NR0B1 suppresses ferroptosis through upregulation of NRF2/c-JUN-CBS signaling pathway in lung cancer cells.

Ferroptosis has demonstrated significant potential in treating radiochemotherapy-resistant cancers, but its efficacy can be affected by recently discovered ferroptosis suppressors. In this study, we discovered that NR0B1 protects against erastin- or RSL3-induced ferroptosis in lung cancer cells. Transcriptomic analysis revealed that NR0B1 significantly interfered with the expression of 12 ferroptosis-related genes, and the expression level of NR0B1 positively correlated with that of c-JUN, NRF2, and CBS. We further revealed that NR0B1 suppression of ferroptosis depended on the activities of c-JUN, NRF2, and CBS. NR0B1 directly promoted the expression of NRF2 and c-JUN and indirectly upregulated CBS expression through enhancing NRF2 and/or c-JUN transcription. Moreover, we showed that NR0B1 depletion restrained xenograft tumor growth and facilitated RSL3-induced ferroptosis in the tumors. In conclusion, our findings uncover that NR0B1 suppresses ferroptosis by activating the c-JUN/NRF2-CBS signaling pathway in lung cancer cells, providing new evidence for the involvement of NR0B1 in drug resistance during cancer therapy.

The predictive accuracy of CT radiomics combined with machine learning in predicting the invasiveness of small nodular lung adenocarcinoma.

Background: Conventionally, the judgment of whether small pulmonary nodules are invasive is mainly made by thoracic surgeons according to the chest computed tomography (CT) features of patients. However, there are limits to how much useful information can be obtained from this approach. A large number of feature information was extracted from CT images by CT radiomics. The machine learning algorithm was used to construct models based on radiomic characteristics to predict the invasiveness of lung adenocarcinoma (LUAD) with a good prediction accuracy. Methods: A total of 416 patients with pathologically confirmed preinvasive lesions and LUAD after video-assisted thoracoscopic surgery (VATS) in the Department of Thoracic Surgery of the First People's Hospital of Yunnan Province from February 2020 to February 2022 were retrospectively analyzed. According to random classification, patients were divided into 2 groups. The RadCloud platform was used to extract radiomics features, and the most relevant radiomics features were selected by continuous dimension reduction method. Then, 6 machine learning algorithms were used to establish and verify the prediction model of small lung nodular adenocarcinoma invasiveness. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the predictive performance. Results: There were 78 cases of pre-invasive lesions and 226 cases of invasive lesions in the training group, and 34 cases of pre-invasive lesions and 78 cases of invasive lesions in the validation group. In the training group, the AUC values of the 6 models were all more than 0.914, the 95% confidence interval (CI) was 0.857-1.00, the sensitivity was equal or more than 0.87, and the specificity was equal or more than 0.85. In the validation group, the AUC values of the 6 models were all equal or more than 0.732, the 95% CI was 0.651-1.00, the sensitivity was equal or more than 0.7, and the specificity was more than 0.77. Conclusions: Machine learning algorithms were used to construct models to predict the invasiveness of small nodular LUAD based on radiomics features, which it could provide more evidence for doctors to make diagnoses and more personalized treatment plans for patients.

Quantitative detection, sources exploration and reduction of in-cabin benzene series hazards of electric buses through climate chamber experiments.

In this study, a large-scale in-cabin benzene series hazard detection is firstly performed on 20 electric buses by a full-scale climate chamber. The sources of BTEX are analyzed deeply by parts detection, and a series of effective measures are performed to reduce BTEX. Firstly, the in-cabin BTEX pollution with considerations of a series of parameters, such as interior configuration, environment temperature, vehicle age, and ventilation mode, is analyzed. The result shows that: 1) The VOCs concentrations decrease with vehicle age, higher configuration level and better ventilation system (particularly, fresh wind mode reduce VOCs fastly), while increases with environment temperature; 2) BTEX in bus cabins occupy approximatively 70.1% of TVOC, thus the BTEX overproof is the main culprit which causes VOCs to exceed standard. Then, measurements on components/materials VOCs releases were performed in a small climate chamber to discriminate key species and their sources. Xylene released from glues materials is found as a key species that causes BTEX/VOC to exceed limitation. Lastly, some measures, such as optimizations of materials selection and manufacturing crafts, are adopted to improve in-cabin pollution, and positive effects are obtained. For example, ethylbenzene and xylene released from HL 125 (a polyurethane adhesive) decrease by 2456% and 1930% respectively after improvement. And in-cabin xylene and TVOC decrease by 2274% and 222%, respectively, and all of them are lower than limitation value.

CLOCK and BMAL1 stabilize and activate RHOA to promote F-actin formation in cancer cells.

Circadian genes control most of the physiological functions in cancer cells, including cell proliferation, migration, and invasion. The CLOCK and BMAL1 complex plays a central role in circadian rhythms. Previous studies have shown that circadian genes may act as oncogenes or tumor-suppressor genes. In addition, F-actin, regulated by RHOA, has been shown to participate in tumor progression. However, the roles of the CLOCK and BMAL1 genes in the regulation of tumor progression via the RHOA-ROCK-CFL pathway remain largely unclear. Here we first indicate that the rearrangement of F-actin is regulated by CLOCK and BMAL1. We found that CLOCK and BMAL1 can upregulate RHOA expression by inhibiting CUL3-mediated ubiquitination and activate RHOA by reducing the interaction between RHOA and RhoGDI. Consequently, CLOCK and BMAL1 control the expression of the components of the RHOA-ROCK-CFL pathway, which alters the dynamics of F-actin/G-actin turnover and promotes cancer cell proliferation, migration, and invasion. In conclusion, our research proposes a novel insight into the role of CLOCK and BMAL1 in tumor cells.

Factors Affecting Consumer Acceptance of an Online Health Information Portal Among Young Internet Users.

Despite the proliferation of health and nursing informatics applications in the past decade, factors influencing consumer acceptance of the applications are not well understood. This study was conducted to investigate factors affecting acceptance of a consumer-used nursing informatics application (ie, online health information portal) within the framework of the Technology Acceptance Model. A cross-sectional study was conducted in which 201 Chinese young adults were invited to participate in usability testing with a typical health information portal and to complete a self-report questionnaire measuring the model's constructs and five hypothesized variables drawn from consumer and portal characteristics. Hierarchical regression analyses were used to test research hypotheses. Fifteen of the 22 research hypotheses were supported. Perceived ease of use and perceived usefulness predicted satisfaction and behavioral intention, respectively, over and above the portal and consumer characteristics examined in the study. All portal and consumer characteristics had significant, although varied, impacts on the original model constructs. This study demonstrated that an adapted Technology Acceptance Model, extended with portal and consumer characteristics, provides an effective means to understand consumer acceptance of health portals. The findings hold important implications for design and implementation strategies to increase the likelihood of acceptance of consumer-used nursing informatics applications.

Clock1a affects mesoderm development and primitive hematopoiesis by regulating Nodal-Smad3 signaling in the zebrafish embryo.

Circadian clock and Smad2/3/4-mediated Nodal signaling regulate multiple physiological and pathological processes. However, it remains unknown whether Clock directly cross-talks with Nodal signaling and how this would regulate embryonic development. Here we show that Clock1a coordinated mesoderm development and primitive hematopoiesis in zebrafish embryos by directly up-regulating Nodal-Smad3 signaling. We found that Clock1a is expressed both maternally and zygotically throughout early zebrafish development. We also noted that Clock1a alterations produce embryonic defects with shortened body length, lack of the ventral tail fin, or partial defect of the eyes. Clock1a regulates the expression of the mesodermal markers ntl, gsc, and eve1 and of the hematopoietic markers scl, lmo2, and fli1a Biochemical analyses revealed that Clock1a stimulates Nodal signaling by increasing expression of Smad2/3/4. Mechanistically, Clock1a activates the smad3a promoter via its E-box1 element (CAGATG). Taken together, these findings provide mechanistic insight into the role of Clock1a in the regulation of mesoderm development and primitive hematopoiesis via modulation of Nodal-Smad3 signaling and indicate that Smad3a is directly controlled by the circadian clock in zebrafish.

[Inhibitory effect of isorhmnetin on telomerase activity of HeLa cells].

OBJECTIVE: To investigate the growth-inhibiting and apoptosis-inducing effects of isorhmnetin on HeLa cells and to disclose the role of telomerase activity of tumor cells. METHODS: The methods of cell culture in vitro were adopted. HeLa cells were treated with isorhmnetin in different concentrations for 2 days, and then were observed and analyzed by use of MTT, Flow-Cytometry (FCM) and TRAP-ELIAS technique for inspecting the HeLa cells' growth and telomerase activity. RESULTS: The growth of HeLa cells was inhibited evidently after treatment by isorhmnetin. The rate of apoptosis was 31.7% after the HeLa cells were treated with 20 micrograms/ml isorhmnetin. Isorhmnetin could inhibit the activity of telomerase. CONCLUSION: By inhibiting the activity of telomerase, isorhmnetin can inhibit the growth of HeLa cells.