ZSWIM1 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma Cells through the STK38/MEKK2/ERK1/2 Axis.

Investigating the functions of the proteins with no or less functional annotations is an important goal of the HPP (Human Proteome Project) Grand Project. In this study, we investigated the function of such a protein, ZSWIM1 (C20orf162), its gene located on chromosome 20. Its expression is upregulated in lung adenocarcinoma compared with the adjacent normal tissues and negatively correlated with the overall survival. Overexpressing ZSWIM1 markedly promotes the proliferation, migration, invasion as well as epithelial-to-mesenchymal transition in lung adenocarcinoma cells, while knocking down ZSWIM1 functions oppositely. The interactome of ZSWIM1 was identified by immunoprecipitation-mass spectrometry, and we verified the interaction of ZSWIM1 with the potential partner, STK38. ZSWIM1 antagonized the function of STK38. Mechanically, ZSWIM1 promoted the activation of MEKK2/ERK1/2 pathway through interacting with STK38, leading to the release of MEKK2. Taken together, ZSWIM1 can be annotated as an oncogene in lung adenocarcinoma, and the STK38/MEKK2/ERK1/2 axis mediates its promoting role in lung adenocarcinoma.

Differential response of luminal and basal breast cancer cells to acute and chronic hypoxia.

Hypoxia is linked to disease progression and poor prognosis in several cancers, including breast cancer. Cancer cells can encounter acute, chronic, and/or intermittent periods of oxygen deprivation and it is poorly understood how the different breast cancer subtypes respond to such hypoxia regimes. Here, we assessed the response of representative cell lines for the luminal and basal A subtype to acute (24 h) and chronic hypoxia (5 days). High throughput targeted transcriptomics analysis showed that HIF-related pathways are significantly activated in both subtypes. Indeed, HIF1⍺ nuclear accumulation and activation of the HIF1⍺ target gene CA9 were comparable. Based on the number of differentially expressed genes: (i) 5 days of exposure to hypoxia induced a more profound transcriptional reprogramming than 24 h, and (ii) basal A cells were less affected by acute and chronic hypoxia as compared to luminal cells. Hypoxia-regulated gene networks were identified of which hub genes were associated with worse survival in breast cancer patients. Notably, while chronic hypoxia altered the regulation of the cell cycle in both cell lines, it induced two distinct adaptation programs in these subtypes. Mainly genes controlling central carbon metabolism were affected in the luminal cells whereas genes controlling the cytoskeleton were affected in the basal A cells. In agreement, in response to chronic hypoxia, lactate secretion was more prominently increased in the luminal cell lines which were associated with the upregulation of the GAPDH glycolytic enzyme. This was not observed in the basal A cell lines. In contrast, basal A cells displayed enhanced cell migration associated with more F-actin stress fibers whereas luminal cells did not. Altogether, these data show distinct responses to acute and chronic hypoxia that differ considerably between luminal and basal A cells. This differential adaptation is expected to play a role in the progression of these different breast cancer subtypes.

Fibroadipose vascular anomaly: a clinicopathological study of 75 cases.

AIMS: Fibroadipose vascular anomaly (FAVA) is a complex vascular malformation that is likely to be under-recognised. In this study we aimed to report the pathological features and somatic PIK3CA mutations associated with the most common clinicopathological features. METHODS AND RESULTS: Cases were identified by reviewing the lesions resected from patients with FAVA registered at our Haemangioma Surgery Centre and unusual intramuscular vascular anomalies in our pathology database. There were 23 males and 52 females, who ranged in age from 1 to 51 years. Most cases occurred in the lower extremities (n = 62). The majority of the lesions were intramuscular, with a few disrupting the overlying fascia and involving subcutaneous fat (19 of 75), and a minority of the cases had cutaneous vascular stains (13 of 75). Histopathologically, the lesion was composed of anomalous vascular components that were intertwined with mature adipocytic and dense fibrous tissues and vascular components with: (a) clusters of thin-walled channels, some with blood-filled nodules and others with thin walls resembling pulmonary alveoli; (b) numerous small vessels (arteries, veins and indeterminate channels) - proliferative small blood vessels were often mixed with adipose tissue; (c) larger abnormal venous channels usually irregularly and sometimes excessively muscularised; (d) lymphoid aggregates or lymphoplasmacytic aggregates were usually observed; and (e) lymphatic malformations were sometimes seen as minor elements. All patients had their lessons subjected to PCR, and 53 patients had somatic PIK3CA mutations (53 of 75). CONCLUSIONS: FAVA is a slow-flow vascular malformation with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for targeted therapy.

Drought-induced increase in tree mortality and corresponding decrease in the carbon sink capacity of Canada's boreal forests from 1970 to 2020.

Canada's boreal forests, which occupy approximately 30% of boreal forests worldwide, play an important role in the global carbon budget. However, there is little quantitative information available regarding the spatiotemporal changes in the drought-induced tree mortality of Canada's boreal forests overall and their associated impacts on biomass carbon dynamics. Here, we develop spatiotemporally explicit estimates of drought-induced tree mortality and corresponding biomass carbon sink capacity changes in Canada's boreal forests from 1970 to 2020. We show that the average annual tree mortality rate is approximately 2.7%. Approximately 43% of Canada's boreal forests have experienced significantly increasing tree mortality trends (71% of which are located in the western region of the country), and these trends have accelerated since 2002. This increase in tree mortality has resulted in significant biomass carbon losses at an approximate rate of 1.51 ± 0.29 MgC ha-1  year-1 (95% confidence interval) with an approximate total loss of 0.46 ± 0.09 PgC year-1 (95% confidence interval). Under the drought condition increases predicted for this century, the capacity of Canada's boreal forests to act as a carbon sink will be further reduced, potentially leading to a significant positive climate feedback effect.

Design, synthesis, and anti-triple negative breast cancer activity of novel Toosendanin derivatives.

Toosendanin (TSN) is a natural anti-cancer compound that is isolated from the traditional Chinese herbal Melia toosendan Sieb et Zucc. However, the research effect of TSN in the treatment of Triple negative breast cancer (TNBC) is still far from ideal. In this work, we investigated TSN and its derivatives in terms of their actions against MDA-MB-231 and HCC1806 TNBC cell lines. The results indicated that TSN and its derivative 11 showed excellent antitumor activity. Preliminary mechanistic studies showed that both compounds TSN and 11 induced S-phase arrest and G2/M phase cell number decrease in HCC1806 cells. Also, TSN and 11 significantly reduced the protein level of the well-known cancer suppressor gene p53, reduced the phosphorylation of AKT and ERK, and also induced the accumulation of phosphorylated p38 and p21.

An 8-gene predicting survival model of hepatocellular carcinoma (HCC) related to pyroptosis and cuproptosis.

BACKGROUND: The study aimed to establish a prognostic survival model with 8 pyroptosis-and-cuproptosis-related genes to examine the prognostic effect in patients of hepatocellular carcinoma (HCC). METHODS: We downloaded gene expression data and clinical information of HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The clustering analysis and cox regression with LASSO were used for constructing an 8 PCmRNAs survival model. Using TCGA, ICGC and GEO cohort, the overall survival (OS) between high- and low- risk group was determined. We also evaluated independent prognostic indicators using univariate and multivariate analyses. The relatively bioinformatics analysis, including immune cell infiltration, function enrichment and drug sensitivity analyses, was performed as well. The gene expression of 8 PCmRNAs in vitro were validated in several HCC cell lines by qRT-PCR and Western blot. The relationship between GZMA and Fludarabine were further checked by CCK-8 assay. RESULTS: The survival prognostic model was constructed with ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA using data from TCGA cohort. The ICGC and GEO cohort were used for model validation. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. Risk scores had the highest predictable value for survival among Stage, Age, Gender and Grade. Most Immune cells and immune functions were decreased in high-risk group. Besides, function enrichment analyses showed that steroid metabolic process, hormone metabolic process, collagen - containing extracellular matrix, oxidoreductase activity and pyruvate metabolism were enriched. Potential drugs targeted different PCDEGs like Nelarabine, Dexamethasone and Fludarabine were found as well. ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NOD1 were upregulated while NLRP6 and GZMA were downregulated in most HCC cell lines. The potential therapy of Fludarabine was demonstrated when GZMA was low expressed in Huh7 cell line. CONCLUSION: We constructed a novel 8-gene (ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA) prognostic model and explored potential functional information and microenvironment of HCC, which might be worthy of clinical application. In addition, several potential chemotherapy drugs were screened and Fludarabine might be effective for HCC patients whose GZMA was low expressed.

Radiomics-based machine learning approach in differentiating fibro-adipose vascular anomaly from venous malformation.

BACKGROUND: As a complex vascular malformation, fibro-adipose vascular anomaly was first proposed in 2014. Its overlap with other vascular malformations regarding imaging and clinical features often leads to misdiagnosis and improper management. OBJECTIVE: To construct a radiomics-based machine learning model to help radiologists differentiate fibro-adipose vascular anomaly from common venous malformations. MATERIALS AND METHODS: We retrospectively analyzed 178 children, adolescents and young adults with vascular malformations (41 fibro-adipose vascular anomaly and 137 common vascular malformation cases) who underwent MRI before surgery between May 2012 to January 2021. We extracted radiomics features from T1-weighted images and fat-saturated (FS) T2-weighted images and further selected features through least absolute shrinkage and selection operator (LASSO) and Boruta methods. We established eight weighted logistic regression classification models based on various combinations of feature-selection strategies (LASSO or Boruta) and sequence types (single- or multi-sequence). Finally, we evaluated the performance of each model by the mean area under the receiver operating characteristics curve (ROC-AUC), sensitivity and specificity in 10 runs of repeated k-fold (k = 10) cross-validation. RESULTS: Two multi-sequence models based on axial FS T2-W, coronal FS T2-W and axial T1-W images showed promising performance. The LASSO-based multi-sequence model achieved an AUC of 97%±3.8, a sensitivity of 94%±12.4 and a specificity of 89%±9.0. The Boruta-based multi-sequence model achieved an AUC of 97%±3.7, a sensitivity of 95%±10.5 and a specificity of 87%±9.0. CONCLUSION: The radiomics-based machine learning model can provide a promising tool to help distinguish fibro-adipose vascular anomaly from common venous malformations.

GRHL2 Regulation of Growth/Motility Balance in Luminal versus Basal Breast Cancer.

The transcription factor Grainyhead-like 2 (GRHL2) is a critical transcription factor for epithelial tissues that has been reported to promote cancer growth in some and suppress aspects of cancer progression in other studies. We investigated its role in different breast cancer subtypes. In breast cancer patients, GRHL2 expression was increased in all subtypes and inversely correlated with overall survival in basal-like breast cancer patients. In a large cell line panel, GRHL2 was expressed in luminal and basal A cells, but low or absent in basal B cells. The intersection of ChIP-Seq analysis in 3 luminal and 3 basal A cell lines identified conserved GRHL2 binding sites for both subtypes. A pathway analysis of ChIP-seq data revealed cell-cell junction regulation and epithelial migration as well as epithelial proliferation, as candidate GRHL2-regulated processes and further analysis of hub genes in these pathways showed similar regulatory networks in both subtypes. However, GRHL2 deletion in a luminal cell line caused cell cycle arrest while this was less prominent in a basal A cell line. Conversely, GRHL2 loss triggered enhanced migration in the basal A cells but failed to do so in the luminal cell line. ChIP-Seq and ChIP-qPCR demonstrated GRHL2 binding to CLDN4 and OVOL2 in both subtypes but not to other GRHL2 targets controlling cell-cell adhesion that were previously identified in other cell types, including CDH1 and ZEB1. Nevertheless, E-cadherin protein expression was decreased upon GRHL2 deletion especially in the luminal line and, in agreement with its selectively enhanced migration, only the basal A cell line showed concomitant induction of vimentin and N-cadherin. To address how the balance between growth reduction and aspects of EMT upon loss of GRHL2 affected in vivo behavior, we used a mouse basal A orthotopic transplantation model in which the GRHL2 gene was silenced. This resulted in reduced primary tumor growth and a reduction in number and size of lung colonies, indicating that growth suppression was the predominant consequence of GRHL2 loss. Altogether, these findings point to largely common but also distinct roles for GRHL2 in luminal and basal breast cancers with respect to growth and motility and indicate that, in agreement with its negative association with patient survival, growth suppression is the dominant response to GRHL2 loss.

Acute vs. chronic vs. intermittent hypoxia in breast Cancer: a review on its application in in vitro research.

Hypoxia has been linked to elevated instances of therapeutic resistance in breast cancer. The exposure of proliferating cancer cells to hypoxia has been shown to induce an aggressive phenotype conducive to invasion and metastasis. Regions of the primary tumors in the breast may be exposed to different types of hypoxia including acute, chronic or intermittent. Intermittent hypoxia (IH), also called cyclic hypoxia, is caused by exposure to cycles of hypoxia and reoxygenation (H-R cycles). Importantly, there is currently no consensus amongst the scientific community on the total duration of hypoxia, the oxygen level, and the possible presence of H-R cycles. In this review, we discuss current methods of hypoxia research, to explore how exposure regimes used in experiments are connected to signaling by different hypoxia inducible factors (HIFs) and to distinct cellular responses in the context of the hallmarks of cancer. We highlight discrepancies in the existing literature on hypoxia research within the field of breast cancer in particular and propose a clear definition of acute, chronic, and intermittent hypoxia based on HIF activation and cellular responses: (i) acute hypoxia is when the cells are exposed for no more than 24 h to an environment with 1% O2 or less; (ii) chronic hypoxia is when the cells are exposed for more than 48 h to an environment with 1% O2 or less and (iii) intermittent hypoxia is when the cells are exposed to at least two rounds of hypoxia (1% O2 or less) separated by at least one period of reoxygenation by exposure to normoxia (8.5% O2 or higher). Our review provides for the first time a guideline for definition of hypoxia related terms and a clear foundation for hypoxia related in vitro (breast) cancer research.

Prognostic value of neutrophils to lymphocytes and platelets ratio for 28-day mortality in patients with acute respiratory distress syndrome: a retrospective study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a rapidly progressive and fatal respiratory failure disease that often occurs in critically ill patients. Since ARDS is associated with immune dysregulation and coagulation abnormalities, it is necessary to identify an appropriate predictor that can accurately predict ARDS mortality based on its pathophysiology. Therefore, this study aimed to evaluate the clinical value of neutrophils to lymphocytes and platelets ratio (N/LPR) in predicting 28-day mortality in ARDS patients. METHODS: From July 2018 to October 2021, the medical records of ARDS patients were retrospective reviewed. Neutrophil count, lymphocyte count, and platelet count were collected, and the neutrophil-to-lymphocyte ratio (NLR) and N/LPR were calculated. Multivariate logistic regression analyses were performed to identify independent predictors of 28-day mortality in ARDS. Receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate optimal cut-off values for 28-day mortality in ARDS. Kaplan-Meier analysis was used to estimate the 28-day survival probabilities stratified by optimal cut-off values of N/LPR and NLR. RESULTS: A total of 136 ARDS patients were included in this study and were further divided into survivors (n = 69) and non-survivors (n = 67) groups according to their survival status on day 28. There were no significant differences between the two groups in age, sex, history of smoking and drinking, comorbidities, and reasons of admission (P > 0.05). Non-survivors had significantly higher neutrophil counts, NLR and N/LPR and had significantly lower platelet counts than survivors (P < 0.05). Multivariate regression analysis revealed that N/LPR, NLR and platelet counts were independent predictors for 28-day mortality in ARDS (P < 0.05). The ROC analyses showed that N/LPR with optimal cut-off value of 10.57 (sensitivity: 74.6%; specificity: 72.5%) is a more reliable predictor for 28-day mortality in ARDS than NLR and platelet count (AUC: 0.785 vs. 0.679 vs. 0.326). Further subgroup analysis confirmed that ARDS patients with N/LPR < 10.57 had significantly lower 28-day mortality than patients with N/LPR ≥ 10.57 (P < 0.001). Kaplan-Meier analysis also confirmed that ARDS patients with N/LPR < 10.57 had significantly longer survival. CONCLUSION: N/LPR is an independent risk factor associated with 28-day mortality in ARDS patients and shows better performance in predicting mortality rate than NLR.

Hypoxia Triggers TAZ Phosphorylation in Basal A Triple Negative Breast Cancer Cells.

Hypoxia and HIF signaling drive cancer progression and therapy resistance and have been demonstrated in breast cancer. To what extent breast cancer subtypes differ in their response to hypoxia has not been resolved. Here, we show that hypoxia similarly triggers HIF1 stabilization in luminal and basal A triple negative breast cancer cells and we use high throughput targeted RNA sequencing to analyze its effects on gene expression in these subtypes. We focus on regulation of YAP/TAZ/TEAD targets and find overlapping as well as distinct target genes being modulated in luminal and basal A cells under hypoxia. We reveal a HIF1 mediated, basal A specific response to hypoxia by which TAZ, but not YAP, is phosphorylated at Ser89. While total YAP/TAZ localization is not affected by hypoxia, hypoxia drives a shift of [p-TAZ(Ser89)/p-YAP(Ser127)] from the nucleus to the cytoplasm in basal A but not luminal breast cancer cells. Cell fractionation and YAP knock-out experiments confirm cytoplasmic sequestration of TAZ(Ser89) in hypoxic basal A cells. Pharmacological and genetic interference experiments identify c-Src and CDK3 as kinases involved in such phosphorylation of TAZ at Ser89 in hypoxic basal A cells. Hypoxia attenuates growth of basal A cells and the effect of verteporfin, a disruptor of YAP/TAZ-TEAD-mediated transcription, is diminished under those conditions, while expression of a TAZ-S89A mutant does not confer basal A cells with a growth advantage under hypoxic conditions, indicating that other hypoxia regulated pathways suppressing cell growth are dominant.

Development of an AI system for accurately diagnose hepatocellular carcinoma from computed tomography imaging data.

BACKGROUND AND AIMS: Computed tomography (CT) scan is frequently used to detect hepatocellular carcinoma (HCC) in routine clinical practice. The aim of this study is to develop a deep-learning AI system to improve the diagnostic accuracy of HCC by analysing liver CT imaging data. METHODS: We developed a deep-learning AI system by training on CT images from 7512 patients at Henan Provincial Peoples' Hospital. Its performance was validated on one internal test set (Henan Provincial Peoples' Hospital, n = 385) and one external test set (Henan Provincial Cancer Hospital, n = 556). The area under the receiver-operating characteristic curve (AUROC) was used as the primary classification metric. Accuracy, sensitivity, specificity, precision, negative predictive value and F1 metric were used to measure the performance of AI systems and radiologists. RESULTS: AI system achieved high performance in identifying HCC patients, with AUROC of 0.887 (95% CI 0.855-0.919) on the internal test set and 0.883 (95% CI 0.855-0.911) on the external test set. For internal test set, accuracy was 81.0% (76.8-84.8%), sensitivity was 78.4% (72.4-83.7%), specificity was 84.4% (78.0-89.6%) and F1 (harmonic average of precision and recall rate) was 0.824. For external test set, accuracy was 81.3% (77.8-84.5%), sensitivity was 89.4% (85.0-92.8%), specificity was 74.0% (68.5-78.9%) and F1 was 0.819. Compared with radiologists, AI system achieved comparable accuracy and F1 metric on internal test set (0.853 versus 0.818, P = 0.107; 0.863 vs. 0.824, P = 0.082) and external test set (0.805 vs. 0.793, P = 0.663; 0.810 vs. 0.814, P = 0.866). The predicted HCC risk scores by AI system in HCC patients with multiple tumours and high fibrosis stage were higher than those with solitary tumour and low fibrosis stage (tumour number: 0.197 vs. 0.138, P = 0.006; fibrosis stage: 0.183 vs. 0.127, P < 0.001). Radiologists' review showed that the accuracy of saliency heatmaps predicted by algorithms was 92.1% (95% CI: 89.2-95.0%). CONCLUSIONS: AI system achieved high performance in the detection of HCC compared with a group of specialised radiologists. Further investigation by prospective clinical trials was necessitated to verify this model.

SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer.

BACKGROUND: Colorectal cancer is the third most common diagnosis. Oxaliplatin is used as first-line treatment of colon cancer. However, oxaliplatin resistance greatly reduces its therapeutic effect. SRPK1 involves in pre-mRNA splicing and tumorigenesis. How SRPK1 mediates drug resistance in colon cancer is unknown. METHODS: The expression of SRPK1 was analyzed in the TCGA and the CPTAC pan-cancer samples and detected in colon cancer cell lines and tissues by IHC and western blot. The MTT and TUNEL assay were used to verify the anti-apoptosis ability of colon cancer cell. The activation of NF-κB was determined by luciferase assay and qRT-PCR. AKT, IKK, IκB and their phosphorylation level were verified by western blot. RESULTS: We found that SRPK1 expression was the second highest in TCGA and the CPTAC pan-cancer samples. The mRNA and protein levels of SRPK1 were increased in tissues from patients with colon cancer. SRPK1 was associated with clinical stage and TNM classifications in 148 cases of colon cancer patients. High SRPK1 levels correlated with poor prognosis (p < 0.001). SRPK1 overexpression enhanced the anti-apoptosis ability of colon cancer cells, whereas SRPK1 silencing had the opposite effect under oxaliplatin treatment. Mechanistically, SRPK1 enhances IKK kinase and IκB phosphorylation to promote NF-κB nuclear translocation to confer oxaliplatin resistance. CONCLUSIONS: Our findings suggest that SRPK1 participates in colon cancer progression and enhances the anti-apoptosis capacity to induce drug resistance in colon cancer cells via NF-κB pathway activation, and thus might be a potential pharmaceutically target for colon cancer treatment.

Extragastrointestinal stromal tumor presenting as a recurrent vulvar mass.

Extragastrointestinal stromal tumors (EGIST) primarily arising from the female genital tract are extremely rare. We report a case of EGIST presenting as a recurrent vulvar mass with genetic analyses. A 59-year-old woman was found to have a 4-cm recurrent mass in the right vulva after 6 months of the first resection. Histological findings showed that the uniform spindle cells formed interlacing bundles, with high cellular density and mild to moderate atypia. Mitotic activity averaged 10 mitoses per 50 high-power fields. Immunohistochemical evaluation revealed that the tumor cells exhibited strong and diffuse staining for CD117, CD34 and DOG1. Ki67 labeling was approximately 15%. Molecular analysis showed an in-frame protein deletion (P551_Q556del) at exon 11 of c-KIT. The tumor was diagnosed as an EGIST. The patient was treated with imatinib, and was healthy at 12-month follow-up. EGIST should be considered in the differential diagnosis of vulvar mesenchymal tumors.

Potential future changes in soil carbon dynamics in the Ziwuling Forest, China under different climate change scenarios.

Soil carbon (C) cycling processes in terrestrial ecosystems are significantly influenced by global changes, and soil microorganisms play a crucial role in soil organic carbon (SOC) and its feedbacks to climate change. To investigate the potential future changes in soil C dynamics under different scenarios in the Ziwuling Forest region, China, we conducted a soil observation and sampling experiment from April 2021 to July 2022. By utilizing a microbial ecological model (MEND), we aimed to predict the future dynamics of soil C under different scenarios in the area. Our results demonstrate that under the RCP2.6 (Representative Concentration Pathway) scenario, SOC showed a rapid increase, SOC under the RCP2.6 scenario will be significantly higher than those under the RCP4.5 scenario and RCP8.5 scenario in the topsoil and whole soil. Furthermore, the positive correlation between total litter carbon (LC) and SOC under the RCP2.6 scenario highlights the potential role of total litter carbon in driving SOC dynamics. Our study also revealed that the low greenhouse gas (GHG) emission scenario favors the accumulation of SOC in the study area, while the high GHG emission scenario leads to greater soil carbon loss. Overall, these results underscore the importance of considering the impact of climate change, especially global warming, on soil ecosystems in the future. Protecting the soil ecosystem of the Loess Plateau is critical for maintaining soil carbon sinks, preventing soil erosion, and improving and regulating the surrounding environmental climate.

City-level livestock methane emissions in China from 2010 to 2020.

Livestock constitute the world's largest anthropogenic source of methane (CH4), providing high-protein food to humans but also causing notable climate risks. With rapid urbanization and increasing income levels in China, the livestock sector will face even higher emission pressures, which could jeopardize China's carbon neutrality target. To formulate targeted methane reduction measures, it is crucial to estimate historical and current emissions on fine geographical scales, considering the high spatial heterogeneity and temporal variability of livestock emissions. However, there is currently a lack of time-series data on city-level livestock methane emissions in China, despite the flourishing livestock industry and large amount of meat consumed. In this study, we constructed a city-level livestock methane emission inventory with dynamic spatial-temporal emission factors considering biological, management, and environmental factors from 2010 to 2020 in China. This inventory could serve as a basic database for related research and future methane mitigation policy formulation, given the population boom and dietary changes.

Research trends and hotspots of polyphyllin in high-incidence cancers: A bibliometric analysis.

Background: Polyphyllin, a natural compound derived primarily from the Paris genus, manifests its anticancer properties. Extensive research on its therapeutic potential in cancers has been reported. However, there is no systematical analysis of the general aspects of research on polyphyllin by bibliometric analysis. The aim of this study is to visualize emerging trends and hotspots and predict potential research directions in this field. Methods: In this study, we collected relevant research articles from the Web of Science Core Collection Bibliometrics. Using R-bibliometrix, we analyzed the research status, hotspots, frontiers, and development trends of polyphyllin in high-incidence cancers. To conduct a comprehensive visual analysis, CiteSpace and VOSviewer were used for visual analysis of authors, countries, institutions, keywords, and co-cited references within the published articles. Results: A total of 257 articles focusing on the research of polyphyllin in high-incidence cancers were retrieved from the WOSCC database, covering the period from 2005 to 2023. The analysis revealed a consistent increasing trend in annual publications during this timeframe. Notably, China emerged as the most productive country, with Tianjin University leading the institutions. The Journal of Ethnopharmacology stood out as the most prominent journal in this field, while Gao WY emerged as the most prolific author. Polyphyllin VI, polyphyllin II, and polyphyllin VII have emerged as the latest research hotspots. Additionally, the investigation of autophagy and its associated mechanisms has gained significant attention as a novel research direction. Conclusion: This study presents a novel visualization of the research on polyphyllin saponins in the field of highly prevalent cancers using bibliometric analysis. The investigation of polyphyllin D has emerged as a primary focus in this field, with lung cancer, breast cancer, and liver cancer being the key areas of current research. Lastly, polyphyllin saponins show potential application in the field of cancer.

GSK3ß/ITCH/c-FLIP Axis Counteracts TRAIL-induced Apoptosis in Human Lung Adenocarcinoma Cells.

AIMS: Further investigation on the mechanism of action of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in NSCLC would shed light on the understanding of TRAIL resistance and provide new clues for the counter-strategy. BACKGROUND: Cellular FLICE-inhibitory protein (c-FLIP) is a critical inhibitor of TRAIL-induced apoptosis. Our previous study suggested that glycogen synthase kinase 3ß (GSK3ß) positively regulated c-FLIP expression in human lung adenocarcinoma cells. Meanwhile, other studies reported that c-FLIP was degraded by HECT-type E3 ligase ITCH (Itchy E3 Ubiquitin Protein Ligase) via the proteasome pathway. OBJECTIVE: We will explore whether ITCH is involved in the expression regulation of c-FLIP positively controlled by GSK3ß during the treatment of TRAIL. METHODS: Human lung adenocarcinoma cells were used to stably overexpress and knockdown GSK3ß. Quantitative real-time PCR (qRT-PCR) assay was used to test the expressional level of mRNA of genes. Western blot analysis was employed to detect the expression of proteins at the protein level. siRNA of ITCH was used to knock down its expression. TRAIL treatment was used to cause apoptosis. RESULTS: In the present study, we have confirmed the degradation of c-FLIP by ITCH protein and the downregulation of ITCH expression by GSK3ß in lung adenocarcinoma cells. Moreover, ITCH silencing reversed the downregulation of c-FLIP protein caused by GSK3ß-knockdown in the cells. Accordingly, TRAIL-induced apoptosis facilitated by GSK3ß knockdown was blocked by the combined interference of ITCH. CONCLUSION: These results suggested that GSK3ß/ITCH axis regulated the stability of c-FLIP and influenced TRAIL-induced apoptosis. Taken together, our study revealed a GSK3ß/ITCH/c-FLIP axis, which counteracts TRAIL-induced apoptosis in human lung adenocarcinoma cells.

Accelerated three-dimensional susceptibility weighted imaging of the whole spine of fetus at 3T.

OBJECTIVES: To investigate the image quality and capability of generalized auto-calibrating partially parallel acquisition (GRAPPA) accelerated Three-dimensional (3D) susceptibility weighted imaging (SWI) of the whole spine at 3T. METHODS: A total of 37 pregnant women (gestation age 22 to 39 weeks, average 29 ± 3 weeks) with suspected fetal vertebral anomalies by ultrasound (US) screening underwent 3.0T MR imaging with 3D SWI, conventional two-dimensional (2D) half-flourier acquisition single-shot turbo spin-echo (HASTE) and 3D true fast imaging with steady-state precession (True FISP). The acquisition time of each protocol was recorded. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were determined in representative interest regions of fetal thoracic vertebrae and compared among three pulse sequences. Two radiologists rated image quality independently in random order on a 5-point scale. Kappa coefficients were computed to assess inter-observer reliability. Receiver operating characteristic curves were generated, and the area under the curve (AUC) was used to compare the diagnostic performance of each protocol in vertebral deformities. RESULTS: The acquisition time was 15 s for 3D-SWI and 17 s for 3D True FISP, significantly shorter than conventional HASTE (37 s; both P < 0.01). Of the three protocols, The SNR was highest on 3D True FISP, while the CNR was highest on 3D SWI. Visualization of all segments of the whole spine by 3D SWI was comparable with 3D True FISP. In contrast, 3D SWI and 3D True FISP depicted cervical and sacrococcygeal vertebrae better than HASTE. The weighted kappa statistic was 0.70-0.89 to evaluate the image quality of all segments of the whole spine, indicating good to excellent interobserver agreement. 3D SWI had the highest diagnostic performance for detecting fetal vertebral anomalies (AUC = 0.92). CONCLUSIONS: 3D-SWI is feasible for improved visualization of the whole fetal vertebral column and its congenital malformations with adequate image quality and high accuracy, thereby providing a supplementary method to conventional MR imaging.

City-level decoupling between livestock and crop production and its effect on fertilizer usage: Evidence from China.

China is one of the largest producers of livestock production and also with tremendous fertilizer consumption in crop production, regional decoupling between livestock and crop production often results in fertilizer overuse and environmental pollution. However, city-level coupling analysis between livestock and crop production is rare, and its impact on fertilizer usage also remains unclear. Here, we evaluated the nitrogen (N) nutrient supply from the livestock breeding sector and the N nutrient demand of cropland during the 2007-2020 period in a typical agricultural region in China. The city-level coupling degree of livestock and crop production and the effect on fertilizer usage were explored with spatial analysis and regression methods. Our results show that the province level has a relatively high coupling degree. However, significant spatial heterogeneity was found at the city level, especially in western Sichuan Province due to the highly unbalanced distribution of livestock and crop production, and this decoupling phenomenon may hinder fertilizer reduction. Furthermore, we reveal that technological development is not an effective way to achieve sustainable agriculture without other policy instruments, such as livestock spatial relocation, which must be considered when formulating crop-livestock integration policies. The findings expand city-level knowledge of the livestock-crop system and provide important implications for adjusting agricultural practices to realize sustainable agricultural development.