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The fluorine-engineered exosomes (exo@FPG3) could overcome the biological barriers for efficient cytosolic delivery and enhance biological function of exosomes.

Triple-negative breast cancer (TNBC) is a special kind of breast cancer with strong ability of invasion and metastasis. UCHL1 belongs to the ubiquitin carboxy-terminal hydrolase family and is found to be increased in a variety of malignancies, but its expression in TNBC is unknown.First, we analyzed the expression of UCHL1 in 128 TNBC specimens and paired adjacent normal tissues from 17 TNBC patients undergoing curative resection by immunohistochemistry. Then, the relationship between UCHL1 and cancer stemness was investigated by cell flow cytometry, spheroid formation assays and western blot. Moreover, cell scratch assay and Transwell assays were performed to explore whether UCHL1 promotes the migration and invasion of TNBC cells. Finally, we constructed a xenografts model of TNBC cell lines to observe the effect of UCHL1 on tumorigenesis in vivo.UCHL1 was overexpressed in TNBC tissues and associated with poor prognosis. UCHL1 promoted stem cancer cells properties, including the percentage of CD44UCHL1 may play a role in the malignant progression of TNBC by maintaining the stemness and promoting cell invasion and is expected to become a potential therapeutic target for TNBC patients.

Background. Hypoxia was considered to be a prognostic indicator in a variety of solid tumors. This study aims at identifying the hypoxia-related genes (HRGs) in breast cancer (BC) and the feasibility of HRGs as a prognostic indicator. Methods. We downloaded the mRNA expression data of BC patients from TCGA and GEO databases. The LASSO Cox regression analysis was applied to screen the hub HRGs to establish a prognostic Risk Score. The independence of Risk Score was assessed by multivariate Cox regression analysis. And the immune checkpoint analysis was also performed. In addition, we also detected the expression level of hub HRGs in MCF-10A cells, MCF-7 cells, and SK-BR-3 cells by RT-qPCR. Results. Three HRGs were identified as hub genes with prognostic value in BC, including CA9, PGK1, and SDC1. The Risk Score constructed by these three genes could efficiently distinguish the prognosis of different BC patients and has been shown to be an independent prognostic indicator. In the high-risk group, patients had lower overall survival and poorer prognosis. In addition, the expression levels of five immune checkpoints (PD1, CTLA4, TIGIT, LAG3, and TIM3) in the high-risk group were significantly higher than those in the low-risk group. Moreover, the expression levels of PGK1 and SDC1 in BC cells were significantly increased. Conclusion. In this study, we established an efficiently model based on three optimal HRGs (CA9, PGK1, and SDC1) could clearly distinguish the prognosis of different BC patients.

Sorafenib, a pan-protein kinase inhibitor, inhibits the activity of various kinases (like vascular endothelial growth factor, platelet-derived growth factor, and rapidly accelerated fibrosarcoma) and clinically has been used to treat different human cancers. This study investigated its antitumor activity in ovarian cancer and the underlying molecular events. To achieve that, ovarian cancer SKOV-3 cells were treated with or without sorafenib (10 µM), transforming growth factor (TGF)-β1 (10 ng/mL), sorafenib (10 µM) + TGF-β1 (10 ng/mL), and TGF-β1 (10 ng/mL) + Ly2157299 (5 µM), followed by 8-Gy radiation. The cells were then subjected to cell viability, wound healing, Transwell, caspase-3 activity, and western blot assays. TGF-β1 treatment enhanced ovarian cancer cell epithelial–mesenchymal transition (EMT), whereas sorafenib and a selective TGF-β1 inhibitor Ly2157299 reversed tumor cell EMT, invasion, and expression of EMT markers (E-cadherin and vimentin). Sorafenib and Ly2157299 treatment also significantly reduced the tumor cell viability. Furthermore, both sorafenib and Ly2157299 significantly enhanced ovarian cancer cell radiosensitivity, as assessed by a caspase-3 activity assay. In conclusion, sorafenib inhibited ovarian cancer cell proliferation and mobility and induced tumor cell radiosensitivity. Molecularly, sorafenib could inhibit the TGF-β1-mediated EMT. Future studies will assess sorafenib anti-ovarian cancer activity plus TGF-β1 inhibitors in ovarian cancer in vivo.

Background Patients with extensive-stage small-cell lung cancer (ES-SCLC) have a particularly poor prognosis. And the treatment options for patients with relapsed or refractory ES-SCLC are limited. Thus, we conducted an open-label, multicenter, single-arm phase II clinical trial to assess the efficacy and safety of apatinib plus etoposide capsules as the third- or further-line treatment in ES-SCLC patients. Methods Patients with ES-SCLC who experienced disease progression following 2 to 3 previous therapies from 11 medical centers in China were enrolled to receive apatinib (250 mg/d, continuously) and etoposide capsules (50 mg/d, on day 1-21, per 28 days). The treatment continued until disease progression, treatment intolerance, or death. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. Results Fifty-six patients with relapsed or refractory ES-SCLC were enrolled from January 2018 to February 2020 and 53 of them were eventually included in the evaluation population. The median follow-up was 9.8 months. At the data cut-off time (March 5, 2020), 39 patients (74%) had died and 44 (83%) had progressed. The median PFS was 3.0 months (95% CI, 2.1-3.9) and the median OS was 5.0 months (95% CI, 3.6-6.4). No complete responses were seen. Eleven patients (21%) showed a best response of partial response and 37 (70%) patients achieved stable disease. The ORR was 20.8% (11/53), and the disease control rate (DCR) was 90.6% (48/53). The 6-month OS rate was 40.1% (95% CI, 26.2-54). After 12 months, the OS rate was 18.4% (95% CI, 4.7-32.1). Possible treatment-related grade III/IV adverse events included leukopenia [8 (15.1%)], neutropenia [7 (13.2%)], anemia [4 (7.4%)], and hand-foot syndrome [2 (3.8%)]. During the study, no mortality occurred as a consequence of treatment. Conclusions Apatinib combined with etoposide capsules exhibits efficacy and has an acceptable safety profile. It could be used as a later-line treatment for ES-SCLC patients who have been heavily pretreated with standard therapies. Further exploration of apatinib combined with etoposide capsules in phase III trials is warranted.

This work presents a dataset which provides information on the influence of aromatic nuclei on the carbon isotope of gases. Gases analyzed herein were obtained by pyrolysis of model compounds and kerogens. The carbon isotope of gases from paraffin cracking with and without the addition of aromatic nuclei is summarized. We also obtained carbon isotope data for the gases from different type of kerogens, which indicate the role of aromatic nuclei in the formation of natural gases from kerogen cracking. Further interpretation and discussion of these data can be found in the related research article entitled “The methylation of aromatic nuclei — I: Implications for the geochemical evolution of gas” [1]. Keywords: Aromatic nuclei, Carbon isotope, Natural gas, Pyrolysis experiment

The Junggar Basin located in NW China is a large, intracontinental superimposed basin. Samples were collected from the Lower-Middle Jurassic coal-bearing strata of the eastern Junggar Basin and include mudstones, carbargilites and coal. The origin of organic matter, thermal maturity, paleoenvironment of sediment deposition and hydrocarbon potential of drill core samples was investigated. Organic geochemical analysis performed on 65 source rock samples indicates a wide range of TOC values from 0.81 wt % to 81.06 wt %. This study combined sedimentology, biomarker, organic petrography, and stable carbon isotopic composition of kerogen and extracts analysis demonstrating the organic matter of the source rocks is derived from terrestrial higher plants with a minor contribution of aquatic algae and microbes. Rock-Eval data, elemental composition of kerogen and odd over even normal alkane distribution reveal immaturity to low maturity with a humic - type organic matter. The source rocks were deposited in a freshwater oxic to sub-oxic environment indicated by high Pr/Ph ratios, a predominance of C29 steranes, low tricyclic terpanes and a low gammacerane index. High dia/regular C29 sterane ratios and moderate to high C29/C30 hopane ratios found in most samples are related to the presence of clay minerals. Based on the following parameters: H/C vs. O/C, TOC, S1+S2, hydrogen index, saturated hydrocarbons, aromatic hydrocarbons and Chloroform A, we concluded that the samples collected from organic-rich coal-bearing strata may yield not only gas, but also have the capability to generate and release liquid hydrocarbons.

Five crude oil samples from five wells and 33 oil-containing sandstone reservoir rock samples from six wells of Chang 7 sub-unit were systematically studied to determine hydrocarbons in these oil r...

A series of anhydrous closed-system pyrolysis experiments were performed on pure pristane and octacosane and a sample from the Maoming oil shale to measure the effect of thermal maturation on pristane and phytane carbon isotopic fractionation compared with individual n-alkanes. The result showed that pyrolysis of pure pristane and octacosane caused 1.8‰ and 5.1‰ increase in δ13C values, respectively. Experiments on the oil shale sample showed 2.0‰ and 2.2‰ variations in pristane and phytane δ13C values, respectively, but an average 5.5‰ enrichment in 13C for the individual n-alkanes. This indicates that the effect of thermal maturation on pristane and phytane δ13C values is weaker compared with n-alkanes. The results further suggest that the stable carbon isotopic distribution of pristane and phytane can be used as a correlation tool.

Surface soils from the tourist areas of the northwest Qinling Mountains were analyzed to determine the concentrations, probable sources and potential risks of hydrocarbons. Concentrations of aliphatic and aromatic hydrocarbons ranged from 4.18 to 3240 ng g−1 and 0.0462 to 101 ng g−1 dry weight, respectively. The extent of soil contamination by hydrocarbons was generally typified by unpolluted to slightly polluted levels. The incremental lifetime cancer risks (ILCRs) for exposure to soil-borne PAHs indicated complete safety for tourists. Early diagenesis of natural products, bacteria activities and petroleum were the three main sources of aliphatic hydrocarbons, while the transport of air pollutants from pyrolytic processes was the main origin of PAHs. Because the photochemical reaction of PAHs in the atmosphere would produce lower ratios for Ant/(Ant + Phe), BaA/(BaA + Chr) and IcdP/(IcdP + BghiP), but a higher ratio for Fla/(Fla + Pyr), the source classification highly depended on the diagnostic ...

Anhydrous closed-system pyrolysis experiments were conducted on the pure alkyl naphthalenes, n-alkanes and three crude oils at the highly to over mature stage in order to investigate compositional and isotopic changes of individual aromatic hydrocarbons during laboratory maturation. On the whole, aromatic hydrocarbons have better thermal stability than n-alkanes. While the carbon isotopic composition of substituted aromatic hydrocarbons exhibits a positive correlation with increasing thermal maturity, there is no significant fractionation in the carbon isotopic composition of unsubstituted aromatic hydrocarbons. This finding suggests that the carbon isotopic distribution of unsubstituted aromatic hydrocarbons can be used as an effective tool for oil-oil and oil-source correlation, especially for highly-over mature fields.

182 Background: Apatinib is a small molecule TKI inhibitor, which had been approved in China for treatment of advanced gastric cancer refractory to two or more lines of prior chemotherapy. Its efficacy and safety have been demonstrated in previous randomized controlled clinical studies. However, the efficacy and safety of apatinib in real world is lacking. This study aimed to evaluate the anti-tumor activity and toxicity of apatinib in real world. Methods: Patients older than 18 years with histologically diagnosed with gastric cancer were enrolled and treated with either apatinib alone or in combination with other drugs. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), overall response rate (ORR) and disease control rate (DCR). The adverse events were also recorded. Results: From March 2018 to March 2019, a total of 1000 patients were enrolled. Among them, 48(0.48%), 13(0.13%), 225 (22.5%), 389 (38.9%), and 325 (32.5%) patients received apatinib as postoperative auxiliary-, neoadjuvant-, first-, second-, and third- or higher line therapy, respectively. Efficacy evaluation was performed in 901 patients. Thirty-five patients achieved complete response (CR), 116 patients achieved partial response (PR), 596 patients achieved stable disease (SD), and 154 patients had progressive disease (PD), illustrating an ORR of 16.76% and a DCR of 82.91%. The mPFS was 5.32 months (95% CI, 4.93-5.75), and mOS was 9.76 months (95% CI, 8.97-10.81). In addition, the mOS of apatinib in first-line, second-line, and third-line treatments were 12.68 months, 9.49 months, and 7.62 months, respectively. Patients received apatinib in combination with other drugs had longer survival than apatinib alone, with mPFS 5.62 months vs 4.47 months and mOS 10.81 months vs 7.95 months. Such phenomenon was also observed in ORR (18.21% vs 13.04%, P< 0.001) and DCR (84.88% vs 77.87%, P< 0.001). The main adverse events (AE) were anemia (67.2%), thrombocytopenia (36.2%), leukopenia (34.5%)and anorexia (37.6%). The most common grade 3-4 adverse events included neutropenia, anemia and thrombocytopenia. Conclusions: In the real world, apatinib showed promising efficacy and manageable toxicities in patients with gastric cancer. Patients benefit more when received apatinib combination therapy. Clinical trial information: NCT03478943.

Background: Altered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients. Methods: Paraffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model. Results: The data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression ( r = −0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes ( r = −0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression ( r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage ( P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender ( P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels. Conclusions: The levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.

Aromatic hydrocarbons are an important component in crude oil and sediments. Furthermore, the structure of macromolecular organic matter (such as kerogen) is also based on aromatic nuclei. The earlier methylation and later demethylation of various aromatic nuclei would affect the chemical components and carbon isotopes of aromatics as well as saturated hydrocarbons and gaseous hydrocarbons. The scope of the present study was to investigate the role of aromatic nuclei in the formation and geochemical evolution of natural gas in complex geological systems. The use of model compounds could simplify the complex system, and n-tricosane (n-C23), n-tetracosane (n-C24), and naphthalene (N) were selected as model compounds for paraffins and aromatic hydrocarbons and subjected to pyrolysis experiments. The results showed that aromatic nuclei had a slight influence on the gas generation without using a catalyst. However, the gaseous components were substantially affected by aromatic nuclei under the catalysis of clay, when the temperature was lower than 400 °C. The ratios of isoparaffin to n-alkane of gaseous hydrocarbons were reduced by the aromatic nuclei. As carbon isotopically lighter methyls preferred to combine with the aromatic nuclei, the gas productions were reduced, and there was a 13C depletion of methane with increasing temperature, which is contrary to the case of paraffin cracking alone. This trend can also be observed in the pyrolysis gases formed from the type II and III kerogens. The macromolecular aromatic nuclei played a similar role with the small aromatic hydrocarbons. These effects would mainly occur in the mature to highly mature stage of the organic matter (the paleo-geothermal temperature is ≤ 150 °C). The above explorative experiments suggested that a large number of aromatic nuclei and their methylation reactions could exert a significant influence on the distributions and the carbon isotopic compositions of gaseous hydrocarbons in the evolution of sedimentary organic matter. This research also provided a new explanation for the carbon isotopic abnormality (the 13C-depleted methane and the increasing δ13C2-δ13C1 values) of deep natural gas of the Tarim Basin, in northwest China.