.754-0.885). CONCLUSION: The CECT-derived imaging features, including TNR, Thickness, tumor margin, and their combination, can be used as predictors of LVI status for patients with ESCC.

Phytoestrogen arctigenin preserves the mucus barrier in inflammatory bowel diseases by inhibiting goblet cell apoptosis via the ERß/TRIM21/PHB1 pathway.

Intestinal mucus barrier dysfunction is closely involved in the pathogenesis of inflammatory bowel diseases (IBD). To investigate the protective effect and underlying mechanism of arctigenin, a phytoestrogen isolated from the fruits of Arctium lappa L., on the intestinal mucus barrier under colitis condition. The role of arctigenin on the intestinal mucus barrier and the apoptosis of goblet cells were examined by using both in vitro and in vivo assays. Arctigenin was demonstrated to promote the mucus secretion and maintain the integrity of mucus barrier, which might be achieved by an increase in the number of goblet cells via inhibiting apoptosis. Arctigenin selectively inhibited the mitochondrial pathway-mediated apoptosis. Moreover, arctigenin elevated the protein level of prohibitin 1 (PHB1) through blocking the ubiquitination via activation of estrogen receptor ß (ERß) to competitively interact with PHB1 and disrupt the binding of tripartite motif 21 (TRIM21) with PHB1. ERß knock down in the colons of mice with DSS-induced colitis resulted in significant reduction of the protection of arctigenin and DPN against the mucosal barrier. Arctigenin can maintain the integrity of the mucus barrier by inhibiting the apoptosis of goblet cells through the ERß/TRIM21/PHB1 pathway.

Improving Ki67 assessment concordance by the use of an artificial intelligence-empowered microscope: a multi-institutional ring study.

AIMS: The nuclear proliferation biomarker Ki67 plays potential prognostic and predictive roles in breast cancer treatment. However, the lack of interpathologist consistency in Ki67 assessment limits the clinical use of Ki67. The aim of this article was to report a solution utilising an artificial intelligence (AI)-empowered microscope to improve Ki67 scoring concordance. METHODS AND RESULTS: We developed an AI-empowered microscope in which the conventional microscope was equipped with AI algorithms, and AI results were provided to pathologists in real time through augmented reality. We recruited 30 pathologists with various experience levels from five institutes to assess the Ki67 labelling index on 100 Ki67-stained slides from invasive breast cancer patients. In the first round, pathologists conducted visual assessment on a conventional microscope; in the second round, they were assisted with reference cards; and in the third round, they were assisted with an AI-empowered microscope. Experienced pathologists had better reproducibility and accuracy [intraclass correlation coefficient (ICC) = 0.864, mean error = 8.25%] than inexperienced pathologists (ICC = 0.807, mean error = 11.0%) in visual assessment. Moreover, with reference cards, inexperienced pathologists (ICC = 0.836, mean error = 10.7%) and experienced pathologists (ICC = 0.875, mean error = 7.56%) improved their reproducibility and accuracy. Finally, both experienced pathologists (ICC = 0.937, mean error = 4.36%) and inexperienced pathologists (ICC = 0.923, mean error = 4.71%) improved the reproducibility and accuracy significantly with the AI-empowered microscope. CONCLUSION: The AI-empowered microscope allows seamless integration of the AI solution into the clinical workflow, and helps pathologists to obtain higher consistency and accuracy for Ki67 assessment.

LINC01605, regulated by the EP300-SMYD2 complex, potentiates the binding between METTL3 and SPTBN2 in colorectal cancer.

BACKGROUND: Colorectal cancer (CC) is one of the major contributors to tumor-related death worldwide, and its main cause of death is distant metastasis. Dysregulation of long non-coding RNA (lncRNA) LINC01605 has been implicated in CC. However, its role in metastasis of CC remains elusive. The goal of the study is to uncover the biological function and molecular mechanism of LINC01605 in CC. METHODS: The differentially expressed lncRNAs were first screened from GSE97300, GSE84983, GSE110715, GSE70880, and GSE75970 microarrays. The correlation between the expression of LINC01605 and the clinical phenotypes of enrolled CC patients (n = 134) was subsequently analyzed. The upstream and downstream regulatory mechanisms of LINC01605 in CC were identified through bioinformatics and RNA-seq analyses. Finally, the effects of related factors on CC cell growth and metastasis were confirmed through functional validation experiments. RESULTS: LINC01605, significantly highly expressed in CC, was a prognostic factor for patients with CC. Functional experiments revealed that LINC01605 knockdown inhibited the proliferatory and metastatic potential of CC cells in vitro and in vivo. Moreover, LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone H3K4me3 as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. CONCLUSIONS: Overexpression of LINC01605, regulated by SMYD2-EP300-mediated H3K27ac and H3K4me3 modifications, bound to METTL3 protein to promote m6A modification of SPTBN2 mRNA, leading to the development of CC.

Extracellular vesicles-derived microRNA-222 promotes immune escape via interacting with ATF3 to regulate AKT1 transcription in colorectal cancer.

BACKGROUND: Immunotherapy has been recently established as a new direction for the treatment of colorectal cancer (CRC), a gastrointestinal cancer. In this investigation, we aimed to expound how the posttranscriptional regulation modulated by microRNA-222 (miR-222) from mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) affected the AKT pathway and the immune escape in CRC. METHODS: CRC cell malignant phenotype, including proliferation, migration, invasion, and apoptosis, was firstly detected after co-culture with MSC-EVs. miRNAs with differential changes in CRC cells before and after EVs treatment were filtered by microarray analysis. miR-222 was then downregulated to examine its role in CRC cells in response to EVs. Cells were implanted in mice to induce xenograft tumors, and infiltrating T cells was assessed by immunohistochemistry. The mRNA microarray was used to screen target genes, followed by rescue experiments. ChIP and western blot were conducted to validate the downstream biomolecule of ATF3. RESULTS: After treatment of CRC cells with MSC-EVs, the expression of miR-222 was upregulated, and cell activity was increased. Inhibition of miR-222 decreased CRC malignant aggressiveness in vitro and reduced tumorigenesis and immune escape in vivo. miR-222 targeted and bound to ATF3. Downregulation of ATF3 enhanced CRC cell malignant aggressiveness, tumorigenic capacity and immune escape. Mechanistically, ATF3 inhibited AKT1 transcription and mediated the AKT pathway. CONCLUSION: MSC-EVs carry miR-222 to promote CRC cell malignant aggressiveness and immune escape. miR-222 targets and binds to ATF3, which inhibits AKT1 transcriptional activity and thereby mediates the AKT pathway.

FOSL1 promotes tumorigenesis in colorectal carcinoma by mediating the FBXL2/Wnt/ß-catenin axis via Smurf1.

Colorectal carcinoma (CC), one of the most prevalent digestive cancers with high mortality and morbidity globally, still lacks powerful therapies to improve the prognosis. Here, we established that the expression of fos-like antigen-1 (Fosl1) was elevated in CC tissues versus adjacent tissues. Importantly, high Fosl1 expression was related to dismal prognosis among CC patients. Functional assays displayed that Fosl1 increased the viability, epithelial-to-mesenchymal transition (EMT), migration and invasion of CC cells. Additionally, a xenograft assay showed that silencing of Fosl1 in CC cells retarded lung, liver and kidney metastases in vivo. Further investigation demonstrated that Fosl1 was involved in malignant aggressiveness of CC cells by binding to smad ubiquitination regulatory factor 1 (Smurf1). Mechanistically, Smurf1-induced F-Box and leucine rich repeat protein 2 (FBXL2) ubiquitination resulted in its degradation, while FBXL2 disrupted the activation of the Wnt/ß-catenin signaling. In summary, Fosl1 plays a pro-metastatic and carcinogenetic role in CC, and we provided forceful evidence that Fosl1 inhibition might act as a prognostic and therapeutic option in CC.

Combining Dual-Light Emissions to Achieve Efficient Broadband Yellowish-Green Luminescence in One-Dimensional Hybrid Lead Halides.

In recent years, low-dimensional lead halides have emerged as some of most attractive photoelectric materials due to their intrinsic broadband emissions with a potential application in white-light emitting diodes. To achieve the desired performance, tremendous research has emphasized the modulation of inorganic components as optical centers; however, less work has paid attention to the direct contribution of the organic components. Herein, we successfully assembled two new hybrid lead halides of [H2BPP]Pb2X6 (X = Br, 1, and Cl, 2) containing one-dimensional double [Pb2X6]2- chains using optically active 1,3-bis(4-pyridyl)-propane (BPP) as an organic cation. Under UV-light excitation, compounds 1 and 2 exhibit broadband yellowish-green emissions, which were verified by promising photoluminescence quantum efficiencies (PLQEs) of 8.10% and 4.84%, respectively. The broadband light emissions are derived from the combination of dual higher-energy blue and lower-energy yellow light spectra, which can be attributed to the individual contributions of the organic and inorganic components, respectively, according to the time-resolved and temperature-dependent emission spectra as well as theoretical calculations. This work proves the great contribution of organic components to the photophysical properties and provides a new design strategy to realize broadband light emission by rationally combining the dual-emitting properties of different assembly blocks.

NEDD4 triggers FOXA1 ubiquitination and promotes colon cancer progression under microRNA-340-5p suppression and ATF1 upregulation.

NEDD4 is an E3 ubiquitin ligase that recognizes substrates through protein-protein interactions and is involved in cancer development. This study aimed to elucidate the function of NEDD4 in colon cancer (CC) progression and its mechanism of action. NEDD4 was abundantly expressed in CC tissues and cells, and the overexpression of NEDD4 promoted the growth and metastasis of xenograft tumours as well as the tumorigenesis rate of primary CC in mouse models. In in vitro experiments, the silencing (or upregulation) of NEDD4 inhibited (or increased) the viability, invasion, and epithelial-to-mesenchymal transition of CC cells. The binding relationships between NEDD4 and FOXA1, FOXA1 and microRNA (miRNA)-340-5p, and miR-340-5p and ATF1 were validated by Co-immunoprecipitation, chromatin immunoprecipitation and luciferase assays, and NEDD4 was demonstrated to trigger FOXA1 ubiquitination and degradation. FOXA1 transcriptionally activated miR-340-5p, which subsequently bound to ATF1 mRNA. The upregulation of FOXA1 or miR-340-5p or the downregulation of ATF1 blocked certain functions of NEDD4 in CC cells. Altogether, NEDD4 was demonstrated to trigger FOXA1 ubiquitination and promote CC progression under the involvement of microRNA-340-5p suppression and ATF1 upregulation.

Examining the carbon footprint of rice production and consumption in Hubei, China: A life cycle assessment and uncertainty analysis approach.

This study aimed to quantify greenhouse gas emissions derived from the production-consumption of rice in Hubei-a major rice-producing province in central China. This research employed primary and secondary data collection methods. Primary data sources included interviews and experimental observations from seven counties in Hubei collected from June 2016 to December 2016. Secondary data sources-including national datasets, inter-governmental reports, and peer-reviewed articles-were used to extract relevant data, such as emission factors, and national and provincial rice output. Life Cycle Assessment was employed to build a comprehensive inventory and map of the rice carbon footprint, including the following five stages: production inputs, farm management, growth period, processing and sale, and consumption. Uncertainty analysis was performed to validate the reliability of carbon footprint estimations. Results showed that the carbon footprint for every 1 ton of polished rice in Hubei ranged between 4.19-6.81 t CO2e/t and was 5.39 t CO2e/t on average. Greenhouse gas emissions were primarily produced from rice fields during the growth stage (over 60% of greenhouse gas emissions of the whole life cycle of rice), followed by the consumption stage, and the production and transportation of agricultural inputs. Uncertainty analysis estimations indicated acceptable levels of reliability. This study's results indicate that the production and consumption of rice is a significant contributor to agricultural carbon emissions in Hubei-consistent with national estimates that place China as the largest carbon dioxide emitter globally. This research provides further insight into future policies and targeted initiatives for the efficient use of low-carbon agricultural inputs for rice production and consumption stages in China.

Ischemia-Modified Albumin Is Associated with Arterial Stiffness in Hemodialysis Patients.

Increased arterial stiffness is strongly associated with cardiovascular morbidity and mortality in dialysis patients. Ischemia-modified albumin (IMA) is a useful biomarker of cardiac ischemia. This study was aimed to explore the association between IMA and arterial stiffness in hemodialysis patients. An observational study was conducted with 120 hemodialysis patients. Clinical data and laboratory characteristics were collected. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). Hemodialysis patients had extensive arterial stiffness and high levels of IMA. Comparing to hemodialysis patients with normal baPWV, those with high baPWV had significantly higher levels of IMA (93.7 ± 8.6 versus 73.1 ± 10.7 Ku/L, P = 0.027). The multiple linear regression analysis showed that IMA was significantly associated with arterial stiffness in hemodialysis patients (ß = 0.43, P < 0.001). Moreover, IMA, with a threshold value of 90.4 Ku/L, provided 77.4% sensitivity and 86.6% specificity for predicting arterial stiffness. Hemodialysis patients with arterial stiffness had high levels of IMA. IMA was a good predictive marker of arterial stiffness for hemodialysis patients.

A Boron Nitride Nanosheets Composite Membrane for a Long-Life Zinc-Based Flow Battery.

The capability to maintain a constant system temperature is vital in nature, since it endows the system with enhanced lifetime. This trait also works for zinc-based batteries, because their cycle-life is limited by notorious zinc dendrite/accumulation, which are highly affected by the inhomogeneous distribution of temperature on electrode and relatively low mechanical strength of membrane. Herein, boron nitride nanosheets (BNNSs) with high mechanical strength serving as heat-porter are introduced onto a porous substrate to enable uniform deposition of zinc and further a zinc-based flow battery with long-cycle life. The results indicate that BNNSs can effectively adjust the deposited zinc from needle-like to French fries-like morphology, thus affording the battery with a stable performance for nearly 500 cycles at 80 mA cm-2 . Most importantly, an energy efficiency of above 80 % can be obtained even at 200 mA cm-2 , which is by far the highest value ever reported among zinc-based flow batteries.