SYT7 promotes breast cancer cells growth through the PI3K/AKT pathway.

Background: Breast cancer is one of the most malignant tumors in the reproductive system and has a poor prognosis. The aim of this study was to investigate the function and underlying mechanism of synaptotagmin 7 (SYT7) in breast cancer. Methods: We utilized The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter database to assess the correlation between SYT7 expression and the prognosis of breast cancer patients. The efficacy of SYT7 knockdown was evaluated through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Furthermore, we examined the impact of SYT7 on breast cancer cell proliferation and apoptosis using Cell Counting Kit-8 (CCK-8), clone formation assays, and flow cytometry. Through Western blot analysis, we investigated the influence of SYT7 on the expression of apoptosis-related markers and the PI3K/AKT signaling pathway in breast cancer. Results: The TCGA database data analysis revealed a significant up-regulation of SYT7 expression in breast cancer tissues compared to normal tissues (P<0.001). A correlation was observed between SYT7 expression and tumor size (P=0.009), as well as estrogen receptor (ER) expression level (P<0.001) and progesterone receptor (PR) expression level (P<0.001) in breast cancer patients. Analysis of the Kaplan-Meier plotter database indicated that high SYT7 expression was associated with a shorter overall survival (OS) (P=0.009). The mRNA expression results indicated higher SYT7 expression in breast cancer tissues compared to adjacent normal tissues (P=0.005). CCK-8, clone formation assay, and flow cytometry results demonstrated that SYT7 promoted the proliferation and inhibited the apoptosis of breast cancer cells. Western blot assay confirmed the activation of PI3K/AKT signaling by SYT7. Conclusions: The findings suggest that SYT7 is highly expressed in breast cancer and that its high expression is linked to clinical characteristics and prognosis. Inhibition of SYT7 through knockdown can suppress proliferation and promote apoptosis of breast cancer cells, making it a potential target for breast cancer diagnosis and treatment.

The "double-edged sword effect" of nicotine.

As the main effect substances of tobacco products, the physiological effects of nicotine have attracted the attention of researchers, especially in recent years, the discussion on the benefits and harms of nicotine (or tobacco products) has become increasingly fierce. In this review, the structure, distribution and physiological effects of nicotinic acetylcholine receptor (nAchR) are summarized. The absorption, distribution, metabolism and excretion of nicotine in the body were introduced. Further, the positive effects of low-dose and short-term nicotine exposure on mitochondrial function regulation, stem cell proliferation and differentiation, nervous system protection and analgesia were elucidated. At the same time, it is also discussed that high-dose and long-term nicotine exposure can activate the oxidative stress effect, mediate abnormal epigenetic modification, and enhance the immune inflammatory response, and then produce negative effects on the body. To sum up, this review suggests that there is a "double-edged sword" effect of nicotine, which on the one hand helps people to understand the physiological effects of nicotine more comprehensively and carefully, and on the other hand provides some theoretical basis for the rational use of nicotine and the innovative development of related products.

Research progress and prospect on the safety of heated tobacco products.

In recent years, Heated tobacco products (HTP) have gradually entered the market and become more and more popular with consumers because of their low risk (compared with traditional cigarette). With the increasing popularity and proportion of HTP in the international market, people pay more and more attention to the safety evaluation of HTP, but there is still a lack of systematic review of HTP safety research. In this review, the harmful components of HTP, multi-organ functional programming effects (including respiratory system, cardiovascular system, etc.), and mechanism of the effect generation (including oxidative stress, inflammatory response, etc.) were systematically reviewed, the safety effects of HTP and traditional cigarettes were compared in detail, and the shortcomings and future research directions in the field of HTP safety were discussed. In summary, this review conforms to the general trend of contemporary "tobacco and health", helps people to understand and evaluate HTP more systematically, and provides a strong theoretical support and literature basis for the tobacco industry to carry out HTP risk assessment and exposure improvement.

The Prognostic Value of ADAMTS8 and Its Role as a Tumor Suppressor in Breast Cancer.

A disintegrin-like and metalloprotease with therombospondin type1 motif 8 (ADAMTS8) plays an important role in many malignancies. However, the clinical and biological significance of ADAMTS8 in breast cancer remain unknown. In this study, the clinical data from 1066 breast cancer patients were analyzed by The Cancer Genome Atlas (TCGA) database, and were analyzed using the correlation between ADAMTS8 expression and the clinicopathological features and prognoses. The CCK-8 assay, clone formation assay, flow cytometry and Transwell assay were used to characterize the effects of ADAMTS8 on proliferation, migration and invasion of breast cancer cells. Gene set enrichment analysis (GSEA) and western blotting were used to identify the potential molecular mechanism on how ADAMTS8 exert its biological function. ADAMTS8 overexpression correlated longer overall survival (OS) and progression-free survival (PFS). ADAMTS8 was considered as an independent prognostic factor for OS. ADAMTS8 overexpression inhibited breast cancer cell proliferation, migration and invasion in vitro, and induced G2/M cell cycle arrest. ADAMTS8 was also involved in cell cycle regulation and was associated with the EGFR/Akt signaling pathway. ADAMTS8 knockdown showed the reverse effect. Together, the results showed that ADAMTS8 functioned as a tumor suppressor gene (TGS) and could be a prognostic biomarker for breast cancer.

Effects of potassium additives on the combustion behavior of chrysanthemum biochar blended with graphite carbon as a heating source for heat-not-burn tobacco.

Heat-not-burn tobacco with an external heating source is a cleaner alternative to conventional cigarettes due to its lower emission of nicotine, CO and tar in the smoke, and the co-combustion of the composite carbon source (chrysanthemum biochar blended with graphite carbon) is a promising carbon heating source for a heat-not-burn tobacco product. This work has investigated the effect of the blending ratio of the graphite carbon on the co-combustion characteristics (i.e., the minimum ignition temperature, the burnout temperature, etc.) of the composite carbon source, as well as the effect of K2CO3 on the co-combustion behaviors. The results indicate that the minimum ignition temperature is mainly controlled by the ignition of the biochar while the burnout temperature is dominated by that of the graphite. The minimum ignition temperature of the carbon mixture is decreased by only 2-17 °C with K2CO3 because the ignition temperature of the biochar is difficult to reduce further by adding K2CO3. Simultaneously, the burnout temperature can be reduced by 30-60 °C since the graphite firing can be significantly improved by the presence of K2CO3. Moreover, the promotion effect of K2CO3 on the co-firing process is not always proportional to the addition amount of the catalyst, especially when the mass fraction of the graphite exceeds the threshold value of 30% based on the observation of the activation energies from the third-order kinetic model analysis.

BTNL9 is frequently downregulated and inhibits proliferation and metastasis via the P53/CDC25C and P53/GADD45 pathways in breast cancer.

Breast cancer (BC) threatens the life and health of women worldwide because of its high morbidity and mortality. The present study aimed to explore the biological functions and potential mechanism of BTNL9 in BC. RNA sequence and clinical data extracted from the Kaplan-Meier plotter database and The Cancer Genome Atlas (TCGA) were utilized to analyze the relationship between the expression level of BTNL9 in BC tissues and clinicopathological features and the effects of BTNL9 expression on the prognosis of BC. The diagnostic efficacy of BTNL9 expression was estimated by receiver operating characteristic (ROC) curve analysis. The mRNA and protein expression levels of BTNL9 in BC cell lines and in BC tissue were determined by quantitative real-time PCR (qPCR) and western blotting, respectively. The functions of BTNL9 were measured by colony formation, CCK-8, Transwell, flow cytometry and EdU assays. Western blotting analysis was also performed to explore the latent mechanism of BTNL9. The results showed that the expression of BTNL9 declined in BC tissues and cell lines. Low expression of BTNL9 was significantly associated with early progression of T stage, relapse-free survival (RFS), and poor overall survival (OS). Ectopic expression of BTNL9 inhibited cell proliferation, colony formation and metastasis and induced apoptosis in BC, while knockdown of BTNL9 had the opposite result. Furthermore, BTNL9 blocked BC cells in the G2/M phase via the P53/CDC25C and P53/GADD45 pathways. Our results suggest that BTNL9 may play a tumor-suppressive role in BC and has the potency to become a new biomarker for early BC diagnosis.

Effects of potassium additives on the combustion characteristics of graphite as a heating source of heat-not-burn tobacco.

"Heat-not-burn" tobacco with an external heating source is a cleaner alternative to conventional cigarettes due to its lower emission of nicotine, CO and tar in the smoke, and graphite is a promising carbon heating source for a "heat-not-burn" tobacco product yet is not easy to be fired. This work aims to improve the combustion properties of graphite using potassium catalysts. Thermal gravimetric analysis is performed to investigate the combustion properties, and a first-order kinetic model is applied to describe the combustion process. Scanning electron microscopy is used to observe the surface morphology, and the mineral and elemental composition are investigated by powder X-ray diffraction and energy dispersive spectrometry, respectively. The results indicate that the potassium additives can significantly decrease the ignition temperature of the graphite samples by 51-124 °C, and the promotion effects are closely related to the potassium and oxygen content of the additives. Further kinetic analysis implies that K and O can decrease the activation energy required for the oxidation reactions by 45.1% from 194.5 to 106.8 kJ mol-1, thereby improving the graphite combustion. Moreover, potassium can play the role of "O2 transfer", which can transfer atmospheric oxygen to support graphite combustion. K2CO3 is a suitable catalyst for graphite combustion, and the suggested addition amount is 0.88% in weight.

Biochar alleviates combined stress of ammonium and acids by firstly enriching Methanosaeta and then Methanosarcina.

This investigation evaluated the effectiveness of biochar of different particle sizes in alleviating ammonium (NH4(+)) inhibition (up to 7 g-N/L) during anaerobic digestion of 6 g/L glucose. Compared to the control treatment without biochar addition, treatments that included biochar particles 2-5 mm, 0.5-1 mm and 75-150 µm in size reduced the methanization lag phase by 23.9%, 23.8% and 5.9%, respectively, and increased the maximum methane production rate by 47.1%, 23.5% and 44.1%, respectively. These results confirmed that biochar accelerated the initiation of methanization during anaerobic digestion under double inhibition risk from both ammonium and acids. Furthermore, fine biochar significantly promoted the production of volatile fatty acids (VFAs). Comparative analysis on the archaeal and bacterial diversity at the early and later stages of digestion, and in the suspended, biochar loosely bound, and biochar tightly bound fractions suggested that, in suspended fractions, hydrogenotrophic Methanobacterium was actively resistant to ammonium. However, acetoclastic Methanosaeta can survive at VFAs concentrations up to 60-80 mmol-C/L by improved affinity to conductive biochar, resulting in the accelerated initiation of acetate degradation. Improved methanogenesis was followed by the colonization of the biochar tightly bound fractions by Methanosarcina. The selection of appropriate biochar particles sizes was important in facilitating the initial colonization of microbial cells.

Application of eco-compatible biochar in anaerobic digestion to relieve acid stress and promote the selective colonization of functional microbes.

The addition of 0.5­1 mm biostable biochar (10 g/L) to mesophilic anaerobic digesters inoculated with crushed granules (1 g-VS/L) and fed with 4, 6 and 8 g/L glucose shortened the methanogenic lag phase by 11.4%, 30.3% and 21.6% and raised the maximum methane production rate by 86.6%, 21.4% and 5.2%, respectively, compared with the controls without biochar. 75 µm biochar further shortened the lag phase by 38.0% and increased the methane production rate by 70.6% at 6 g/L glucose loading. Biochar also simultaneously enhanced the production and degradation of intermediate acids. The fingerprint and sequencing analysis used to examine the spatial distribution and temporal evolution of communities revealed that proportion of Archaea was higher in the biochar-added treatments and in the tightly-bound fractions. Methanosarcina located in the tightly-bound fractions on the biochar surface, and was most abundant in the larger 2­5 mm biochar particles. Methanosaeta was enriched in the loosely-bound fractions by all-size biochar particles and within the tightly-bound fractions by small biochar particles. Because biochar is cost-effective and can remain in digestate for direct use as soil amendment without separation, eco-compatible biochar may serve as a good substrate for highly-loaded digestion by inducing selective colonization of functional microbes.

Humification characterization of biochar and its potential as a composting amendment.

Biochar has received increasing attention due to its applications as a soil amendment. Here, the chemical properties of solid and water-extractable fractions of four biochar samples were investigated. The results showed that wood biochar and bamboo biochar samples were 60%-80% more hydrophobic than those of rice husk biochar and rice husk ash. In addition, the acidity was 3.88 mmol/g from the total functional groups and 1.03 mmol/g from the carboxyl groups/lactones/phenols found in the wood biochar sample, which were about 1.5 times greater than those of the bamboo biochar sample. These functional groups could be used to determine the sorptive capacity of biochar for ionic solutes and water content and to increase the degradation of compost organics. The wood biochar sample was found to have the most humification materials (fulvic acid-like material + humic acid-like material) in the water-extractable fraction, which was 3-10 times higher than that in the rice husk biochar and rice husk ash; humified materials were not detected in the bamboo biochar sample. Humification materials in biochar may be involved in increasing the proportion of humic acid-like materials in humic-like substances within the compost product. Wood biochar had better hydrophobic, sorptive, aromatic, and humification properties compared to other biochars, suggesting that it may be used in composting in order to exert its effect as both a bulking agent and a composting amendment during the solid waste composting process.

Effect of vanillin and ethyl vanillin on cytochrome P450 activity in vitro and in vivo.

Food safety is of extreme importance to human health. Vanillin and ethyl vanillin are the widely used food additives and spices in foods, beverages, cosmetics and drugs. The objective of the present work was to evaluate the impact of vanillin and ethyl vanillin on the activities of CYP2C9, CYP2E1, CYP3A4, CYP2B6 and CYP1A2 in human liver microsomes (HLM) in vitro, and impact on the activities of CYP1A2, CYP2C, CYP3A and CYP2E1 in rat liver microsomes (RLM) in vivo. The in vitro results demonstrated that vanillin and ethyl vanillin had no significant effect on the activity of five human CYP450 enzymes with concentration ranged from 8 to 128 µM. However, after rats were orally administered vanillin or ethyl vanillin once a day for seven consecutive days, CYP2E1 activity was increased and CYP1A2 activity was decreased in RLM. The in vivo results revealed that drug interaction between vanillin/ethyl vanillin and the CYP2E1/CYP1A2-metabolizing drugs might be possible, and also suggested that the application of the above additives in foods and drugs should not be unlimited so as to avoid the adverse interaction.