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Polycyclic aromatic hydrocarbons (PAHs) are major pollutants in urban areas, and thus present a high risk to the resident health. However, studies on local PAH emissions and associated health risks related to urbanization are scarce. Here, the concentrations of PAHs were determined in 57 surface soil samples obtained from two rural districts in 2018 in Tianjin, China. The sources, risks, and the linkage between urbanization and PAH contamination of soils in 2018 were compared with PAH data in 2001 from a previous study to investigate the changes induced by urbanization. Results show an increase in PAH concentrations from 2001 to 2018, with in particular the predominance of anthracene and dibenz[a,h]anthracene. The major sources of soil PAHs changed from coal combustion 32.9%, petroleum sources 32.1%, and traffic sources 22.1% in 2001, to traffic sources 63.7%, and petroleum and biomass combustion 18.7% in 2018. The carcinogenic risk of soil PAHs to residents also increased from safe level to low level, and dermal contact was the prevailing pathway of PAH exposure. The increase in cancer risk is mainly due to the changes in PAH sources.

Metformin, an antidiabetic drug, shows some potent antitumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here, we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), a key enzyme in this pathway. Our results further demonstrated that metformin downregulated HMGCS1 expression through inhibition of transcription factor nuclear factor E2-related factor 2. In addition, we determined that HMGCS1 was highly expressed in human liver and lung cancer tissues and associated with lower survival rates. In summary, our study indicated that metformin suppresses tumorigenesis through inhibition of the nuclear factor E2-related factor 2-HMGCS1 axis, which might be a potential target in cancer prevention and treatment.

Due to infrequent rainfall, high temperatures, and degraded land, the Sahel region often suffers from droughts. The Sahel region is considered as one of the world’s driest and extreme environmental conditions. In order to assess spatiotemporal vulnerability of potential drought impacts, we used remote sensing and ground station data to evaluate drought conditions in the Sahel region from 1985 to 2015. The standard precipitation index (SPI), standard precipitation evapotranspiration index (SPEI), vegetation condition index (VCI) anomaly, along with socioeconomic indicators were performed. In addition, Pearson correlation coefficient (PCC) was computed between drought indices and three main crops (sorghum, millet, and maize) in the region to estimate the effects. The analysis showed that temperature increased by 0.78°C from 1985 to 2015, which had a significant impact on crop yield for sorghum, maize, and millet with a statistical significance value of P > 0.05. In the decade spanning 1994 to 2005 alone, the temperature increased by 0.57°C, which resulted in extreme drought in Algeria, Sudan, Chad, Nigeria, and Mauritania. For the effect of drought on crop production, high significance was noted on the SPI and SPEI-3 timescale: sorghum with SPI-3 (r = 0.71) and SPEI-3 (r = 0.65), millet with SPI-3 (r = 0.61) and SPEI-3 (r = 0.72), and maize with SPI-3 (r = 0.81) and SPEI-3 (r = 0.65) during the study period. In the growing season, VCI anomaly had strong correlations with sorghum and millet (r = 0.67 and 0.75, respectively). A significant agreement was also noticed between the combined drought index (CDI) and vulnerability index (VI) in Burkina Faso (r = −0.676; P < 0.00), Mali (r = −0.768; P < 0.00), Mauritania (r = 0.843; P < 0.001), Niger (r = −0.625; P < 0.001), and Nigeria (r = −0.75; P < 0.005). The results show that the above indices are effective in assessing agricultural drought and its impact on crop production in the Sahel, and in identifying areas most affected by drought.

The large-scale transformation of natural ecosystems to socio-economic development land types under human activities was a primary reason for the decline of regional ecosystem services. It is a key issue for regional ecosystem planning and management to reveal the relationship between ecosystem services of different land use types under different socio-economic driving degrees. However, the current related research was not in-depth. Based on the land use data of Wuhan City in 1980, 1990, 2000, 2010, and 2020, this study classified land use into three categories according to the different degrees of human activities on natural ecosystem development: the land use of a natural ecosystem (LUNE), the land use of a productive ecosystem (LUPE), and the land use of a socio-economic system (LUSE). The InVEST model was used to simulate five ecosystem services (grain yield, water yield, carbon storage, habitat quality, and water purification), and the spatio-temporal distribution and functional transformation of the three land use types were analyzed. Results showed that with the intensified urban expansion in Wuhan, the LUSE types increased to 2.7 times that of the original. However, the natural land types basically maintained a stable area, coupling with the large-scale transformation between the LUPE and LUSE types. Land use change resulted in significant spatial changes of five ecosystem services, especially carbon storage and habitat quality. The correlation analysis indicated that the five kinds of ecosystem services mainly showed a synergistic relationship, meanwhile the LUSE type denoted the most significant correlation with ecosystem services among these three category types. This study indicated that besides the protection of natural ecosystems, the LUSE type would become the key land use type in the planning and management of improving regional ecological function.

How to manage multiple ecosystem services (ES) in complex social-ecological systems during rapid urbanization is a key challenge for sustainable development. We used the ES bundles method to identify counties with similar dominant ES and then determine low- and high-value ES areas in the Beijing-Tianjin-Hebei Metropolitan Area (BTH), China. Seven vital ES, including provision of grains, vegetables, fruits, carbon storage, and water, soil, and sand retention were analyzed in 202 BTH counties to determine their spatial patterns, pairwise relationships, and relationships with nine social-ecological factors. There were synergies within provisioning and regulating services and trade-offs between groups. Five distinct ES bundles were identified, which were consistent with land use in the BTH, and the proportions of forestland and cropland were the major factors determining ES patterns. The 45 counties within the “urban-water bundle” and the 64 counties within the “suburban bundle” provided only 4% carbon storage, were suggested to increase the green space thereby increasing the capacity of ES providing. The “high regulating ES bundle” comprised 33 counties and provided 74% carbon storage, 75% soil retention, and 54% water retention for the BTH. The “sand retention bundle”, including 17 counties, provided 78% sand retention. These two ES bundles were suggested to be protected from land development for urbanization and reclamation. The “suburban bundle” and the “agriculture bundle”, which provided 78% of the grains, were the main source of food and responsible for avoiding the conversion of cropland to construction land. Overall, these results suggest that ES bundle analyses can not only identify the dominant services, but also demonstrate the multiple functions of landscape. The characteristics of each ES bundle can provide information to find potential win-win solutions for the land management.

Background Stereotactic radiosurgery (SRS) is an important treatment option. This report evaluated the efficacy and safety of SRS in patients with large cerebellum metastases from lung cancer. Methods Between September 2016 and January 2020, a total of 44 patients with large cerebellum metastases >2 cm from lung cancer were evaluated. A median dose of 20 Gy (range, 8-24 Gy) was delivered in 1 to 3 fractions for SRS treatment. The survival rate was analyzed with SPSS software 21.0 and compared by log-rank test using the Kaplan-Meier method. Results The median overall survival (OS) and neurological progression-free survival (PFS) were 10.5 months (range, 1-32 months) and 9.0 months (range, 1-32 months), respectively. The median diameter and volume of the metastases were 3.5 cm (range, 2.1-5.7 cm) and 12.5 cc (range, 1.8-39.7 cc), respectively. The median volume of peritumoral edema was 36.3 cc (range, 3.7-100.3 cc). The median ratio of tumor volume to cerebellum volume was 8.7% (range, 1.3-27.0%). The median ratio of peritumoral edema volume to cerebellum volume was 25.0% (range, 2.5-68.6%). Neurological symptoms were present in 97.7% (43/44) of patients. After SRS treatment, symptoms improved in 83.7% (36/44) patients, stabilized in 11.6% (5/44) patients, whilst two patients experienced symptomatic progression. Of the latter, one patient accepted emergency surgery and the other accepted palliative care. Conclusions Large cerebellum metastases are amongst the most severe forms of brain tumors. Increased tumor volume and peritumoral edema volume correlate with the most severe symptoms. SRS may be an effective alternative treatment for large cerebellum metastases from lung cancer and may preserve neurological function.

To evaluate the risk of a pipe in the water supply network of Beijing, we used the accident records of the gridding urban management (GUM) system. In addition, road and building information derived from a three-dimensional (3D) electronic map was also employed. A machine learning algorithm, the decision tree, was employed to train and evaluate the dataset. The results show that the contributions of the surrounding buildings and roads are neglectable, except for super-high-rise buildings, which have limited contributions. This finding is consistent with the results of other studies. The decision tree identifies dominant features and isolates the risk contribution of such features. The output tree structure indicated that the time since the last accident is a dominant factor, to which super-high-rise buildings contribute slightly. A cut-off value of 0.019 was chosen to predict high-risk regions. Approximately 0.4% of the data were predicted to be high risk, and the corresponding gain in risk rate was approximately 19.2. This model may be used in cities where detailed profiles of water supply pipes and maintenance records are not available or are expensive to achieve.

Polycyclic aromatic hydrocarbons (PAHs) in urban soils are of increasing concern because of their potential toxicity and persistence. However, there is limited information about PAHs in Tianjin coastal new region, although it is an important economic and industrial center in Northern China. Here we determined the concentrations of PAHs in 210 surface soil samples collected from this region according to administrative divisions covering Han’gu district, Tanggu district, and Dagang district, to evaluate their contamination and potential cancer risks. The concentrations of 16 PAHs ranged from 58.2 to 9160 ng g−1, and the highest concentration was found in Han’gu district. According to the incremental lifetime cancer risk (ILCR) model, the soils from Han’gu district and Dagang district posed a moderate carcinogenic risk to residents, and dermal contact was the main exposure pathway. Besides, ILCRs for children through ingestion were comparable to those for adults but apparently higher than adolescents, while ILCRs of dermal contact for adults were higher than children and adolescents. Comparisons between the layout of industrial zones and the distributions of PAHs as well as ILCRs indicate that PAHs accumulating in soils and then incurring risk areas is partly controlled by the economic and industrial structure.

Background Exhausted T cells and regulatory T cells (Tregs) comprise diverse subsets of tumor immunosuppressive microenvironment that play key roles in tumor progress. Understanding subset diversity in T cells is a critical question for developing cancer immunotherapy. Methods A total of 235 specimens from surgical resections of hepatocellular carcinoma (HCC) patients were examined for infiltration of exhausted T cell (Tex) in tumor and adjacent tissue. We conducted deep single‐cell targeted immune profiling on CD3+ cells collected from tumor tissues, adjacent normal tissues (ANTs) and peripheral blood of HCC patients. Total 10 cell clusters were identified with distinct distributions and characteristics. Results We observed transitional differentiation of exhausted CD8+T cells and Tregs increasingly enriched in tumor tissue. The accumulation and location of Tex were related to the differences in the long‐term clinical outcome of HCC. Furthermore, data of single‐cell RNA‐seq showed that (1) cells transforming from effector CD8+ T cells to exhausted CD8+ T cells simultaneously expressed upregulated effector molecules and inhibitory receptors, (2) indicated alteration of gene expression related to stress response and cell cycle at early exhaustion stage, and (3) immunosuppressive Treg had profound activation in comparison to resting Tregs. Conclusions T cell exhaustion is a progressive process, and the gene‐expression profiling displayed T cell exhaustion and anergy are different. Accordingly, it is possible that functional exhaustion is caused by the combination effects of passive defects and overactivation in stress response. The results help to understand the dynamic framework of T cells function in cancer which is important for designing rational cancer immunotherapies.

Ecological benefits provided by ecosystem assets play an important role in improving human wellbeing. However, there are few feasible methods to combine data on the quantity and quality of ecosystem assets to describe their state and trend. Here, we developed a new remote-sensing-based indicator by synthesizing ecosystem asset quantity and quality data for effective assessment at a regional or national scale. The new indicator includes a typological ecosystem asset index (TEAI) (e.g., forest ecosystem asset index) and an integrated ecosystem asset index (IEAI). The TEAI and IEAI can be used to assess the state and trend of a specific ecosystem or set of regional ecosystems, respectively. We applied the new indicator in the context of ecological protection policy in the Three-Rivers Source Region (TRSR), a region known as the ‘Chinese water tower’. From 2000 to 2015, the IEAI increased by 4.02% due to an increase in the ecosystem asset area (0.2%) and the ecosystem asset quality (0.66% and 0.02% increases in excellent and good level ecosystem assets, respectively). The implementation of ecological protection and ecological restoration programs was the main direct driver of regional ecological asset improvement. Our results suggest the new indicator is feasible for quickly and accurately evaluating the state and trend of ecosystem assets and can be used to guide ecosystem management at a large regional scale.

Application of Siwei Xiaoliuyin in glioma mice. Explore the effect of Siwei Xiaoliuyin on angiogenesis of nude mice glioma and its mechanism.Establish human glioma cell line U87 tumor model. Mice were randomized to the saline group, the conventional dose of Siwei Xiaoliuyin, high dose group of Siwei Xiaoliuyin, TMZ group, combination therapy group, record the tumor volume. Using the method of Weidner counted the microvessel density. ELISA enzyme-linked adsorption method to detect the content of nude mice serum VEGF and ES. The difference was statistically significant (P0.05).The tumor volume and MVD of conventional dose group, large dose group, Siwei Xiaoliuyin combined temozolomide group was smaller than the blank group，the difference was statistically significant (P0.05). VEGF levels in three groups of nude mice were lower than the blank group and ES content is higher than blank group, the difference was statistically significant (P0.05).Siwei Xiaoliuyin can inhibit glioma angiogenesis. Its mechanism of glioma angiogenesis inhibition may be through regulation VEGF and down-regulation of endostatin expression of vascular endothelial growth factor achieved. Down-regulation of endostatin expression of vascular endothelial growth factor achieved.

To provide evidence for the mechanism of Chinese medicine to treat glioma. We observe the effects of Si wei xiao xiu yin combined with chemotherapy on the growth of subcutaneous xenografts in nude mice and the expression of miRNA-21 and miRNA-221 in tumor tissues.The subcutaneous transplantation model of nude mice was established by subcutaneous inoculation of glioma U87 cell suspension. They were randomly divided into saline group, traditional Chinese medicine group, temozolomide group and traditional Chinese medicine combined with temozolomide group to observe the changes in body weight, and the tumor weight, length, short diameter, volume of mice. The relative expression levels of miRNA-21 and miRNA-221 in tumor tissues were detected by qRT-PCR, and the differences between groups were compared.After 28 days of gavage, the tumor growth of the other three groups was slower than that of saline group, and the difference was most significant in the combination group (P=0.0080.05), besides, the relative expression of the three groups of miRNA-21 and miRNA-221 was significantly inhibited compared with saline group, and the difference was significant in the combination group (F=8.918, P=0.0100.05).To some extent, Si wei xiao xiu yin combined with temozolomide can inhibit the growth of subcutaneous xenografts in glioma nude mice. The mechanism may be related to the inhibition of miRNA-21 and miRNA-221 expression.

Vision is the most important source of information for Unmanned Underwater Vehicle(UUV), only a clear image can make it possible for a UUV to operate automatically, Due to strong absorption and light scattering for water, the image of underwater imaging has a serious degradation, whether in distance or in quality. Based on classical Retinex theory, this paper proposed an underwater image enhanced algorithm. For different channel of underwater image has apparently different energy, especially green channel has overwhelming power than others, we added a step to energy balance of the RGB three channel in classical Multi-Scale Retinex (MSR). Experiment data show that, compared to the traditional three-channel simple addition, our improvement can get more natural recovered underwater image.

Objective: To provide evidence for the mechanism of Chinese medicine to treat glioma. We observe the effects of Si wei xiao xiu yin combined with chemotherapy on the growth of subcutaneous xenografts in nude mice and the expression of miRNA-21 and miRNA-221 in tumor tissues. Methods: The subcutaneous transplantation model of nude mice was established by subcutaneous inoculation of glioma U87 cell suspension. They were randomly divided into saline group, traditional Chinese medicine group, temozolomide group and traditional Chinese medicine combined with temozolomide group to observe the changes in body weight, and the tumor weight, length, short diameter, volume of mice. The relative expression levels of miRNA-21 and miRNA-221 in tumor tissues were detected by qRT-PCR, and the differences between groups were compared. Results: After 28 days of gavage, the tumor growth of the other three groups was slower than that of saline group, and the difference was most significant in the combination group (P = 0.008 Conclusion: To some extent, Si wei xiao xiu yin combined with temozolomide can inhibit the growth of subcutaneous xenografts in glioma nude mice. The mechanism may be related to the inhibition of miRNA-21 and miRNA-221 expression.

The application of controlled release urea (CRU) has been proposed as a crucial method to reduce the adverse environmental effects induced by conventional urea (CU). Yet, a systematic and quantitative analysis on how CRU affects staple crop production including wheat (Triticum aestivum L.), maize (Zea mays L.), and rice (Oryza sativa L.) is lacking. Here, a meta-analysis was conducted to determine how CRU influences soil chemical properties, total nitrogen (TN) uptake, grain yield, and nitrogen use efficiency (NUE) of staple crop in China. The results indicated that CRU application significantly increased soil organic carbon (SOC), TN, and available nitrogen (AN) by 5.93%, 3.89% and 13.98% respectively overall, while soil pH showed no significant changes. Compared to the application of CU, applying CRU significantly increased grain yield by 7.23%, which was mainly owing to the higher TN uptake (9.13%) across all the studies. In addition, the application of CRU significantly increased NUE, nitrogen agronomy efficiency (NAE), utilization rate of nitrogen fertilizer (NUR), and nitrogen physiological efficiency (NPE) by an average of 23.4%, 34.65%, 25.83% and 15.8% respectively which could be attributed to the slow nitrogen (N) release characteristics of CRU. The positive effect of CRU on grain yield and NUE of staple crop was greatest when the content of SOC and TN were extremely low, indicating that it was most effective to improve grain production of infertile soil by applying CRU. The finding of this study indicated that the application of CRU should be promoted for grain production, especially for infertile soil.

Objective: Application of Siwei Xiaoliuyin in glioma mice. Explore the effect of Siwei Xiaoliuyin on angiogenesis of nude mice glioma and its mechanism. Methods: Establish human glioma cell line U87 tumor model. Mice were randomized to the saline group, the conventional dose of Siwei Xiaoliuyin, high dose group of Siwei Xiaoliuyin, TMZ group, combination therapy group, record the tumor volume. Using the method of Weidner counted the microvessel density. ELISA enzyme-linked adsorption method to detect the content of nude mice serum VEGF and ES. The difference was statistically significant (P Results: The tumor volume and MVD of conventional dose group, large dose group, Siwei Xiaoliuyin combined temozolomide group was smaller than the blank group，the difference was statistically significant (P Conclusion: Siwei Xiaoliuyin can inhibit glioma angiogenesis. Its mechanism of glioma angiogenesis inhibition may be through regulation VEGF and down-regulation of endostatin expression of vascular endothelial growth factor achieved. Down-regulation of endostatin expression of vascular endothelial growth factor achieved.

OBJECTIVE To retrospective analyze 10 patients with intracranial primary yolk sac tumors(YST) for exploring an optimal treatment strategy. METHODS Ten patients with YST were confirmed by pathological diagnosis (9 male and 1 female), with a median age of 13 years. Except for 1 case was lost to follow-up, 9 patients were treated with partial resection, followed by WBRT and local boosts, and then adjuvant chemotherapy. The time it took for serum AFP to decrease to the lowest level (including abnormal situation) or to return to the normal level was recorded. The brain tumor apoplexies before and after treatment were studied. Finally, OS and PFS of the patients were analyzed. RESULTS The patients were followed-up to 02-2019, with a mean follow-up time of 25.44 months. The analysis showed that the mOS and mPFS were 18 months and 7 months, respectively, and that 1y-OS and 2y-OS were 77.8% and 22.2%, while 1y-PFS and 2y-PFS were 22.2% and 11.1%. The time it took for serum AFP to decrease to the lowest level or to return to the normal level was 0–382 days, with a median time of 144 days (165.22±131.71 days). After being followed-up to 02-2019, 4 patients still survived; 4 patients died of tumor recurrence; 1 patient died of severe pneumonia. Although one of the 4 patients (tumor recurrence) was treated with 3 times of surgeries, died of tumor progression, with a survival time of 17 months. The other one patient had a 1y-PFS of 3 months, and he received surgery and chemotherapy for recurrent tumors, achieving a 2y-PFS up to 71+ months. CONCLUSION YST has a low incidence rate and is easy to recurrence, with a poor prognosis. Resection combined with chemoradiotherapy can prolong the survival time of patients, but the optimal treatment strategy remains unclear and needs further research.

Songjiang Wu, Yanying Yang, Feiping Li, Lifu Huang, Zihua Han, Guanfu Wang, Hongyuan Yu, Haiping Li Department of Urology, Enze Hospital of Taizhou Enze Medical Center (Group), Taizhou, China Introduction: Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE), a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in prostate cancer cells were studied for the first time. Methods: In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis. Results: Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE. Conclusion: Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer. Keywords: chelerythrine, reactive oxygen species, endoplasmic reticulum stress, apoptosis, prostate cancer

BACKGROUND the FLAURA study established Osimertinib to be the priority choice for the treatment of metastatic non-small cell lung cancer (NSCLC) harboring mutated epidermal growth factor receptor (EGFR). However, like many previous studies, the FLAURA study excluded patients with symptomatic CNS metastases. Hence, we performed a systematic review and meta-analyses of studies to assess the efficiency and safety of Osimertinib for the treatment of NSCLC with leptomeningeal metastases (LM). METHODS We included studies published between 2010 and 2021 that evaluated the efficacy and toxicity of Osimertinib in NSCLC patients with LM. We searched PubMed, Embase, and oncology meeting abstracts (ASCO, ESMO and WCLC). Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate. We used the random-effects model to generate pooled estimates for proportions. Newcastle-Ottawa Scale (NOS) was used to assess the certainty in the evidence. RESULTS Twelve studies reporting on 367 patients were included in the meta-analysis. Most patients (≥90%) received Osimertinib as at least second line of treatment. The objective response rate was 42% (95% CI, 24%-59%; n = 184), and CNS disease control rate was 90% (95% CI, 85%-94%; n = 154). Intracranial progression free survival and overall survival ranged from 3.7 to 15.6 months, and 11.0 to 18.8 months, respectively. Adverse events were similar with previous studies and Common Terminology Criteria for Adverse Events (version 3.0) grade 3 or higher adverse event rates was acceptable. CONCLUSION This meta-analysis confirmed that for advanced NSCLC with LM harboring EGFR-TKI-sensitizing mutations, Osimertinib showed impressive antitumor activity and acceptable toxicity.