Search

The carbon emission trading scheme (ETS), a market-based environmental regulation, is critical for in combating climate change in China. According to the Porter effect, ETS can promote green innovation, while the specific impact of carbon price on a company's green innovation, and the role of price signals, remain unclear. This study examines the impact of carbon price on green innovation, utilizing a dataset of A-share listed companies spanning from 2010 to 2020. The difference-in-differences estimation results demonstrate that carbon price significantly increases green innovation, promoting both invention patents and utility model patents. Our findings further indicate that moderating variables such as ESG disclosure, larger institutional investor shareholding, local environmental penalties, price stabilization mechanisms, and free quotas allocation can all amplify the constructive influence of carbon pricing on sustainable innovation. Moreover, heterogeneity analysis suggests that state-owned and large-scale companies, particularly those in the power sector and polluting sector, are more sensitive to price signals impacting green innovation. Additionally, we discovered a spatial externality of carbon pricing on green innovation in a radius ranging from 150 km to 300 km. This paper provides specific policy recommendations to stabilize the carbon price signal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Xanthomonas citri pv. fuscans ( Xcf ) and Xanthomonas phaseoli pv. phaseoli ( Xpp ) are responsible for the Common Bacterial Blight (CBB), a major common bean ( Phaseolus vulgaris ) disease. The pathogenicity of Xcf and Xpp is known to be dependent upon a functional Type III Secretion System (T3SS) allowing the injection of numerous bacterial Type III Effectors (T3Es) into plant cells. T3Es have been described as able to disrupt plant defence and manipulate plant metabolism. In this work we described the transcriptomic response of one susceptible (Flavert) and one resistant (Vezer) cultivars of P. vulgaris to the inoculation of the virulent strain Xcf CFBP4885 or its avirulent T3SS-defective hrcV mutant (CFBP13802). Leaves of both bean cultivars were infiltrated with water or bacterial suspensions. Inoculated leaves were sampled at 24 or 48 h post inoculation (hpi). The experiment was independently repeated three times for total RNA extraction and sequencing analysis. Library construction and total RNA sequencing were performed with BGISEQ-500 at Beijing Genomics Institute (BGI, Hong-Kong), generating an average of 24M of paired-end reads of 100bp per sample. FastQC was used to check reads quality. Mapping analyses were made using a quasi-mapping alignment from Salmon (version 1.2.1) against the Phaseolus vulgaris reference genome (version 2.1), revealing the expression profiles of 36,978 transcripts in leaf tissues. Fastq raw data and count files from 36 samples are available in the Gene Expression Omnibus (GEO) repository of the National Center for Biotechnology Information (NCBI) under the accession number GSE271236. This dataset is a valuable resource to investigate the role of T3Es in subverting the cellular functions of bean., (© 2024 Published by Elsevier Inc.)

Carbon emissions trading scheme (ETS) will change the internal and external operating environment of related companies, increase new carbon reduction costs, and may affect their investment behavior and decision-making. This study constructs the policy effect evaluation model to evaluate the net effect of China's ETS pilot policy on the investment efficiency of related companies in high-carbon industries. This study indicates that: first, China's ETS pilot policy has reduced the inefficient investment of related companies by 11.40% during the sample period. Second, innovation ability plays an enhanced moderating effect in the inhibitory effect of China's ETS pilot policy on the inefficient investment of related companies in the short term, but the effect is weakened in the long-term. Third, the policy effect is relatively obvious for non-state-owned companies and companies with more institutional shareholdings. This research has important reference value for the continuous improvement of China's national carbon market, and the steady transformation from simple investment-driven to investment-efficiency-driven economic development in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

E74-like factor 3 (ELF3) is an important member of the E-twenty-six (ETS) transcription factor family. ELF3 is expressed in various types of cells and regulates a variety of biological behaviors, such as cell proliferation, differentiation, apoptosis, migration, and invasion, by binding to DNA to regulate the expression of other genes. In recent years, studies have shown that ELF3 plays an important role in the occurrence and development of many tumors and inflammation and immune related diseases. ELF3 has different functions and expression patterns in different tumors; it can function as a tumor suppressor gene or an oncogene, highlighting its dual effects of tumor promotion and inhibition. ELF3 also affects the levels of tumor immunity-related cytokines and is involved in the regulation and expression of multiple signaling pathways. In tumor therapy, ELF3 is a complex and multifunctional gene and has become a key focus of targeted treatment research. An in-depth study of the biological function of ELF3 can help to elucidate its role in biological processes and provide ideas and a basis for the development and clinical application of ELF3-related therapeutic methods. This review introduces the structure and physiological and cellular functions of the ELF3 gene, summarizes the mechanisms of action of ELF3 in different types of malignant tumors and its role in immune regulation, inflammation, etc., and discusses treatment methods for ELF3-related diseases, providing significant reference value for scholars studying the ELF3 gene and related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

GGAA motifs in the human TP53 and HELB gene promoters play a part in responding to trans ‑resveratrol (Rsv) in HeLa S3 cells. This sequence is also present in the 5'‑upstream region of the human CDC45 gene, which encodes a component of CMG DNA helicase protein complex. The cells were treated with Rsv (20 µM), then transcripts and the translated protein were analyzed by quantitative RT‑PCR and western blotting, respectively. The results showed that the CDC45 gene and protein expression levels were induced after the treatment. To examine whether they were due to the activation of transcription, a 5'‑upstream 556‑bp of the CDC45 gene was cloned and inserted into a multi‑cloning site of the Luciferase (Luc) expression vector. In the present study, various deletion/point mutation‑introduced Luc expression plasmids were constructed and they were used for the transient transfection assay. The results showed that the GGAA motif, which is included in a putative RELB protein recognizing sequence, plays a part in the promoter activity with response to Rsv in HeLa S3 cells.

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

This study examines the effects of China's carbon trading policy on firm emissions and explores its impact mechanisms through financial and physical asset investments. The empirical analysis utilizes a fuzzy regression discontinuity design based on a sample of 427 industrial firms in China between 2014 and 2019. The results indicate that China's carbon trading policy incentivized firms to increase their financial investments while simultaneously discouraging physical capital investments. These shifts in investment patterns helped firms achieve their emission reduction targets. The study reveals that carbon trading policy in China has contributed to the financialization of firms, resulting in the erosion of firm assets and a decline in their overall competitiveness. Based on these findings, some policy recommendations are put forward., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Certain nations have opted for stimulus-based regulations to curtail emissions, build a liveable, environmentally friendly setting, and work towards aspirational mitigation targets. New Zealand (NZ) prefers an Emission Trading Scheme (ETS) to taxation, mitigating emissions on one hand while retaining incentives for economic growth on the other. As a result, NZ has initiated a legal framework since 2008 to allow its economic sectors to engage in ETS and minimize emissions. Yet, selecting the appropriate sectors and effectively adjusting sector-specific regulations remain critical and complex challenges in the global design of ETS since both excessive and insufficient intervention can lead to inefficiencies in the system's functioning. Therefore, this study begins validating the NZ ETS's abatement potential regarding sectoral carbon intensity by executing the double machine learning techniques, consolidating the ETS efficacy that has robustly mitigated sectoral carbon intensity in NZ during 2006-2020. However, this conclusion seems invalid at the disaggregated level when focusing on forward-backward linkages, where NZ's input-output tables furnish a compelling scenario of sectoral dependencies and the products (residuals) they provide. Altogether, the regulatory requirements are either too strict or too lax, leaving out five of the 24 (as a whole) key sectors. Rather, the ETS could be powerful, providing these five key sectors are well tackled, necessitating a reformulation of the ongoing ETS regulatory regime., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Noncoding mutation hotspots have been identified in melanoma and many of them occur at the binding sites of E26 transformation-specific (ETS) proteins; however, their formation mechanism and functional impacts are not fully understood. Here, we used UV (Ultraviolet) damage sequencing data and analyzed cyclobutane pyrimidine dimer (CPD) formation, DNA repair, and CPD deamination in human cells at single-nucleotide resolution. Our data show prominent CPD hotspots immediately after UV irradiation at ETS binding sites, particularly at sites with a conserved TTCCGG motif, which correlate with mutation hotspots identified in cutaneous melanoma. Additionally, CPDs are repaired slower at ETS binding sites than in flanking DNA. Cytosine deamination in CPDs to uracil is suggested as an important step for UV mutagenesis. However, we found that CPD deamination is significantly suppressed at ETS binding sites, particularly for the CPD hotspot on the 5' side of the ETS motif, arguing against a role for CPD deamination in promoting ETS-associated UV mutations. Finally, we analyzed a subset of frequently mutated promoters, including the ribosomal protein genes RPL13A and RPS20 , and found that mutations in the ETS motif can significantly reduce the promoter activity. Thus, our data identify high UV damage and low repair, but not CPD deamination, as the main mechanism for ETS-associated mutations in melanoma and uncover important roles of often-overlooked mutation hotspots in perturbing gene transcription., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background. Blood cannot be artificially manufactured, and there is currently no substitute for human blood. The supply of blood in transfusion facilities requires constant and timely collection of blood from donors. Modeling and forecasting trends in blood collections are critical for determining both the current and future capacity requirements and appropriate models of adequate blood provision. Objectives. The objective of this study is to determine blood collection or donation patterns and develop time-series models that can be updated and refined in predicting future blood donations in Zimbabwe when given the historical data. Materials and Methods. Monthly blood donation data for the period 2009 to 2019 were collected retrospectively from the National Blood Service Zimbabwe database. Time-series models (i.e., the Seasonal Autoregressive Integrated Moving Average [SARIMA] and Error, Trend and Seasonal [ETS]) models were applied and compared. The models were chosen because of their ability to handle the seasonality and other time-series components evident in the blood donation data. Expert opinions and experience were used in selecting the models and in making inferences in the analysis. Results. Time-series plots of blood donations showed seasonal patterns, with significant drops in blood donations in months associated with Zimbabwe's school holidays (April, August, and December) and public holidays. During these holidays, there is a reduced number of school donors, while at about the same time, there is increasing blood demand as a result of road accidents. Model identification procedures established the SARIMA ( 1 , 1 , 2 ) ( 0 , 1 , 1 ) 12 model as the appropriate model for forecasting total blood donation in Zimbabwe. The results and forecasts show an upward trend in blood donations. According to the accuracy measures used, the SARIMA model outperforms the ETS model. Conclusions. Expert knowledge in the blood donation process, coupled with statistical models, can help explain trends exhibited in blood donation data in Zimbabwe. These findings help the blood authorities plan for blood donor campaign drives. The findings are key indicators of where to allocate more resources toward blood donation and when to collect more blood units. The increasing blood donation projections ensure a stable blood bank inventory in the near future., Highlights: A SARIMA model can be used to predict the flow of blood donations in Zimbabwe.The seasonal blood donation pattern peaks in the months of March, June/July, and September.The donations troughs are in the months of April, August, December, and January. These are the months coinciding with school holidays in Zimbabwe.Both the SARIMA and ETS models provided similar forecasts, but measures of fit and expert knowledge gave a slight preference to the SARIMA ( 1 , 1 , 2 ) ( 0 , 1 , 1 ) 12 model in predicting the flow of blood donations in Zimbabwe.These model results are useful for guiding allocation of blood donation resources and blood donation drive timing., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors received no financial support for the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Genetic alterations of the repressive ETS family transcription factor gene ETV6 are recurrent in several categories of hematopoietic malignancy, including subsets of B-cell and T-cell acute lymphoblastic leukemias (B-ALL and T-ALL), myeloid neoplasms, and mature B-cell lymphomas. ETV6 is essential for adult hematopoietic stem cells (HSCs), contributes to specific functions of some mature immune cells, and plays a key role in thrombopoiesis as demonstrated by familial ETV6 mutations associated with thrombocytopenia and predisposition to hematopoietic cancers, particularly B-ALL. ETV6 appears to have a tumor suppressor role in several hematopoietic lineages, as demonstrated by recurrent somatic loss-of-function (LoF) and putative dominant-negative alterations in leukemias and lymphomas. ETV6 rearrangements contribute to recurrent fusion oncogenes such as the B-ALL-associated transcription factor (TF) fusions ETV6::RUNX1 and PAX5::ETV6, rare drivers such as ETV6::NCOA6, and a spectrum of tyrosine kinase gene fusions encoding hyperactive signaling proteins that self-associate via the ETV6 N-terminal pointed domain. Another subset of recurrent rearrangements involving the ETV6 gene locus appear to function primarily to drive overexpression of the partner gene. This review surveys what is known about the biochemical and genome regulatory properties of ETV6 as well as our current understanding of how alterations in these functions contribute to hematopoietic and nonhematopoietic cancers., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Transcription factors (TFs) play a crucial role in regulating the dynamic and precise patterns of gene expression required for the initial specification of endothelial cells (ECs), and during endothelial growth and differentiation. While sharing many core features, ECs can be highly heterogeneous. Differential gene expression between ECs is essential to pattern the hierarchical vascular network into arteries, veins and capillaries, to drive angiogenic growth of new vessels, and to direct specialization in response to local signals. Unlike many other cell types, ECs have no single master regulator, instead relying on differing combinations of a necessarily limited repertoire of TFs to achieve tight spatial and temporal activation and repression of gene expression. Here, we will discuss the cohort of TFs known to be involved in directing gene expression during different stages of mammalian vasculogenesis and angiogenesis, with a primary focus on development., (© 2023 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Background: Endoscopic transsphenoidal surgery is the primary method used to treat pituitary adenomas (PAs) at present; however, this technique is associated with certain risks, including cerebrospinal fluid leakage (CFL) and residual tumors (RTs). In this study, we aimed to identify specific risk factors for intraoperative CFL (ioCFL) and postoperative RT in patients with pituitary adenoma and construct a corresponding nomogram for risk assessment., Methods: We collected a range of information from 782 patients who underwent endoscopic transsphenoidal PA resection in the Department of Neurosurgery at Beijing Tiantan Hospital between 2019 and 2021. Patients were then randomly assigned to training and validation groups (in a 8:2 ratio) with R software. Univariate and multivariable logistic regression models were then used to screen variables related to ioCFL and RT. These variables were then used to construct a predictive nomogram. Finally, the accuracy of the nomogram was validated by receiver operating characteristic curve (ROC) analysis, calibration plots, and decision curve analysis (DCA)., Results: Univariate and multivariable logistic regression models identified four risk factors for ioCFL (Hardy grade, tumor size, position, and consistency) and five risk factors for RT (operation time, tumor size, consistency, Knosp grade, and primary/recurrence type). The area under the ROC curve (AUC) for the ioCFL risk model was 0.666 and 0.697 for the training and validation groups, respectively. For RT, the AUCs for the two groups were 0.788 and 0.754, respectively. The calibration plots for the ioCFL and RT models showed high calibration quality and DCA analysis yielded excellent efficiency with regards to clinical decision making., Conclusion: Tumor size, growth characteristics, and invasion location were identified as the main factors affecting intraoperative CFL and RT. With our novel nomogram, surgeons can identify high-risk patients according to preoperative and intraoperative tumor performance and reduce the probability of complications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Seasonal influenza is a serious public health issue in China. This study aimed to develop a new hybrid model for seasonal influenza incidence prediction and provide reference information for early warning management before outbreaks., Methodology: Data on the monthly incidence of seasonal influenza between 2004 and 2018 were obtained from the China Public Health Science Data Center website. A single seasonal autoregressive integrated moving average (SARIMA) model and a single error trend and seasonality (ETS) model were built. On this basis, we constructed SARIMA, ETS, and support vector regression (SARIMA-ETS-SVR) hybrid model. The prediction performance was determined by comparing mean absolute error (MAE), mean square error (MSE), mean absolute percentage error (MAPE), and root mean square error (RMSE) indices., Results: The optimum SARIMA model was SARIMA (0,1,0) (0,0,1)12. Error trend and seasonality (ETS) (M,A,M) was the SARIMA optimal model. For the fitting performance, the SARIMA-ETS-SVR hybrid model achieved the lowest values of MAE, MSE, and RMSE, in addition to the MAPE. In terms of predictive performance, the SARIMA-ETS-SVR hybrid model had the lowest MAE, MSE, MAPE, and RMSE values among the three models., Conclusions: The study demonstrated that the SARIMA-ETS-SVR hybrid model provides better generalization ability than a single SARIMA model and a single ETS model, and the predictions will provide a useful tool for preventing this infectious disease., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Daren Zhao, Ruihua Zhang.)

Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Background: ETS transcription factors, known as the E26 transformation-specific factors, assume a critical role in the regulation of various vital biological processes in animals, including cell differentiation, the cell cycle, and cell apoptosis. However, their characterization in mollusks is currently lacking., Results: The current study focused on a comprehensive analysis of the ETS genes in blood clam Tegillarca granosa and other mollusk genomes. Our phylogenetic analysis revealed the absence of the SPI and ETV subfamilies in mollusks compared to humans. Additionally, several ETS genes in mollusks were found to lack the PNT domain, potentially resulting in a diminished ability of ETS proteins to bind target genes. Interestingly, the bivalve ETS1 genes exhibited significantly high expression levels during the multicellular proliferation stage and in gill tissues. Furthermore, qRT-PCR results showed that Tg-ETS-14 (ETS1) is upregulated in the high total hemocyte counts (THC) population of T. granosa, suggesting it plays a significant role in stimulating hemocyte proliferation., Conclusion: Our study significantly contributes to the comprehension of the evolutionary aspects concerning the ETS gene family, while also providing valuable insights into its role in fostering hemocyte proliferation across mollusks., (© 2023. The Author(s).)

Background: Ajania Poljakov, an Asteraceae family member, grows mostly in Asia's arid and semi-desert areas and is a significant commercial and decorative plant. Nevertheless, the genus' classification has been disputed, and the evolutionary connections within the genus have not been thoroughly defined. Hence, we sequenced and analyzed Ajania's plastid genomes and combined them with ETS data to assess their phylogenetic relationships., Results: We obtained a total of six new Ajania plastid genomes and nine ETS sequences. The whole plastome lengths of the six species sampled ranged from 151,002 bp to 151,115 bp, showing conserved structures. Combined with publicly available data from GenBank, we constructed six datasets to reconstruct the phylogenetic relationships, detecting nucleoplasmic clashes. Our results reveal the affinities of Artemisia, Chrysanthemum and Stilpnolepis to Ajania and validate the early taxonomy reclassification. Some of the plastid genes with low phylogenetic information and gene trees with topological differences may have contributed to the ambiguous phylogenetic results of Ajania. There is extensive evolutionary rate heterogeneity in plastid genes. The psbH and ycf2 genes, which are involved in photosynthesis and ATP transport, are under selective pressure. Plastomes from Ajania species diverged, and structural aspects of plastomes may indicate some of the real evolutionary connections. We suggest the ycf1 gene as a viable plastid DNA barcode because it has significant nucleotide diversity and better reflects evolutionary connections., Conclusion: Our findings validate the early Ajania taxonomy reclassification and show evolutionary rate heterogeneity, genetic variety, and phylogenetic heterogeneity of plastid genes. This research might provide new insights into the taxonomy and evolution of Ajania, as well as provide useful information for germplasm innovation and genetic enhancement in horticultural species., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Backgrounds: Endoscopic thoracic sympathectomy (ETS) is a permanent and effective treatment for primary hyperhidrosis and facial blushing; however, severe compensatory sweating (SCS) remains a devastating complication. We aimed to (i) construct a nomogram to predict the risk of SCS, and (ii) investigate factors associated with the level of satisfaction., Methods: From Jan 2014 to Mar 2020, 347 patients underwent ETS by a single surgeon. These patients were asked to complete an online questionnaire regarding primary symptom resolution, level of satisfaction, and development of compensatory sweating. Multivariable analysis was conducted via logistic regression and ordinal regression to predict SCS and satisfaction level respectively. Nomogram was developed based on significant predictors., Results: In total, 298 (85.9%) patients responded to the questionnaire with a mean follow up of 4.9 ± 1.8 years. Significant factors associated with SCS in the nomogram included older age (OR 1.05, 95% CI 1.02-1.09, P = 0.001), primary indication other than palmar hyperhidrosis (OR 2.30, 95% CI 1.03-5.12, P = 0.04), and current smoking (OR 5.91, 95% CI 2.46-14.20, P < 0.001). The area under receiver operating characteristic curve was 0.713. Multivariable analysis revealed that longer follow up (β = -0.201 ± 0.078, P = 0.01), gustatory hyperhidrosis (β = -0.781 ± 0.267, P = 0.003), primary indication other than palmar hyperhidrosis (β = -1.524 ± 0.292, P < 0.001), and SCS (β = -3.061 ± 0.404, P < 0.001) were independently associated with a lower degree of patient satisfaction., Conclusion: The novel nomogram can provide a personalized numerical risk estimate to assist both the clinician and patient weigh the pros and cons as part of the decision-making process, mitigating the chance of patient dissatisfaction., (© 2023 Royal Australasian College of Surgeons.)

Background: A diverse and balanced human gut microbiota is crucial for maintaining normal human physiological functions. However, the impact of indoor microbiome and metabolites on gut microbiota is not well understood., Methods: A self-administered questionnaire was used to collect information on more than 40 personal and environmental characteristics and dietary habits from 56 children in Shanghai, China. Shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS) were used to characterize the indoor microbiome and metabolomic/chemical exposure in children's living rooms. PacBio full-length 16 S rRNA sequencing was used to characterize children's gut microbiota. Associations between environmental characteristics and gut microbiota diversity/composition were assessed using PERMANOVA and regression., Results: In total, 6247 and 318 indoor and gut microbial species and 1442 indoor metabolites were characterized. Age of children (R 2  = 0.033, p = 0.008), age start kindergarten (R 2  = 0.029, p = 0.03), living adjacent to heavy traffic (R 2  = 0.031, p = 0.01) and drinking soft drinks (R 2  = 0.028, p = 0.04) significantly impacted overall gut microbial composition, consistent with previous studies. Having pets/plants and frequent vegetable intake were positively associated with gut microbiota diversity and the Gut Microbiome Health Index (GMHI), while frequent juice and fries intake decreased gut microbiota diversity (p < 0.05). The abundance of indoor Clostridia and Bacilli was positively associated with gut microbial diversity and GMHI (p < 0.01). Total indoor indole derivatives and 6 indole metabolites (L-tryptophan, indole, 3-methylindole, indole-3-acetate, 5-hydroxy-L-tryptophan and indolelactic acid, p < 0.05) were positively associated with the abundance of total protective gut bacteria, suggesting a potential role in promoting gut health. Neural network analysis revealed that these indole derivatives were derived from indoor microorganisms., Conclusions: The study is the first to report associations between indoor microbiome/metabolites and gut microbiota, highlighting the potential role of indoor microbiome in shaping human gut microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal and environmental characteristics. The indoor microbiome and metabolites from vacuumed indoor dust were profiled via shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS). The nasal and oral microbiota in children was characterized using full-length 16S rRNA sequencing from PacBio. Associations between personal/environmental characteristics and the nasal/oral microbiota were calculated using PERMANOVA and regression analyses. We identified 6247, 431, and 342 microbial species in the indoor dust, nasal, and oral cavities, respectively. The overall nasal and oral microbial composition showed significant associations with environmental tobacco smoke (ETS) exposure during pregnancy and early childhood ( p = 0.005 and 0.03, respectively), and the abundance of total indoor flavonoids and two mycotoxins (deoxynivalenol and nivalenol) ( p = 0.01, 0.02, and 0.03, respectively). Notably, the abundance of several flavonoids, such as baicalein, eupatilin, isoliquiritigenin, tangeritin, and hesperidin, showed positive correlations with alpha diversity and the abundance of protective microbial taxa in nasal and oral cavities ( p < 0.02), suggesting their potential beneficial roles in promoting nasal/oral health. Conversely, high carbohydrate/fat food intake and ETS exposure diminished protective microorganisms while augmenting risky microorganisms in the nasal/oral cavities. Further, potential microbial transfer was observed from the indoor environment to the childhood oral cavity ( Moraxella catarrhalis , Streptococcus mitis , and Streptococcus salivarius ), which could potentially increase virulence factors related to adherence and immune modulation and vancomycin resistance genes in children. This is the first study to reveal the association between the indoor microbiome/metabolites and nasal/oral microbiota using multi-omic approaches. These findings reveal potential protective and risk factors related to the indoor microbial environment.

Glia play multifaceted roles in nervous systems in response to injury. Depending on the species, extent of injury and glial cell type in question, glia can help or hinder the regeneration of neurons. Studying glia in the context of successful regeneration could reveal features of pro-regenerative glia that could be exploited for new human therapies. Planarian flatworms completely regenerate their nervous systems after injury - including glia - and thus provide a strong model system for exploring glia in the context of regeneration. Here, we report that planarian glia regenerate after neurons, and that neurons are required for correct glial numbers and localization during regeneration. We also identify the planarian transcription factor-encoding gene ets-1 as a key regulator of glial cell maintenance and regeneration. Using ets-1 (RNAi) to perturb glia, we show that glial loss is associated with altered neuronal gene expression, impeded animal movement and impaired nervous system architecture - particularly within the neuropil. Importantly, our work reveals the inter-relationships of glia and neurons in the context of robust neural regeneration., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

The Water Quality Index (WQI) is used to monitor the health and usability of a water body. In this study, we aimed to construct time series prediction models using groundwater WQI (GW-WQI) at four sites: IISCO-Asansol, Durgapur Town, Burdwan University, and Burdwan Station. While statistical spatio-temporal analysis has been reported earlier, no time series analysis of the data or predictive modelling has been done. Pre-monsoon and post-monsoon physico-chemical data from 2010 to 2022 were obtained from the West Bengal Pollution Control Board website to calculate the GW-WQI. Prediction modelling was performed using R 4.1.3 software. Best fit forecast models were selected to predict future trends of GW-WQI with 80% of the data. Subsequently, the models were validated using R-squared, root mean square error (RMSE), mean absolute error (MAE), maximum absolute percentage error (MAPE), and Thiel's U for the model using 20% of the data. Our results show that GW-WQI was good in pre-monsoon but unfit for drinking in post-monsoon in IISCO-Asansol, Durgapur Town, Burdwan University, and Burdwan Station. Arsenic, fluoride, and mercury were the major contaminants resulting in poor GW-WQI. Seasonal ARIMA was the best model for Burdwan University and IISCO-Asansol, ETS for Durgapur Station, and BaggedARIMA for Burdwan Station. The forecast model for Durgapur and Burdwan Station predicted a sharp increase until 2027 but was fluctuating for IISCO-Asansol and Burdwan University. Thus, GW-WQI is a major problem in the industrial belt of West Bengal that is likely to remain high or worsen in the future., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The experience of the COVID-19 pandemic showed the importance of timely monitoring of admissions to the ICU admissions. The ability to promptly forecast the epidemic impact on the occupancy of beds in the ICU is a key issue for adequate management of the health care system.Despite this, most of the literature on predictive COVID-19 models in Italy has focused on predicting the number of infections, leaving trends in ordinary hospitalizations and ICU occupancies in the background.This work aims to present an ETS approach (Exponential Smoothing Time Series) time series forecasting tool for admissions to the ICU admissions based on ETS models. The results of the forecasting model are presented for the regions most affected by the epidemic, such as Veneto, Lombardy, Emilia-Romagna, and Piedmont.The mean absolute percentage errors (MAPE) between observed and predicted admissions to the ICU admissions remain lower than 11% for all considered geographical areas.In this epidemiological context, the proposed ETS forecasting model could be suitable to monitor, in a timely manner, the impact of COVID-19 disease on the health care system, not only during the early stages of the pandemic but also during the vaccination campaign, to quickly adapt possible preventive interventions., (© 2023. The Author(s).)

Background: Accelerated globalization especially in the late 1980s has provided opportunities for economic progress in the world of emerging economies. The BRICS nations' economies are distinguishable from other emerging economies due to their rate of expansion and sheer size. As a result of their economic prosperity, health spending in the BRICS countries has been increasing. However, health security is still a distant dream in these countries due to low public health spending, lack of pre-paid health coverage, and heavy out-of-pocket spending. There is a need for changing the health expenditure composition to address the challenge of regressive health spending and ensure equitable access to comprehensive healthcare services., Objective: Present study examined the health expenditure trend among the BRICS from 2000 to 2019 and made predictions with an emphasis on public, pre-paid, and out-of-pocket expenditures for 2035., Methods: Health expenditure data for 2000-2019 were taken from the OECD iLibrary database. The exponential smoothing model in R software (ets ()) was used for forecasting., Results: Except for India and Brazil, all of the BRICS countries show a long-term increase in per capita PPP health expenditure. Only India's health expenditure is expected to decrease as a share of GDP after the completion of the SDG years. China accounts for the steepest rise in per capita expenditure until 2035, while Russia is expected to achieve the highest absolute values., Conclusion: The BRICS countries have the potential to be important leaders in a variety of social policies such as health. Each BRICS country has set a national pledge to the right to health and is working on health system reforms to achieve universal health coverage (UHC). The estimations of future health expenditures by these emerging market powers should help policymakers decide how to allocate resources to achieve this goal., (© 2023. The Author(s).)

Background: Injury induces profound transcriptional remodeling events, which could lead to only wound healing, partial tissue repair, or perfect regeneration in different species. Injury-responsive enhancers (IREs) are cis-regulatory elements activated in response to injury signals, and have been demonstrated to promote tissue regeneration in some organisms such as zebrafish and flies. However, the functional significances of IREs in mammals remain elusive. Moreover, whether the transcriptional responses elicited by IREs upon injury are conserved or specialized in different species, and what sequence features may underlie the functional variations of IREs have not been elucidated., Results: We identified a set of IREs that are activated in both regenerative and non-regenerative neonatal mouse hearts upon myocardial ischemia-induced damage by integrative epigenomic and transcriptomic analyses. Motif enrichment analysis showed that AP-1 and ETS transcription factor binding motifs are significantly enriched in both zebrafish and mouse IREs. However, the IRE-associated genes vary considerably between the two species. We further found that the IRE-related sequences in zebrafish and mice diverge greatly, with the loss of IRE inducibility accompanied by a reduction in AP-1 and ETS motif frequencies. The functional turnover of IREs between zebrafish and mice is correlated with changes in transcriptional responses of the IRE-associated genes upon injury. Using mouse cardiomyocytes as a model, we demonstrated that the reduction in AP-1 or ETS motif frequency attenuates the activation of IREs in response to hypoxia-induced damage., Conclusions: By performing comparative genomics analyses on IREs, we demonstrated that inter-species variations in AP-1 and ETS motifs may play an important role in defining the functions of enhancers during injury response. Our findings provide important insights for understanding the molecular mechanisms of transcriptional remodeling in response to injury across species., (© 2023. The Author(s).)

Climate policies could improve air quality, thereby generating health benefits and thus increasing labour input for economic growth. Nevertheless, health benefits are usually overlooked in evaluation frameworks of climate policies. In this paper, a dynamic recursive computable general equilibrium (CGE) model is adopted to define how climate policies are related to air pollution, namely [Formula: see text] concentrations. Health benefits of climate policies are divided into reduction of [Formula: see text]-related morbidity and mortality. The CGE model results show that both carbon tax and emission trading scheme (ETS) decrease morbidity and mortality; therefore, under climate policies, [Formula: see text]-related labour loss decreases, and thus increasing labour input triggers an economic boom. Carbon tax generates more health benefits in short term, while health benefits of ETS policy will gradually increase in long term. Hence, we conclude that regarding health benefits, a long-term ETS policy is preferable to a long-term carbon tax. This finding implies that the recently established nationwide ETS market in China is meaningful, as it will generate more health benefits in future. Nevertheless, the quantified health benefits in this paper still cannot compensate GDP loss induced by climate policy implementations, implying that it is a challenging task to unbiasedly model health benefits of climate policies. Hence, we have recommended that the scopes and contents of health benefits should be expanded in evaluations of climate policies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Salivary gland (SG) development, maturation, and homeostasis require coordinated roles of transcription factors (TFs) that dictate specific cell identities and fate. The ETS family of proteins are important transcriptional drivers of diverse cell lineages, tissue development, and differentiation programs and hence are also likely to play an important role in the SG. Here we have leveraged genomic and epigenomic data of the SG to examine the expression profile of ETS genes and identified 2 closely related paralogs, Elf5 and Ehf, that are highly expressed in distinct epithelial subpopulations. By using a well-defined mouse knockout model of Elf5, we show that Elf5, despite its enriched expression in the acinar cells, is functionally dispensable for maintaining the homeostatic state of the adult SG epithelium. The lack of a discernible phenotype of the Elf5-null SG might be due to possible functional redundancy with Ehf or other ETS factors. To probe this possibility and to examine the specific consequences of Ehf loss in the SG, we used CRISPR-Cas9 to generate mice in which the DNA-binding ETS domain of Ehf is disrupted due to an insertion mutation. We demonstrate that the Ehf mutant (EhfMut) mice exhibit a distinct cellular phenotype with decreased granular convoluted tubules that are accompanied by an increased accumulation of the intercalated Sox9-positive ductal cell population. Interestingly, the ductal phenotype of the EhfMut animals is highly pronounced in males, reaffirming the established sexual dimorphism of the SG that exists in rodents. Our results show that unlike Elf5, Ehf plays a nonredundant role in directing ductal cell differentiation of the SG and highlights the phenotypic subtlety in mutant mice of closely related TFs and the importance of careful consideration of cell type-specific studies.

The notochord is a defining feature of all chordates. The transcription factors Zic and ETS regulate enhancer activity within the notochord. We conduct high-throughput screens of genomic elements within developing Ciona embryos to understand how Zic and ETS sites encode notochord activity. Our screen discovers an enhancer located near Lama, a gene critical for notochord development. Reversing the orientation of an ETS site within this enhancer abolishes expression, indicating that enhancer grammar is critical for notochord activity. Similarly organized clusters of Zic and ETS sites occur within mouse and human Lama1 introns. Within a Brachyury (Bra) enhancer, FoxA and Bra, in combination with Zic and ETS binding sites, are necessary and sufficient for notochord expression. This binding site logic also occurs within other Ciona and vertebrate Bra enhancers. Collectively, this study uncovers the importance of grammar within notochord enhancers and discovers signatures of enhancer logic and grammar conserved across chordates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

To achieve China's "dual carbon" and common prosperity goals, corporate green governance is crucial. A key tool for promoting green growth is environmental legislation, particularly market-based regulation. With China's carbon emission trading as a natural experiment, we adopt the DID method to quantitatively compare the gap between ESG performance of pilot and non-pilot carbon trading enterprises before and after policy implementation, thereby examining the impact, mechanism and optimization conditions of market-based environmental policy on corporate green governance based on panel data of China's A-share listed companies from 2007 to 2019. In addition, PSM-DID and other methods are employed for preventing estimation bias caused by sample self-selection bias. It is found that: (1) the green governance level of pilot firms can be considerably improved by a carbon emission trading scheme (ETS); (2) the ETS primarily encourages enterprises to uphold their ESG obligations through increasing regulatory pressure from the government and corporate involvement in clean innovation; (3) enhancing regional marketization can strengthen the impact of carbon trading policy, and enterprises that are large and non-state-owned exhibit better performance with regard to green governance as a result of carbon trading policy. This paper provides practical experience for promoting corporate green governance to achieve the "dual carbon" goal based on a market mechanism from a micro perspective.

Salicornia is a highly taxonomically problematic genus due to the reduced morphological observable characters. Ten Eurasian species are currently recognized: S. alpini , S. europaea , S. fruticosa , S. hispanica , S. lagascae , S. perennans , S. perennis , S. persica , S. procumbens , and S. pruinosa . In addition, eleven subspecies are accepted, mainly based on their distribution areas. Along the Venetian coasts and in Sardinia, in the past, an endemic species called S. veneta was recognized, but this name was later synonymized with S. procumbens subsp. procumbens . The aim of the present research is investigating different Italian Salicornia populations by a molecular point of view, using the nuclear ribosomal external transcribed spacer ETS and the plastid psb A- trn H intergenic spacer. A particular focus is on the comparison between Venetian (including those occurring in locus classicus of S. veneta ) and Sardinian S. procumbens and other Italian populations of this species. The molecular analyses based on the plastid marker highlight that the Italian S. procumbens populations form two well distinct groups. In particular, some of the Venetian ( Locus classicus of S. veneta ) and all the Sardinian specimens are genetically distinct (=plastid haplotype 1) from the other investigated populations (=plastid haplotype 2). This indicates that the psb A -trn H haplotype 1 glassworts represent a distinct entity, which we suppose to coincide with the former S. veneta . Therefore, we suggest to recognize this taxonomic entity at the subspecies rank, as S. procumbens subsp. veneta comb. and stat. nov. However, contrary to the results found with the plastid psb A -trn H intergenic spacer, the ETS locus does not show a separation into two distinct clades for S. procumbens , probably due to a different evolution of the two loci. Nevertheless, in the ETS phylogenetic reconstruction, the Sardinian specimens (=ribotypes 2 and 3) are placed, together with a Moroccan sample, in a subclade separated from all the other S. procumbens . These results suggest that the Sardinian populations can represent a subspecies/incipient speciation process, probably due to geographic isolation. In the light of this, morphometric analyses (k-means, MANOVA, PCA, DA, and Box-Plot) have been carried out on the Sardinian and Venetian populations to verify if this distinction is detectable also by a morphological point of view. The morphometric analyses highlight the existence of two groups, concerning both the nuclear and plastid trees. Six characters were found to be diagnostic.

Introduction: In metastatic colorectal cancer (mCRC), the efficacy of immune checkpoint blockade (ICB) has so far been limited to patients with microsatellite instability high tumors (MSI-H). Unfortunately, most mCRC patients suffer from non-immunogenic microsatellite stable (MSS) tumors. Therefore, new combinatorial strategies are urgently needed to enhance the immunogenicity of MSS tumors to finally increase the number of patients benefiting from ICB., Methods: The AVETUX trial aimed to combine the PD-L1 antibody avelumab with the standard of care chemotherapy combination FOLFOX and the anti-EGFR antibody cetuximab. Furthermore, we performed a central radiological review of the pre- and on-treatment computed tomography scans to better define the individual response to treatment., Results and Discussion: In total, 43 patients were treated of which 39 patients were confirmed as RAS/BRAF wildtype in central tissue review and finally response evaluated. A final progression-free survival (PFS) of 11.1 (range: 0.8 to 22.3 months) and a herein updated final overall survival (OS) of 32.9 months (range: 0.8 to 47.1 months) was reached. We observed a strong median depth of response of 67.5% tumor shrinkage and deepness of response correlated significantly with survival. On the other hand, early tumor shrinkage was not an indicator of better outcome at a cut-off of 20% (median values). In a next step, we correlated the individual best radiological response with potential ICB response biomarkers and found that the clonality and diversity, but not frequency of tumor infiltrating lymphocytes (TiLs) and peripheral blood mononuclear cells (PBMCs), strongly correlated with response. In summary, we report the final overall survival of the AVETUX trial and propose T cell clonality and diversity as a potential marker to predict response to chemo-immunotherapy combinations in MSS mCRC by performing a central radiological review., Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT03174405)., Competing Interests: AS received institutional research grants from Merck, BMS, Roche, Sanofi, Servier and honoraria for lectures and advisory board meetings by Merck, Roche, Amgen, Lilly, Sanofi- Aventis, Servier, Bayer, BMS, MSD and Sirtex. S-EA-B has an advisory role with Merck, Roche, Celgene, Lilly, Nordic Pharma, Bristol- Myers Squibb, Astellas and MSD Sharp & Dohme; is a speaker for Roche, Celgene, Lilly, Nordic Pharma, AIO gGmbH, MCI, promedicis, Forum für Medizinische Fortbildung and Taiho pharma; he is CEO/founder of IKF Klinische Krebsforschung GmbH at Northwest Hospital; and has received research grants from Sanofi, Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly, Eurozyto, German Cancer Aid (Krebshilfe), German Research Foundation and the Federal Ministry of Education and Research. UP received institutional research grants from Celgene, BMS, Amgen, Lilly, Roche, Sanofi and Servier and honoraria for lectures and advisory board meetings by Roche, Celgene, Amgen, Lilly, Sanofi- Aventis, Servier, Bayer and BMS. AH received honoraria for lectures from Roche. CB received institutional research grants and honoraria for lectures and advisory board meetings from Merck, BMS, Roche, Sanofi, Servier, Bayer, BMS, Astrazeneca, Lilly, Mundipharma, Hexal, MSD and GSO. MBi received institutional research grants from Merck, BMS, Hexal, German Cancer Aid (Krebshilfe), German Research Foundation and the Federal Ministry of Education and Research as well as honoraria for lectures and advisory board meetings by Celgene, Janssen, Gilead, Merck, Roche, Amgen, Sanofi-Aventis and BMS., (Copyright © 2022 Tintelnot, Ristow, Sauer, Simnica, Schultheiß, Scholz, Goekkurt, von Wenserski, Willscher, Paschold, Lorenzen, Riera-Knorrenschild, Depenbusch, Ettrich, Dörfel, Al-Batran, Karthaus, Pelzer, Hinke, Bauer, Massa, Seliger, Wickenhauser, Bokemeyer, Hegewisch-Becker, Binder and Stein.)

Background: Critically ill patients on supplemental oxygen therapy eventually develop acute lung injury (ALI). Reactive oxygen species (ROS) produced during ALI perturbs the mitochondrial dynamics resulting in cellular damage. Genetic deletion of the mitochondrial A-kinase anchoring protein 1 (Akap1) in mice resulted in mitochondrial damage, Endoplasmic reticulum (ER) stress, increased expression of mitophagy proteins and pro-inflammatory cytokines, exacerbating hyperoxia-induced Acute Lung Injury (HALI). Objective: Despite a strong causal link between mitochondrial dysfunction and HALI, the mechanisms governing the disease progression at the transcriptome level is unknown. Methods: In this study, RNA sequencing (RNA-seq) analysis was carried out using the lungs of Akap1 knockout ( Akap1 -/- ) mice exposed to normoxia or 48 h of hyperoxia followed by quantitative real time PCR and Ingenuity pathway analysis (IPA). Western blot analysis assessed mitochondrial dysfunction, OXPHOS complex (I-V), apoptosis and antioxidant proteins. Mitochondrial enzymatic assays was used to measure the aconitase, fumarase, citrate synthase activities in isolated mitochondria from Akap1 -/- vs. Wt mice exposed to hyperoxia. Results: Transcriptome analysis of Akap1 -/- exposed to hyperoxia reveals increases in transcripts encoding electron transport chain (ETC) and tricarboxylic acid cycle (TCA) proteins. Ingenuity pathway analysis (IPA) shows enrichment of mitochondrial dysfunction and oxidative phosphorylation in Akap1 -/- mice. Loss of AKAP1, coupled with oxidant injury, significantly decreases the activities of TCA enzymes. Mechanistically, a significant loss of dynamin-related protein 1 (Drp1) phosphorylation at the protein kinase A (PKA) site Serine 637 (Ser637), decreases in Akt phosphorylation at Serine 437 (Ser47) and increase in the expression of pro-apoptotic protein Bax indicate mitochondrial dysfunction. Heme oxygenase-1 (HO-1) levels significantly increased in CD68 positive alveolar macrophages in Akap1 -/- lungs, suggesting a strong antioxidant response to hyperoxia. Conclusion: Overall these results suggest that AKAP1 overexpression and modulation of Drp1 phosphorylation at Ser637 is an important therapeutic strategy for acute lung injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Soundararajan, Hernández-Cuervo, Stearns, Griswold, Patil, Fukumoto, Narala, Galam, Lockey and Kolliputi.)

Purpose: The aim of the study was to investigate the empathy level and caring behaviors perceptions of nursing students., Method: This cross-sectional and correlational study was conducted with 276 nursing students., Results: The mean Empathic Tendency Scale score was 62.71 ± 5.10 (min. 20 to max. 100), indicating a low level of empathy. The mean of the Caring Assessment Questionnaire was 5.42 ± 0.80 (min. 1 to max. 7), showing a good perception of caring behaviors. There was a positive, low, and significant relationship between empathy and caring behaviors (r = 0.286, p < 0.001)., Conclusion: This study revealed that nursing students have low-level empathy and high-level caring behaviors., Practice Implications: Throughout the educational process, the students' caring competencies, which include empathy and caring behaviors, developed. It is suggested that humanistic and value-oriented pedagogical approaches be incorporated into nursing curricula., (© 2022 Wiley Periodicals LLC.)

While there has been a sufficient amount of research and empirical evidence on the factors that influence a company's decisions to voluntarily disclose carbon information, little research has been done on the carbon disclosure practices of ETS-affected companies, in Asian countries, in particular. Considering this, it is essential to shed light on more diverse linkages between carbon performance and voluntary carbon disclosure (VCD) under ETSs taking into account the specific context of each individual country. Drawing on the Korean ETS-affected companies with a contents analysis of their sustainable reports from 2015 to 2019, the present research seeks to address the existing knowledge gaps in the current literature on carbon disclosure. In doing so, hierarchical ordinary least square (OLS) regression analysis is used to infer causality and assess the findings. The findings empirically prove a positive relationship between carbon performance and VCD, which means that the affected companies under the Korean ETS are likely to disclose more when they have favorable carbon reduction performance. Furthermore, this link tends to be amplified for companies with a high percentage of foreign sales, while the role of media visibility interacts differently with carbon performance in influencing VCD.

An important unanswered question in regenerative biology is to what extent regeneration is accomplished by the reactivation of gene regulatory networks used during development versus the activation of regeneration-specific transcriptional programs. Following damage, Drosophila imaginal discs, the larval precursors of adult structures, can regenerate missing portions by localized proliferation of damage-adjacent tissue. Using single-cell transcriptomics in regenerating wing discs, we have obtained a comprehensive view of the transcriptome of regenerating discs and identified two regeneration-specific cell populations within the blastema, Blastema1 and Blastema2. Collectively, these cells upregulate multiple genes encoding secreted proteins that promote regeneration including Pvf1, upd3, asperous, Mmp1, and the maturation delaying factor Ilp8. Expression of the transcription factor Ets21C is restricted to this regenerative secretory zone; it is not expressed in undamaged discs. Ets21C expression is activated by the JNK/AP-1 pathway, and it can function in a type 1 coherent feedforward loop with AP-1 to sustain expression of downstream genes. Without Ets21C function, the blastema cells fail to maintain the expression of a number of genes, which leads to premature differentiation and severely compromised regeneration. As Ets21C is dispensable for normal development, these observations indicate that Ets21C orchestrates a regeneration-specific gene regulatory network. We have also identified cells resembling both Blastema1 and Blastema2 in scribble tumorous discs. They express the Ets21C-dependent gene regulatory network, and eliminating Ets21C function reduces tumorous growth. Thus, mechanisms that function during regeneration can be co-opted by tumors to promote aberrant growth., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Mutations in the promoter of human telomerase reverse transcriptase (hTERT) result in hyperactivation of hTERT. Notably, all mutations are G>A transitions, frequently found in a wide range of cancer types, and causally associated with cancer progression. Initially, the mutations were understood to reactivate hTERT by generating novel E26 transformation-specific (ETS) binding sites. Recent work reveals the role of DNA secondary structure G-quadruplexes, telomere binding factor(s), and chromatin looping in hTERT regulation. Here, we discuss these emerging findings in relation to the clinically significant promoter mutations to provide a broader understanding of the context-dependent outcomes that result in hTERT activation in normal and pathogenic conditions., Competing Interests: Declaration of interests S.C. is a scientific advisor for Rejuvas Biotech India Pvt. Ltd., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Prognostic biomarkers for prostate cancer are needed to improve prediction of disease course and guide treatment decisions. However, biomarker development is complicated by the common multifocality and heterogeneity of the disease. We aimed to determine the prognostic value of candidate biomarkers transcriptional regulator ERG and related ETS family genes, while considering tumor heterogeneity. In a multisampled, prospective, and treatment-naïve radical prostatectomy cohort from one tertiary center (2010-2012, median follow-up 8.1 years), we analyzed ERG protein (480 patients; 2047 tissue cores), and RNA of several ETS genes in a subcohort (165 patients; 778 fresh-frozen tissue samples). Intra- and interfocal heterogeneity was identified in 29% and 33% (ERG protein) and 39% and 27% (ETS RNA) of patients, respectively. ERG protein and ETS RNA was identified exclusively in a nonindex tumor in 31% and 32% of patients, respectively. ERG protein demonstrated independent prognostic value in predicting biochemical (P = 0.04) and clinical recurrence (P = 0.004) and appeared to have greatest prognostic value for patients with Grade Groups 4-5. In conclusion, when heterogeneity is considered, ERG protein is a robust prognostic biomarker for prostate cancer., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

FGF and anti-BMP signals from the Spemann organizer of mesodermal origin are essential for Xenopus neural development from gastrula ectoderm. However, the detailed cellular and molecular mechanisms of signaling, especially those underlying the neural induction process, are still controversial. We show here that the expression of early neural marker genes such as sox2 and otx2 is suppressed both in vivo and in vitro, when ectoderm cells are loaded with a dominant-negative construct of Ets transcription factors or a translation-blocking antisense FGF2 MO or FGF8 MO, respectively. This indicates that the expression of these FGF signaling molecules in ectoderm cells contributes significantly to neural induction, in contrast to the "neural default model" that has been emphasized, in which anti-BMP signaling from the organizer plays a major role in the neural induction in Xenopus. Our results indicate that cell-autonomous FGF signaling between ectoderm cells, rather than paracrine signaling from organizer cells, directly induces the expression of sox2 and otx2 via the FGF2, FGF8/MAPK/Ets pathway at very low signaling levels. This is independent of inhibiting BMP signaling via the FGF/MAPK/Smad pathway, which has been proposed as the primary pathway for FGF signaling in Xenopus neural induction. Using cultured ectoderm cells, we also obtained results suggesting that the mode of contribution of FGF signaling to neural development is altered during the subsequent neural patterning stage. As we increase the amounts of FGF in the culture medium, anterior neural genes activated at low FGF signaling levels are suppressed, and instead position-specific, more posterior neural genes are activated in a dose-dependent manner via the FGF/MAPK/Ets pathway. These results support the claim that morphogenic FGFs from the organizer diffuse in a paracrine manner through the plane of the induced neuroectoderm, causing anteroposterior patterning of neural tissue., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

In cancer biology, ETS transcription factors promote tumorigenesis by mediating transcriptional regulation of numerous genes via the conserved ETS DNA-binding domain. MicroRNAs (miRNAs) act as posttranscriptional regulators to regulate various tumor-promoting or tumor-suppressing factors. Interactions between ETS factors and miRNAs regulate complex tumor-promoting and tumor-suppressing networks. This review discusses the progress of ETS factors and miRNAs in cancer research in detail. We focused on characterizing the interaction of the miRNA/ETS axis with competing endogenous RNAs (ceRNAs) and its regulation in posttranslational modifications (PTMs) and the tumor microenvironment (TME). Finally, we explore the prospect of ETS factors and miRNAs in therapeutic intervention. Generally, interactions between ETS factors and miRNAs provide fresh perspectives into tumorigenesis and development and novel therapeutic approaches for malignant tumors., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Smoking, exposure to environmental tobacco smoke (ETS) and occupational exposure to vapours, gases, dusts or fumes (VGDF) increase asthma symptoms. The impact of combined exposure is less well established. We aimed to evaluate the risk of combined exposure to smoking, ETS and VGDF on the prevalence of current asthma and asthma-related symptoms with a postal survey among a random population of 16,000 adults, aged 20-69 years (response rate 51.5%). The 836 responders with physician-diagnosed asthma were included in the analysis. Of them, 81.9% had current asthma defined as physician-diagnosed asthma with current asthma medication use or reported symptoms. There was a consistently increasing trend in the prevalence of current asthma by increased exposure. The highest prevalence of multiple symptoms was in smokers with VGDF exposure (92.1%) compared to the unexposed (73.9%, p = 0.001). In logistic regression analysis, combined exposure to several exposures increased the risk in all analysed symptoms (p = 0.002-0.007). In conclusion, smoking and exposure to ETS or VGDF increased the prevalence of current asthma and multiple symptoms. The combined exposure carried the highest risk. Preventive strategies are called for to mitigate exposure to tobacco smoke and VGDF., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Development of the Drosophila visceral muscle depends on Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) signaling, which specifies founder cells (FCs) in the circular visceral mesoderm (VM). Although Alk activation by its ligand Jelly Belly (Jeb) is well characterized, few target molecules have been identified. Here, we used targeted DamID (TaDa) to identify Alk targets in embryos overexpressing Jeb versus embryos with abrogated Alk activity, revealing differentially expressed genes, including the Snail/Scratch family transcription factor Kahuli (Kah). We confirmed Kah mRNA and protein expression in the VM, and identified midgut constriction defects in Kah mutants similar to those of pointed (pnt). ChIP and RNA-Seq data analysis defined a Kah target-binding site similar to that of Snail, and identified a set of common target genes putatively regulated by Kah and Pnt during midgut constriction. Taken together, we report a rich dataset of Alk-responsive loci in the embryonic VM and functionally characterize the role of Kah in the regulation of embryonic midgut morphogenesis., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Undifferentiated small round cell sarcomas represent a heterogeneous group of mesenchymal neoplasms. While imprecise, this term nevertheless provides a useful framework for conceptualizing these tumors. This article highlights current trends in their classification based on morphology, immunohistochemistry, and advanced molecular techniques. As next-generation sequencing becomes commonplace in diagnostic laboratories pathologists can expect to differentiate these tumors with increasing confidence, and actively contribute to related discoveries. Ultimately, when synthesized with rigorous clinical outcome data and other investigative techniques, a more robust landscape for the molecular diagnosis and classification of undifferentiated small round cell sarcomas is expected to emerge in the future., Competing Interests: Disclosure Not applicable., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The organelle of eukaryotes is a finely regulated system. Once disturbed, it activates the specific autoregulatory systems, namely, organelle autoregulation. Among which, the Golgi stress response accounts for one. When the abundance and capacity of the Golgi apparatus are insufficient compared with cellular demand, the Golgi stress response is activated to enhance the function of the Golgi apparatus. Although the molecular mechanism of the Golgi stress response has not been well characterized yet, it seems to be an important part of the mammalian stress response. In this review, we discuss the current status of research on the six pathways of the mammalian Golgi stress response (the TFE3, heat shock protein 47, CREB3, E26 transformation specific, proteoglycan, and mucin pathways), which regulate the general function of the Golgi apparatus, anti-apoptosis, pro-apoptosis, proteoglycan glycosylation, and mucin glycosylation, respectively., (© 2021 International Union of Biochemistry and Molecular Biology.)

Objective: We aim to examine the adequacy of an innovation state-space modeling framework (called TBATS) in forecasting the long-term epidemic seasonality and trends of hemorrhagic fever with renal syndrome (HFRS)., Methods: The HFRS morbidity data from January 1995 to December 2020 were taken, and subsequently, the data were split into six different training and testing segments (including 12, 24, 36, 60, 84, and 108 holdout monthly data) to investigate its predictive ability of the TBATS method, and its forecasting performance was compared with the seasonal autoregressive integrated moving average (SARIMA)., Results: The TBATS (0.27, {0,0}, -, {<12,4>}) and SARIMA (0,1,(1,3))(0,1,1) 12 were selected as the best TBATS and SARIMA methods, respectively, for the 12-step ahead prediction. The mean absolute deviation, root mean square error, mean absolute percentage error, mean error rate, and root mean square percentage error were 91.799, 14.772, 123.653, 0.129, and 0.193, respectively, for the preferred TBATS method and were 144.734, 25.049, 161.671, 0.203, and 0.296, respectively, for the preferred SARIMA method. Likewise, for the 24-, 36-, 60-, 84-, and 108-step ahead predictions, the preferred TBATS methods produced smaller forecasting errors over the best SARIMA methods. Further validations also suggested that the TBATS model outperformed the Error-Trend-Seasonal framework, with little exception. HFRS had dual seasonal behaviors, peaking in May-June and November-December. Overall a notable decrease in the HFRS morbidity was seen during the study period (average annual percentage change=-6.767, 95% confidence intervals: -10.592 to -2.778), and yet different stages had different variation trends. Besides, the TBATS model predicted a plateau in the HFRS morbidity in the next ten years., Conclusion: The TBATS approach outperforms the SARIMA approach in estimating the long-term epidemic seasonality and trends of HFRS, which is capable of being deemed as a promising alternative to help stakeholders to inform future preventive policy or practical solutions to tackle the evolving scenarios., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Xiao et al.)

Background: The prognostic potential of early tumor shrinkage (ETS) and depth of response (DpR) in pancreatic cancer (PC) is unclear. Here, we recruited 90 patients with recurrent and metastatic PC (RMPC) who had received chemotherapy as first-line therapy to assess the prognostic potential of these markers., Methods: ETS is characterized as a ≥ 20% depletion in the sum-of-the-longest-diameters (SLD) of measurable tumor lesions at 6-12 weeks than the baseline. DpR is the maximum shrinkage (%) from the baseline to nadir. We evaluated corrections in ETS and DpR with survival., Results: Of the 63 patients in which ETS assessment was possible, 21 (33.3%) achieved ETS. We found a significant association between the incidence of ETS and an improved rate of progression-free survival (PFS; 6.5 vs. 2.2 months; p < 0.001) and overall survival (OS; 12.1 vs. 6.0 months; p = 0.014). The median value of DpR was - 23.66%. DpR was also related to improved PFS (9.3 vs. 3.1 months; p < 0.001) and OS (18.2 vs. 7.3 months; p < 0.001). Patients who had distant metastasis, not local recurrence, with ETS showed markedly better outcomes. In a multivariate model, both ETS and DpR were independent predictors of OS in the whole population., Conclusions: ETS and DpR may predict favorable outcomes for RMPC patients who had received chemotherapy as first-line therapy, independent of the agents used. Further studies on the exploratory analyses of the optimum ETS cut-off value in recurrent PC patients to predict favorable clinical outcomes are required., (© 2021. The Author(s).)

Ets homologous factor (EHF) is a member of the epithelial-specific Ets (ESE) family of transcription factors. To investigate its role in development and epithelial homeostasis, we generated a series of novel mouse strains in which the Ets DNA-binding domain of Ehf was deleted in all tissues (Ehf-/-) or specifically in the gut epithelium. Ehf-/- mice were born at the expected Mendelian ratio, but showed reduced body weight gain, and developed a series of pathologies requiring most Ehf-/- mice to reach an ethical endpoint before reaching 1 year of age. These included papillomas in the facial skin, abscesses in the preputial glands (males) or vulvae (females), and corneal ulcers. Ehf-/-mice also displayed increased susceptibility to experimentally induced colitis, which was confirmed in intestinal-specific Ehf knockout mice. Gut-specific Ehf deletion also impaired goblet cell differentiation, induced extensive transcriptional reprogramming in the colonic epithelium and enhanced Apc-initiated adenoma development. The Ets DNA-binding domain of EHF is therefore essential for postnatal homeostasis of the epidermis and colonic epithelium, and its loss promotes colonic tumour development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

E74-like factor five (ELF5) is a basic transcription factor that plays a key role in breast tissue and gland development. However, the molecular mechanism of ELF5 in breast cancer cells has not been elucidated. In this study, we examined the effect of ELF5 on the human breast cancer cell lines MCF-7 and T47D and confirmed that ELF5 can inhibit cell proliferation, migration and invasion. In further research, the relationship between ELF5 and CD24 was characterized in breast cancer cells. We found that CD24 was a target gene of ELF5 through chromatin immunoprecipitation (ChIP) -Sequence assays, and proved that ELF5 could bind to the ETS cis-element on the proximal promoter of the CD24 gene and regulate the expression of CD24. Moreover, overexpression of ELF5 in MCF-7 cells significantly increased both the mRNA and protein levels of CD24, while knockdown of CD24 expression restored cell proliferation, migration and invasion through adaptive ELF5 expression in MCF-7 cells. Therefore, these data suggest that ELF5 inhibits migration and invasion of breast cancer cells by regulating CD24 expression, which make provides a molecular mechanism for ELF5 to inhibit breast cancer from a new perspective and provides further theoretical support for the treatment and prevention of breast cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The mechanism of extracellular traps (ETs) is important in the cellular response against bacteria. Thus, in the present study, we describe for the first time the capacity of the Nile tilapia (Oreochromis niloticus) microglia in the formation of ETs in Weissella cibaria in vitro infection. Thus, we evaluated the ultrastructure of the microglia culture and observed the formation of ETs 6 h after stimulation with lipopolysaccharide (LPS) and during the course of infection. Our results shed light on the mechanism of formation of ETs in the microglia of teleost fish and the ability of W. cibaria to infect these cells., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

China today has an urgent need to develop low-carbon policies that also address local air pollution. This study uses a difference-in-differences model to estimate the extent to which China's Emissions Trading Scheme (ETS), which directly addresses CO 2 emissions, has also generated cobenefits by reducing PM 2.5 . Using monthly PM 2.5 concentration and weather data for 297 Chinese cities from January 2005 to December 2017, we find that (1) China's ETS has reduced PM 2.5 concentrations by 4.8%, and this reduction effect is strongest in summer. The results are confirmed by robustness tests including propensity score matching, mahalanobis distance matching, two placebo tests, and controlling atmospheric policies. (2) The ETS pilots have positive spillovers on neighboring nonpilot cities within 300 km of the pilot cites, especially for those downwind neighboring nonpilot cities, and the ETS's cobenefits are primarily a result of firms adopting abatement activities and adjusting industrial structure. (3) The cobenefits of China's ETS pilots are greater in regions with larger carbon trading volume and higher carbon trading price. (4) The reduction in PM 2.5 concentration caused by China's ETS may have avoided 23,363 deaths and saved $41.38 billion annually in GDP.

Correct vascular differentiation requires distinct patterns of gene expression in different subtypes of endothelial cells. Members of the ETS transcription factor family are essential for the transcriptional activation of arterial and angiogenesis-specific gene regulatory elements, leading to the hypothesis that they play lineage-defining roles in arterial and angiogenic differentiation directly downstream of VEGFA signalling. However, an alternative explanation is that ETS binding at enhancers and promoters is a general requirement for activation of many endothelial genes regardless of expression pattern, with subtype-specificity provided by additional factors. Here we use analysis of Ephb4 and Coup-TFII (Nr2f2) vein-specific enhancers to demonstrate that ETS factors are equally essential for vein, arterial and angiogenic-specific enhancer activity patterns. Further, we show that ETS factor binding at these vein-specific enhancers is enriched by VEGFA signalling, similar to that seen at arterial and angiogenic enhancers. However, while arterial and angiogenic enhancers can be activated by VEGFA in vivo, the Ephb4 and Coup-TFII venous enhancers are not, suggesting that the specificity of VEGFA-induced arterial and angiogenic enhancer activity occurs via non-ETS transcription factors. These results support a model in which ETS factors are not the primary regulators of specific patterns of gene expression in different endothelial subtypes., Competing Interests: Declaration of competing interest No competing interests declared., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)