Comparative Genomics of Lotus japonicus Reveals Insights into Proanthocyanidin Accumulation and Abiotic Stress Response.

Lotus japonicus, is an important perennial model legume, has been widely used for studying biological processes such as symbiotic nitrogen fixation, proanthocyanidin (PA) biosynthesis, and abiotic stress response. High-quality L. japonicus genomes have been reported recently; however, the genetic basis of genes associated with specific characters including proanthocyanidin distribution in most tissues and tolerance to stress has not been systematically explored yet. Here, based on our previous high-quality L. japonicus genome assembly and annotation, we compared the L. japonicus MG-20 genome with those of other legume species. We revealed the expansive and specific gene families enriched in secondary metabolite biosynthesis and the detection of external stimuli. We suggested that increased copy numbers and transcription of PA-related genes contribute to PA accumulation in the stem, petiole, flower, pod, and seed coat of L. japonicus. Meanwhile, According to shared and unique transcription factors responding to five abiotic stresses, we revealed that MYB and AP2/ERF play more crucial roles in abiotic stresses. Our study provides new insights into the key agricultural traits of L. japonicus including PA biosynthesis and response to abiotic stress. This may provide valuable gene resources for legume forage abiotic stress resistance and nutrient improvement.

EP300 improves endothelial injury and mitochondrial dysfunction in coronary artery disease by regulating histone acetylation of SOCS1 promoter via inhibiting JAK/STAT pathway.

Endothelial cell injury and mitochondrial dysfunction are crucial events during coronary artery disease (CAD). Suppressor of cytokine signaling-1 (SOCS1) is a negative mediator for inflammation, but there are few reports regarding histone acetylation of SOCS1 in CAD. The aim of the current study is to examine the impact of SOCS1 in CAD patients and human umbilical vein endothelial cells (HUVECs). We enrolled patients with CAD and healthy volunteers. HUVECs treated with ox-LDL were used as in vitro model. This study showed that SOCS1 expression was decreased in patients with CAD and ox-LDL-stimulated HUVECs. Overexpressing SOCS1 ameliorated endothelial cell injury and mitochondrial dysfunction induced by ox-LDL in vitro. Moreover, EP300 promoted SOCS1 transcription through increasing the acetylation of SOCS1 and recruiting H3K27ac to the SOCS1 gene promoter in HUVECs induced by ox-LDL. Additionally, SOCS1 repressed JAK/STAT cascade in ox-LDL-stimulated HUVECs. Silencing of EP300 reversed endothelial cell injury and mitochondrial dysfunction ameliorated by overexpression of SOCS1 in ox-LDL-induced HUVECs. In summary, SOCS1 alleviated endothelial injury and mitochondrial dysfunction via enhancing H3K27ac acetylation by recruiting EP300 to promoter region and inhibiting JAK/STAT pathway. These results contribute to discover underlying diagnostic biomarkers and therapeutic targets for CAD.

Identification of antimicrobial peptide genes from transcriptomes in Mandarin fish (Siniperca chuatsi) and their response to infection with Aeromonas hydrophila.

Mandarin fish (Siniperca chuatsi) is a valuable freshwater fish species widely cultured in China. Its aquaculture production is challenged by bacterial septicaemia, which is one of the most common bacterial diseases. Antimicrobial peptides (AMPs) play a critical role in the innate immune system of fish, exhibiting defensive and inhibitory effects against a wide range of pathogens. This study aimed to identify the antimicrobial peptide genes in mandarin fish using transcriptomes data obtained from 17 tissue in our laboratory. Through nucleotide sequence alignment and protein structural domain analysis, 15 antimicrobial peptide genes (moronecidin, pleurocidin, lysozyme g, thymosin ß12, hepcidin, leap 2, ß-defensin, galectin 8, galectin 9, apoB, apoD, apoE, apoF, apoM, and nk-lysin) were identified, of which 9 antimicrobial peptide genes were identified for the first time. In addition, 15 AMPs were subjected to sequence characterization and protein structure analysis. After injection with Aeromonas hydrophila, the number of red blood cells, hemoglobin concentration, and platelet counts in mandarin fish showed a decreasing trend, indicating partial hemolysis. The expression change patterns of 15 AMP genes in the intestine after A. hydrophila infection were examined by using qRT-PCR. The results revealed, marked up-regulation (approximately 116.04) of the hepcidin gene, down-regulation of the piscidin family genes expression. Moreover, most AMP genes were responded in the early stages after A. hydrophila challenge. This study provides fundamental information for investigating the role of the different antimicrobial peptide genes in mandarin fish in defense against A. hydrophila infection.

Co-drivers of Air Pollutant and CO2 Emissions from On-Road Transportation in China 2010-2020.

Co-controlling the emissions of air pollutants and CO2 from automobiles is crucial for addressing the intertwined challenges of air pollution and climate change in China. Here, we analyze the synergetic characteristics of air pollutant and CO2 emissions from China's on-road transportation and identify the co-drivers influencing these trends. Using detailed emission inventories and employing index decomposition analysis, we found that despite notable progress in pollution control, minimizing on-road CO2 emissions remains a formidable task. Over 2010-2020, the estimated sectoral emissions of VOCs, NOx, PM2.5, and CO declined by 49.9%, 25.9%, 75.2%, and 63.5%, respectively, while CO2 emissions increased by 46.1%. Light-duty passenger vehicles and heavy-duty trucks have been identified as the primary contributors to carbon-pollution co-emissions, highlighting the need for tailored policies. The driver analysis indicates that socioeconomic changes are primary drivers of emission growth, while policy controls, particularly advances in emission efficiency, can facilitate co-reductions. Regional disparities emphasize the need for policy refinement, including reducing dependency on fuel vehicles in the passenger subsector and prioritizing co-reduction strategies in high-emission provinces in the freight subsector. Overall, our study confirms the effectiveness of China's on-road control policies and provides valuable insights for future policy makers in China and other similarly positioned developing countries.

Decoding the role of m6A Regulators in identifying and characterizing molecular subtypes of rosacea.

Rosacea is a common skin disease that predominantly affects individuals aged between 30 and 50 years. While the exact cause of the disease remains unclear, various factors have been shown to trigger or exacerbate its symptoms. N6-methyladenosine (m6A) modification is one of the most abundant epigenetic methylation modification in messenger RNA (mRNA) and non-coding RNA (ncRNA), plays a crucial role in RNA splicing, export, stability, and translation. In this study, we aimed to characterize m6A genes in rosacea, identify molecular subtypes based on m6A gene expression, characterize the immune features among subtypes, explore key molecules based on co-expression analysis, and identify potential targets and drugs. To achieve our objectives, we first compared the expression pattern and immune regulation of m6A genes between healthy and diseased groups. Then, we performed clustering to stratify disease samples into different subtypes and analyzed immune regulation and functional enrichment among the subtypes. Then, we conducted differential analysis between subtypes and applied weighted gene co-expression network analysis (WGCNA) in three subtypes. We found hub differential expression analysis (DEG) genes and their potential drug based on the WGCNA results and the drug-gene interaction database (DGIdb). Finally, in vivo and in vitro studies showed significant differences in m6A methyltransferase METTL3 levels in rosacea mice and control mice, as well as in the skin of rosacea patients and healthy people, while reducing METTL3 significantly inhibited the inflammatory response of human fibroblasts (HDFs) stimulated by LL37, suggesting that METTL3 may be associated with changes in overall m6A levels in rosacea. Taken together, our findings provide valuable insights into therapeutic targets and drug predictions for rosacea.

The economy-employment-environmental health transfer and embedded inequities of China's capital metropolitan area: a mixed-methods study.

BACKGROUND: Metropolitan areas have complex trade linkages internally and externally. This complexity stimulates the unequal spatial transfer of environmental health consequences, economy, and employment embodied in internal trade or trade with the outside regions, resulting in unequal exchange. Existing research has rarely discussed this issue at a refined scale, hindering targeted inequity alleviation policies. METHODS: We conducted a mixed-methods study, focusing on the most polluted metropolitan area in the world, the Beijing-Tianjin-Hebei region of China, and developed an integrated modelling framework to downscale the analysis of the trade-driven unequal transfer of PM2·5- related premature deaths, value added, and job opportunities to the city scale within Beijing-Tianjin-Hebei. The study couples a nested Multi-Regional Input-Output model table containing data from 13 Beijing-Tianjin-Hebei cities and 28 outer provinces in 2017 with a bottom-up emission inventory, value added and employment statistical data, the Weather Research and Forecasting-Comprehensive Air Quality Model with Extensions, the Global Exposure Mortality Model, and human capital methods. We also constructed two indices measuring unequal exchanges between PM2·5-related deaths and economic and employment gains embodied in trades between cities in Beijing-Tianjin-Hebei and trades with outside regions. FINDINGS: The Beijing-Tianjin-Hebei region as a single entity shifted 14 985 (95% CI 12 800-16 948) net deaths to regions outside the Beijing-Tianjin-Hebei through trade, most of which occurred in the central region of China. The industrial-based peripheral Beijing-Tianjin-Hebei cities suffered the most serious inequities when trading with other Beijing-Tianjin-Hebei cities and outside regions. While gaining equivalent local jobs, these industrial-based peripheral cities had 250% higher PM2·5-related deaths (10·2 PM2·5-related deaths for obtaining 1000 local jobs) than core cities (2·9 PM2·5-related deaths for obtaining 1000 local jobs) and 57·7% higher PM2·5-related deaths than agricultural-based peripheral cities (6·5 PM2·5-related deaths for obtaining 1000 local jobs). While gaining equivalent value added, industrial-based peripheral cities had 50·6% higher PM2·5-related deaths (¥13·9 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added) than core cities (¥9·2 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added) and 67·4% higher PM2·5-related deaths than agricultural-based peripheral cities (¥8·3 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added). INTERPRETATION: Treating metropolitan areas as a single entity obscured internal heterogeneity, potentially misleading policy makers into imposing strict regulations on the whole metropolitan area to alleviate the inequities it posed on outside regions. However, several peripheral Beijing-Tianjin-Hebei cities were disadvantaged in their trade with core Beijing-Tianjin-Hebei cities and outside regions. Therefore, policies should be tailored for particular cities within metropolitan areas. Future targeted policies should include, but not be limited to, making ecological compensations and incorporating the environment and health costs into the price of pollution-intensive goods and services. FUNDING: National Key Research and Devlopment Program of China, National Natural Science Foundation of China, and Jiangsu Natural Science Foundation.

Revealing Inter-regional Environmental Inequities Hidden in China's Energy Transition.

Energy transition is an important way to control air pollution, but it may conflict with the economic goal of alleviating regional inequality due to its inherently different cost burdens. As one of the effective measures of energy transition, this paper takes small coal-fired boiler (SCB) upgrading as an example to explore the regional mismatch between upgrading costs and health benefits. Here, we construct a boiler-level inventory of SCB upgrades for the North China Plain (NCP) during 2013-2017 and propose an integrated modeling framework to quantify the spatial contribution of economic costs and health benefits associated with SCB upgrading. We find that although the total health benefits could offset the total costs for the entire region, the developed municipalities (Beijing and Tianjin) are likely to gain more health benefits from less-developed neighboring provinces at lower costs. These developed municipalities contribute only 14% to the total health benefits but gain 21% of the benefits within their territories, 56% of which come from neighboring provinces. Their benefits are approximately 5.6 times their costs, which is much higher than the 1.5 benefit-cost ratio in neighboring provinces. Our findings may be useful in shaping more equitable and sound environmental policies in China or other regions of the world with serious coal-related air pollution.

Genomic insight into domestication of rubber tree.

Understanding the genetic basis of rubber tree (Hevea brasiliensis) domestication is crucial for further improving natural rubber production to meet its increasing demand worldwide. Here we provide a high-quality H. brasiliensis genome assembly (1.58 Gb, contig N50 of 11.21 megabases), present a map of genome variations by resequencing 335 accessions and reveal domestication-related molecular signals and a major domestication trait, the higher number of laticifer rings. We further show that HbPSK5, encoding the small-peptide hormone phytosulfokine (PSK), is a key domestication gene and closely correlated with the major domestication trait. The transcriptional activation of HbPSK5 by myelocytomatosis (MYC) members links PSK signaling to jasmonates in regulating the laticifer differentiation in rubber tree. Heterologous overexpression of HbPSK5 in Russian dandelion (Taraxacum kok-saghyz) can increase rubber content by promoting laticifer formation. Our results provide an insight into target genes for improving rubber tree and accelerating the domestication of other rubber-producing plants.

Health impacts under different ozone mitigation pathways in Beijing-Tianjin-Hebei and its surroundings.

To evaluate the effects of the various ozone (O3) control approaches on environmental health and health inequalities, 121 reduction scenarios for nitrogen oxides (NOx) and volatile organic compounds (VOCs) were developed, and their environmental health impacts were calculated. With the target of achieving the 90th percentile of the daily maximum 8 h mean O3 concentration (MDA8-90th) of 160 µg/m3 in Beijing-Tianjin-Hebei and its surroundings ("2 + 26" cities), three typical scenarios namely, High-NOx reduction ratio (HN, NOx/VOCs = 6:1), High-VOCs reduction ratio (HV, NOx/VOCs = 3:7), and Balanced reduction ratio (Balanced, NOx/VOCs = 1:1) were investigated. The results show that O3 formation is currently NOx-limited at the regional scale, while some developed cities are VOC-limited, indicating that NOx mitigation should be the core for achieving the targeted concentration (160 µg/m3) at the regional scale, whereas cities such as Beijing in the short term should focus on VOCs mitigation. The population-weighted O3 concentrations in the HN, Balanced, and HV scenarios were 159.19, 159.19, and 158.44 µg/m3, respectively. In addition, the O3-related premature mortality was 41,320 in "2 + 26" cities; control measures under HN, Balanced, and HV could potentially decrease O3-related premature deaths by 59.94 %, 60.25 %, and 71.48 %, respectively. The HV scenario has been found to be more advantageous in lowering the O3-related environmental health impacts than the HN and Balanced scenarios. It was further found that premature deaths avoided by the HN scenario were mainly concentrated in economically unadvanced regions, whereas those prevented by the HV scenario were mainly concentrated in developed cities. This may lead to geographical inequities in environmental health. As ozone pollution in large cities with high population density is primarily VOC-limited, decrease in VOCs should be focused on in the short term to avoid more O3-related premature deaths, whereas NOx control may be more important in decreasing ozone concentrations and ozone-related mortality in the future.

Source Contributions to PM2.5-Related Mortality and Costs: Evidence for Emission Allocation and Compensation Strategies in China.

The emissions from various pollution sources were not proportional to their contributions to ambient PM2.5 concentrations and associated health burdens. That means even with the same total abatement targets, different abatement allocation strategies across emission sources can have distinct health benefits. Insufficient knowledge of various sources' contributions to health burdens in China, the country suffering substantial PM2.5-related deaths, hindered the government from seeking optimized abatement allocation strategies. In this context, we separated the contributions of 155 emission sources (31 provinces × 5 sectors) to PM2.5-related mortality across China in 2017 by coupling the Comprehensive Air Quality Model with Extensions (CAMx), Weather Research and Forecasting model (WRF), and health impact assessment model. We further identified the priority-control emission sources and quantified interprovincial ecological compensation volumes to alleviate inequality induced by emission allocation strategies. Results showed that PM2.5 pollution caused 899,443 excess deaths and around 127 billion USD costs in 2017. Approximately half of the deaths and costs were attributable to emissions from sources outside the boundary of the regions where the deaths occurred. Twenty-five out of 155 emission sources that contributed to the top 60% mortality burdens and had high marginal abatement efficiencies in China shall be the priority-control emission sources. A 1 µg/m3 decrease of PM2.5 concentration in regions where these key emission sources occur shall be compensated by 76-153 million USD in their receptor regions. Our study sheds light on the sources' contributions to mortality burdens and costs and provides scientific evidence for optimizing the emission allocation and compensation strategies in China. It also has wide implications for other countries suffering similar problems.

Identification and Analysis of Crucial Genes in H. pylori-Associated Gastric Cancer Using an Integrated Bioinformatics Approach.

Background: The relationship between H. pylori infection and gastric cancer (GC) has been widely studied, and H. pylori is considered as the main factor. Utilizing bioinformatics analysis, this study examined gene signatures related to progressing H. pylori-associated GC. Materials and Methods: The dataset GSE13195 was chosen to search for abnormally expressed genes in H. pylori-associated GC and normal tissues. The TCGA-STAD database was chosen to verify the expression of key genes in GC and normal tissues. Results: In GSE13195, a total of 332 differential expression genes (DEGs) were screened. The results of weighted gene co-expression network analysis showed that the light cyan, plum2, black, and magenta4 modules were associated with stages (T3, T2, and T4), while the orangered4, salmon2, pink, and navajowhite2 modules were correlated with lymph node metastasis (N3, N2, and N0). Based on the results of DEGs and hub genes, a total of 7 key genes (ADAM28, FCER1G, MRPL14, SOSTDC1, TYROBP, C1QC, and C3) were screened out. These gene mRNA levels were able to distinguish between normal and H. pylori-associated GC tissue using receiver operating characteristic curves. After transcriptional level verification and survival analysis, ADAM28 and C1QC were excluded. An immune infiltration study revealed that key genes were involved in regulating the infiltration levels of cells associated with innate immune response, antigen presentation process, humoral immune response, or Tcell-mediated immune response. In addition, drugs targeting FCER1G and TYROBP have been approved and are under investigation. Conclusion: Our study identified five key genes involved in H. pylori-associated GC tumorigenesis. Patients with higher levels of C3 expression had a poorer prognosis than those with lower levels. In addition, these key genes may serve as biomarkers and therapeutic targets for H. pylori-associated GC diagnosis, targeted therapy, and immunotherapy in the future.

Chromosome-scale genome assembly and insights into the metabolome and gene regulation of leaf color transition in an important oak species, Quercus dentata.

Quercus dentata Thunb., a dominant forest tree species in northern China, has significant ecological and ornamental value due to its adaptability and beautiful autumn coloration, with color changes from green to yellow into red resulting from the autumnal shifts in leaf pigmentation. However, the key genes and molecular regulatory mechanisms for leaf color transition remain to be investigated. First, we presented a high-quality chromosome-scale assembly for Q. dentata. This 893.54 Mb sized genome (contig N50 = 4.21 Mb, scaffold N50 = 75.55 Mb; 2n = 24) harbors 31 584 protein-coding genes. Second, our metabolome analyses uncovered pelargonidin-3-O-glucoside, cyanidin-3-O-arabinoside, and cyanidin-3-O-glucoside as the main pigments involved in leaf color transition. Third, gene co-expression further identified the MYB-bHLH-WD40 (MBW) transcription activation complex as central to anthocyanin biosynthesis regulation. Notably, transcription factor (TF) QdNAC (QD08G038820) was highly co-expressed with this MBW complex and may regulate anthocyanin accumulation and chlorophyll degradation during leaf senescence through direct interaction with another TF, QdMYB (QD01G020890), as revealed by our further protein-protein and DNA-protein interaction assays. Our high-quality genome assembly, metabolome, and transcriptome resources further enrich Quercus genomics and will facilitate upcoming exploration of ornamental values and environmental adaptability in this important genus.

Developing China's roadmap for air quality improvement: A review on technology development and future prospects.

Air pollution control policies in China have been experiencing profound changes, highlighting a strategic transformation from total pollutant emission control to air quality improvement, along with the shifting targets starting from acid rain and NOx emissions to PM2.5 pollution, and then the emerging O3 challenges. The marvelous achievements have been made with the dramatic decrease of SO2 emission and fundamental improvement of PM2.5 concentration. Despite these achievements, China has proposed Beautiful China target through 2035 and the goal of 2030 carbon peak and 2060 carbon neutrality, which impose stricter requirements on air quality and synergistic mitigation with Greenhouse Gas (GHG) emissions. Against this background, an integrated multi-objective and multi-benefit roadmap is required to provide decision support for China's long-term air quality improvement strategy. This paper systematically reviews the technical system for developing the air quality improvement roadmap, which was integrated from the research output of China's National Key R&D Program for Research on Atmospheric Pollution Factors and Control Technologies (hereafter Special NKP), covering mid- and long-term air quality target setting techniques, quantitative analysis techniques for emission reduction targets corresponding to air quality targets, and pathway optimization techniques for realizing reduction targets. The experience and lessons derived from the reviews have implications for the reformation of China's air quality improvement roadmap in facing challenges of synergistic mitigation of PM2.5 and O3, and the coupling with climate change mitigation.

Evolution of Ozone Pollution in China: What Track Will It Follow?

Increasing surface ozone (O3) concentrations has emerged as a key air pollution problem in many urban regions worldwide in the last decade. A longstanding major issue in tackling ozone pollution is the identification of the O3 formation regime and its sensitivity to precursor emissions. In this work, we propose a new transformed empirical kinetic modeling approach (EKMA) to diagnose the O3 formation regime using regulatory O3 and NO2 observation datasets, which are easily accessible. We demonstrate that mapping of monitored O3 and NO2 data on the modeled regional O3-NO2 relationship diagram can illustrate the ozone formation regime and historical evolution of O3 precursors of the region. By applying this new approach, we show that for most urban regions of China, the O3 formation is currently associated with a volatile organic compound (VOC)-limited regime, which is located within the zone of daytime-produced O3 (DPO3) to an 8h-NO2 concentration ratio below 8.3 ([DPO3]/[8h-NO2] ≤ 8.3). The ozone production and controlling effects of VOCs and NOx in different cities of China were compared according to their historical O3-NO2 evolution routes. The approach developed herein may have broad application potential for evaluating the efficiency of precursor controls and further mitigating O3 pollution, in particular, for regions where comprehensive photochemical studies are unavailable.

Synergistic assessment of air pollution and carbon emissions from the economic perspective in China.

The synergistic evaluation integrating air quality, human health, climate impact, and socioeconomic development is significant for green and low-carbon transition. Here, we quantified the contribution of pollutant emissions in 30 provinces (source) to PM2.5 concentration and related premature mortality in each 20 km grid (receptor) of China in 2020 by an integrated model for the first time. Further, we established a cross-province contribution matrix of health impact intensity (HII, PM2.5-related deaths per GDP). According to HII and CEI (carbon emission intensity, defined as CO2 emission per GDP) levels, 30 provinces were divided into 4 regions including LL, HL, LH and HH. In order to assess the synergy in air pollution and carbon emission, we established an index system consisting of ISEC-AC (index for synergistic assessment) and its two sub index: IHI (index for HII assessment), and ICE (index for CEI assessment). Results showed that the ISEC-AC was more easily influenced by IHI as the variance of IHI was much higher than that of ICE. Influenced by various factors, e.g., economic structure, population density, pollution transport, ISEC-AC exhibited substantial spatial heterogeneity. In general, the ISEC-AC of southeast provinces was higher than that of central and western, indicating the environmental and climate impact per GDP was relatively lower in southeast China. For provinces, ISEC-AC of SH and GD were ~ 16 times higher than NX. For regions, due to low carbon emission intensity and health impact intensity, ISEC-AC of LL was the highest with 176; followed by HL (128), LH (126) and HH (77). Further, we figured out the main control problems and then put forward targeted synergetic control suggestions for air pollution and carbon emission from the perspective of energy structure, industry structure and industry layout, which can provide insights into future green and low-carbon policy making in China and other countries.

A new acidic microenvironment related lncRNA signature predicts the prognosis of liver cancer patients.

Background: The acidic microenvironment (AME), like hypoxia, inflammation, or immunoreaction, is a hallmark of the tumor microenvironment (TME). This work aimed to develop a prediction signature dependent on AME-associated lncRNAs in order to predict the prognosis of LC individuals. Methods: We downloaded RNA-seq information and the corresponding clinical and predictive data from The Cancer Genome Atlas (TCGA) dataset and conducted univariate and multivariate Cox regression analyses to identify AME-associated lncRNAs for the construction of a prediction signature The Kaplan-Meier technique was utilized to determine the overall survival (OS) rate of the high (H)-risk and low (L)-risk groups. Using gene set enrichment analysis (GSEA) the functional variations between the H- and L-risk groups were investigated. The association between the prediction signature and immunological state was investigated using single-sample GSEA (ssGSEA). Additionally, the association between the predicted signature and the therapeutic response of LC individuals was evaluated. Lastly, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to verify the risk model. Results: We generated a signature comprised of seven AME-associated lncRNAs (LINC01116, AC002511.2, LINC00426, ARHGAP31-AS1, LINC01060, TMCC1-AS1, AC012065.1). The H-risk group had a worse prognosis than the L- risk group. The AME-associated lncRNA signature might determine the prognosis of individuals with LC independently. The AME-related lncRNA signature shows a greater predictive effectiveness than clinic-pathological factors, with an area under the receiver operating characteristic (ROC) curve of 0.806%. When participants were categorized based on several clinico-pathological characteristics, the OS of high-risk individuals was shorter compared to low-risk patients. GSEA demonstrated that the metabolism of different acids and the PPAR signaling pathway are closely associated with low-risk individuals. The prognostic signature was substantially associated with the immunological status of LC individuals, as determined by ssGSEA. High risk individuals were more sensitive to some immunotherapies (including anti-TNFSF4 anti-SIRPA, anti-CD276 and anti-TNFSF15) and some conventional chemotherapy drugs (including lapatinib and paclitaxel). Finally, the expression levels of the seven lncRNAs comprising the signature were tested by qRT-PCR. Conclusions: A basis for the mechanism of AME-associated lncRNAs in LC is provided by the prediction signature, which also offers clinical therapeutic recommendations for LC individuals.

Identification of Key Genes in the HBV-Related HCC Immune Microenvironment Using Integrated Bioinformatics Analysis.

Purpose: Hepatocellular carcinoma (HCC) has poor prognosis and high mortality among gastrointestinal tumors because of its insidious onset and strong invasiveness. However, there was little understanding of their pathogenesis. The purpose of this study was to use bioinformatics analysis to identify genes associated with the immune microenvironment in HBV-related HCC and to develop new therapeutic targets to prevent and treat cancer. Methods: RNA-seq data of HBV-related HCC cases were downloaded from TCGA-LIHC database. ESTIMATE and Deseq2 algorithms were used to screen out differentially expressed genes (DEGs). WGCNA was used to construct gene coexpression networks. In key modules, functional enrichment analysis was performed. Protein-protein interaction (PPI) was used to screen hub genes, and survival analysis was conducted to assess their prognostic significance. Following, we search for key genes differentially expressed between cancerous and paracancerous tissues in GSE136247 and GSE121248 datasets. Reveal the potential links between key genes in immune infiltration by using TIMER. Finally, in TCGA-LIHC database, integration of key genes with clinical data were used to further validate their correlation with prognosis. Results: In the cohort of HBV-related HCC patients, immune/stromal/ESTIMATE scores were not significantly associated with patient prognosis. After bioinformatics analysis, screening out five key genes was significantly related to the prognosis of HBV-related HCC. Downregulation of SLAMF1 and TRAF3IP3 suggested poor prognosis and was related to a variety of immune cell infiltration. Furthermore, compared with adjacent nontumor tissues, TRAF3IP3 and SLAMF1 were highly expressed in tumor tissues and were linked to tumor recurrences. Conclusion: In conclusion, SLAMF1 and TRAF3IP3 were identified with higher expression in tumor tissues and associated with tumor recurrence. It will be a new research direction of tumor progress and treatment.

A novel difficulty scoring system of laparoscopic liver resection for liver tumor.

Objectives: To develop a novel difficulty scoring system (NDSS) to predict the surgical difficulty of laparoscopic hepatectomy. Patients and methods: A total of 138 patients with liver tumors performed liver resection (LLR) between March 2017 to June 2022 were selected from Affiliated Hospital of Jiangnan University and Wujin Hospital Affiliated with Jiangsu University.Patient demographics, laboratory tests, intraoperative variables, pathological characteristics were assessed. We also assessed the Child Pugh score and the DSS-B score. Results: Patients were divided into training and testing cohort according to their hospital. Patients in training cohort were divided into high and low difficult groups based on operation time, blood loss and conversion. Higher percentage of patients with malignant liver tumor (87.0% vs. 58.1%; P = 0.003) or history of hepatobiliary surgery (24.1% vs. 7.0%; P = 0.043) in high difficult group than in low difficult group. To improve the difficulty scoring system, we incorporated the history of hepatobiliary surgery and nature of the tumor. A novel difficulty scoring system was established. The results showed that the operation time (P < 0.001), blood loss (P < 0.001), ALT (P < 0.001) and AST (P = 0.001) were associated with the novel difficulty score significantly. Compared with DSS-B, the NDSS has a higher area under the receiver operating characteristic (AUROC) (0.838 vs. 0.814). The nomogram was established according to the NDSS. The AUROCs of the nomogram in training and testing cohort were 0.833 and 0.767. The calibration curves for the probability of adverse event showed optimal agreement between the probability as predicted by the nomogram and the actual probability. Conclusions: We developed a nomogram with the NDSS that can predict the difficulty of LLR. This system could more accurately reflect the difficulty of surgery and help liver surgeons to make the surgical plan and ensure the safety of the operation.

Long noncoding RNA CDKN2B-AS1 silencing protects against esophageal cancer cell invasion and migration by inactivating the TFAP2A/FSCN1 axis.

Esophageal cancer (EC) is the most aggressive malignancy in the gastrointestinal tract. Long noncoding RNA cyclin-dependent kinase inhibitor 2 B antisense RNA 1 (CDKN2B-AS1) is implicated in EC development. However, the specific mechanisms involved remain poorly defined. Therefore, this research aimed to explore the mechanism of action of CDKN2B-AS1 in EC. Quantitative real-time polymerase chain reaction was conducted to measure CDKN2B-AS1 expression in EC cells and western blotting was utilized to evaluate transcription factor AP-2 alpha (TFAP2A) and fascin actin-bundling protein 1 (FSCN1) expression. After gain-of-function and loss-of-function assays, cell proliferation, migration, invasion, apoptosis, and apoptosis-related protein expression were assessed using cell counting kit-8, scratch tests, Transwell assays, flow cytometry, and western blotting, respectively. The binding relationship between CDKN2B-AS1 and TFAP2A was assessed by RNA immunoprecipitation and RNA pull-down assays. The binding relationship between TFAP2A and FSCN1 was evaluated using dual-luciferase reporter and chromatin immunoprecipitation assays. Tumor xenografts from nude mice were used for in vivo verification. CDKN2B-AS1, TFAP2A, and FSCN1 were upregulated in EC cells. Mechanistically, CDKN2B-AS1 transcriptionally activated FSCN1 by recruiting TFAP2A to the FSCN1 promoter. Silencing CDKN2B-AS1 or TFAP2A suppressed EC cell proliferative, migrating, and invasive properties and augmented apoptosis. TFAP2A was bound to CDKN2B-AS1 and the FSCN1 promoter. Overexpression of TFAP2A or FSCN1 abolished the effects of CDKN2B-AS1-silencing on EC cell function. CDKN2B-AS1 silencing curtailed tumorigenesis in nude mice, which was nullified by the upregulation of TFAP2A or FSCN1. Our findings demonstrated the antioncogenic effects of silencing CDKN2B-AS1 in EC through inactivation of the TFAP2A/FSCN1 axis.