The significance of appendectomy in the context of colorectal cancer: impacts on gut microbiota and beyond.

Colorectal cancer (CRC) remains one of the most common malignancies globally, of which the initiative factors are multiple and complex. More recently, the major roles played by gut microbiota in the carcinogenesis of CRC have been uncovered, which indicates that dysbiosis caused by specific bacterial or fungal species may contribute to the malignant progression of CRC. Meanwhile, appendix, classically identified as an evolutionary relict with negligible physiological functions, has been found to play crucial roles in the immune modulation process and microbiome composition of gut by its lymphoid tissue features. In addition, appendectomy, a common surgical operation modality, has also been found to be closely correlated with the clinical outcomes of multiple diseases, including CRC. Naturally, these evidence collectively point to a possibility that the appendectomy may influence the pathological process of CRC through its impacts on gut microbiome.

Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects.

The molecules of Major histocompatibility class I (MHC-I) load peptides and present them on the cell surface, which provided the immune system with the signal to detect and eliminate the infected or cancerous cells. In the context of cancer, owing to the crucial immune-regulatory roles played by MHC-I molecules, the abnormal modulation of MHC-I expression and function could be hijacked by tumor cells to escape the immune surveillance and attack, thereby promoting tumoral progression and impairing the efficacy of cancer immunotherapy. Here we reviewed and discussed the recent studies and discoveries related to the MHC-I molecules and their multidirectional functions in the development of cancer, mainly focusing on the interactions between MHC-I and the multiple participators in the tumor microenvironment and highlighting the significance of targeting MHC-I for optimizing the efficacy of cancer immunotherapy and a deeper understanding of the dynamic nature and functioning mechanism of MHC-I in cancer.

Robotic-assisted laparoscopic tumor enucleation is a feasible technique for renal hilar tumors: A retrospective study.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the safety and efficacy of robot-assisted laparoscopic tumor enucleation (RAE) for the treatment of renal hilar tumors and to describe our experience with renorrhaphy-related surgical techniques. METHODS: Retrospective data were collected from 173 consecutive patients who underwent RAE for localized renal tumors (cT1-cT2N0M0) at our hospital between September 2014 and November 2019. RESULTS: Seventy-five patients had renal hilar tumors and 98 patients had nonhilar tumors. There were no statistical differences between the hilar and nonhilar groups in operation time (190 [115-390] vs. 190 [110-390] min, p = 0.889), warm ischemia time (26 [12-60] vs. 27 [17-41] min, p = 0.257), hospital stay duration (8 [3-16] vs. 7.5 [4-18] days, p = 0.386), renal function (estimated glomerular filtration rate, 102.5 [29.4-144] vs. 101.3 [64.2-134.7] ml/min/1.73 m2 , p = 0.631); creatinine level, (76 [43-169] vs. 78.5 [50-281.3] µmol/L, p = 0.673), perioperative complications rate, or surgical margin status. However, patients with hilar tumors lost significantly more blood than did those with nonhilar tumors (250 [50-1500] vs. 200 [20-1200] ml, p = 0.007). During the follow-up period (median, 30 months), three patients in each group experienced recurrence. The 5-year recurrence-free rates were 93.0% and 95.4% in the hilar and nonhilar tumor groups, respectively (p = 0.640). CONCLUSIONS: For experienced robot laparoscopists, RAE is a safe, effective, and feasible procedure for renal hilar tumors, without increased risk of positive surgical margins or worse midterm oncologic outcomes compared with nonhilar tumors.

Response of mercury accumulation to anthropogenic pollution in the past 1000 years based on Lake Huguangyan sediments, Southern China.

A new 210Pb-dated record of Hg accumulation derived from a sediment core from a Hg-enriched area in Huguangyan Lake (HGY) in South China is presented. Based on synthetic analyses of multi-proxy records including chemical composition, total organic matter, and grain-size distribution in surface sediments and nearby soil samples, it is inferred that the influx of Hg into the lake is mainly a result of atmospheric deposition, with no or minor hydroclimate-induced lithogenic input from the catchment and limited adsorption effects of organic matter and clay. Significantly enhanced anthropogenic input of Hg started in the early 1900s. Since then, several anomalies of Hg accumulation have been the results of wars or intensified economic activities in China. HGY sediments provide a rare and reliable natural archive for detecting atmospheric Hg deposition, which is closely related to anthropogenic activities.

Novel observations in choroidal osteoma by multispectral imaging: a pilot case series.

PURPOSE: To identify novel tumor-specific features of ossification by using multispectral imaging (MSI) in patients diagnosed with choroidal osteoma. METHODS: Six eyes of 5 patients previously diagnosed with choroidal osteoma by ocular ultrasonography and orbital computerized tomography were observed with multispectral imaging (MSI). Traditional multimodal imaging, including color fundus photograph (CFP) and enhanced depth-imaging-optical coherence tomography (EDI-OCT), fundus autofluorescence (FAF), indocyanine green angiography/fundus fluorescein angiography (ICGA/FFA), was performed. Osseous features detected by MSI such as calcification and decalcification were characterized and compared with other imaging modalities. RESULTS: In all 3 eyes with calcified choroidal osteoma (100%), MSI featured by the homogeneous reflectance in 550 nm but the beehive appearance in 600-680 nm and homogenous hyper-reflectance in 780-850 nm', indicating the compact bone in the outer layers and bone trabecula in the middle layer (Sandwich sign). The pigmentary change showed high agreement between MSI and FAF. In other 3 eyes with extensive decalcification, MSI was able to differentiate the inactive portion of the osteoma from the decalcified area. The inactive portion was characterized by geographic hyper-reflective islands with higher reflectivity border (floating island sign). Decalcified portion was featured by increased definition and reflectivity from osteoma. Partial decalcification and total decalcification can be differentiated in one decalcifying eye (33.3%). MSI revealed better the presence and border of the osteoma compared with FFA, FAF and MC (100%) in all six eyes in our study. CONCLUSIONS: MSI presented characteristic osseous-related features of choroidal osteoma, providing clear evidence for differentiating osteoblastic and osteoclastic regions and noncalcifying regions. It can contribute to en-face visualization of choroidal osteomas at different stages, providing new insight into the spectrum behavior of CO.

Primary Tr1 cells from metastatic melanoma eliminate tumor-promoting macrophages through granzyme B- and perforin-dependent mechanisms.

In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells. Tr1 cells were characterized by high interleukin 10 secretion and low Foxp3 expression and were enriched in the CD4+CD49b+LAG-3+ T-cell fraction. Macrophages derived from peripheral blood monocytes in the presence of modified melanoma-conditioned media demonstrated tumor-promoting capacity, exemplified by improving the proliferation of cocultured A375 malignant melanoma cells. But when primary Tr1 cells were present in the macrophage-A375 coculture, the growth of A375 cells was abrogated. The conventional CD25+ Treg cells, however, were unable to inhibit macrophage-mediated increase in tumor cell growth. Further analyses showed that Tr1 cells did not directly eliminate A375 cells, but mediated the killing of tumor-promoting macrophages through the secretion of granzyme B and perforin. The tumor-infiltrating interleukin 10+Foxp3-CD4+ T cells expressed very low levels of granzyme B and perforin, possibly suggested the downregulation of Tr1 cytotoxic capacity in melanoma tumors. Together, these data demonstrated an antitumor function of Tr1 cells through the elimination of tumor-promoting macrophages, which was not shared by conventional Tregs.

CD4+ T cell-mediated cytotoxicity eliminates primary tumor cells in metastatic melanoma through high MHC class II expression and can be enhanced by inhibitory receptor blockade.

Metastatic melanoma is a rapidly progressing disease with high mortality rate and limited treatment options. Immunotherapy based on tumor-targeting cytotoxic T cell responses represents a promising strategy. To assist in its development, we examined the possibility and efficacy of using CD4+ cytotoxic T cells. The regulatory mechanisms controlling CD4+ T cell-mediated cytotoxicity were also investigated. We found that naturally occurring granzyme B and perforin-expressing CD4+ cytotoxic T cells can be recovered from metastatic melanoma patients at significantly elevated frequencies compared to those from healthy controls. These CD4+ cytotoxic T cells were also capable of killing autologous tumor cells harvested from metastatic melanoma, independent of CD8+ T cells or any other cell types. However, several restricting factors were observed. First, the cytolytic activity by CD4+ T cells required high MHC class II expression on melanoma cells, which was not satisfied in a subset of melanomas. Second, the granzyme B and perforin release by activated CD4+ cytotoxic T cells was reduced after coculturing with autologous melanoma cells, characterized by low LAMP-1 expression and low granzyme B and perforin secretion in the supernatant. This suggested that inhibitory mechanisms were present to suppress CD4+ cytotoxic T cells. Indeed, blockade of PD-1 and CTLA-4 had increased the cytolytic activity of CD4+ T cells but was only effective in MHC class II high but not MHC class II low melanomas. Together, our study showed that CD4+ T cell-mediated cytotoxicity could eliminate primary melanoma cells but the efficacy depended on MHC class II expression.

ABT-737 sensitizes curcumin-induced anti-melanoma cell activity through facilitating mPTP death pathway.

In the current study, we studied the potential role of ABT-737, a novel Bcl-2 inhibitor, on curcumin-induced anti-melanoma cell activity in vitro. The associated mechanisms were also investigated. We demonstrated that ABT-737 significantly sensitized curcumin-induced activity against melanoma cells (WM-115 and B16 lines), resulting in substantial cell death and apoptosis with co-administration. At the molecular level, curcumin and ABT-737 synergistically induced mitochondrial permeability transition pore (mPTP) opening in melanoma cells, the latter was evidenced by mitochondrial membrane potential (MPP) reduction and mitochondrial complexation between cyclophilin-D (CyPD) and adenine nucleotide translocator 1 (ANT-1). Significantly, mPTP blockers, including cyclosporin A and sanglifehrin A, remarkably inhibited curcumin and ABT-737 co-administration-induced cytotoxicity against melanoma cells. Meanwhile, siRNA-mediated knockdown of CyPD or ANT-1, the two key components of mPTP, alleviated WM-116 cell death by the co-treatment. Collectively, we show that ABT-737 sensitizes curcumin-induced anti-melanoma cell activity probably through facilitating mPTP death pathway. ABT-737 could be further investigated as a potential curcumin adjuvant in melanoma and other cancer treatment.

Neutron Activation Analysis Based on AB-BNCT Treatment Room.

ABSTRACT: Boron neutron capture therapy (BNCT) is an ideal binary targeted radiotherapy for treating refractory tumors. An accelerator-based BNCT (AB-BNCT) neutron source has attracted more and more attention due to its advantages such as higher neutron yield in the keV energy region, less gamma radiation, and higher safety. In addition to 10B, neutrons also react with other elements in the treatment room during BNCT to produce many activation products. Due to the long half-life of some activation products, there will be residual radiation after the end of treatment and the shutdown of the accelerator, which has adverse effects on radiation workers. Therefore, the ambient dose equivalent rate in the treatment room needs to be evaluated. The AB-BNCT neutron source model proposed by Li is studied in this paper. Based on the Monte Carlo method, the Geant4 platform was used to simulate the dose induced by radionuclides near the Beam Shaping Assembly (BSA) of the source. It is concluded that the concrete wall contributed the most to the radiation dose. The dose rate of 2.45 µSv h-1 after 13 min of shutdown meets the dose rate limit of 2.5 µSv h-1, at which point it is safe for workers to enter the treatment room area.

Gut microbiome changes associated with chronic pancreatitis and pancreatic cancer: A systematic review and Meta-analysis.

BACKGROUND: The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC. METHODS: Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes we focus on. RESULTS: This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC (n=285), CP (n=342), and control (n=649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=-0.33; P=0.002 and SMD=-0.59; P<0.001, respectively) and a statistically significant ß-diversity (P<0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that 4 genera were significantly increased in PDAC patients compared to HC (e.g., Escherichia-Shigella and Veillonella). CP patients had an increase in 4 genera (e.g., Escherichia-Shigella and Klebsiella) and a decrease in 8 genera (e.g., Coprococcus and Bifidobacterium) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients. CONCLUSIONS: Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.

Performance of 18F-FDG PET/MRI and its parameters in staging and neoadjuvant therapy response evaluation in bladder cancer.

18F-FDG PET/MRI shows potential efficacy in the diagnosis of bladder cancer (BLCA). However, the performance of 18F-FDG PET/MRI in staging and neoadjuvant therapy (NAT) response evaluation for BLCA patients remains elusive. Here, we conduct this study to evaluate the performance of 18F-FDG PET/MRI and its derived parameters for tumor staging and NAT response prediction in BLCA. Forty BLCA patients were retrospectively enrolled to evaluate the performance of 18F-FDG PET/MRI in staging and NAT response prediction in BLCA. The feasibility of using 18F-FDG PET/MRI-related parameters for tumor staging and NAT response evaluation was also analyzed. In conclusion, 18F-FDG PET/MRI is found to show good performance in the BLCA staging and NAT response prediction. Moreover, ΔSUVmean is an efficacious candidate parameter for NAT response prediction. This study highlights that 18F-FDG PET/MRI is a promising imaging approach in the clinical diagnosis and treatment for BLCA.

Prognostic and immunological role of Asporin across cancers and exploration in bladder cancer.

BACKGROUND: Asporin (ASPN) has been identified as a player in tumorigenesis, but its precise roles and modulatory function are largely unknown. METHODS: In the present study, ASPN expression was first explored, followed by a prognostic evaluation of ASPN and a comprehensive investigation of the connections between ASPN and immunomodulation, immune cell infiltration and potential compounds on a pancancer level. Finally, ASPN expression was validated in bladder urothelial carcinoma (BLCA) tissues, and the potential function of ASPN, including its effects on migration and invasion capabilities, was investigated in tumor cells. RESULTS: The expression of ASPN exhibited significant variation across cancers and was found to be associated with patient prognosis. In addition, the expression level of APSN was markedly correlated with the abundances of infiltrating immune cells and cancer-associated fibroblasts and the expression levels of immunomodulatory genes based on the results of pancancer analysis. Metastasis and immune-associated signaling pathways were identified in enrichment analysis based on ASPN expression. Finally, we confirmed that ASPN expression increased with the degree of malignancy in BLCA tissues and cell lines and that low expression of ASPN hindered the migration and invasion of cells. CONCLUSIONS: ASPN has the potential to be a biomarker of cancer prognosis and a therapeutic target, and it also has predictive capability for the progression of BLCA.

The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer.

Introduction: Bladder cancer (BLCA) is a highly malignant tumor of the urinary system, but the prognosis and survival rates have little improvement based on current therapeutic strategy. Immune checkpoint inhibitors (ICIs) therapy revolutionized the treatment of BLCA, but the clinical application of ICIs is limited by low response rate. Oxaliplatin (OXP), a second line chemotherapy drug for BLCA, may reshape the tumor immune microenvironment (TIME) via recruiting immune cells. Here, we conducted the study of oxaliplatin combined with anti-PD-1 inhibitor in BLCA mice models. Methods: The 6-8 weeks old female C57BL/6J mice were used to establish subcutaneous model of bladder tumor. After tumors developed, mice were given tail vein injections of PBS or oxaliplatin (2.5 mg/kg) and/or anti-PD-1 antibody (10 mg/kg). Tumor tissue samples and peripheral blood mononuclear cell (PBMC) were collected to systemically evaluate the efficiency and safety of combination OXP and anti-PD-1 inhibitor. The change of immune cells populations and the corresponding phenotypic diversity in TIME and PBMC were analysed by flow cytometry. Results: Tumor growth experiments clarified that the combination therapy was more efficient than medication alone. Flow cytometry analysis of tumor samples showed significant differences between untreated and treated mice. Oxaliplatin influences the TIME by increasing immune cells infiltration, including CD3+ T cells, CD4+ T cells, CD8+ T cells, dendritic cells (DC cells) and natural killer cells (NK cells). As for infiltrating cells, oxaliplatin upregulated the expression of CD134 and downregulated TIM-3 of CD4+ T cells, downregulated the PD-L1 expression of DC cells, which contributed to improve the anti-tumor effect and the treatment response of ICIs. Additionally, the evaluation of PBMC found that there were no significant changes in immune cell subsets and phenotypes, which validated the safety of the combination therapy. These results show the therapeutic potential for the combination of OXP and anti-PD-1 inhibitor in BLCA. Conclusion: OXP could increase the infiltration of immune cells in TIME to promote the anti-tumor activity of anti-PD-1 inhibitor. The present research provided an appropriate rationale of combination chemotherapy and immunotherapy therapy for BLCA.

Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature.

Objectives: To analyze the correlations between the expression and effect of DNA damage repair genes and the immune status and clinical outcomes of urothelial bladder cancer (BLCA) patients. In addition, we evaluate the efficacy and value of utilizing the DNA damage repair genes signature as a prognosis model for BLCA. Methods: Two subtype groups (C1 and C2) were produced based on the varied expression of DNA damage repair genes. Significantly differentiated genes and predicted enriched gene pathways were obtained between the two subtypes. Seven key genes were obtained from the DNA damage repair-related genes and a 7-gene signature prognosis model was established based on the key genes. The efficacy and accuracy of this model in prognosis prediction was evaluated and verified in two independent databases. Also, the difference in biological functions, drug sensitivity, immune infiltration and affinity between the high-risk group and low-risk group was analyzed. Results: The DNA damage repair gene signature could significantly differentiate the BLCA into two molecular subgroups with varied genetic expression and enriched gene pathways. Seven key genes were screened out from the 232 candidate genes for prognosis prediction and a 7-gene signature prognosis model was established based on them. Two independent patient cohorts (TCGA cohort and GEO cohort) were utilized to validate the efficacy of the prognosis model, which demonstrated an effective capability to differentiate and predict the overall survival of BLCA patients. Also, the high-risk group and low-risk group derived from the 7-gene model exhibited significantly differences in drug sensitivity, immune infiltration status and biological pathways enrichment. Conclusions: Our established 7-gene signature model based on the DNA damage repair genes could serve as a novel prognosis predictive tool for BLCA. The differentiation of BLCA patients based on the 7-gene signature model may be of great value for the appropriate selection of specific chemotherapy agents and immune-checkpoint blockade therapy administration.

ALOX5 deficiency contributes to bladder cancer progression by mediating ferroptosis escape.

Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.

[Ri plasmid transformation and metabolism of ginseng products on HepG2 cells].

OBJECTIVE: To study the Ri plasmid transformation and metabolism of ginseng products on HepG2 cells. METHOD: The inhibitory effect of ginseng saponin on hepatoma HepG2 cells was studied. The hairy root-induced conditions were screened by orthogonal experimental design. The culture conditions were determined through hairy root biomass accumulation and saponin content. The effect of ginsenoside on HepG2 cells was determined by MTT assay. RESULT AND CONCLUSION: The optimal ginseng hairy root inducing conditions: A = 0.6, infection time of 10 min, pre-incubation time for the 3 d. The best culture conditions: MS medium, pH 6.1, 24 degrees C. At those conditions the hairy root bio-accumulation and saponin content were higher. The results of ginseng saponins on the inhibitory effect of HepG2 cells showed that inhibition of ginseng saponins on HepG2 was the concentration positively related.

Quantifying the human disturbance intensity of ecosystems and its natural and socioeconomic driving factors in urban agglomeration in South China.

The impact of human activities on terrestrial ecosystems is becoming more intense than ever in history. Human disturbance analyses play important roles in appropriately managing the human-environment relationship. In this study, a human disturbance index (HDI) that uses land use and land cover data from 1980, 2000, 2010, and 2018 is proposed to assess the human disturbance of ecosystems in the Guangdong-Hong Kong-Macao Greater Bay Area. The HDI is first calculated by classifying the human disturbance intensity into seven levels and 13 categories from weak to strong in ecosystems. Then the driving factors of the HDI spatial pattern change are explored using a geographically weighted regression (GWR) model. The results showed that the spatial pattern of the HDI was high in the middle and low in the surrounding areas. The intensity of human disturbance increased, and the medium and high disturbance areas expanded during 1980-2018, especially in Guangzhou, Foshan, Shenzhen, and Dongguan. Human disturbance displayed an obvious spatial heterogeneity. The GWR model had a better explanation effect of the analysis of the HDI change drivers. The driving effect of the socioeconomic conditions was significantly stronger than that of the natural environmental. This study assists in understanding the distribution and change characteristics of the ecological environment in areas with strong human activities and provides a reference for related studies.

Analysis and identification of the necroptosis landscape on therapy and prognosis in bladder cancer.

Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system, but the current therapeutic strategy based on chemotherapy and immune checkpoint inhibitor (ICI) therapy cannot meet the treatment needs, mainly owing to the endogenous or acquired apoptotic resistance of cancer cells. Targeting necroptosis provides a novel strategy for chemotherapy and targeted drugs and improves the efficacy of ICIs because of strong immunogenicity of necroptosis. Therefore, we systemically analyzed the necroptosis landscape on therapy and prognosis in BLCA. We first divided BLCA patients from The Cancer Genome Atlas (TCGA) database into two necroptosis-related clusters (C1 and C2). Necroptosis C2 showed a significantly better prognosis than C1, and the differential genes of C2 and C1 were mainly related to the immune response according to GO and KEGG analyses. Next, we constructed a novel necroptosis-related gene (NRG) signature consisting of SIRT6, FASN, GNLY, FNDC4, SRC, ANXA1, AIM2, and IKBKB to predict the survival of TCGA-BLCA cohort, and the accuracy of the NRG score was also verified by external datasets. In addition, a nomogram combining NRG score and several clinicopathological features was established to more accurately and conveniently predict the BLCA patient's survival. We also found that the NRG score was significantly related to the infiltration levels of CD8 T cells, NK cells, and iDC cells, the gene expression of CTLA4, PD-1, TIGIT, and LAG3 of TME, and the sensitivity to chemotherapy and targeted agents in BLCA patients. In conclusion, the NRG score has an excellent performance in evaluating the prognosis, clinicopathologic features, tumor microenvironment (TME), and therapeutic sensitivity of BLCA patients, which could be utilized as a guide for chemotherapy, ICI therapy, and combination therapy.

Spatial-temporal variations and pollution risks of mercury in water and sediments of urban lakes in Guangzhou City, South China.

This study aims to investigate the spatial and temporal characteristics, pollution degrees, and potential ecological risks of mercury (Hg) in urban lake waters and sediments in Guangzhou, where is a typical area of Hg emission and population-economic-industrial concentration in South China. In different districts of this city, the water from 15 lakes were collected continuously from June 2020 to May 2021, and the sediments from 9 lakes were collected in 2015 and 2021. The seasonal changes of Hg concentration (Hg-C) in the water were found to be high in winter and low in summer. The spatial distribution of Hg-C in sediments showed that it was high in urban central areas and low in suburbs. The Nemero index and geological accumulation index showed that there were uncontaminated of Hg in the collected lake water, and above moderately contaminated in the lake sediments in urban center, respectively. The Hg pollution potential ecological risk index showed that there was low risk in the collected water, high and extremely high risk in the lake sediments in urban center, respectively. The principal component analysis (PCA) and correlation analysis (CA) of Hg and meteorological factors showed that precipitation, temperature, and vapor pressure had negative effects on the seasonal changes of Hg-C in water, and air pressure and wind direction had positive effects. The PCA and CA of Hg and other geochemical elements showed that anthropogenic emissions may be the main sources of Hg in sediments, which was also supported by the data of population density, road density, and motor vehicles per 1000 people. This study provided a reference for urban lake pollution treatment, resident health, and ecological environment protection.