Loss of p53 Attenuates the Contribution of IL-6 Deletion on Suppressed Tumor Progression and Extended Survival in Kras-Driven Murine Lung Cancer

Interleukin-6 (IL-6) is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity in mouse models. Clinical trials in non-small cell lung cancer (NSCLC) reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study. We crossed IL-6-/- mice with KrasG12D mutant mice, which develop lung tumors after activation of mutant KrasG12D, to investigate whether IL-6 inhibition contributes to tumor progression and survival time in vivo. KrasG12D; IL-6-/- mice exhibited increased tumorigenesis, but slower tumor growth and longer survival, than KrasG12D mice. Further, in order to investigate whether IL-6 deletion contributes to suppression of lung cancer metastasis, we generated KrasG12D; p53flox/flox; IL-6-/- mice, which developed lung cancer with a trend for reduced metastases and longer survival than KrasG12D; p53flox/flox mice. Tumors from KrasG12D; IL-6-/- mice showed increased expression of TNFα and decreased expression of CCL-19, CCL-20 and phosphorylated STAT3 (pSTAT3) than KrasG12D mice; however, these changes were not present between tumors from KrasG12D; p53flox/flox; IL-6-/- and KrasG12D; p53flox/flox mice. Upregulation of pSTAT3 and phosphorylated AKT (pAKT) were observed in KrasG12D tumors with p53 deletion. Taken together, these results indicate that IL-6 deletion accelerates tumorigenesis but delays tumor progression and prolongs survival time in a Kras-driven mouse model of lung cancer. However, these effects can be attenuated by p53 deletion

Research through service: Meeting Chinese international college students’ mental health needs

Introduction and backgroundResearch indicates that Chinese International College Students (CICS) encounter considerable cultural and mental health challenges while studying in the United States. However, there has been limited focus on the processes and outcomes of effective mental health intervention programs tailored to their needs. This study adopted a research-through-service approach to design, implement, and evaluate a four-week group intervention program aimed at enhancing the mental health and well-being of CICS.Methods and intervention programThe group intervention was designed with the perspective that effective mental health services for CICS should be culturally specific, growth-oriented, and focused on promoting positive learning outcomes rather than merely addressing problems or solutions. Group sessions were conducted in Chinese and emphasized experiential activities aimed at enhancing participants’ cultural confidence and fostering a growth-oriented, positive mindset. Thirteen CICS voluntarily participated in the group intervention. One to three weeks after the program, twelve participants took part in semi-structured post-group interviews. These interviews explored their reflections on the group experience, their general perspectives on well-being, perceived challenges and strategies for managing those challenges, and their attitudes toward seeking professional help when needed. The interview data were analyzed using the Consensus Qualitative Research (CQR) method (Hill, 2012).ResultsParticipants shared experiences of cultural conflicts and challenges they faced, as well as the active coping strategies they employed. These strategies included confiding in trusted individuals, practicing forbearance and self-regulation, and seeking practical solutions to underlying problems. When reflecting on the group intervention experience, participants reported notable benefits across intellectual, relational, and emotional domains. Additionally, they provided valuable suggestions for enhancing the program’s effectiveness.ConclusionIntervention programs designed to support Chinese International College Students (CICS) should promote cultural confidence, adopt a strength-based and growth-oriented approach, and avoid deficit-focused or problem-centered frameworks

Welfare Effect of Farmers’ Participation in Soil Conservation: Concept, Connotation and Evaluation Index Framework

[Objective] A concept, connotation and evaluation index framework of welfare effect of farmers’ participation in soil conservation practices was systematically reviewed, which could provide a scientifical basis for comprehensive evaluation of the welfare effect of soil conservation. [Methods] By assembling existing publications and relevant standard documents, the concept and connotation of welfare effect of soil conservation were formulated, and the logical relationship between soil conservation benefits and soil conservation welfare effect. Furthermore, the evaluation scale of the welfare effect of soil conservation was sorted out, and an evaluation index framework for the welfare effect was proposed. [Results] The welfare effect of soil conservation had intrinsic characteristics of clear evaluation objects, monetizable value, high correlation with participation degree, individual difference, and group consistency. It is also considered to be deepened and expanded understandings of the benefits of soil conservation, and this relationship is inter-contained and inter-included. Evaluation of the soil conservation welfare effect should be based on a comprehensive evaluation of soil conservation benefits, and its index framework should include multiple elements such as economic welfare, social welfare, and ecological welfare. [Conclusion] The welfare effect of farmers’ participation in soil and water conservation has not yet gained enough attention currently. The evaluation of the welfare effect of soil and water conservation only focuses on policy-based soil and water conservation projects, and its evaluation indicators and methods have not formed a unified understanding. It is necessary to further study the theory and methodology of the welfare effect of soil and water conservation, thereby providing references for decision-making in the construction of soil and water conservation in the new era

Vascular changes of the choroid and their correlations with visual acuity in diabetic retinopathy

ObjectiveTo investigate changes in the choroidal vasculature and their correlations with visual acuity in diabetic retinopathy (DR).MethodsThe cohort was composed of 225 eyes from 225 subjects, including 60 eyes from 60 subjects with healthy control, 55 eyes from 55 subjects without DR, 46 eyes from 46 subjects with nonproliferative diabetic retinopathy (NPDR), 21 eyes from 21 subjects with proliferative diabetic retinopathy (PDR), and 43 eyes from 43 subjects with clinically significant macular edema (CSME). Swept-source optical coherence tomography (SS-OCT) was used to image the eyes with a 12-mm radial line scan protocol. The parameters for 6-mm diameters of region centered on the macular fovea were analyzed. Initially, a custom deep learning algorithm based on a modified residual U-Net architecture was utilized for choroidal boundary segmentation. Subsequently, the SS-OCT image was binarized and the Niblack-based automatic local threshold algorithm was employed to calibrate subfoveal choroidal thickness (SFCT), luminal area (LA), and stromal area (SA) by determining the distance between the two boundaries. Finally, the ratio of LA and total choroidal area (SA + LA) was defined as the choroidal vascularity index (CVI). The choroidal parameters in five groups were compared, and correlations of the choroidal parameters with age, gender, duration of diabetes mellitus (DM), glycated hemoglobin (HbA1c), fasting blood sugar, SFCT and best-corrected visual acuity (BCVA) were analyzed.ResultsThe CVI, SFCT, LA, and SA values of patients with DR were found to be significantly lower compared to both healthy patients and patients without DR (P < 0.05). The SFCT was significantly higher in NPDR group compared to the No DR group (P < 0.001). Additionally, the SFCT was lower in the PDR group compared to the NPDR group (P = 0.014). Furthermore, there was a gradual decrease in CVI with progression of diabetic retinopathy, reaching its lowest value in the PDR group. However, the CVI of the CSME group exhibited a marginally closer proximity to that of the NPDR group. The multivariate regression analysis revealed a positive correlation between CVI and the duration of DM as well as LA (P < 0.05). The results of both univariate and multivariate regression analyses demonstrated a significant positive correlation between CVI and BCVA (P = 0.003).ConclusionChoroidal vascular alterations, especially decreased CVI, occurred in patients with DR. The CVI decreased with duration of DM and was correlated with visual impairment, indicating that the CVI might be a reliable imaging biomarker to monitor the progression of DR

Synthèse de dérivés et analogues des acides dicinnamoyl quiniques nouvelle et évaluation de leur activité insecticide

The use of conventional pesticides, especially the synthetic chemical pesticides, has greatly reduced the crop losses and gained a commercial success. However, the excessive use of pesticides lacking toxic specificity has caused a series of environmental and public health problems. The research interest toward new naturally-occurring biopesticides with novel modes of actions aims at a better balance between the efficiency of pesticide and reducing possible harms to environment and humans. Botanicals are an important source of biopesticides. Cinnamoyl quinic acids (CQA), isolated from various plants and shown to exhibit in vivo and in vitro a wide spectrum of biological activities, have attracted the attention with potential as biopesticides based on the patented toxicity of 3,5-di-O-caffeoylquinic acid against the larvae of Myzus persicae. The investigation of the insecticidal activity of CQA including their mode of action and the study of some structure-activity relationships could benefit from the synthesis of different CQA derivatives and analogs. A series of natural CQA derivatives natural 3,4- and 4,5-dicinnmamoylquinic acid derivatives but also analogs like 4-deoxy-3,5-dicinnamoylquinic acids were so synthesized. Seven targeted 4-deoxy CQA analogs were subjected to insecticidal assays, and two compounds were found to exhibit higher insecticidal activities than natural 3,5-dicaffeoylquinic acid. As perspectives to this work, confirming the activity of the synthesized compounds on other aphid species of agronomic importance could be performed. Furthermore, other collaborations could be established with biologists dedicated to measure other bioactivities of the synthesized compounds or use them as tools to investigate various biological pathways.L'utilisation de pesticides conventionnels, en particulier les pesticides chimiques de synthèse, a considérablement réduit les pertes de récoltes et a connu un succès commercial. Cependant, l'utilisation excessive de pesticides chimiques qui manquent de toxicité spécifique a provoqué une série de problèmes environnementaux et de santé publique. L'intérêt de la recherche vers de nouveaux biopesticides naturels avec de nouveaux modes d'actions vise à un meilleur équilibre entre l'efficacité des pesticides et la réduction des méfaits possibles pour l'environnement et les humains. Les plantes sont une source importante de biopesticides. Les acides chlorogéniques (CQA), isolés à partir de diverses plantes et présentent in vivo et in vitro un large spectre d'activités biologiques, ont attiré l'attention avec un potentiel comme biopesticides basé sur la toxicité brevetée de l'acide 3,5-di-O-caféoylquinique contre les larves de Myzus persicae. L'étude des propriété insecticides notamment la mode d'action et l'étude de certaines relations structure-activité pourrait bénéficier de la synthèse de différents dérivés et analogues de CQA. Des analogues des acides 4-désoxy-3,5-dicinnamoy quiniques et 3,4- et 4,5-dicinnamoylquiniques naturels ont été synthétisés. Sept analogues dans la série 4-désoxy ont été soumis à des essais insecticides et deux composés présentent une activité insecticide plus élevée que l'acide 3,5-dicaféoylquinique naturel. Comme perspectives à ce travail, confirmer l'activité des composés synthétisés sur d'autres espèces de pucerons d'importance agronomique pourrait être réalisé. De plus, d’autres collaborations avec des biologistes pourraient être établies afin d’évaluer d'autres activités des composés synthétisés ou les utiliser comme outils pour étudier des mécanismes de biosynthése