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

Spatial and Temporal Changes in Soil Water Erosion in Baisha River Basin from 2007 to 2020

[Objective] The spatial-temporal variations of soil water erosion before and after the Wenchuan earthquake in the Baisha River basin of Dujiangyan City, Sichuan Province were assessed to support water source protection efforts and comprehensive control of soil erosion in the earthquake-stricken area. [Methods] The characteristics of soil water erosion (i. e., area, intensity, and spatial distribution) in the Baisha River basin from 2007 to 2020 were quantitatively analyzed by using the Chinese Soil Loss Equation (CSLE). [Results] ① The intensity of soil water erosion after the Wenchuan earthquake in the Baisha River basin initially increased and then decreased. The average soil erosion modulus values for the Baisha River asin were 817.51, 3 000.11, 5 828.89, 1 549.76, and 1 558.37 t/(km2·a) in 2007, 2008, 2013, 2018, and 2020, respectively. The intensity of soil erosion in 2020 was mainly classified as light erosion, and the average soil erosion modulus was 48.1% lower than in 2008. ② The average soil erosion modulus gradually increased with increasing slope gradient or altitude. Soil erosion amount contributed by regions with slope greater than 35° and elevation above 2 000 m accounted for 85.44% and 68.20%, respectively, of the total erosion amount in 2020. In addition, the extremely severe erosion area with an average soil erosion modulus of more than 5 000 t/(km2·a) mainly occurred in areas with elevation above 4 000 m. ③ Although the average vegetation coverage in the Baisha River basin in the past 10 years was between 60% and 74%, the proportion of the area classified as having moderate and more severe erosion was still greater than before the earthquake. In 2020, the proportion of moderate and more severe erosion area was 4.13 times greater than in 2007. [Conclusion] Even though the soil water erosion situation has effectively improved between 2013 and 2020, areas of intense and more severe erosion remain in the middle and upper reaches of the study area, and the topographic conditions and rainfall erosivity had an obvious impact on the change in erosion area

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

Uplift History of the Eastern Pamir Inferred from Inversion of Thermochronometric Data and River Profile

The Pamir salient accommodates a great amount of Cenozoic India-Eurasia convergence in the forms of thrusting, strike-slip faulting, extension, and gneiss dome formation. It thus becomes a key location for exploring the orogenic tectonic evolution. Here, we focus on the Eastern Pamir where extensional deformation dominates during the late Cenozoic. We conducted low-temperature thermochronological dating on bedrock samples collected from the footwall of the Kongur Shan normal fault together with inversion of the longitudinal river profile of the Gez River. Our new zircon and apatite (U-Th)/He (ZHe and AHe) data reveal young ages in proximity to the normal fault and older ages adjacent to the western Tarim Basin. By inverting the Gez River profile together with published and new thermochronological ages, we obtained a sustained uplift rate of ~3 mm/yr in the Kongur Shan dome since ~8 Ma, contrasting with no significant uplift to the east of the dome before the Pliocene. This uplift pattern can be interpreted as a result of the upward extrusion of crust materials along a flat–ramp–flat thrust fault at depth under the context of convergence

Construction of frailty and risk prediction models in maintenance hemodialysis patients: a cross-sectional study

ObjectiveAs the prevalence of diabetic nephropathy and hypertensive nephropathy increases with age in mainland China, the number of patients with end-stage renal disease is increasing, leading to an increase in the number of patients receiving maintenance hemodialysis. Considering the harmful effects of frailty on the health of maintenance hemodialysis patients, this study aims to identify hemodialysis patients at risk for frailty at an early stage, in order to prevent or delay the progression of frailty in the early stage, so as to prevent the adverse consequences of frailty.MethodsA total of 479 patients admitted to the blood purification centers of two grade tertiary hospitals in Anhui Province, China, using convenient sampling. The Frailty Scale, the SARC-F questionnaire, the Simplified Food Appetite Questionnaire (SNAQ) and the mini nutritional assessment short-form (MNA-SF) were used in the study. Pearson correlation analysis was used to explore the correlation among the frailty influencing factors.ResultsThe incidence of frailty was 24.0% among 479 Chinese hemodialysis patients. Gender (p < 0.05), Malnutrition (p < 0.001), sarcopenia (p < 0.001), and feel tired after dialysis (p < 0.001) were highly correlated with frailty in Chinese hemodialysis patients. Serum albumin concentration (p < 0.05) was a protective factor of frailty.ConclusionThis survey shows that frailty was highly prevalent among Chinese hemodialysis patients. Medical staff and their families should make early judgments and carry out interventions on the risk of frailty

Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene

Existing animal models of cystic fibrosis (CF) have provided key insights into CF pathogenesis but have been limited by short lifespans, absence of key phenotypes, and/or high maintenance costs. Here, we report the CRISPR/Cas9-mediated generation of CF rabbits, a model with a relatively long lifespan and affordable maintenance and care costs. CF rabbits supplemented solely with oral osmotic laxative had a median survival of approximately 40 days and died of gastrointestinal disease, but therapeutic regimens directed toward restoring gastrointestinal transit extended median survival to approximately 80 days. Surrogate markers of exocrine pancreas disorders were found in CF rabbits with declining health. CFTR expression patterns in WT rabbit airways mimicked humans, with widespread distribution in nasal respiratory and olfactory epithelia, as well as proximal and distal lower airways. CF rabbits exhibited human CF-like abnormalities in the bioelectric properties of the nasal and tracheal epithelia. No spontaneous respiratory disease was detected in young CF rabbits. However, abnormal phenotypes were observed in surviving 1-year-old CF rabbits as compared with WT littermates, and these were especially evident in the nasal respiratory and olfactory epithelium. The CF rabbit model may serve as a useful tool for understanding gut and lung CF pathogenesis and for the practical development of CF therapeutics

The lived experience of family members of older people who have committed suicide in rural China

Abstract Background: China has the largest older population in the world. With the increasing trend of ageing, the problem of suicide among old people is increasing rapidly, especially in rural areas. The pressures and challenges faced by family members of loved ones who have committed suicide has been studied closely around the world. However, the impact of suicide on the lives of family members have not received enough attention in China. Therefore, it is very important to understand the lived experience of the family members of older people who have committed suicide. The study aims to understand the lived experiences of family members who have experienced their older family member’s suicide in a rural area based in Shaanxi Province, China.Methods: Interpretative phenomenological analysis (IPA) was used for this study. Semi-structured individual interviews with five family members of older people who have committed suicide recruited from a rural area of Shaanxi Province, China.Results: Three main themes emerged from the study: (a) Initial reactions; (b) Continual effects; (c) Social attitudes.Conclusions: With the development of China’s economic, social and cultural changes, the suicide of the older people in rural China poses a challenge to the future living quality of their family members. It shows that it is necessary to pay attention to families of older people who have committed suicide. It also shows that more support is required to improve the quality of life of families of older people who have committed suicide in rural China.</jats:p