Transcriptomic analyses of treatment-naïve pediatric ulcerative colitis patients and exploration of underlying disease pathogenesis.

BACKGROUND: Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease of nonspecific origin. This study used an RNA-Sequencing (RNA-Seq) approach to evaluate the transcriptomic landscape of a well-stratified treatment-naïve pediatric UC patient population by comparing them with healthy control children. The data were analyzed to evaluate the mechanisms driving UC-related intestinal inflammation and fibrosis. METHODS: Intestinal mucosal samples from five pediatric UC patients and five healthy controls were analyzed by RNA-Seq, and results were verified by qPCR. A CRISPR/Cas9 approach was used to knock out the expression of HLA-DRB5, and molecular biology techniques were used for additional mechanistic studies. RESULTS: In these analyses, 2290 genes were found to be differentially expressed between the UC and control samples, of which 1258 and 1032 were upregulated and downregulated, respectively. Gene Ontology analysis showed that these genes were enriched in extracellular matrix (ECM)-related processes and that 7 of 8 differentially expressed genes of interest (PIK3CD, IL1ß, IL1α, TIMP1, MMP1, MMP12, COL6A3, and HLADRB5) were upregulated and involved in ECM-receptor interaction and inflammatory bowel disease-related pathways. Increased HLA-DRB5 expression driven by intestinal bacteria was found to promote IL-1α secretion, leading to intestinal inflammation and fibrosis, suggesting a possible target for the treatment of UC. CONCLUSION: These data suggest that intestinal inflammation is present in pediatric UC patients for extended periods before the onset of symptoms, and intestinal fibrosis begins even during the early stages of UC. Intestinal bacteria were also found to trigger intestinal inflammation and fibrosis, with HLA-DRB5 playing a central role in this process.

Feed-in tariffs and the carbon emission trading scheme under China's peak emission target: A dynamic CGE analysis for the development of renewable electricity.

Thermal power industry is one of China's leading sources of carbon emissions. China has launched a national carbon emissions trading scheme (ETS) and renewable energy incentive programs to achieve its peak emission target by 2030. However, since 2021, China no longer provides a central feed-in tariff (FIT) for new centrally located solar photovoltaic (PV) power plants, commercial and industrially distributed PV projects, and newly approved onshore wind power projects. This change in policy may threaten China's carbon reduction targets and economic development. Using a dynamic computable general equilibrium (CGE) model, we assess the combined effects of carbon ETS and FIT on China's electricity sector, carbon emission peak target, renewable energy and economic development. In terms of policy overlap and integration, we analyze the impact of these policies and estimate how to coordinate FIT and carbon ETS policies to ensure their effectiveness. Results show that the overall effects of FIT subsidies are superior to phasing-out FIT scenarios. The fiscal pressure caused by FIT is lower than its actual expenditure because it stimulates economic activity and boosts government revenue. However, considering the multiplier effect of the FIT on promoting government revenue growth and GDP growth, the most effective FIT should be terminated in 2025, followed by subsidies ending in 2030 and 2035.

How financial clustering influences China's green development: Mechanism investigation and empirical discussion.

Understanding the significance of financial clustering in the context of green development holds immense importance for China as it strives towards achieving high-quality green development. Using a balanced panel dataset encompassing China's 283 cities from 2009 to 2020, we aim to explore the impact of financial clustering on green development from both linear and nonlinear perspectives. Empirical evidence suggests that when the level of financial clustering increases by 1%, the city-level green development increases by 0.1012%. A mediation effect model certifies that there are three essential channels through which financial clustering robustly boosts green development: technical, structural and scale effects. Subsequently, a novel program handling endogeneity is designed and verifies the nonlinear nexus between financial clustering and green development. Moreover, the spatial Durbin model demonstrates that financial clustering significantly sustains local green development, despite its relatively weak spill over effects. Heterogeneity analysis presents that the promoting effect is particularly predominant in Central China, as well as in cities characterized by high levels of financial clustering and large population sizes.

Insight into the Humidity Dependent Pseudo-n-Type Response of p-CuScO2 toward Ammonia.

Metal oxide semiconductor (MOS) gas sensors operated at room temperature (RT) hold great promise for environmental monitoring in the emerging smart society. An in-depth understanding of the gas/MOS interfacial charge exchange under the ambient moist atmosphere is essential for subsequent molecule recognition. Herein, delafossite p-CuScO2 with a unique oxygen intercalation property was utilized. Eight orders of resistance tuning could be rationally achieved via controlling oxygen intercalation realized by air annealing (without altering the size and morphological properties), which allows extraction of both the intrinsic (gas/MOS interaction, p-type response) and extrinsic (gas/H2O/MOS interaction, pseudo-n-type response) sensing mechanisms upon exposure to ammonia molecules. This work could provide an insight into the underlying sensing mechanism of RT sensors working in an ambient moist atmosphere, and the unique n- to p-type switching contains rich molecule related features that could be potentially explored for molecule recognition.

Reciprocal costimulatory molecules control the activation of mucosal type 3 innate lymphoid cells during engagement with B cells.

Innate lymphoid cells (ILCs) are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells. Inducible T-cell costimulator (ICOS) is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues. However, the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear. Here, we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s. ICOS costimulation enhanced the survival, proliferation, and capacity of ILC3s to produce cytokines (IL-22, IL-17A, IFN-γ, TNF, and GM-CSF). Via synergistic effects of ICOS and CD40 signaling, B cells promoted ILC3 functions, and ILC3-induced T-cell-independent B-cell IgA and IgM secretion primarily required CD40 signaling. Hence, ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.

The Impacts of COVID-19 Shock on Intergenerational Income Mobility: Evidence from China.

The COVID-19 crisis has caused a huge negative shock to economic activities worldwide, leading to a reduction in income and changes in income distribution. Intergenerational mobility is an important indicator of sustainable social development. This paper explores the short-term impacts of the sudden COVID-19 pandemic on intergenerational income mobility and personal income in China. Using the variation in the number of confirmed cases across provinces, we construct a province-level pandemic intensity index and combine it with individual data from the China Family Panel Studies (CFPS). We apply a general difference-in-difference strategy to identify the causal effect of the pandemic on intergenerational income mobility. We find that personal income is positively related to parental income, and that the COVID-19 crisis has caused a decline in individual income and exacerbated intergenerational income persistence. A more intense COVID-19 pandemic shock is associated with a larger increase in intergenerational income elasticity and intergenerational income rank-rank slope. We found that with one standard deviation increase in local pandemic intensity, the intergenerational income elasticity increases by 0.315 and the intergenerational income rank-rank slope increases by 0.198 on average. The mechanism testing suggests that heterogeneous effects among different groups are the force underlying the results. Low-income, low-skilled, and low-parental-income individuals have suffered a more severe impact from the pandemic shock.

The macro-economic and CO2 emissions impacts of COVID-19 and recovery policies in China.

The outbreak and ongoing evolution of the COVID-19 pandemic have dramatically impacted economic development and CO2 emissions. China is under simultaneous pressure to recover from the outbreak and meet its carbon reduction targets, and the government is endeavouring to stimulate economic recovery through fiscal and monetary policies. This paper uses a computable general equilibrium model to measure the impact on China's economic recovery and carbon emissions by incorporating the pandemic shock and related economic recovery policies of loan prime rate (LPR) and value-added tax (VAT) reduction. The study found that COVID-19 led to a simultaneous shock on China's supply and demand sides in which GDP dropped by 2.62% and carbon emissions fell by 2.53%, compared to the period prior to COVID-19. Although the LPR and VAT reduction effectively mitigated economic loss, the combined LPR and VAT reduction had a more substantial effect on boosting GDP than the single policies. The VAT cut expands production and was used to overcome supply-side shocks, while lowering LPR mitigates the damage of demand-side shocks. Compared to the VAT reduction policy, reduced LPR has smaller carbon emissions per unit of GDP output. Consequently, we recommend that the government concentrate on a combination of policies to navigate pandemic shocks, as the two economic stimulus policies are confirmed to complement one another in terms of strengths and shortcomings.

Synergistic effect of carbon ETS and carbon tax under China's peak emission target: A dynamic CGE analysis.

Global warming resulting from greenhouse gas emissions poses threats to humankind and has become a worldwide issue. As the top CO2 emitter in the world, China has committed to achieving its carbon emission peak by no later than 2030; in this context, how to best use and apply carbon emission reduction policy is particularly critical. By constructing a dynamic computable general equilibrium (CGE) model, we first examine a pure ETS included only the electricity sector in 2021, and the eight sectors starting in 2022, considering a declining carbon intensity rate of 4.5% and a higher rate of 4.8%. With the carbon intensity rates of 4.3% and 4.5%, we further evaluate two-hybrid systems of the carbon tax and carbon ETS, where the carbon tax of 10 yuan per ton is the starting levied rate in 2022 and increases at 4 yuan per ton year by year. The results proved that hybrid emission reduction policy can help reach a carbon emissions peak before 2030 and do so at a lower economic cost compared to the effect of pure carbon ETS. Besides, the coordinated use of a carbon tax and a carbon ETS can promote optimization of energy consumption structures and accelerate the decline of energy intensity and carbon intensity; this can contribute to curbing the growth of total energy consumption and total carbon emissions.

An input-output structural decomposition analysis of changes in China's renewable energy consumption.

Governments actively encourage renewable energy use to deal with climate change and achieve carbon emission reduction targets. It is crucial to find out the driving factors that affect the utilization of renewable energy. Therefore, based on China's 2010-2016 input-output table, this paper uses the input-output model and structural decomposition analysis (SDA) to analyze the driving factors of renewable energy changes in the production end, household end, and the aggregate economy. The results show that the changes in the consumption structure (F) is the most crucial factor for renewable energy use, followed by technology progress (T) and final demand per capita (V). Sector SEHW (supply of electric power, heat power, and water) and MCRP (manufacture of coke and refined petroleum products) are the two vital sectors to achieve China's energy transition of the production level. However, as for households, the proportion of renewable energy has been declining. Hence, the government should promote renewable energy use and achieve the green transition in production and household levels.

Mesenchymal Stem Cells Alleviate Inflammatory Bowel Disease Via Tr1 Cells.

Mesenchymal stem cells (MSCs) have been used to achieve exciting therapeutic outcomes in many animal studies and clinical trials for various autoimmune diseases, including inflammatory bowel disease (IBD). Type 1 regulatory T (Tr1) cells are the main source of interleukin (IL) 10 in the intestine. Whether Tr1 cells are involved during MSC-mediated IBD treatment is unclear. We treated a murine model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis with human umbilical cord-derived MSCs (hUCMSCs) and found that the disease severity was alleviated significantly in a dose-dependent manner. hUCMSCs increased the proportion of Tr1 cells and decreased that of T helper (Th)-1 and Th17 cells in the spleen and mesenteric lymph nodes in different stages of colitis. We found that the upregulation of Tr1 cells by hUCMSCs was abrogated after blocking indoleamine-2,3-dioxygenase (IDO), and IDO knockdown in hUCMSCs reversed the increase in Tr1 cell proportions caused by hUCMSCs in colitis. Moreover, hUCMSCs inhibited apoptosis and promoted the proliferation of Tr1 cells. Our results suggest that Tr1 cells play an important role in the amelioration of IBD by MSCs, and they are the target population for the alleviation of IBD by MSCs, providing meaningful references for the study of therapeutic mechanisms of MSCs in other inflammatory diseases.

Correlation Between Immune Lymphoid Cells and Plasmacytoid Dendritic Cells in Human Colon Cancer.

Background: Innate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumor types and are correlated with poor prognosis. pDCs can promote HIV-1-induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in human colon cancer and their correlation with other immune cells, especially pDCs, remain unclear. Methods: We characterized ILCs and pDCs in the tumor microenvironment of 58 colon cancer patients by flow cytometry and selected three patients for RNA sequencing. Results: ILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological stage. There was a negative correlation between the numbers of ILC3s and pDCs in tumor tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumor immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumor-like microenvironment. Conclusions: One of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.

Comprehensive analysis of long non­coding RNA using an associated competitive endogenous RNA network in Wilms tumor.

Wilms tumor (WT) is the most common malignant renal neoplasm in children; however, the underlying molecular mechanisms are not well understood. According to the competing endogenous RNA (ceRNA) theory, long non­coding RNAs (lncRNAs) can regulate the expression of target genes by adsorbing microRNAs (miRNAs/miRs). However, the role of lncRNAs in WT has not been fully elucidated. The aim of the present study was to construct a ceRNA network to identify the potential lncRNAs involved in WT. The expression profiles of lncRNAs, miRNAs and mRNAs in 120 WT and six normal tissues were obtained from the Therapeutically Applicable Research to Generate Effective Treatments database. A total of 442 lncRNAs, 214 miRNAs and 4,912 mRNAs were identified as differentially expressed in WT and were enriched in 472 Gene Ontology terms (355 biological processes, 89 cellular components and 29 molecular functions) and 18 Kyoto Encyclopedia of Genes and Genomes pathways. A lncRNA­miRNA­mRNA ceRNA network of WT consisting of with 32 lncRNAs, 14 miRNAs and 158 mRNAs was constructed, based on the bioinformatics analysis of the miR target prediction database and the miRNAcode, miRTarBase and TargetScan databases. Subsequently, three lncRNAs, three miRNAs and 17 mRNAs, which had a significant effect on the overall survival rate of patients with WT, were identified based on the survival analysis. The three lncRNAs were also differentially expressed in the late and early stages of WT and were validated using the GSE66405 dataset obtained from the Gene Expression Omnibus database. In conclusion, the present study generated a specific lncRNA­related ceRNA network of WT, which may provide a novel perspective on the molecular mechanisms underlying the progression and prognosis of the disease.

Case report on alimentary tract hemorrhage and liver injury after therapy with oseltamivir: A case report.

RATIONALE: Oseltamivir-induced alimentary tract hemorrhage and liver injury are rarely reported in children and adult individuals. In this study, we described the clinical features and outcomes of oseltamivir-induced alimentary tract hemorrhage and liver injury in a child. PATIENT CONCERNS: Here, we present a case of a 6-year-old Asian boy with hematemesis and elevated alanine aminotransferase (ALT) (80 U/L) and aspartate aminotransferase (AST) (69 U/L) levels on day 2 of oseltamivir administration. The presence of alimentary tract hemorrhage and liver injury was diagnosed. The ALT level reached 1931.3 U/L, accompanied by an increase in total bilirubin (TBIL) to 53.3 µmol/L on day 15 after oseltamivir administration. Additional tests were performed to determine the presence of viruses that can cause hepatitis and autoantibodies, and the results from these tests were all negative. DIAGNOSIS: Drug-induced liver injury was considered. INTERVENTIONS: This patient was treated with compound glycyrrhizin and reduced glutathione and glucocorticoid. OUTCOMES: The liver enzymes recovered within 6 weeks without any symptoms of liver-related diseases after treatment with glucocorticoid. This treatment therefore helps reduce ALT and TBIL levels and protects the liver from further injury. LESSONS: Oral oseltamivir is widely used to treat influenza and the adverse effects of this drug were mostly mild. However, clinicians should always be alert for oseltamivir-induced alimentary tract hemorrhage and liver injury when prescribing oseltamivir for children.