Enhancing tumor photodynamic synergistic therapy efficacy through generation of carbon radicals by Prussian blue nanomedicine.

Significant progress has been achieved in tumor therapies utilizing nano-enzymes which could convert hydrogen peroxide into reactive oxygen species (ROS). However, the ROS generated by these enzymes possess a short half-life and exhibit limited diffusion within cells, making it challenging to inflict substantial damage on major organelles for effective tumor therapy. Therefore, it becomes crucial to develop a novel nanoplatform that could extend radicals half-life. Artesunate (ATS) is a Fe (II)-dependent drug, while the limited availability of iron (II), coupled with the poor aqueous solubility of ATS, limits its application. Here, Prussian blue (PB) was selected as a nano-carrier to release Fe (II), thus constructing a hollow Prussian blue/artesunate/methylene blue (HPB/ATS/MB) nanoplatform. HPB degraded and released iron(III), ATS and MB, under the combined effects of NIR irradiation and the unique tumor microenvironment. Moreover, Fe (III) exploited GSH to formation of Fe (II), disturbing the redox homeostasis of tumor cells and Fe (II) reacted with H2O2 and ATS to generate carbon radicals with a long half-life in situ. Furthermore, MB generates 1O2 under laser irradiation conditions. In vitro and in vivo experiments have demonstrated that the HPB/ATS/MB NPs exhibit a synergistic therapeutic effect through photothermal therapy, photodynamic therapy and radical therapy.

The influence of processing methods on polyphenol profiling of tea leaves from the same large-leaf cultivar (Camellia sinensis var. assamica cv. Yunkang-10): nontargeted/targeted polyphenomics and electronic sensory analysis.

Tea polyphenols transform under processing methods, but a systematic study on their changes in the same large-leaf tea cultivar is lacking. Here, Camellia sinensis var. assamica cv. Yunkang-10 leaves underwent six processing methods and were assessed using optimized nontargeted (UHPLC-Q-Exactive Orbitrap-MS) and targeted (UHPLC-QqQ-MS) polyphenomics, along with molecular networking analysis. 903 and 52 polyphenolic compounds (catechins, flavones and flavonols, and phenolic acids) were respectively relatively and absolutely quantified for the first time. Dark and black teas, with the lowest polyphenol content, differed from the other four tea types, although variations existed among these four teas. However, some flavonol and flavone aglycones (e.g. kaempferol, apigenin), as well as some phenolic acids (e.g. ellagic acid, gallic acid), exhibited higher levels in dark and black teas. Correlations between polyphenolic composition and electronic sensory characteristics were observed using E-tongue and E-eye. This study enriches understanding of polyphenol profiles in Chinese teas post diverse processing.

Retrospective Analysis of Pyrotinib-Based Therapy for Metastatic Breast Cancer: Promising Efficacy in Combination with Trastuzumab.

Purpose: To evaluate the efficacy and safety of a pyrotinib-based therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in the real world. Methods: Clinical data of 218 patients with HER2-positive MBC who received a pyrotinib-based therapy from January 2020 to March 2023 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results: Finally, 195 patients were included in the efficacy cohort. The median progression-free survival (PFS) in the total population is 12.4 months (95% CI, 9.8-15.0 months). More than half of the patients in the efficacy cohort received pyrotinib mono-targeted therapy (103 cases, 52.8%). Among the remaining patients, 74 (37.9%) patients chose a combined trastuzumab-targeted therapy and 17 (8.7%) chose to combine inetetamab. Median PFS in the pyrotinib group vs pyrotinib plus trastuzumab group was 10.5 months vs 20.1 months (P<0.001). The median PFS of primary trastuzumab resistance population reached to 20.1 months in pyrotinib plus trastuzumab group. Double-targets' advantage was also observed in the brain metastases subgroup (17.9 months vs 10.0 months, P=0.386). The patients who received pyrotinib plus inetetamab as second and higher-line treatment reached a median PFS of 7.9 months (95% CI, 4.0-11.8 months). Forty-one (19.8%) of 207 patients included in the safety cohort experienced grade 3 or higher diarrhea, the most common adverse event in safety analysis, and no adverse event-related deaths. Conclusion: The combination of pyrotinib and trastuzumab demonstrated promising efficacy in the treatment of HER2-positive metastatic breast cancer, including those who had primary resistance to trastuzumab and brain metastases. Pyrotinib plus trastuzumab is expected to be a potent option in the first-line. Additionally, the concurrent administration of pyrotinib and inetetamab could be an alternative to consider in the second and higher-line treatment for metastatic breast cancer. The adverse reactions of pyrotinib were tolerable in general.

Prussian blue nanoparticle-based pH-responsive self-assembly for enhanced photothermal and chemotherapy of tumors.

In recent years, there has been growing interest in size-transformable nanoplatforms that exhibit active responses to acidic microenvironments, presenting promising prospects in the field of nanomedicine for tumor therapy. However, the design and fabrication of such size-adjustable nanotherapeutics pose significant challenges compared to size-fixed nanocomposites, primarily due to their distinct pH-responsive requirements. In this study, we developed pH-activated-aggregating nanosystems to integrate chemotherapy and photothermal therapy by creating size-transformable nanoparticles based on Prussian blue nanoparticles (PB NPs) anchored with acid-responsive polyoxometalates (POMs) quantum dots via electrostatic interactions (PPP NPs). Subsequently, we utilized doxorubicin (DOX) as a representative drug to formulate PPPD NPs. Notably, PPPD NPs exhibited a significant response to acidic conditions, resulting in changes in surface charge and rapid aggregation of PPP NPs. Furthermore, the aggregated PPP NPs demonstrated excellent photothermal properties under near-infrared laser irradiation. Importantly, PPPD NPs prolonged their retention time in tumor cells via a size-transformation approach. In vitro cellular assays revealed that the anticancer efficacy of PPPD NPs was significantly enhanced. The IC50 values for the PPPD NPs groupand the PPPD NPs + NIR group were 50.11 µg/mL and 30.9 µg/mL. Overall, this study introduces a novel strategy for cancer therapy by developing size-aggregating nano-drugs with stimuli-responsive properties, holding promise for improved therapeutic outcomes in future combination approaches involving photothermal therapy and chemotherapy.

Secondary Metabolites from the Genus Eurotium and Their Biological Activities.

Eurotium is the teleomorph genus associated with the section Aspergillus. Eurotium comprises approximately 20 species, which are widely distributed in nature and human environments. Eurotium is usually the key microorganism for the fermentation of traditional food, such as Fuzhuan brick tea, Liupao tea, Meju, and Karebushi; thus, Eurotium is an important fungus in the food industry. Eurotium has been extensively studied because it contains a series of interesting, structurally diverse, and biologically important secondary metabolites, including anthraquinones, benzaldehyde derivatives, and indol diketopiperazine alkaloids. These secondary metabolites have shown multiple biological activities, including antioxidative, antimicrobial, cytotoxic, antitumor, insecticidal, antimalarial, and anti-inflammatory activities. This study presents an up-to-date review of the phytochemistry and biological activities of all Eurotium species. This review will provide recent advances on the secondary metabolites and their bioactivities in the genus Eurotium for the first time and serve as a database for future research and drug development from the genus Eurotium.

Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for HER2-positive breast cancer: a prospective cohort study.

BACKGROUND: This prospective study aims to investigate the efficacy and safety of pyrotinib (P) combined with 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of taxane and trastuzumab (P + EC-TH) regimen as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer and to investigate the predictive value of p53, p63, and epidermal growth factor receptor (EGFR) status for neoadjuvant efficacy. METHODS: A total of 138 HER2-positive breast cancer patients who received neoadjuvant therapy and underwent surgery were included. Case group: 55 patients received P + EC-TH regimen. CONTROL GROUP: 83 patients received EC-TH regimen. The chi-square test, Fisher's exact test, and logistic regression analysis were applied. The primary endpoint was total pathologic complete response (tpCR), and the secondary endpoints were breast pathologic complete response (bpCR), overall response rate (ORR), and adverse events (AEs). RESULTS: In the case group, the tpCR rate was 63.64% (35/55), the bpCR rate was 69.09% (38/55), and the ORR was 100.00% (55/55). In the control group, the tpCR rate was 39.76% (33/83), the bpCR rate was 44.58% (37/83), and the ORR was 95.18% (79/83). The case group had significantly higher tpCR and bpCR rates than those of the control group (P < 0.05), but there was no significant difference in ORR (P > 0.05). The tpCR was associated with the status of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), and the patients with any negative ER, PR, AR, or combined, were more likely to achieve tpCR than those with positive results (P < 0.05). The p53-positive patients were more likely to achieve tpCR and bpCR than p53-negative patients (P < 0.05). The incidence of hypokalemia and diarrhea in the case group was higher than that in the control group (P < 0.05). The AEs developed were all manageable, and no treatment-related death occurred. CONCLUSION: The efficacy and safety of the P + EC-TH regimen were verified by this study. The HER2-positive breast cancer patients treated with the EC-TH neoadjuvant regimen were more likely to achieve tpCR or bpCR if pyrotinib was administered simultaneously.

Effects of solid-state fermentation with Bacillus subtilis LK-1 on the volatile profile, catechins composition and antioxidant activity of dark teas.

In this study, the solid-state fermentation (SSF) of dark tea was carried out using Bacillus subtilis LK-1, which was isolated from Fu brick tea (FBT). The effects of SSF with B. subtilis on volatile organic compounds (VOCs), non-volatile metabolites, and antioxidant activities of dark tea was investigated. A total of 45 VOCs were identified, primarily consisting of ketones (18), hydrocarbons (8), aldehydes (7), and alcohols (6). Following fermentation, the content of key odor active substances such as linalool, ß-ionone, and 3,5-octadiene-2-one significantly increased, resulting in an enhanced floral and fruity aroma of dark tea. Furthermore, new flavor substances like geranyl isovalerate and decanal were produced during SSF, enriching the aroma profile of dark tea. Non-ester catechins demonstrated a drastic increase, while ester catechins remarkably decreased after SSF. Furthermore, SSF led to a slight decrease in the total polyphenols content and antioxidant activity of dark tea. There is a close relationship between VOCs and the main non-volatile metabolites during SSF. Overall, this study highlighted the great impact of SSF with B. subtilis on the metabolites of dark tea and provided valuable insights into the role of bacteria in shaping the metabolite profile of FBT.

Developing a method to detect lipoarabinomannan in pleural fluid and assessing its diagnostic efficacy for tuberculous pleural effusion.

Objectives: The diagnosis of tuberculosis pleural effusion (TPE) remains challenging, traditional diagnostic tests have limited diagnostic efficacy. This study aimed to assess the diagnostic performance of pleural fluid (PF) lipoarabinomannan (LAM) in TPE. Methods: A diagnostic method for PF LAM (LAM-PF) was established using LEDBIO's AIMLAM kit. The diagnostic performance of LAM-PF was evaluated in 162 HIV-negative patients with suspected TPE. Results: The LAM-PF method established in this study exhibited good linearity and recovery rate, with a limit of detection (LOD) of 2.90 pg/mL. Using a cut-off value of 5.33 pg/mL, the sensitivity and specificity of LAM-PF in diagnosing TPE (n = 128) were 47.7% and 100.0%, respectively. The sensitivity in patients with probable TPE (n = 29) and definite TPE (n = 99) were 41.4% and 49.5%, respectively. LAM-PF displayed a significantly higher sensitivity in probable TPE compared to other tuberculosis detection methods. Combined testing of adenosine deaminase (ADA)and LAM increased the detection sensitivity of TPE to 68.0%, and the area under the curve was 0.84 (0.77-0.89). Conclusion: This study successfully established a method for detecting LAM in PF, which exhibited favorable diagnostic performance for TPE, particularly in challenging cases of probable TPE. Combined detection of LAM and ADA in PF significantly improves TPE diagnostic efficiency.

Dietary assessment of ochratoxin A in Chinese dark tea and inhibitory effects of tea polyphenols on ochratoxigenic Aspergillus niger.

In recent years, there has been an increasingly heated debate on whether Chinese dark tea is contaminated with mycotoxins and whether it poses health risks to consumers. In this study, a rapid method based on high-performance liquid chromatography was used to detect ochratoxin A (OTA) in Chinese dark tea samples from different regions of China and different years. Of the 228 Chinese dark tea samples tested, 21 were detected for OTA contamination, with a concentration ranging from 2.51 ± 0.16 to 12.62 ± 0.72 µg/kg. Subsequently, a dark tea drinking risk assessment was conducted, and the hazard quotient for each group was far below the acceptable level of 1.0. Of the 12 Aspergillus spp. strains isolated, one strain of Aspergillus niger had the ability to produce OTA. We also found that tea polyphenols and epigallocatechin gallate inhibited the growth of ochratoxin-producing Aspergillus niger and the expression of non-ribosomal peptide synthetase (NRPS), a key gene for ochratoxin synthesis. Thus, OTA contamination of dark tea is at an acceptable risk level, and the inhibition of ochratoxigenic Aspergillus niger by polyphenols provides new insights into the safety of dark tea consumption.

Transcriptome and Metabolome Analysis Revealing the Improved ε-Poly-l-Lysine Production Induced by a Microbial Call from Botrytis cinerea.

ε-Poly-l-lysine (ε-PL) is a wide-spectrum antimicrobial agent, while its biosynthesis-inducing signals are rarely reported. This study found that Botrytis cinerea extracts could act as a microbial call to induce a physiological modification of Streptomyces albulus for ε-PL efficient biosynthesis and thereby resulted in ε-PL production (34.2 g/liter) 1.34-fold higher than control. The elicitors could be primary isolated by ethanol and butanol extraction, which resulted in more vibrant, aggregate and stronger mycelia. The elicitor-derived physiological changes focused on three aspects: ε-PL synthase, energy metabolism, and lysine biosynthesis. After elicitor addition, upregulated sigma factor hrdD and improved transcription and expression of pls directly contributed to the high ε-PL productivity; upregulated genes in tricarboxylic acid (TCA) cycle and energy metabolism promoted activities of citrate synthase and the electron transport system; in addition, pool enlargements of ATP, ADP, and NADH guaranteed the ATP provision for ε-PL assembly. Lysine biosynthesis was also increased based on enhancements of gene transcription, key enzyme activities, and intracellular metabolite pools related to carbon source utilization, the Embden-Meyerhof pathway (EMP), the diaminopimelic acid pathway (DAP), and the replenishment pathway. Interestingly, the elicitors stimulated the gene transcription for the quorum-sensing system and resulted in upregulation of genes for other antibiotic production. These results indicated that the Botrytis cinerea could produce inducing signals to change the Streptomyces mycelial physiology and accelerate the ε-PL biosynthesis. IMPORTANCE This work identified the role of microbial elicitors on ε-PL production and disclosed the underlying mechanism through analysis of gene transcription, key enzyme activities, and intracellular metabolite pools, including transcriptome and metabolome analysis. It was the first report for the inducing effects of the "microbial call" to Streptomyces albulus and ε-PL biosynthesis, and these elicitors could be potentially obtained from decayed fruits infected by Botrytis cinerea; hence, this may be a way of turning a biohazard into bioproduct wealth. This study provided a reference for application of microbial signals in secondary metabolite production, which is of theoretical and practical significance in industrial antibiotic production.

Dynamic changes in the diversity and function of bacterial community during black tea processing.

Among all types of tea, black tea is produced in the largest amount worldwide, and its consumption is still increasing. Enzymatic fermentation is considered majorly contribute to quality formation of black tea, and the information about the roles of bacterial community in black tea processing is scarce. This study aimed to analyze the dynamic changes in composition, structure, and function of microbial communities during black tea processing and reveal the roles of bacterial community in black tea processing. Results showed that the genera Sphingomonas and Variovorax were dominant throughout the processing of black tea. Prediction function analysis of bacterial community showed that the mean proportions of glucuronoarabinoxylan endo - 1,4 - beta - xylanase, aminopeptidase B, phosphoserine phosphatase, homoserine O-acetyltransferase, glycolysis related enzymes, pyruvate dehydrogenase, tricarboxylic acid cycle related enzymes, and glyoxylate bypass were significantly elevated in the rolling and fermentation stages. The contents of amino acids, soluble sugar, theaflavins, thearubigins, and theabrownins increased greatly during the rolling and fermentation processes. Redundancy and Pearson's correlation analyses showed that the relative abundance of bacteria was closely related to the contents of water extract, tea polyphenols, epigallocatechin, epicatechin gallate, catechin gallate, thearubigins, theaflavins, and theabrownins. Overall, the findings provided new insights into the variation of bacterial community during black tea processing and improved our understanding of the core functional bacteria involved in black tea processing.

Comparison of the Fungal Community, Chemical Composition, Antioxidant Activity, and Taste Characteristics of Fu Brick Tea in Different Regions of China.

In this study, the fungal community structure, metabolites, antioxidant ability, and taste characteristics of five Fu brick tea (FBT) from different regions of China were determined and compared. A total of 69 operational taxonomic units (OTUs) were identified and assigned into 5 phyla and 27 genera, with Eurotium as the predominant genus in all samples. Hunan (HN) sample had the strongest fungal diversity and richness, followed by Guangxi (GX) sample, and Zhejiang (ZJ) sample had the lowest. GX sample had higher amounts of gallic acid (GA), total catechins, gallocatechin (GC), and epicatechin gallate (ECG) as well as antioxidant activity than the other samples. The levels of total phenolics, total flavonoids, epigallocatechin (EGC), catechin, epicatechin (EC), thearubigins (TRs), and theaflavins (TFs) were the highest in the ZJ sample. Guizhou (GZ) and Shaanxi (SX) samples contained the highest contents of epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG), respectively. Total phenolics, GA, EC, CG, and TFs were positively associated with most of fungal genera. Total phenolic content (TPC), total flavonoid content (TFC), and most of catechins contributed to the antioxidant activities of FBT. HN sample had the strongest sourness and sweetness, ZJ sample had the strongest saltiness, SX sample had the strongest umami, and GZ sample had the strongest astringency, which was ascribed to the varied metabolites. This work reveals that FBT in different regions vary greatly in fungal community, metabolites, antioxidant activity, and taste characteristics, and provides new insight into the quality characteristics formation of FBT in different regions.

Integrative analysis of transcriptome and metabolome reveals the mechanism of foliar application of Bacillus amyloliquefaciens to improve summer tea quality (Camellia sinensis).

Bacillus amyloliquefaciens is a promising microbial agent for quality improvement in crops; however, the effects of B. amyloliquefaciens biofertilizers on tea leaf metabolites are relatively unknown. Herein, a combination of metabolome profiling and transcriptome analysis was employed to investigate the effects of foliar spraying with B. amyloliquefaciens biofertilizers on tea leaf quality. The tea polyphenol to amino acid ratio (TP/AA), catechin, and caffeine levels decreased, but theanine level increased in tea leaves after foliar spraying with B. amyloliquefaciens. The differentially accumulated metabolites included flavonoids, phenolic acids, organic acids, amino acids, and carbohydrates. The decrease in catechin was correlated with the catechin/flavonoid biosynthesis pathway. The AMPD gene was highly associated with caffeine content, while the GOGAT gene was associated with theanine accumulation. Foliar spraying with B. amyloliquefaciens biofertilizers may improve summer tea quality. Our findings provide a basis for the application of B. amyloliquefaciens biofertilizers in tea plants and new insights on summer tea leaf resource utilization.

Breast Cancer Stem Cells-derived Extracellular Vesicles Affect PPARG Expression by Delivering MicroRNA-197 in Breast Cancer Cells.

BACKGROUND: Breast cancer (BC) is the most frequently diagnosed cancer in women, and over 90% of BC-related deaths are associated with metastasis. The effects of BC stem cells-derived extracellular vesicles (BCSCs-EVs) have been implicated in cancer control. This work aims to probe to the relevance of BCSCs-EVs to liver metastases of BC cells and the molecules involved. METHODS: First, EVs were extracted from BCSCs for MDA-MB-231 and SUM149PT cell co-culture. The effects of BCSCs-EVs on the proliferation of BC cells in vitro and in vivo as well as liver metastasis were evaluated. Subsequently, we analyzed differentially expressed microRNAs (miRNAs) after BCSCs-EVs by microRNA microarray and had them verified by RT-qPCR. Bioinformatics analysis was conducted to analyze target mRNAs of miR-197. The binding relationship of miR-197 to PPARG mRNA was examined. Finally, MDA-MB-231 and SUM149PT cells co-cultured with BCSCs-EVs were treated with miR-197 inhibitor or a PPARG-specific agonist. RESULTS: BCSCs-EVs promoted the growth of MDA-MB-231 and SUM149PT cells in vitro and in vivo as well as liver metastasis. BCSCs-EVs increased the expression of miR-197 in MDA-MB-231 and SUM149PT cells, and miR-197 could target PPARG mRNA. BCSCs-EVs treatment inhibited the mRNA and protein expression of PPARG in cells, thereby activating epithelial-mesenchymal transition (EMT). Knockdown of miR-197 or activation of PPARG in BCSCs-EVs-treated cells significantly counteracted the promoting effect of BCSCs-EVs on BC cell growth and metastasis. CONCLUSION: BCSCs-EVs facilitated EMT of BC cells by delivering miR-197 to BC cells and inhibiting PPARG expression, thereby promoting growth and metastasis of BC cells.

Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer.

BACKGROUND: Breast cancer (BC) threatens the health of women around the world. Researchers have proved that hsa_circ_0005505 (circ_IRAK3) facilitates BC cell invasion and migration, but the regulatory mechanisms of circ_IRAK3 in BC remain mostly unknown. We aim to explore a new mechanism by which circ_IRAK3 promotes BC progression. METHODS: Levels of circ_IRAK3, microRNA (miR)-603, and kinesin family member 2A (KIF2A) mRNA in BC tissues and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, colony formation, and proliferation of BC cells were evaluated by flow cytometry, plate clone, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays. The migration, invasion, and apoptosis of BC cells were determined by transwell or flow cytometry assays. Several protein levels were detected using western blotting. The targeting relationship between circ_IRAK3 or KIF2A and miR-603 was verified via dual-luciferase reporter assay. The role of circ_IRAK3 in vivo was verified by xenograft assay. RESULTS: We observed higher levels of circ_IRAK3 in BC tissues and cell lines than their respective controls. Functional experiments presented that circ_IRAK3 silencing induced BC cell apoptosis, curbed cell proliferation, migration, and invasion in vitro, and decreased tumor growth in vivo. Mechanistically, circ_IRAK3 could modulate kinesin family member 2A (KIF2A) expression through acting as a microRNA (miR)-603 sponge. miR-603 silencing impaired the effects of circ_IRAK3 inhibition on the malignant behaviors of BC cells. Also, the repressive effects of miR-603 mimic on the malignant behaviors of BC cells were weakened by KIF2A overexpression. CONCLUSIONS: circ_IRAK3 exerted a promoting effect on BC progression by modulating the miR-603/KIF2A axis, providing a piece of novel evidence for circ_IRAK3 as a therapeutic target for BC.

Transcription Factor FOSL1 Enhances Drug Resistance of Breast Cancer through DUSP7-Mediated Dephosphorylation of PEA15.

Breast cancer is one of the commonest malignancies in women with first occurrence and fifth mortality in the world. However, drug resistance has always been a major obstacle to cancer treatment. Transcription factors have been reported to have close association with drug resistance of tumors. Recently, by analyzing the data from Gene Expression Omnibus database (GSE76540), we found that transcription factor FOS like 1, AP-1 transcription factor subunit (FOSL1) was significantly upregulated in the transcriptome of doxorubicin-resistant breast cancer cells compared with that in sensitive parental cells. Therefore, we aim to explore the regulatory mechanism of FOSL1 in affecting the drug resistance of breast cancer cells. FOSL1 expression in doxorubicin-resistant breast cancer cells was firstly examined through qRT-PCR, and then its influence on the drug resistance of breast cancer cells was explored through a series of in vitro and in vivo mechanism assays. Results showed that FOSL1 promoted the drug resistance of breast cancer cells to doxorubicin both in intro and in vivo. It positively regulated the transcription of dual specificity phosphatase 7 (DUSP7) in breast cancer doxorubicin-resistant cells and DUSP7 also enhanced the drug resistance of breast cancer cells. Furthermore, FOSL1 promoted the dephosphorylation of proliferation and apoptosis adaptor protein 15 (PEA15) through DUSP7. In conclusion, it was verified that FOSL1 promoted the drug resistance in breast cancer through DUSP7-mediated dephosphorylation of PEA15. IMPLICATIONS: These initial findings suggest that the FOSL1/DUSP7/PEA15 pathway may provide a theoretical guidance for breast cancer treatment.

Coexpression Module Construction by Weighted Gene Coexpression Network Analysis and Identify Potential Prognostic Markers of Breast Cancer.

Background: Breast cancer (BC) is a malignant tumor with the highest morbidity among women, disrupting millions of their lives worldwide each year. However, the molecular mechanisms underlying remain unclear. Materials and Methods: The RNA-Sequencing and clinical data of BC patients from The Cancer Genome Atlas (TCGA) database were analyzed by weighted gene coexpression network analysis (WGCNA). Additionally, coexpressed modules were used to detect their correlation with the clinical traits of BC. Next, nodes of the most significant coexpression modules were used for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, mRNA-lncRNA coexpression network and survival analyses. Results: In total, 2056 differentially expressed mRNAs (DEmRNAs) and 297 differentially expressed lncRNAs (DElncRNAs) were identified and subjected to WGCNA analysis, and 12 coexpression modules were generated. The top five significant modules (turquoise, green, red, brown, and blue modules) were related to one or more clinical traits of BC. In particular, the turquoise and green modules were chosen for further analysis. Next, by lncRNA-mRNA coexpression analysis of the turquoise and green modules, 12 DEmRNAs and 2 DElncRNAs were identified as hub nodes. The lncRNA-associated mRNAs of the networks were commonly related to several cancer-related pathways. Moreover, these networks also revealed central roles for RP11-389C8.2 and TGFBR2 in the turquoise module and MYLK, KIT, and RP11-394O4.5 in the green module. Furthermore, 16 DEmRNAs and 3 DElncRNAs in these two modules were significantly correlated with the overall survival of BC patients. Conclusions: The authors' study identified some prognostic biomarkers that might play important roles in the development and treatment of BC. In particular, lncRNAs AC016995.3, RP1-193H18.2, and RP11-166D19.1 were novel biomarkers for BC.

The R2R3 Transcription Factor CsMYB59 Regulates Polyphenol Oxidase Gene CsPPO1 in Tea Plants (Camellia sinensis).

Polyphenol oxidase (PPO) plays a role in stress response, secondary metabolism, and other physiological processes during plant growth and development, and is also a critical enzyme in black tea production. However, the regulatory mechanisms of PPO genes and their activity in tea plants are still unclear. In this study, we measured PPO activity in two different tea cultivars, Taoyuandaye (TYDY) and Bixiangzao (BXZ), which are commonly used to produce black tea and green tea, respectively. The expression pattern of CsPPO1 was assessed and validated via transcriptomics and quantitative polymerase chain reaction in both tea varieties. In addition, we isolated and identified an R2R3-MYB transcription factor CsMYB59 that may regulate CsPPO1 expression. CsMYB59 was found to be a nuclear protein, and its expression in tea leaves was positively correlated with CsPPO1 expression and PPO activity. Transcriptional activity analysis showed that CsMYB59 was a transcriptional activator, and the dual-luciferase assay indicated that CsMYB59 could activate the expression of CsPPO1 in tobacco leaves. In summary, our study demonstrates that CsMYB59 represents a transcriptional activator in tea plants and may mediate the regulation of PPO activity by activating CsPPO1 expression. These findings provide novel insights into the regulatory mechanism of PPO gene in Camellia sinensis, which might help to breed tea cultivars with high PPO activity.

Polyphenols from Fu Brick Tea Reduce Obesity via Modulation of Gut Microbiota and Gut Microbiota-Related Intestinal Oxidative Stress and Barrier Function.

Fu brick tea (FBT) is a microbial-fermented tea, which is produced by the solid-state fermentation of tea leaves. Previous studies have proved that FBT aqueous extracts could attenuate obesity and gut microbiota dysbiosis. However, the bioactive components in FBT that contribute to these activities remain unclear. In this study, we aimed to investigate the effects of FBT polyphenols (FBTPs) on obesity, gut microbiota, and gut microbiota-related intestinal oxidative stress and barrier function and to further investigate whether the antiobesity effect of FBTPs was dependent on the alteration of gut microbiota. The results showed that FBTP supplementation effectively attenuated obesity in high-fat diet (HFD)-fed rats. FBTP supplementation improved the intestinal oxidative stress and intestinal barrier function, including intestinal inflammation and the integrity of the intestinal barrier. Furthermore, FBTP intervention significantly attenuated HFD-induced gut microbiota dysbiosis, characterized by increased phylogenetic diversity and decreased Firmicutes/Bacteroidetes ratio. Certain core microbes, including Akkermansia muciniphila, Alloprevotella, Bacteroides, and Faecalibaculum, were also found to be improved by FBTPs. Moreover, the antiobesity effect of FBTPs was gut microbiota-dependent, as demonstrated by a fecal microbiota transplantation experiment. Collectively, we concluded that FBTPs reduced obesity by modulating the gut microbiota and gut microbiota-related intestinal oxidative stress and barrier function. Therefore, FBTPs may be used as prebiotic agents to treat obesity and gut microbiota dysbiosis in obese individuals.

Combination of Mussel Inspired Method and "Thiol-Michael" Click Reaction for Biocompatible Alginate-Modified Carbon Nanotubes.

Carbon nanotubes (CNTs) have attracted great interest in biomedical fields. However, the potential toxicity and poor dispersion of CNTs have greatly limited its application. In this work, a mussel-inspired method combined with the "thiol-Michael" click reaction was used to modify the surface of CNT and improve its properties. Firstly, a CNT was treated with dopamine, and then alginate grafted with L-cysteine was anchored onto the surface of CNT via click reaction, which realized the long-time dispersion of CNT in water. Furthermore, the in vitro test also demonstrated that the alginate may improve the biocompatibility of CNT, and thus may broaden the application of CNT in the biomedical field.