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1.
Heliyon ; 10(9): e30712, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38765131

ABSTRACT

Objectives: We aimed to evaluate and compare the diagnostic performance of RNA-mNGS and DNA-mNGS workflow in bacterial pneumonia, fungal pneumonia and tuberculosis. Methods: A total of 134 cases suspected pneumonia undergoing both DNA and RNA based mNGS of bronchoalveolar lavage fluid (BALF) and also traditional etiological examination were evaluated retrospectively.Sensitivity, specificity, PPV, NPV and accuracy rate of DNA and RNA based mNGS were estimated. Results: In the diagnosis performance of bacterial pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS(82.3 % vs. 61.9 %, P < 0.01). There was no significant difference of sensitivity between the two process(71.4 % vs. 85.7 %, P = 0.375).In the diagnosis performance of fungal pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS (72.3 % vs. 27.3 %,p < 0.001). There was no significant difference of sensitivity between the two process(96.5 % vs. 98.8 %,p = 0.125).In the diagnosis performance of tuberculosis in LRTIs,the sensitivity of DNA-mNGS was higher than that of RNA-mNGS (91.7 % vs. 33.3 %,p = 0.016),the specificity was similar in the two process (100 %). Conclusions: RNA-mNGS may reduced the misdiagnosis rate of bacterial and fungal pathogens in LRTIs.Compared to RNA-mNGS, DNA-mNGS may could improve the diagnostic rate of tuberculosis.

2.
Sci Total Environ ; 939: 173320, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-38777055

ABSTRACT

Climate change has profoundly impacted Tibetan Plateau grasslands, necessitating a comprehensive analysis of the historical and future responses across diverse grassland types, with the integration of an elevated atmospheric CO2 concentration (eCO2) and climatic factors. In this study, the response of the Tibetan Plateau grassland was investigated, with a focus on the fractional vegetation cover (FVC). By employing an enhanced ecohydrological model for the baseline (1985-2014) and future (2031-2070) periods under shared socioeconomic pathway (SSP) scenarios, the responses of FVC to climate change were predicted across all grassland types. The alpine steppe exhibited the most rapid growth, with average FVC increases projected to reach 37 ± 7 %-81 ± 15 % for alpine meadow, 82 ± 22 %-185 ± 55 % for alpine steppe, and 50 ± 8 %-95 ± 23 % for temperate grassland by the 2060s. During the baseline, eCO2 primarily caused the FVC increases in alpine meadow and temperate grassland, while warming governed alpine steppe growth. Interannual variability in the FVC of alpine grasslands was temperature-driven, while that of the temperate grasslands was driven by precipitation. An increase in the FVC of the alpine steppe was caused by warming under both low- and high-emissions scenarios. For the alpine meadow and temperate grasslands, precipitation was dominant for FVC changes in the SSP1-2.6 scenario, and eCO2 was dominant in the SSP3-7.0 and SSP5-8.5 scenarios. These findings provide a vital foundation for grassland management, carbon cycling comprehension, and vegetation feedback estimations on the Tibetan Plateau.

3.
Heliyon ; 10(5): e26471, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38439891

ABSTRACT

The purpose of this study is to expand and deepen research in the field of safety production, explore the role of enterprises as decision-making entities in safety production, analyze the role of different types of decision-making behaviors in the process of enterprise safety production, and provide certain theoretical guidance for multi-agent decision-making in safety production. By summarizing and comparing the existing dual system of supply chain safety management, this study proposes dividing supply chain safety management into the two categories of safety organization and safety research and development (safety R&D) in the context of digitalization. Differential equations are established to describe a two-level supply chain safety management problem including manufacturers and suppliers. The research results show that, compared with the Nash equilibrium, when there are strong manufacturers involved in safety management cooperation, the manufacturer's safety R&D subsidy to suppliers improves the total revenue of the supply chain. When the manufacturer's safety organization supervision efficiency is high, the Stackelberg equilibrium is lower. It is a Pareto improvement for the manufacturer to supervise the supplier's safety organization to the Nash equilibrium. In the case of dual safety cooperation in the supply chain, when there are strong manufacturers, R&D subsidies have a crowding out effect on the safety organization cooperation. Finally, based on the example analysis, relevant suggestions are put forward for supply chain safety management.

4.
Front Public Health ; 12: 1295536, 2024.
Article in English | MEDLINE | ID: mdl-38384886

ABSTRACT

Due to the clustering of risk factors, industrial park safety accidents can easily trigger a domino effect. Work safety investment is the foundation of enterprise work safety in industrial parks. Therefore, increasing the work safety investment of enterprises in industrial parks is the key condition to prevent accidents. However, due to the typical negative externalities of industrial park work safety accidents, the decision-making process of work safety in park enterprises is influenced by other enterprises within the park, including imitation behaviors. This makes the decision-making of work safety in park enterprises very specific. In order to clarify the influencing factors and effects of work safety investment in industrial park enterprises, this study uses a behavioral experiment method and conducts decision-making experiments using the experimental platform O-Tree. The study recruits 76 participants who play the role of decision-makers in park enterprises. This study uses a lottery price experiment and a dictator experiment to measure the risk preference and altruism preference of the participants, respectively. The study introduces the real background of work safety investment in industrial park enterprises and collects data on work safety investment by the participants in different experimental scenarios. The research results show that the safety attitudes of decision-makers, altruism preference, accident experience, government work safety supervision, park management measures, and safety benefits positively influence work safety investment in park enterprises. The risk preference of decision-makers and the resource capability of work safety negatively influence work safety investment in park enterprises. Work safety investment in park enterprises is influenced by the work safety investment of other enterprises within the park.


Subject(s)
Industry , Safety Management , Humans , Accidents, Occupational/prevention & control , Risk Factors
5.
Eur J Med Res ; 29(1): 5, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38173033

ABSTRACT

BACKGROUND: Mechanical power (MP) is the total energy released into the entire respiratory system per minute which mainly comprises three components: elastic static power, Elastic dynamic power and resistive power. However, the energy to overcome resistance to the gas flow is not the key factor in causing lung injury, but the elastic power (EP) which generates the baseline stretch of the lung fibers and overcomes respiratory system elastance may be closely related to the ARDS severity. Thus, this study aimed to investigate whether EP is superior to other ventilator variables for predicting the severity of lung injury in ARDS patients. METHODS: We retrieved patient data from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The retrieved data involved adults (≥ 18 years) diagnosed with ARDS and subjected to invasive mechanical ventilation for ≥ 48 h. We employed univariate and multivariate logistic regression analyses to investigate the correlation between EP and development of moderate-severe ARDS. Furthermore, we utilized restricted cubic spline models to assess whether there is a linear association between EP and incidence of moderate-severe ARDS. In addition, we employed a stratified linear regression model and likelihood ratio test in subgroups to identify potential modifications and interactions. RESULTS: Moderate-severe ARDS occurred in 73.4% (296/403) of the patients analyzed. EP and MP were significantly associated with moderate-severe ARDS (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.15-1.28, p < 0.001; and OR 1.15, 95%CI 1.11-1.20, p < 0.001; respectively), but EP showed a higher area-under-curve (95%CI 0.72-0.82, p < 0.001) than plateau pressure, driving pressure, and static lung compliance in predicting ARDS severity. The optimal cutoff value for EP was 14.6 J/min with a sensitivity of 75% and specificity of 66%. Quartile analysis revealed that the relationship between EP and ARDS severity remained robust and reliable in subgroup analysis. CONCLUSION: EP is a good ventilator variable associated with ARDS severity and can be used for grading ARDS severity. Close monitoring of EP is advised in patients undergoing mechanical ventilation. Additional experimental trials are needed to investigate whether adjusting ventilator variables according to EP can yield significant improvements in clinical outcomes.


Subject(s)
Lung Injury , Respiratory Distress Syndrome , Adult , Humans , Respiration, Artificial , Retrospective Studies , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/epidemiology , Lung
6.
Heliyon ; 9(10): e20494, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37810846

ABSTRACT

The disclosure of work safety information of listed companies in high-risk industries is an important aspect of their social responsibility, and it is also an inevitable requirement to meet the right of stakeholders to know, which has a far-reaching impact on the development of enterprises. In order to clarify the impact mechanism of work safety information disclosure on enterprise performance of listed companies in high-risk industries. 222 listed companies in high-risk industries were taken as the research object, and the multiple regression analysis method was used to analyze the relationship between the level of work safety information disclosure of enterprises and their financial performance, safety performance and social reputation. The results show that the work safety information disclosure of listed companies in high-risk industries has a positive impact on corporate financial performance, safety performance and social reputation; unabsorbed slack resources have a positive U-shaped regulatory effect on work safety information disclosure and enterprise social reputation; The shareholding ratio of institutional investors has an inverted U-shaped regulatory effect on the positive relationship between work safety information disclosure and enterprise social reputation. This study has enriched the theoretical and practical exploration of research on work safety information disclosure. It can help improve the level of work safety information disclosure and safety management in enterprises, while guiding the sustainable development of occupational health and safety within these organizations.

7.
Medicine (Baltimore) ; 102(35): e34851, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37657028

ABSTRACT

Studies have shown that aging significantly impacts tumorigenesis, survival outcome, and treatment efficacy in various tumors, covering high-grade serous ovarian cancer (HGSOC). Therefore, the objective for this investigation is to construct an aging-relevant risk signature for the first time, which will help evaluate the immunogenicity and survival status for patients with HGSOC. Totaling 1727 patients with HGSOC, along with their mRNA genomic data and clinical survival data, were obtained based on 5 independent cohorts. The Lasso-Cox regression model was utilized to identify the aging genes that had the most significant impact on prognosis. The risk signature was developed by integrating the determined gene expression and accordant model weights. Additionally, immunocytes in the microenvironment, signaling pathways, and immune-relevant signatures were assessed based on distinct risk subgroups. Finally, 2 cohorts that underwent treatment with immune checkpoint inhibitor (ICI) were employed to confirm the effects of identified risk signature on ICI efficacy. An aging signature was constructed from 12 relevant genes, which showed improved survival outcomes in low-risk HGSOC patients across discovery and 4 validation cohorts (all P < .05). The low-risk subgroup showed better immunocyte infiltration and higher enrichment of immune pathways and ICI predictors based on further immunology analysis. Notably, in the immunotherapeutic cohorts, low-risk aging signature was observed to link to better immunotherapeutic outcomes and increased response rates. Together, our constructed signature of aging has the potential to assess not only the prognosis outcome and immunogenicity, but also, importantly, the efficacy of ICI treatment. This signature provides valuable insights for prognosis prediction and immunotherapeutic effect evaluation, ultimately promoting individualized treatment for HGSOC patients.


Subject(s)
Cystadenocarcinoma, Serous , Ovarian Neoplasms , Female , Humans , Carcinogenesis , Aging , Cystadenocarcinoma, Serous/genetics , Ovarian Neoplasms/genetics , Tumor Microenvironment/genetics
8.
Heliyon ; 9(6): e16717, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37484320

ABSTRACT

Industrial parks make great contributions to the local economy, society, and culture, but they have also encountered many problems, such as limited resources, the longevity of ecological restoration, and the contagion of safety accidents. As a socioeconomic and ecological composite system formed by the interaction of multiple stakeholders, the solutions to succeed in workplace sustainability in industrial parks are still not known. The purpose of this study is to explore how to integrate existing resources to achieve a win-win situation in industrial park safety and environmental protection issues. According to Actor-network Theory and a systematic search, this study identifies the relevant subjects from selected 24 studies and clarifies the interactions made by these subjects. In sum, this study concludes two main modes of developing workplace sustainability in the park from multiple actors' perspectives: self-regulation of inner park subjects and the driving force of exterior park subjects.

9.
Cell Mol Immunol ; 19(10): 1141-1152, 2022 10.
Article in English | MEDLINE | ID: mdl-36050480

ABSTRACT

Inflammasomes are essential components of the innate immune system and its defense against infections, whereas the dysregulation of inflammasome activation has a detrimental effect on human health. The activation of inflammasomes is subjected to tight regulation to maintain immune homeostasis, yet the underlying mechanism remains elusive. Here, we identify USP3 as a direct deubiquitinating enzyme (DUB) for ASC, the central adapter mediating the assembly and activation of most inflammasomes. USP3 removes the K48-linked ubiquitination on ASC and strengthens its stability by blocking proteasomal degradation. Additionally, USP3 promotes inflammasome activation, and this function was confirmed in mouse models of aluminum (Alum)-induced peritonitis, F. novicida infection and flagellin-induced pneumonia in vivo. Our work unveils that USP3 functions as a key regulator of ASC ubiquitination and maintains the physiological role of ASC in mediating inflammasome activation, and we propose a new mechanism by which the ubiquitination of ASC regulates inflammasome activation.


Subject(s)
CARD Signaling Adaptor Proteins , Inflammasomes , Adaptor Proteins, Signal Transducing/metabolism , Aluminum/metabolism , Animals , Deubiquitinating Enzymes/metabolism , Flagellin/metabolism , Humans , Inflammasomes/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Ubiquitin-Specific Proteases/metabolism
10.
Mol Immunol ; 151: 41-51, 2022 11.
Article in English | MEDLINE | ID: mdl-36084515

ABSTRACT

The inflammation is considered to be the crucial determinants of lesion progression and plaque stability during atherogenesis. Tnfaip2 appears to be a regulator for carcinogenesis and infectious diseases. But its role in atherosclerosis is not clear. Here we first report that Tnfaip2 promotes the formation of atherosclerosis through enhancing the inflammation under oxidative stress condition. Although the endogenous expression of Tnfaip2 was upregulated under oxidative stress condition, the overexpressed Tnfaip2 could promote cells proliferation. This might result from the ability of promoting cells entering G2/M phase. Conversely, the cells proliferation and migration were significantly reduced in Tnfaip2 knockdown cells through inhibiting the activation of NF-κB/MAPK/Akt signaling pathways. However, the efferocytosis increased markedly due to the upregulation of "eat me" receptors, such as CD36, SR-A, and SR-B1, and the downregulation of "don't eat me" signal CD47. As a consequence, Tnfaip2 deficiency in bone marrow-derived cells inhibited atherosclerosis development in Ldlr-/- mice fed a high-fat diet accompanied by decreased inflammatory cytokines and shTnfaip2 could reduce the plaque lesions in ApoE-/- mice. These results indicate that Tnfaip2 might play an important role during atherogenesis.


Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Tumor Necrosis Factors/metabolism , Animals , Apolipoproteins E/metabolism , Atherosclerosis/genetics , Atherosclerosis/metabolism , CD47 Antigen , Cytokines/metabolism , Inflammation , Mice , NF-kappa B/metabolism , Oxidative Stress , Plaque, Atherosclerotic/genetics , Proto-Oncogene Proteins c-akt/metabolism
11.
Front Psychol ; 13: 827694, 2022.
Article in English | MEDLINE | ID: mdl-35783799

ABSTRACT

Recently, the promotion of safety participation (SP) has become a hot spot in behavioral safety research and safety management practice. To explore the relationship between safety leadership (SL) and SP, a theoretical model was established and 33 articles (35 independent samples) on work safety from 2000 to 2021 were selected for a meta-analysis. By evaluating the impact of SL, which incorporates transformational, transactional, and passive leadership styles, on work safety. The results show that SL has a positive impact on both safety climate (SC) and SP. Both safety transactional leadership (STAL) and safety transformational leadership (STFL) positively impact SP, and the impact of STFL is greater, while safety passive leadership (SPL) has no impact on SP. The study establishes that SC plays a partial mediating role between transformational SL and employee SP. Under the condition of a developed economic level or high-risk industry, SL indicated a greater influence on SP. Hence, it is recommended that when enhancing the SP of employees, the influence of the macro environment and SC should not be undermined.

12.
Front Psychol ; 13: 880205, 2022.
Article in English | MEDLINE | ID: mdl-35651561

ABSTRACT

Due to the limited work safety resources and the poor awareness of work safety from business owners with absolute decision-making power, safety accidents frequently occur in Chinese micro and small enterprises (MSEs) in high-risk industries. This study identifies the influencing factors of work safety behavior from MSEs, government safety supervision departments, and work safety service agencies. Based on the theory of planned behavior (TPB), the mechanism model of work safety behavior is built from the aspects of behavior attitude, subjective norms, behavior control cognition, past behaviors, and risk awareness of the enterprise. Based on the interview with nearly 600 MSEs in the east of China over 6 months, the results show that the work safety awareness of the business owner determines the work safety lever of the enterprise, and the work safety behavior of MSEs is a passive restraint behavior. Our findings provide a new perspective on the formation of MSEs' work safety behavior in high-risk industries.

13.
Int J Occup Saf Ergon ; 28(4): 2426-2438, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35635538

ABSTRACT

Employee safety behavior is a basic element of enterprise work safety. The results of accident investigations and risk assessments in enterprises indicate that management factors are some of the most important factors that affect employee safety behavior. The purpose of this study is to explore the relationship between the behavior of front-line managers (FLMs) and employee safety behavior by integrating a qualitative method, i.e., the interpretive structural model (ISM), and a quantitative method, i.e., the Bayesian network (BN). The results of the BN analysis showed that safety incentives and safety communication were the best predictors of safety participation, while safety supervision and safety control were the best predictors of safety compliance. Moreover, the results revealed that an instantaneous improvement of safety communication, safety incentives, safety supervision and safety guidance was the most effective joint measure to reach a high-level of safety behavior of employees in the workplace.


Subject(s)
Safety Management , Workplace , Humans , Bayes Theorem , Safety Management/methods , Health Behavior
14.
Front Public Health ; 10: 841345, 2022.
Article in English | MEDLINE | ID: mdl-35372180

ABSTRACT

Background: Although positive safety leadership has attracted increasingly academic and practical attention due to its critical effects on followers' safety compliance behavior, far fewer steps have been taken to study the safety impact of laissez-faire leadership. Objective: This study examines the relationships between safety-specific leader reward and punishment omission (laissez-faire leadership) and followers' safety compliance, and the mediations of safety-specific distributive justice and role ambiguity. Methods: On a two-wave online survey of 307 workers from high-risk enterprises in China, these relationships were tested by structural equations modeling and bootstrapping procedures. Results: Findings show that safety-specific leader reward omission was negatively associated with followers' safety compliance through the mediating effects of safety-specific distributive justice and role ambiguity. Safety-specific leader punishment omission was also negatively associated with followers' safety compliance through the mediating effect of safety-specific role ambiguity, while safety-specific distributive justice was an insignificant mediator. Originality: The study addresses and closes more gaps by explaining how two contextualized laissez-faire leadership measures relate to followers' safety behaviors, following the contextualization and matching principles between predictors, mediators and criteria, and by revealing two mechanisms behind the detrimental effects of laissez-faire leadership on safety outcomes.


Subject(s)
Leadership , Punishment , Reward , Safety , China , Guideline Adherence , Humans , Social Justice
15.
J Environ Manage ; 313: 114947, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35421694

ABSTRACT

With global climate change, frequent flash droughts have critically impacted vegetation productivity. Based on the new definition on flash drought onset and duration, the temporal and spatial evolution patterns of the flash drought over the Hai River Basin (HRB) was analysed. Among the events, the flash drought in 2019 lasted for 40 days, from the day of the year (DOY) 120 to DOY160, which was the strongest and mainly concentrated in the south-eastern part of the basin. Solar-induced chlorophyll fluorescence (SIF) and vegetation indices were used to explore the responses of different vegetation types to this flash drought. Compared to forest and grassland, the SIF and SIFyield (SIF normalized by the absorbed photosynthetically active radiation (APAR)) values of cropland were more sensitive to water losses and replenishment. By analysing different radiation conditions which would affect SIF and photosynthesis, low radiation was found altering the linear relationship between fluorescence and photosynthesis. The flash drought event caused gross primary productivity (GPP) losses in 40% of the basin and the maximum loss reached 0.16 kg C m-2, indicating that the impact of this flash drought on vegetation productivity was quite serious. The results obtained in this work can be used to understand the mechanisms with which the vegetation photosynthetic capacity responds to flash droughts and to evaluate the impact of flash droughts on terrestrial ecosystems.


Subject(s)
Droughts , Ecosystem , China , Chlorophyll , Fluorescence , Photosynthesis , Rivers , Seasons
16.
Healthcare (Basel) ; 10(2)2022 Jan 22.
Article in English | MEDLINE | ID: mdl-35206830

ABSTRACT

Since the emergence of COVID-19, the aviation sector has been one of the numerous industries which have been affected the most. In this present paper, the thought of death among aviation workers as an indicator of anxiety at a time when the availability, access to, and use of Personal Protective Equipment (PPE) remains paramount to the survival of work in the line of duties and its influence on different work behaviors was assessed. The theoretical foundation of the study was built on the process efficiency theory, attentional interference theory, and the terror management theory (TMT), which focuses on both the psychological and emotional responses exhibited by people due to fear or worry about a specific situation. The study adopted an exploratory study design that incorporates a cross-sectional and self-reported survey among 646 frontline workers across 12 international airlines and the Ghana Airport Company Limited (GACL), Accra, Ghana using simple random sampling and convenient sampling techniques. After all the preliminary tests were performed, the path analysis estimated by Structural Equation Modelling (SEM) indicated that anxiety has a significant influence on workers' stress-adaptive performance and task performance, but recorded no significant causal link with interpersonal performance. The findings indicated that all three proxies of employee work behaviours, which focus on both adaptive and task performance, were significantly related to workers' access, availability, and use of PPE (APPE). The association between anxiety and APPE was also found to be significant. Bootstrapping mediation analysis shows that anxiety partially mediates the influence APPE has on both stress-adaptive performance and task performance, but did not show any mediating effect on the association between APPE and interpersonal performance. Among the three dimensions of death anxiety, both the fear of death (FDE) and death intrusion (DINT) indicated a significant partial mediating effect on the influence APPE has on all three multidimensional constructs of work behaviours. The findings literally prove that worrying about the fatality risk associated with COVID-19 is highly predictive.

17.
Int J Occup Saf Ergon ; 28(2): 1235-1243, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33563144

ABSTRACT

The evaluation index system of non-rigid demand service quality in safety production delineates the production safety-related services that are procured by enterprises from service organizations and are not mandatory by the state. Construction of the evaluation index system of non-rigid demand service quality in safety production is an effective way to improve the quality of the demand service. Based on the INDSERV model and on-site interviews, this study constructs a whole-process safety production non-rigid demand service quality evaluation model, clarifies the evaluation indicators and conducts on-site investigations to verify the effectiveness of the model, and further analyzes the data to determine each evaluation index weight. A safety production non-rigid demand service quality evaluation index and evaluation scale were constructed. Effective exploration was performed on the evaluation index system of non-rigid demand service quality in safety production, which provides a guarantee for promoting the development of the non-rigid demand service market.

18.
Inflamm Bowel Dis ; 28(5): 764-774, 2022 05 04.
Article in English | MEDLINE | ID: mdl-34894222

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer in the United States, and inflammatory bowel disease patients have an increased risk of developing CRC due to chronic intestinal inflammation with it being the cause of death in 10% to 15% of inflammatory bowel disease patients. TIPE2 (TNF-alpha-induced protein 8-like 2) is a phospholipid transporter that is highly expressed in immune cells and is an important regulator of immune cell function. METHODS: The azoxymethane/dextran sulfate sodium murine model of colitis-associated colon cancer (CAC) was employed in Tipe2 -/- and wild-type mice, along with colonoid studies, to determine the role of TIPE2 in CAC. RESULTS: Early on, loss of TIPE2 led to significantly less numbers of visible tumors, which was in line with its previously described role in myeloid-derived suppressor cells. However, as time went on, loss of TIPE2 promoted tumor progression, with larger tumors appearing in Tipe2 -/- mice. This was associated with increased interleukin-22/STAT3 phosphorylation signaling. Similar effects were also observed in primary colonoid cultures, together demonstrating that TIPE2 also directly regulated colonocytes in addition to immune cells. CONCLUSIONS: This work demonstrates that TIPE2 has dual effects in CAC. In the colonocytes, it works as a tumor suppressor. However, in the immune system, TIPE2 may promote tumorigenesis through suppressor cells or inhibit it through IL-22 secretion. Going forward, this work suggests that targeting TIPE2 for CRC therapy requires cell- and pathway-specific approaches and serves as a cautionary tale for immunotherapy approaches in general in terms of colon cancer, as intestinal inflammation can both promote and inhibit cancer.


TIPE2 (TNF-alpha-induced protein 8-like 2) regulates immune function. Here, we find that it differentially regulates the initiation and progression of its immunoregulatory properties affect murine colitis-associated colon cancer initiation and progression. Surprisingly, we found that TIPE2 a novel tumor suppressor in enterocytes, a cell compartment it was not previously known to directly regulate.


Subject(s)
Colitis-Associated Neoplasms , Colitis , Inflammatory Bowel Diseases , Animals , Azoxymethane/toxicity , Cell Transformation, Neoplastic/pathology , Colitis/chemically induced , Colitis/complications , Colitis-Associated Neoplasms/genetics , Colon/pathology , Dextran Sulfate/toxicity , Disease Models, Animal , Inflammation/pathology , Inflammatory Bowel Diseases/complications , Intracellular Signaling Peptides and Proteins/genetics , Mice , Mice, Inbred C57BL
19.
Cell Death Dis ; 12(11): 1001, 2021 10 26.
Article in English | MEDLINE | ID: mdl-34702807

ABSTRACT

Aging is a natural and progressive process characterized by an increased frequency of age-related diseases such as cancer. But its mechanism is unclear. TNFAIP8L2 (Tipe2) is an important negative regulator for homeostasis through inhibiting TLR and TCR signaling. Our work reveals that Tipe2 might have dual function by regulating senescence. One side, the overexpression of Tipe2 in CRC cells could induce typical senescent phenotype, especially exposure to oxidative stress. Tipe2 inhibits telomerase activity by regulating c-Myc and c-Est-2 binding to the hTERT promotor. Interestingly, Tipe2 KO mice treated with D-Gal showed a less serious inverse of CD4:CD8 ratio, a lower percentage of Treg compared to WT. Besides, Tipe2 KO mice were more tolerant to the initiation of AOM/DSS-induced CRC, accompanied by a lower level of Treg within IEL. Therefore, specific antibodies against CD25 effectively ameliorate tumorigenesis. These data suggest strongly that the overexpressed Tipe2 suppresses tumor cells proliferation and survival, but endogenous Tipe2 promotes the initiation of tumorigenesis when exposure to dangerous environment such as AOM/DSS-related inflammation.


Subject(s)
Cell Transformation, Neoplastic/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Animals , Cell Line, Tumor , Cell Proliferation , Disease Models, Animal , Humans , Mice , Signal Transduction
20.
Biomed Res Int ; 2021: 4156162, 2021.
Article in English | MEDLINE | ID: mdl-34513990

ABSTRACT

METHODS: A total of 121 patients with moderate to severe ARDS admitted to the intensive care unit (ICU) from June 2017 to April 2020 and treated with invasive mechanical ventilation were sequentially included in this study. Their general information was collected, and MP was recorded at 0 h, 24 h, 48 h, and 72 h after admission to the ICU. Professionally trained researchers performed the LUS assessments. Patients were divided into the death and survival groups according to their 28-day prognosis. The trend of MP and LUS at the four time points was analyzed. A receiver operating characteristic curve (ROC) was used to analyze the predictive value of MP and LUS scores at 0 h and 72 h for the prognosis (28-day mortality rate) of patients with moderate to severe ARDS. RESULTS: 121 patients were included in the analysis, of which 73 were male and 48 were female. When patients entered the ICU, their oxygenation index (t: 30885, P < 0.01), APACHE II score (t: 2.105, P < 0.05), and SOFA score (t: 4.134, P < 0.001) were higher in the death group than the survival group. The death group had significantly higher MP and LUS at each time point (0 h, 24 h, 48 h, and 72 h) compared to the survival group (all P < 0.05). There was a significant upward trend over time in the MP and LUS of the death group, contrasting to a significant downward trend in the survival group (all P < 0.05). The Pearson correlation analysis showed that MP and LUS were significantly positively correlated at each time point (r values: 0 h: 0.3027; 24 h: 0.3705; 48 h: 0.3902; 72 h: 0.5916; all P < 0.01). The ROC curves showed that MP and LUS at 72 h were of significant value in predicting the prognosis of ARDS patients, with areas under the curve of 0.866 ± 0.032 and 0.839 ± 0.037, respectively. CONCLUSION: There was a significant correlation between the MP and LUS of ARDS patients at four time points from 0 to 72 h, which has a clinical value in evaluating severity and prognosis.


Subject(s)
Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/physiopathology , Adult , Aged , China , Female , Humans , Intensive Care Units , Lung/diagnostic imaging , Lung/physiopathology , Male , Middle Aged , Prognosis , ROC Curve , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Retrospective Studies , Severity of Illness Index , Ultrasonography/methods
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