Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting

Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma

Analysis of spatiotemporal heterogeneity and influencing factors of soil erosion in a typical erosion zone of the southern red soil region, China

The southern red soil region (SRSR) of China, a region that is environmentally sensitive, suffers severe soil erosion (SE) as a result of climate change and human activity. The factors driving SE changes in the SRSR of China under changing settings have, however, only been the subject of a small number of research. Changting County is a typical SE area in the SRSR of China. The spatiotemporal variation characteristics of SE in Changting County from 2000 to 2020 were investigated using the revised universal soil loss equation (RUSLE), while the dominant factors influencing the spatiotemporal dynamic change of SE were analyzed using the optimal parametric geographical detector (OPGD) and logarithmic mean Divisia Index (LMDI). The results showed that the average annual soil erosion modulus in Changting County shows a decreasing trend, with the SE modulus decreased from 10.00 t·hm−2·a−1 in 2000 to 3.38 t·hm−2·a−1 in 2020. Slight SE intensity was the dominant SE class, accounting for more than 75% of the total area, and the proportion is trending upwards. Natural and anthropogenic factors showed significant effects on the spatial variation of SE, of which land use and vegetation cover were the main factors influencing the spatial distribution of SE. Furthermore, the interaction between these two dominant factors explained greatly the spatial variation of SE. The mitigation of SE was mainly attributed to the increase in vegetation cover following the implementation of various ecological projects, contributing to the reduction of SE by 68.7%. In addition, the changes in land use types and rainfall amounts also played positive roles in reducing SE, showing contributions of 20.2% and 11.1%, respectively

High PANX1 Expression Leads to Neutrophil Recruitment and the Formation of a High Adenosine Immunosuppressive Tumor Microenvironment in Basal-like Breast Cancer

Background: A high adenosine level is an important characteristic of the tumor microenvironment (TME) in breast cancer. Pannexin 1 (PANX1) can release intracellular ATP to the extracellular space and elevate extracellular ATP (exATP) levels under physiological conditions. Methods: We performed public database bioinformatics analysis, surgical specimen histological validation, RNA sequencing, and exATP/extracellular adenosine (exADO) assays to reveal the role of PANX1 in regulating the immune microenvironment of basal-like breast cancer. Results: Our results revealed that PANX1 acted as a poor prognostic factor for breast cancer and had high expression in basal-like breast cancer. PANX1 expression was positively correlated with exATP and exADO levels in basal-like breast cancer TME. PANX1 expression was also positively correlated with tumor-associated neutrophil (TAN) infiltration in breast cancer TME and TANs highly expressed ENTPD1 (CD39)/NT5E (CD73). Conclusions: This study suggests that high PANX1 expression is associated with high TAN infiltration and adenosine production to induce local immunosuppression in basal-like breast cancer TME

Speciation Distribution and Influencing Factors of Heavy Metals in Rhizosphere Soil of Miscanthus Floridulus in the Tailing Reservoir Area of Dabaoshan Iron Polymetallic Mine in Northern Guangdong

Through field investigation and experimental analysis, the forms, contents and distribution of heavy metals (Zn, Pb, Cu, Cd, Ni, Cr) in rhizosphere and non-rhizosphere soils of Miscanthus floridulus growing everywhere in Tielongwei mine pond (sample plot 1), Caoduikeng tailings pond (sample plot 2), Donghua tailings pond (sample plot 3) and Small tailings pond (sample plot 4) in Dabaoshan, Guangdong Province were studied. The results showed that the main forms and distributions of heavy metals in rhizosphere and non-rhizosphere soils are basically the same, which shows that the mineral content accounts for most of the total amount of heavy metals, while the exchange content is low. Compared with non-rhizosphere soil, the proportion of exchangeable and organic heavy metals in rhizosphere soil increased significantly, in which the proportion of organic-bound Cu increased by 53.25%, the proportion of organic-bound Cd and Pb increased by more than 17%, and the proportion of Zn increased by 5.67%. At the same time, the contents of carbonate-bound and iron manganese oxide-bound decreased. Statistical analyses showed that the morphological distribution of Zn, Pb, Cu, Cd, Ni and Cr in rhizosphere soil was closely related to soil pH value, organic matter content, plant growth and other factors. The results of this study provided a basis for the restoration of heavy metal-contaminated sites by Miscanthus

Spatiotemporal Dynamics of Scrub Typhus in Jiangxi Province, China, from 2006 to 2018

Background: Scrub typhus (ST) has become a significant potential threat to public health in Jiangxi. Further investigation is essential for the control and management of the spatiotemporal patterns of the disease. Methods: Time-series analyses, spatial distribution analyses, spatial autocorrelation analysis, and space-time scan statistics were performed to detect spatiotemporal dynamics distribution of the incidence of ST. Results: From 2006 to 2018, a total of 5508 ST cases occurred in Jiangxi, covering 79 counties. The number of ST cases increased continuously from 2006 to 2018, and there was obvious seasonality during the variation process in each year, with a primary peak in autumn (September to October) and a smaller peak in summer (June to August). From 2007 to 2018, the spatial distribution of the ST epidemic was significant heterogeneity, and Nanfeng, Huichang, Xunwu, Anyuan, Longnan, and Xinfeng were hotspots. Seven spatiotemporal clusters were observed using Kulldorff’s space-time scan statistic, and the most likely cluster only included one county, Nanfeng county. The high-risk areas of the disease were in the mountainous, hilly region of Wuyi and the southern mountainous region of Jiangxi. Conclusions: Targeted interventions should be executed in high-risk regions for the precise prevention and control of ST

The Infratentorial Localization of Brain Metastases May Correlate with Specific Clinical Characteristics and Portend Worse Outcomes Based on Voxel-Wise Mapping

The infratentorial regions are vulnerable to develop brain metastases (BMs). However, the associations between the infratentorial localization of BMs and clinical characteristics remained unclear. We retrospectively studied 1102 patients with 4365 BM lesions. Voxel-wise mapping of MRI was applied to construct the tumor frequency heatmaps after normalization and segmentation. The analysis of differential involvement (ADIFFI) was further used to obtain statistically significant clusters. Kaplan-Meier method and Cox regression were used to analyze the prognosis. The parietal, insular and left occipital lobes, and cerebellum were vulnerable to BMs with high relative metastatic risks. Infratentorial areas were site-specifically affected by the lung, breast, and colorectal cancer BMs, but inversely avoided by melanoma BMs. Significant infratentorial clusters were associated with young age, male sex, lung neuroendocrine and squamous cell carcinomas, high expression of Ki-67 of primaries and BMs, and patients with poorer prognosis. Inferior OS was observed in patients with ≥3 BMs and those who received whole-brain radiotherapy alone. Infratentorial involvement of BMs was an independent risk factor of poor prognosis for patients who received surgery (p = 0.023, hazard ratio = 1.473, 95% confidence interval = 1.055–2.058). The current study may add valuable clinical recognition of BMs and provide references for BMs diagnosis, treatment evaluation, and prognostic prediction