Mechanisms of Yiai Fuzheng formula in the treatment of triple-negative breast cancer based on UPLC-Q-Orbitrap-HRMS, network pharmacology, and experimental validation.

Ethnopharmacological relevance: Yiai Fuzheng formula (YAFZF), as a Traditional Chinese Medicine (TCM) prescription, has been used widely at Zhongnan Hospital of Wuhan University for its therapeutic effects and high safety on triple-negative breast cancer (TNBC). Objective: In this study, we employed ultra-high-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS), network pharmacology, and experimental validation to elucidate the underlying action mechanism of YAFZF in the treatment of TNBC. Methods: The key active ingredients in YAFZF were analyzed using UPLC-Q-Orbitrap-HRMS, and then the potential components, target genes and signalling pathways of YAFZF were predicted using the network pharmacological method. We then used molecular docking to visualize the combination characteristics between major active components and macromolecules in the crucial pathway. In vitro experiments were conducted to investigate the inhibitory effects of YAFZF treatment on the cell viability, invasion, and migration of 4T1 and MDA-MB-231 cells. The xenograft TNBC models were constructed using female Balb/c mice, and their body weights, tumour volumes, and weights were monitored during YAFZF treatment. Quantitative real-time PCR (qRT-PCR), Hematoxylin-eosin (HE), immunohistochemistry (IHC) staining, Western blot (WB), and terminal deoxynucleotidyl transferase (TdT)-dUTP nick-end labeling (TUNEL) staining were used for further experimental validation. Results: Based on UPLC-Q-Orbitrap-HRMS and network pharmacology analysis, 6 major bioactive components and 153 intersecting genes were obtained for YAFZF against TNBC. Functional enrichment analysis identified that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway might be the mechanism of action of YAFZF in the treatment of TNBC. Molecular docking results suggested that the main active compounds in YAFZF had strong binding energies with the proteins in the PI3K/Akt pathway. In vitro experiments showed that YAFZF inhibited the cell viability, invasion, and migration abilities of TNBC cells. Animal experiments confirmed that YAFZF treatment suppressed tumour cell proliferation and increased apoptotic cells. PCR, HE, WB, and IHC results indicated that YAFZF could suppress xenograft tumour metastases by inhibiting the PI3K/AKT/mTOR pathway regulating the epithelial-mesenchymal transition (EMT) process. Conclusion: YAFZF therapy showed its potential for reducing proliferation, invasion, and migration abilities, increasing apoptosis of TNBC cells. Furthermore, YAFZF treated TNBC by inhibiting xenograft tumour distant metastases via the regulation of EMT by the PI3K/Akt/mTOR pathway, suggesting that it may be useful as an adjuvant treatment.

Total ammonia nitrogen inhibits medium-chain fatty acid biosynthesis by disrupting hydrolysis, acidification, chain elongation, substrate transmembrane transport and ATP synthesis processes.

This study used 16S rRNA gene sequencing and metatranscriptomic analysis to comprehensively illustrate how ammonia stress influenced medium-chain fatty acids (MCFA) biosynthesis. MCFA synthesis was inhibited at total ammonia nitrogen (TAN) concentrations above 1000 mg N/L. TAN stress hindered organic hydrolysis, acidification, and volatile fatty acids elongation. Chain-elongating bacteria (e.g., Clostridium_sensu_stricto_12, Clostridium_sensu_stricto_1, Caproiciproducens) abundance remained unchanged, but their activity decreased, partially due to the increased reactive oxygen species. Metatranscriptomic analysis revealed reduced activity of enzymes critical for MCFA production under TAN stress. Fatty acid biosynthesis pathway rather than reverse ß-oxidation pathway primarily contributed to MCFA production, and was inhibited under TAN stress. Functional populations likely survived TAN stress through osmoprotectant generation and potassium uptake regulation to maintain osmotic pressure, with NADH-ubiquinone oxidoreductase potentially compensating for ATP loss. This study enhances understanding of MCFA biosynthesis under TAN stress, aiding MCFA production system stability and efficiency improvement.

Helicobacter pylori triggers inflammation and oncogenic transformation by perturbing the immune microenvironment.

The immune microenvironment plays a critical regulatory role in the pathogenesis of Helicobacter pylori (H. pylori). Understanding the mechanisms that drive the transition from chronic inflammation to cancer may provide new insights for early detection of gastric cancer. Although chronic inflammation is frequent in precancerous gastric conditions, the monitoring function of the inflammatory microenvironment in the progression from H. pylori-induced chronic inflammation to gastric cancer remains unclear. This literature review summarizes significant findings on how H. pylori triggers inflammatory responses and facilitates cancer development through the immune microenvironment. Furthermore, the implications for future research and clinical applications are also addressed. The review is divided into four main sections: inflammatory response and immune evasion mechanisms induced by H. pylori, immune dysregulation associated with gastric cancer, therapeutic implications, and future perspectives on H. pylori-induced gastric carcinogenesis with a focus on the immune microenvironment.

Study on the Antifungal Activity of Gallic Acid and Its Azole Derivatives against Fusarium graminearum.

The wheat scab caused by Fusarium graminearum (F. graminearum) has seriously affected the yield and quality of wheat in China. In this study, gallic acid (GA), a natural polyphenol, was used to synthesize three azole-modified gallic acid derivatives (AGAs1-3). The antifungal activity of GA and its derivatives against F. graminearum was studied through mycelial growth rate experiments and field efficacy experiments. The results of the mycelial growth rate test showed that the EC50 of AGAs-2 was 0.49 mg/mL, and that of AGAs-3 was 0.42 mg/mL. The biological activity of AGAs-3 on F. graminearum is significantly better than that of GA. The results of field efficacy tests showed that AGAs-2 and AGAs-3 significantly reduced the incidence rate and disease index of wheat scab, and the control effect reached 68.86% and 72.11%, respectively. In addition, preliminary investigation was performed on the possible interaction between AGAs-3 and F. graminearum using density functional theory (DFT). These results indicate that compound AGAs-3, because of its characteristic of imidazolium salts, has potential for use as a green and environmentally friendly plant-derived antifungal agent for plant pathogenic fungi.

Two Novel and Three Recurrent Mutations in the Mevalonate Pathway Genes in Chinese Patients with Porokeratosis.

Purpose: Porokeratosis (PK) is a chronic autosomal-dominant cutaneous keratinization disorder exhibiting clinical and genetic heterogeneity. Mevalonate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), phosphomevalonate kinase(PMVK), and mevalonate kinase genes(MVK), which encode the mevalonate pathway, are disease-causing genes in PK. Patients and Methods: Data and blood samples were collected from two Chinese families and five sporadic patients with porokeratosis. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients. Results: Five heterozygous mutations were identified, including a novel FDPS stop-gain mutation c.438T>G (p.Tyr146Ter), a novel MVD missense mutation c.683G>C (p.R228P), and three previously reported MVD mutations: c.746T>C (p.F249S), c.875A>G (p.N292S), and c.1111_1113del (p.371_371del). The novel FDPS c.438T>G mutation was predicted as "disease-causing" (p = 1) by Mutation Taster. The other novel MVD c.683G>C was also predicted as "deleterious" (score = 0.00) by Sorting Intolerant From Tolerant (SIFT), "probably damaging" (score = 1) by PolyPhen2, and "disease-causing" (p = 0.999) by Mutation Taster. Conclusion: Our results extended the mutation spectrum of mevalonate pathway genes in porokeratosis and provided useful strategies for a more accurate diagnosis and genetic counseling.

Autocrine motility factor receptor promotes the malignancy of glioblastoma by regulating cell migration and invasion.

OBJECTIVE: One of the important causes of death in cancer patients is malignant metastasis, invasion, and metastasis of tumor cells. Metastasis is also the most basic physiological characteristics and pathogenesis of various tumors. Previously published studies have suggested that autocrine motor factor receptor (AMFR) is the key regulator of tumor cell migration and invasion. Meanwhile, AMFR is highly expressed in esophageal tumors, gastrointestinal tumors, and bladder cancer, and it is also involved in its pathogenesis. However, the role of AMFR in glioblastoma has not been reported. METHODS: In order to study the role of AMFR in the cell migration and invasion of glioblastoma, AMFR was silenced using siRNA and overexpressed using cDNA. Immunoblotting analysis and real-time quantitative polymerase chain reaction (PCR) were employed to assess the expression of AMFR. We conducted wound healing assay, cell migration assay, and tumorsphere formation assay to detect the invasion and metastatic ability of glioblastoma. RESULTS: This study found that the level of AMFR expression was significantly correlated with the malignant degree of glioma tissue in clinic samples. AMFR silencing decreased cell migration and invasion of LN229. Overexpression of AMFR significantly increased cell migration and invasion of U251. CONCLUSION: This study suggests that AMFR could be used as a therapeutic strategy for the clinical treatment of glioblastoma.

Effect of Chestnut (Castanea Mollissima Blume) Bur Polyphenol Extract on Shigella dysenteriae: Antibacterial Activity and the Mechanism.

Shigella dysenteriae is a highly pathogenic microorganism that can cause human bacillary dysentery by contaminating food and drinking water. This study investigated the antibacterial activity of chestnut bur polyphenol extract (CBPE) on S. dysenteriae and the underlying mechanism. The results showed that the minimum inhibitory concentration (MIC) of CBPE for S. dysenteriae was 0.4 mg/mL, and the minimum bactericidal concentration (MBC) was 1.6 mg/mL. CBPE treatment irreversibly disrupted cell morphology, decreased cell activity, and increased cell membrane permeability, cell membrane depolarization, and cell content leakage of S. dysenteriae, indicating that CBPE has obvious destructive effects on the cell membrane and cell wall of S. dysenteriae. Combined transcriptomic and metabolomics analysis revealed that CBPE inhibits S. dysenteriae by interfering with ABC protein transport, sulfur metabolism, purine metabolism, amino acid metabolism, glycerophospholipid metabolism, and some other pathways. These findings provide a theoretical basis for the prevention and treatment of S. dysenteriae infection with extract from chestnut burs.

Evaluation of Flavonoid-rich Fraction of Portulaca Grandiflora Aerial Part Extract in Atherogenic Diet-induced Atherosclerosis.

BACKGROUND: Portulaca grandiflora is a tiny, upright herb that contains a variety of chemical components, including alkaloids, glycosides, mucilage, proteins, tannins, flavonoids, saponins, polysaccharides, and triterpenoids possessing properties that may help with atherosclerosis. The reported pharmacological properties of Portulaca grandiflora are antioxidant, antidiabetic, antiasthmatic, antibacterial, antiulcer and anti-inflammatory properties. OBJECTIVES: The yield of methanol extract is higher than that of ethanol and acetone, and its phytoconstituents, like flavonoids and polyphenols, and has potent antioxidant properties. In order to determine the effectiveness ofPortulaca grandiflora methanol extract fraction against high-fat diet (HFD)-induced hyperlipidemia, hemodynamic change, antioxidant levels, and vascular dysfunction in rats, a study was carried out on a flavonoid-rich methanol extract fraction of the aerial part of Portulaca grandiflora Hook. METHODS: This method involves a study of 30 days involving male Wistar rats (240-250 g) (n=5) that were fed with an Ath diet. Study groups were divided into (i) The Control Group, (ii) the Diseases Control Group, (iii) Disease + Standard drug (Atorvastatin 20mg/kg, orally, (iv) Disease + Test Extract dose 1 (Portulaca grandiflora 200mg/kg orally), and (v) Disease + Test Extract dose 2 (Portulaca grandiflora 400mg/kg orally). Both the test drug Portulaca grandiflora and the standard drug Atorvastatin were given orally for 30 days. RESULTS: At the end of the study, blood samples were taken to measure the serum lipid profile, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and levels of oxidative tissue stress. Hemodynamic parameters and aortic staining were performed. Portulaca grandiflora treatment improved the lipid profile and considerably reduced oxidative stress levels. Aortic staining examination revealed a marked reduction in atherosclerotic lesions. CONCLUSION: These results revealed that Portulaca grandiflora is an effective treatment approach in preventing atherosclerotic lesion progression, which is attributed to its protection against oxidative stress and various enzymatic activities in the Atherogenic model.

CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis.

BACKGROUND: Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied. METHODS: The location of circRNA_15430 in GC cells were detected by nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays, and circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of circRNA_15430 in GC cells were examined by using colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy. The protein levels were detected by Western blotting. Whether circRNA_15430 sponges miR-382-5p was monitored with a dual-luciferase reporter assay. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice. RESULTS: CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells. CONCLUSIONS: Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.

Two Novel and a Recurrent ATP2C1 Mutations in Chinese Population with Hailey-Hailey Disease.

Purpose: Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited blistering dermatosis. Pathogenic variants in ATP2C1 have been associated with HHD since 2000. This study aimed to identify the mutations in the ATP2C1 gene in two Chinese pedigrees and two sporadic cases with HHD. Patients and Methods: Two Chinese pedigrees and two sporadic cases were included in this study. Whole-exome sequencing and Sanger sequencing were performed to detect the mutation of the ATP2C1 gene. Predictions of protein structure and function were performed using bioinformatics tools, including Mutation Taster, Polyphen-2, SIFT, and Swiss-Model. Results: In this study, we detected three heterozygous mutations, including novel compound mutations of (c.1840-4delA and c.1840_1844delGTTGC), splice site mutation of c.1570+3A>C, and a previously known nonsense mutation c.1402C>T in the ATP2C1 gene. Combined with our previous study, ten patients with c.1402C>T mutation in the ATP2C1 gene have been identified, and all these patients originated from Jiangxi Province. Conclusion: c.1402C>T mutation in the ATP2C1 gene was considered a regional highly prevalent mutation in the Chinese population with HHD. The results added new variants to the database of ATP2C1 mutations associated with HHD.

Synergistic Effects of Graphene Oxide and Pesticides on Fall Armyworm, Spodoptera frugiperda.

Fall armyworm Spodoptera frugiperda, a native insect pest in tropical and subtropical America, has rapidly spread to most parts of China and become a major pest of corn and other crops since invading in early January 2019. As an emergency and important control measure, chemical control of S. frugiperda has the advantages of quick effect and low cost. However, long-term and large-scale use of pesticides might pollute the environment and increase pest resistance. By improving the control effect and reducing the dosage of chemical pesticides, graphene oxide (GO) is used synergistically with insecticides to increase control efficacy to achieve low-cost and sustainable management of insect pests as a new type of synergist. In this study, graphene oxide was compounded with insecticides to form nanocomposites. To clarify pest physiological responses, the laboratory toxicity of graphene oxide-insecticide nanocomposites was measured on the larvae of S. frugiperda. The results demonstrated that GO could enhance the activity of four selected pesticides: chlorantraniliprole (Chl), beta cypermethrin (Bet), methoxyhydrazide (Met) and spinetoram (Spi). Compared with pesticides alone, the toxicity of Chl-GO, Bet-GO, Met-GO and Spi-GO mixtures to the third instar larvae of S. frugiperda increased by 1.56, 1.54, 2.53 and 1.74 times, respectively. The easy preparation and higher bioactivity of GO-pesticide nanocomposites indicated their promising application potential in pest control.

Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne.

Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. This study aimed to explore the pathogenesis of acne and the therapeutic mechanism of isotretinoin from the metabolic perspective in coal tar-induced acne in rabbits. Methods: Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was used to identify skin metabolites in groups C (blank control), M (model group) and T (isotretinoin group). Multivariate statistical analysis was used to process the metabolomics data. Results: 98 differential metabolites in group C and group M were identified. The highest proportion of differential metabolites were organic acids and derivatives, lipid metabolites, organic heterocyclic compounds, and nucleoside metabolites. The most significant metabolic pathways included protein digestion and absorption, central carbon metabolism in cancer, ABC transporters, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, and sphingolipid signaling pathway. Isotretinoin treatment normalized eight of these metabolites. Conclusions: Our study will help to further elucidate the pathogenesis of acne, the mechanism of isotretinoin at the metabolite level, and identify new therapeutic targets for treating acne.

A new POLH mutation in a consanguineous Chinese family with xeroderma pigmentosum variant type.

We report a Chinese consanguineous family with a variant type of xeroderma pigmentosum (XPV), and identified one novel mutation in the patient. Our study expands the mutational spectrum of XPV. Click here for the corresponding questions to this CME article.

Bioactive constituents of animal-derived traditional Chinese medicinal materials for breast cancer: opportunities and challenges.

Breast cancer is globally the most common invasive cancer in women and remains one of the leading causes of cancer-related deaths. Surgery, radiotherapy, chemotherapy, immunotherapy, and endocrine therapy are currently the main treatments for this cancer type. However, some breast cancer patients are prone to drug resistance related to chemotherapy or immunotherapy, resulting in limited treatment efficacy. Consequently, traditional Chinese medicinal materials (TCMMs) as natural products have become an attractive source of novel drugs. In this review, we summarized the current knowledge on the active components of animal-derived TCMMs, including Ophiocordycepssinensis-derived cordycepin, the aqueous and ethanolic extracts of O.sinensis, norcantharidin (NCTD), Chansu, bee venom, deer antlers, Ostreagigas, and scorpion venom, with reference to marked anti-breast cancer effects due to regulating cell cycle arrest, proliferation, apoptosis, metastasis, and drug resistance. In future studies, the underlying mechanisms for the antitumor effects of these components need to be further investigated by utilizing multi-omics technologies. Furthermore, large-scale clinical trials are necessary to validate the efficacy of bioactive constituents alone or in combination with chemotherapeutic drugs for breast cancer treatment.

Protein tyrosine phosphatase, receptor type B is a potential biomarker and facilitates cervical cancer metastasis via epithelial-mesenchymal transition.

Cervical cancer (CC) is one of the most common malignant tumors. This study analyzed the impact of protein tyrosine phosphatase, receptor type B (PTPRB) on malignant behavior of CC and explored its possible molecular mechanism. RT-PCR, western blot and Immunohistochemistry were applied to examine the expression of PTPRB in CC specimens and cells. Aberrant PTPRB expression in CC and survival outcomes were constructed using The Cancer Genome Atlas (TCGA) database and tissue microarray cervical squamous cell carcinoma cohort. Cultured human CC cells were assayed for viability, apoptosis, migration, and invasion in vitro and in vivo. Kyoto Encyclopedia of Genes and Genomes (KEGG) assays and gene set enrichment analysis (GSEA) assays were used to delve into PTPRB-related pathways using TCGA datasets. The levels of proteins associated with the epithelial-mesenchymal transition (EMT) pathway and modulated by PTPRB were examined through Western blot. We found that the levels of PTPRB in CC tissues and cells were distinctly up-regulated. PTPRB was also an unfavorable prognostic factor for CC patients. Functionally, PTPRB knockdown exhibits tumor-suppressive function via reducing cell proliferation and metastasis and inducing cell apoptosis. KEGG assays and GSEA assays suggested PTPRB overexpression was associated with several tumor-related pathways. The results of Western blot assays suggested that N-cadherin was decreased in the PTPRB-knockdown CC cells, while E-cadherin was increased. Overall, PTPRB is highly expressed in CC and can effectively enhance the proliferation, metastasis and EMT process of tumor cells. PTPRB is expected to be a therapeutic target for CC.

Effect of weimaining on apoptosis and Caspase-3 expression in a breast cancer mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Weimaining (WMN) is a condensed Tannin compound extracted from Fagopyrum cymosum (Trevir.) Meisn., which comes from the roots of buckwheat, a type of Chinese herbal medicine, was first recorded in "Bencao Shiyi". WMN has inhibitory effects on multiple cancer types and is widely used in clinical practice; however, the mechanism underlying the anti-tumor effect of WMN is still unclear. AIM OF THE STUDY: To investigate the effect of WMN on the cellular activity and apoptosis of mouse breast cancer 4T1-luc2 cells, and caspase-3 and cleaved-caspase-3 expression. MATERIALS AND METHODS: Luciferase-labeled mouse breast cancer 4T1-luc2 cells were inoculated into the mouse breast pad to establish a luciferase-labeled mouse breast cancer cell model. BALB/C-nu mice were randomly divided into model, WMN, and low-molecular-weight heparin (LMWH) groups (n = 10). Another 10 mice served as the normal control group (no cancer cell injection). The WMN group was administered WMN 250 mg/kg per day for 14 days, the LMWH group was given LMWH (1500 U/kg) daily for 14 days by intraperitoneal injection, and the model and normal control groups were given an equal dose of 0.9% NaCl. The number and distribution of transplanted tumors in 4T1-luc2 breast cancer cells were observed in nude mice by an in vivo imaging system at the time of inoculation after successful modeling, and on days 7 and 14 after drug administration. Tumor cell apoptosis was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method; caspase-3 mRNA expression was detected by RT-PCR and Western blotting was applied to detect the levels of caspase-3 and cleaved-caspase-3 protein expression. RESULTS: The apoptosis index (AI) of the WMN group was detected by the TUNEL method, and the AI increased with the increase of treatment time. Compared with the model group, the mRNA expression of caspase-3 and the protein levels of caspase-3 and cleaved-caspase-3 were notably elevated in the WMN group. After in vivo bioluminescent imaging, the total photon number of the WMN group was found to be lower than that of the LWMH group on day 14 after administration. Additionally, the AI and expression levels of caspase-3 mRNA, caspase-3, and cleaved-caspase-3 protein of the WMN group were higher than those of the LWMH group. CONCLUSION: WMN can effectively suppress the growth of 4T1-luc2 breast cancer xenografts in mice, and promote the apoptosis of breast cancer cells by upregulating the expression of caspase-3.

Chemo-immunotherapy with doxorubicin prodrug and erythrocyte membrane-enveloped polymer nano-vaccine enhances antitumor activity.

There are plenty of evidences to show that combining of chemotherapy and immunotherapy should be a very potent anti-cancer therapeutic method. In this research, we evaluated the anti-tumor activity of doxorubicin prodrug combined with erythrocyte membrane-enveloped polymer nano-vaccine against tumor in vitro and in vivo. We also analyzed the immune cell populations to investigate the effect in the tumor microenvironment and explored the inhibitory of lung metastasis. Our study showed that chemo-immunotherapy could inhibit the growth of melanoma tumor in mice. This combination approach promoted a stronger immune response by up-regulating the expression of dendritic cells and cytotoxic T cells in lymph nodes and increased the secretion of cytokines. It also restricted the immunosuppressive environment through inhibiting expression of regulatory T cells. It suggested that combination of prodrug and nano-vaccine achieved better anti-tumor effect than monotherapy, which should be widely valued and further studied to establish in a more economical and efficient way, expected to apply in the future clinical practice of cancer treatment.

Compound Opening Arrow Mixture exerts anti-tumor effects in a mouse model of breast cancer.

Compound Opening Arrow Mixture (COAM) has demonstrated therapeutic effects in patients with breast cancer. We explored the underlying molecular mechanisms of COAM using a mouse model of breast cancer. Luciferase-labeled 4T1-Luc2 cells were inoculated into the breast pad of BALB/c-nu mice, which were divided into model group (saline), COAM (6 g/ml high-dose, 3 g/ml medium-dose, and 1.5 g/ml low-dose) groups, and low-molecular-weight heparin (LMWH, 1500 U/Kg) group. The number and distribution of 4T1-luc2 tumors were measured by an in vivo imaging system. Tumor cell apoptosis was measured through TUNEL and quantitating the expression of Caspase-3 mRNA and protein. Compared with the model group, in vivo tumor growth was lower in the LMWH- and COAM-treated groups. Tumor apoptosis was time-dependent and dose-dependent, as shown by a higher TUNEL apoptotic index and higher Caspase-3 mRNA and Caspase-3/cleaved-Caspase-3 proteins levels on the 14th day than the 7th day. The COAM high-dose group had the highest apoptotic index and the most activation of Caspase-3. Collectively, COAM significantly inhibits the growth of 4T1-luc2 breast cancer in mice and induces tumor apoptosis by activating Caspase-3, which provides a preliminary explanation of therapeutic effects of COAM.

Well-Defined Single-Atom Cobalt Catalyst for Electrocatalytic Flue Gas CO2 Reduction.

Single-atom Co catalyst Co-Tpy-C with well-defined sites is synthesized by pyrolysis of a Co terpyridine (Tpy) organometallic complex. The Co-Tpy-C catalyst exhibits excellent activity for the electrochemical CO2 reduction reaction in aqueous electrolyte, with CO faradaic efficiency (FE) of over 95% from -0.7 to -1.0 V (vs RHE). By comparison, catalysts without Co or Tpy ligand added do not show any high CO FE. When simulated flue gas with 15% of CO2 is used as the source of CO2 , CO FE is kept at 90.1% at -0.5 V versus RHE. During gas phase flow electrolysis using simulated flue gas, the CO partial current density is further increased to 86.4 mA cm-2 and CO FE reached >90% at the cell voltage of 3.4 V. Experiments and density functional theory calculations indicate that uniform single-atom Co-N4 sites mainly contribute to the high activity for CO2 reduction.