Approaching Ultimate Synthesis Reaction Rate of Ni-Rich Layered Cathodes for Lithium-Ion Batteries.

Nickel-rich layered oxide LiNixCoyMnzO2 (NCM, x + y + z = 1) is the most promising cathode material for high-energy lithium-ion batteries. However, conventional synthesis methods are limited by the slow heating rate, sluggish reaction dynamics, high energy consumption, and long reaction time. To overcome these challenges, we first employed a high-temperature shock (HTS) strategy for fast synthesis of the NCM, and the approaching ultimate reaction rate of solid phase transition is deeply investigated for the first time. In the HTS process, ultrafast average reaction rate of phase transition from Ni0.6Co0.2Mn0.2(OH)2 to Li- containing oxides is 66.7 (% s-1), that is, taking only 1.5 s. An ultrahigh heating rate leads to fast reaction kinetics, which induces the rapid phase transition of NCM cathodes. The HTS-synthesized nickel-rich layered oxides perform good cycling performances (94% for NCM523, 94% for NCM622, and 80% for NCM811 after 200 cycles at 4.3 V). These findings might also assist to pave the way for preparing effectively Ni-rich layered oxides for lithium-ion batteries.

Coupling Antisite Defect and Lattice Tensile Stimulates Facile Isotropic Li-Ion Diffusion.

Despite widely used as a commercial cathode, the anisotropic 1D channel hopping of lithium ions along the [010] direction in LiFePO4 prevents its application in fast charging conditions. Herein, an ultrafast nonequilibrium high-temperature shock technology is employed to controllably introduce the Li-Fe antisite defects and tensile strain into the lattice of LiFePO4. This design makes the study of the effect of the strain field on the performance further extended from the theoretical calculation to the experimental perspective. The existence of Li-Fe antisite defects makes it feasible for Li+ to move from the 4a site of the edge-sharing octahedra across the ab plane to 4c site of corner-sharing octahedra, producing a new diffusion channel different from [010]. Meanwhile, the presence of a tensile strain field reduces the energy barrier of the new 2D diffusion path. In the combination of electrochemical experiments and first-principles calculations, the unique multiscale coupling structure of Li-Fe antisite defects and lattice strain promotes isotropic 2D interchannel Li+ hopping, leading to excellent fast charging performance and cycling stability (high-capacity retention of 84.4% after 2000 cycles at 10 C). The new mechanism of Li+ diffusion kinetics accelerated by multiscale coupling can guide the design of high-rate electrodes.

Derivation and external validation of dendritic cell-related gene signatures for predicting prognosis and immunotherapy efficacy in bladder urothelial carcinoma.

Background: In the regulation of tumor-related immunity, dendritic cells (DCs) are crucial sentinel cells; they are powerful to present antigens and initiate immune responses. Therefore, we concentrated on investigating the DC-related gene profile, prognosis, and gene mutations in bladder urothelial carcinoma (BLCA) patients to identify sensitivity to immunotherapy of patients. Methods: According to DC infiltration, BLCA patients were divided into two subgroups, and differentially expressed genes (DEGs) were obtained. Patients were classified by unsupervised clustering into new subgroups. The least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression were used to develop a DC-related risk model. CIBERSORT, xCell, and GSEA were used to infer immune cells' relative abundance separately and enriched immune pathways. Results: A total of 29 prognosis-related DEGs were identified from the unsupervised cluster. Among them, 22 genes were selected for constructing the DC-related risk model. The dendritic cell-related risk score (DCRS) can accurately distinguish patients with different sensitive responses to immunotherapy and overall survival outcomes. Furthermore, patients with ryanodine receptor 2 (RYR2) mutation had a better prognosis. Conclusions: The DCRS played an essential part in immunity pathway and formation of TME diversity. Our study indicated that RYR2 mutation combined with DCRS is useful for predicting the prognosis and discovering appropriate patients for immunotherapy.

Case report: An ectopic adrenocortical adenoma in the renal sinus.

Background: Ectopic adrenal tissue is rare in adults, with an incidence of only about 1%. We report a rare case of ectopic adrenocortical adenoma in the left renal sinus. Case Preentation: A 57-year-old woman was admitted to the Department of Urology due to "a left kidney tumor" on physical examination. Multislice helical computed tomography (CT) showed the left kidney with an anterior lip mass near the hilum, approximately 2.3 cm × 2.2 cm in size. Preoperative renal artery CT angiography (CTA) showed no obvious abnormality. Laparoscopic resection of the left renal sinus mass was performed, and postoperative pathological findings showed ectopic adrenocortical adenoma. The tumor was a nonfunctional adenoma. Conclusion: Renal ectopic adrenal cortical adenoma is rare. Most of them are nonfunctional adenomas, which cannot be clearly diagnosed by preoperative imaging examination and can often be diagnosed by postoperative pathology.

Effect of Bicalutamide Combined with Docetaxel on Serum PSA and VEGF Levels in Patients with Advanced Prostate Carcinoma.

Objective: To investigate the effect of bicalutamide combined with docetaxel on the levels of prostate-specific antigen (PSA) in serum and vascular endothelial growth factor (VEGF) in patients with advanced prostate carcinoma (PCa). Methods: The clinical data of 103 patients with advanced PCa at our hospital between Feb. 2020 and Feb. 2021 were retrospectively analyzed, the 90 of whom screened by inclusion and exclusion criteria were finally chosen as research objects. They were divided into a control group and an experimental group according to the order of admission, with 45 cases in each group. The control group was treated with conventional treatment, while the experimental group underwent the combination of bicalutamide and docetaxel, and the clinical indices of the two groups were compared. Results: After treatment, the serum indices in the experimental group were remarkably lower than those in the control group (P < 0.001), with remarkably lower incidence of toxic and side effects (P < 0.05) and higher Expanded Prostate Cancer Index Composite (EPIC) scores (P < 0.001) in the experimental group than in the control group. Conclusion: The implementation of bicalutamide combined with docetaxel in patients with advanced PCa is effective in reducing the inflammatory expression and improving quality of life and has a higher safety profile. Compared with conventional treatment, this method is of high application value, and further studies will help establish a better solution for such patients.

[Long-term Trends and Sources of Atmospheric Halocarbons at Mount Taishan, Northern China].

Halocarbons are hot topics in atmospheric environment and climate change research. Combining observational data from six field campaigns at the summit of Mount Taishan (36.25°N, 117.10°E, 1534 m above sea level) with backward trajectory and receptor source analyses, this study analyzed the long-term trends and major emission sources of halocarbons in the regional background atmosphere of the North China Plain (NCP) from 2003 to 2018. The results showed that the volume fraction of species eliminated by the Montreal Protocol (MP) showed a significant downward trend; however, the MP-controlled and unregulated species showed an overall upward trend. Meanwhile, the median volume fraction of the MP-controlled and unregulated species at Mount Taishan were significantly higher than the mid-latitude median background values in the northern hemisphere. Mount Taishan air was mainly affected by four types of air masses, of which the air mass originating from NCP accounted for the highest proportion (41%). The major sources of halocarbons were biomass/biofuel burning (38.1%), refrigeration (26.2%), industrial and domestic solvent use (21.7%), solvent use in the electronic industry (8.7%), and leakage of chlorofluorocarbon (CFCs) banks (5.3%). This study fully demonstrates that MP has been effectively implemented in China and provides evidence and recommendations to further reduce and control the volume fraction of halocarbons.

Upregulation of AQP2 mediated by transcription factor FOXO1 inhibits TGF-ß-induced fibrosis in human urothelial cells.

Bladder outlet obstruction (BOO) is a common urological disease, and inhibition of TGF-ß-induced bladder tissue fibrosis may serve as an alternative strategy for BOO treatment. Aquaporin (AQP)2 was reported to be aberrantly expressed in rat BOO, but its specific role was not clarified. The aim of the present study was to explore the role of AQP2 in TGF-ß-induced urothelial cell fibrosis and elucidate the potential underlying mechanism. The SV-HUC-1 human urinary tract epithelial cell line was treated with TGF-ß1 to establish an in vitro model of bladder fibrosis. Cell Counting Kit-8 and wound healing assays were performed to measure cell viability and migration, respectively. Cell transfection was conducted to silence/overexpress AQP2 and Forkhead box O1 (FOXO1). Protein expression was measured using western blotting. Luciferase reporter and chromatin immunoprecipitation assays were used to verify the predicted interaction between AQP2 and FOXO1. The present study found that AQP2 expression was downregulated in TGF-ß1-treated urothelial cells. Overexpression of AQP2 significantly suppressed cell viability, migration and epithelial-to-mesenchymal transition in TGF-ß1-treated SV-HUC-1 cells. In addition, FOXO1 overexpression exerted similar effects as AQP2 overexpression on TGF-ß-treated SV-HUC-1 cells, but these changes were partially abolished by AQP2 knockdown. It was also found that FOXO1 was able to bind to the AQP2 promoter and regulate AQP2 expression. In conclusion, the transcription factor FOXO1 may upregulate AQP2 expression, thereby inhibiting TGF-ß-induced fibrosis in human urothelial cells. The findings of the present study may provide a novel potential strategy for the clinical treatment of BOO by targeting AQP2.

Hypoxia-induced microRNA-155 overexpression in extracellular vesicles promotes renal cell carcinoma progression by targeting FOXO3.

Renal cell carcinoma (RCC) is a form of cancer arising from the renal epithelium, with high mortality rates that have reached stable levels over the past decade. The tumor microenvironment is an essential regulator of tumor progression and survival, and extracellular vesicles (EVs) are an important facet of this microenvironment. Herein, we explored the impact of hypoxia-induced miR-155 expression in EVs on FOXO3 expression in RCC cells and their associated oncogenic activity. We found that RCC patients exhibited elevated miR-155 expression in EVs relative to healthy controls, suggesting that this miRNA may be important in the context of RCC progression. We then characterized EVs produced from RCC cell lines (Caki-1 and 786-O) under normoxic and hypoxic conditions, revealing that hypoxia-induced EVs contained higher levels of miR-155 and promoted cell proliferation. Then, we identified FOXO3 as a miR-155 target. Lastly, hypoxia-induced EVs were found to be able to significantly inhibit FOXO3 activation via facilitating miR-155 up-regulation. Together, these findings indicate that hypoxia can promote the upregulation of miR-155 in EVs and that this miRNA can act in RCC cells to suppress FOXO3 expression, thereby enhancing cellular tumor progression.

LINC01106 post-transcriptionally regulates ELK3 and HOXD8 to promote bladder cancer progression.

Bladder cancer (BCa) is a kind of common urogenital malignancy worldwide. Emerging evidence indicated that long noncoding RNAs (lncRNAs) play critical roles in the progression of BCa. In this study, we discovered a novel lncRNA LINC01116 whose expression increased with stages in BCa patients and closely related to the survival rate of BCa patients. However, the molecular mechanism dictating the role of LINC01116 in BCa has not been well elucidated so far. In our study, we detected that the expression of LINC01116 was boosted in BCa cells. Moreover, the results of a series of functional assays showed that LINC01116 knockdown suppressed the proliferation, migration, and invasion of BCa cells. Thereafter, GEPIA indicated the closest correlation of LINC01116 with two protein-coding genes, ELK3 and HOXD8. Interestingly, LINC01116 was mainly a cytoplasmic lncRNA in BCa cells, and it could modulate ELK3 and HOXD8 at post-transcriptional level. Mechanically, LINC01116 increased the expression of ELK3 by adsorbing miR-3612, and also stabilized HOXD8 mRNA by binding with DKC1. Rescue experiments further demonstrated that the restraining influence of LINC01116 knockdown on the progression of BCa, was partly rescued by ELK3 promotion, but absolutely reversed by the co-enhancement of ELK3 and HOXD8. More intriguingly, HOXD8 acted as a transcription factor to activate LINC01116 in BCa. In conclusion, HOXD8-enhanced LINC01116 contributes to the progression of BCa via targeting ELK3 and HOXD8, which might provide new targets for treating patients with BCa.

Ethanol extract of Patrinia scabiosaefolia induces the death of human renal cell carcinoma 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions.

Recently, natural plant extracts have shown tremendous potential as novel antitumor drugs. Patrinia scabiosaefolia, a traditional prescription for inflammatory diseases, has been reported to effectively suppress various types of cancers. However, the mechanisms underlying its antitumor properties remain elusive. In the present study, we investigated the antitumor effects of an ethanol extract of Patrinia scabiosaefolia (EPS) on human renal cell carcinoma 786-O cells. After 24 h of incubation with EPS, the cell viability and colony number of 786-O cells were significantly decreased in a concentration-dependent manner as compared to the control group as determined by MTT and colony formation assays, respectively. The necrotic rate and apoptotic rate in the EPS exposure group were significantly higher than these rates noted in the control group as revealed by LDH release assay and Hoechst 33342/ PI double staining, respectively. At the concentration of 1.0 mg/ml, the necrotic and apoptotic rates reached 41.7±6.6 and 7.8±1.4%, respectively (P<0.01). However, the fluorescence intensity of intracellular calcium concentration ([Ca2+]i) was markedly elevated from 0.029±0.0007 to 0.060±0.003 (P<0.001) after the intervention of EPS. Moreover, the fluorescence intensity of intracellular ROS in the EPS exposure group was significantly higher (0.074±0.005) compared to that observed in the control group (0.033±0.001, P<0.001), which was partly attenuated by the specific antioxidant N-acetylcysteine (NAC). Furthermore, our results demonstrated that EPS significantly downregulated the expression of SIRT-1 and obviously induced the dephosphorylation of mTOR. Moreover, combined treatment with the SIRT-1 inhibitor nicotinamide and EPS was able to significantly enhance the induction of necrosis and reduction in cell viability of 786-O cells noted following treatment with EPS alone. In summary, we conclude that EPS induced the death of 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions, which provide novel insight into the application of natural plant extracts for the treatment of cancers.

Baicalein inhibits prostate cancer cell growth and metastasis via the caveolin-1/AKT/mTOR pathway.

Prostate cancer (PCa) is lethal type of genitourinary cancer due to its high morbidity and gradual resistance to androgen deprivation therapy. Accumulating evidence has recently suggested that the daily intake of flavonoids is negatively correlated with the risk of cancer. In this study, we aimed to investigate the potential effects of baicalein on androgen-independent PCa cells and the underlying mechanisms through which baicalein exerts its actions. Cell viability and flow cytometric apoptosis assays indicated that baicalein potently suppressed the growth and induced the apoptosis of DU145 and PC-3 cells in a time- and dose-dependent manner. Consistently, the inhibitory effects of baicalein on migration and invasion were also observed in vitro. Mechanistically, we found that baicalein can suppress caveolin-1 and the phosphorylation of AKT and mTOR in a time- and dose-dependent manner. Moreover, the inhibition of the activation of AKT with LY294002 significantly promoted the apoptosis and metastasis induced by baicalein. In conclusion, these findings suggested that baicalein can induce apoptosis and inhibit metastasis of androgen-independent PCa cells through inhibition of the caveolin-1/AKT/mTOR pathway, which implies that baicalein may be a potential therapeutic agent for the treatment of androgen-independent prostate cancer patients.

Somatostatin Derivate (smsDX) Attenuates the TAM-Stimulated Proliferation, Migration and Invasion of Prostate Cancer via NF-κB Regulation.

Tumor development and progression are influenced by macrophages of the surrounding microenvironment. To investigate the influences of an inflammatory tumor microenvironment on the growth and metastasis of prostate cancer, the present study used a co-culture model of prostate cancer (PCa) cells with tumor-associated macrophage (TAM)-conditioned medium (MCM). MCM promoted PCa cell (LNCaP, DU145 and PC-3) growth, and a xenograft model in nude mice consistently demonstrated that MCM could promote tumor growth. MCM also stimulated migration and invasion in vitro. Somatostatin derivate (smsDX) significantly attenuated the TAM-stimulated proliferation, migration and invasion of prostate cancer. Immunohistochemistry revealed that NF-κB was over-expressed in PCa and BPH with chronic inflammatory tissue specimens and was positively correlated with macrophage infiltration. Further investigation into the underlying mechanism revealed that NF-κB played an important role in macrophage infiltration. SmsDX inhibited the paracrine loop between TAM and PCa cells and may represent a potential therapeutic agent for PCa.

Nitidine chloride induces apoptosis and inhibits tumor cell proliferation via suppressing ERK signaling pathway in renal cancer.

Nitidine chloride (NC), a natural bioactive alkaloid derived from Zanthoxylum nitidum (Roxb) DC, has been shown to have inhibitory effects on various tumors. However, whether NC could exert anti-cancer activity and the underlying mechanisms have not been elucidated in renal cancer cells. In this study, we demonstrated the growth inhibitory and pro-apoptotic effects of NC on renal cancer cells both in vitro and in vivo. With cell viability and flow cytometric apoptosis assays, we found that NC potently suppressed the growth of 786-O and A498 cells in a time- and dose- dependent manner. Consistently, the xenograft model performed in nude mice exhibited reduced tumor growth with NC treatment. Mechanically, we presented that NC significantly decreased phosphorylation of ERK and Akt, accompanied by up-regulation of P53, Bax, cleavage caspase-3 and cleavage PARP, downregulation of Bcl-2, caspase-3 and PARP. Furthermore, a specific MEK inhibitor, PD98059, could potentiate the pro-apoptotic effects of NC, which indicated that NC might trigger apoptosis in renal cancer cells partly via inhibition of ERK activity. Taken together, our results imply that NC could be developed as a potential anticancer agent to renal cancer and worthy of further studies.

Nitidine chloride inhibits renal cancer cell metastasis via suppressing AKT signaling pathway.

Nitidine Chloride (NC) has been shown to have anti-cancer effects on various tumors. However, whether NC could exert anti-metastasis activity in renal cancer cells and the underlying mechanisms have not been elucidated. In this work, our data demonstrated the anti-metastasis effects of NC on renal cancer cells in vitro. With scratch assay and transwell assays, we found that NC potently suppressed the migration and invasion of 786-O and A498 cells. Mechanistically, we presented that NC significantly decreased phosphorylation of AKT, accompanied by down-regulation of MMP-2 and MMP-9. Furthermore, a specific AKT inhibitor, LY294002, could enhance the anti-metastasis effects of NC, which indicated that NC suppressed metastasis of renal cancer cells partly via inhibition of AKT activity. Taken together, our results imply that NC can be developed as a potential anti-metastasis agent to renal cancer.

Simvastatin inhibits renal cancer cell growth and metastasis via AKT/mTOR, ERK and JAK2/STAT3 pathway.

Renal cell carcinoma (RCC) is the most lethal type of genitourinary cancer due to its occult onset and resistance to chemotherapy and radiation. Recently, accumulating evidence has suggested stains, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, were associated with the risk reduction of cancer. In the present study, we aimed to investigate the potential effects of simvastatin on RCC cells and the underlying mechanisms by which simvastatin exerted its actions. With cell viability, colony formation, and flow cytometric apoptosis assays, we found that simvastatin potently suppressed cell growth of A498 and 786-O cells in a time- and dose- dependent manner. Consistently, the xenograft model performed in nude mice exhibited reduced tumor growth with simvastatin treatment. In addition, the inhibitory effects of simvastatin on migration and invasion were also observed in vitro. Mechanically, we presented that simvastatin could suppress the proliferation and motility of RCC cells via inhibiting the phosphorylation of AKT, mTOR, and ERK in a time- and dose- dependent manner. Further investigation of the underlying mechanism revealed simvastatin could exert the anti-tumor effects by suppressing IL-6-induced phosphorylation of JAK2 and STAT3. In conclusion, these findings suggested that simvastatin-induced apoptosis and its anti-metastasis activity in RCC cells were accompanied by inhibition of AKT/mTOR, ERK, and JAK2/STAT3 pathways, which imply that simvastatin may be a potential therapeutic agent for the treatment of RCC patients.

Somatostatin derivative (smsDX) targets cellular metabolism in prostate cancer cells after androgen deprivation therapy.

Cancer cell metabolism responsive to androgen deprivation therapy (ADT) may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-deprivation therapy. To investigate the metabolism regulation effects on androgen-independent growth of prostate cancer, an established LNCaP-s cell model that resembles the clinical scenario of castration-resistant prostate cancer (CRPC), was used in this current study. This cell line was cultured from androgen-sensitive LNCaP parental cells, in an androgen-reduced condition, resembling clinical androgen deprivation therapy. To assess the effects of smsDX on the invasiveness of prostate cancer cells we used wound healing assay and Matrigel™ invasion assay. We evaluated differentially expressed proteins of the parental LNCaP cells and LNCaP-s cells after ADT by means of two-dimensional gel electrophoresis (2-DE) followed by MALDI-TOF mass spectrometric analysis. The covered area in the wound and the number of cells invading through a Matrigel chamber were significantly smaller for cells treated with smsDX than they were for control cells treated with vehicle. 56 proteins were found differentially expressed in LNCaP-s cells compared to LNCaP cells, majority of them were down-regulated after ADT treatment. 104 proteins of LNCaP cells and 86 in LNCaP-s cells, separately, were found differentially expressed after treatment with smsDX, When we explored these protein functions within the website UniProtKB/Swiss-Prot, surprisingly, most of the proteins were found to be involved in the cellular metabolism and mitochondrial function regulation. LNCaP-s as potential metastatic androgen-independent cancer cells, its metabolism and mitochondrial functions could be altered by a new somatostatin derivative smsDX, the smsDX regulatory effects on metabolism in LNCaP-s deliver more therapeutic information with the treatment of CRPC.