2D Tantalum Disulfide Reduction Strategy Customized Ta2O5/rGO Heterointerface Aerogel Toward Boosting Electromagnetic Wave Absorption and Flame Retardancy.

The exceptional and substantial electron affinity, as well as the excellent chemical and thermal stability of transition metal oxides (TMOs), infuse infinite vitality into multifunctional applications, especially in the field of electromagnetic wave (EMW) absorption. Nonetheless, the suboptimal structural mechanical properties and absence of structural regulation continue to hinder the advancement of TMOs-based aerogels. Herein, a novel 2D tantalum disulfide (2H-TaS2) reduction strategy is demonstrated to synthesize Ta2O5/reduced graphene oxide (rGO) heterointerface aerogels with unique characters. As the prerequisite, the defects, interfaces, and configurations of aerogels are regulated by varying the concentration of 2H-TaS2 to ensure the Ta2O5/rGO heterointerface aerogels with appealing EMW absorption properties such as a minimum reflection loss (RLmin) of -61.93 dB and an effective absorption bandwidth (EAB) of 8.54 GHz (7.80-16.34 GHz). This strategy provides valuable insights for designing advanced EMW absorbers. Meanwhile, the aerogel exhibits favorable thermal insulation performance with a value of 36 mW m-1 K-1, outstanding fire resistance capability, and exceptional mechanical energy dissipation performance, making it promising for applications in the aerospace industry and consumer electronics devices.

Camellia sinensis polysaccharide attenuates inflammatory responses via the ROS-mediated pathway by endocytosis.

Polysaccharide CSTPs extracted from Camellia sinensis tea-leaves possessed unique against oxidative damage by scavenging ROS. Herein, acid tea polysaccharide CSTPs-2 with tightly packed molecular structure was isolated, purified and characterized in this research. Furthermore, the effects of CSTPs-2 on ROS-involved inflammatory responses and its underlying mechanisms were investigated. The results suggest that CSTPs-2 dramatically reduced the inflammatory cytokines overexpression and LPS-stimulated cell damage. CSTPs-2 could trigger the dephosphorylation of downstream AKT/MAPK/NF-κB signaling proteins and inhibit nuclear transfer of p-NF-κB to regulate the synthesis and release of inflammatory mediators in LPS-stimulated cells by ROS scavenging. Importantly, the impact of CSTPs-2 in downregulating pro-inflammatory cytokines and mitigating ROS overproduction is associated with clathrin- or caveolae-mediated endocytosis uptake mechanisms, rather than TLR-4 receptor-mediated endocytosis. This study presents a novel perspective for investigating the cellular uptake mechanism of polysaccharides in the context of anti-inflammatory mechanisms.

Enhancing the Interaction of Carbon Nanotubes by Metal-Organic Decomposition with Improved Mechanical Strength and Ultra-Broadband EMI Shielding Performance.

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 105 S m-1, and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 µm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices.

Single-case design meta-analyses in education and psychology: a systematic review of methodology.

Meta-analysis is of increasing importance as this quantitative synthesis technique has the potential to summarize a tremendous amount of research evidence, which can help making evidence-based decisions in policy, practice, and theory. This paper examines the single-case meta-analyses within the Education and Psychology fields. The amount of methodological studies related to the meta-analysis of Single-Case Experimental Designs (SCEDs) is increasing rapidly, especially in these fields. This underscores the necessity of a succinct summary to help methodologists identify areas for further development in Education and Psychology research. It also aids applied researchers and research synthesists in discerning when to use meta-analytic techniques for SCED studies based on criteria such as bias, mean squared error, 95% confidence intervals, Type I error rates, and statistical power. Based on the summary of empirical evidence from 18 reports identified through a systematic search procedure, information related to meta-analytic techniques, data generation and analysis models, design conditions, statistical properties, conditions under which the meta-analytic technique is appropriate, and the study purpose(s) were extracted. The results indicate that three-level hierarchical linear modeling is the most empirically validated SCED meta-analytic technique, and parameter bias is the most prominent statistical property investigated. A large number of primary studies (more than 30) and at least 20 measurement occasions per participant are recommended for usage of SCED meta-analysis in Education and Psychology fields.

Specific genetic aberrations of parathyroid in Chinese patients with tertiary hyperparathyroidism using whole-exome sequencing.

Background: Tertiary hyperparathyroidism (THPT) is a peculiar subtype of hyperparathyroidism that usually develops from chronic kidney disease (CKD) and persists even after kidney transplantation. Unlike its precursor, secondary hyperparathyroidism (SHPT), THPT is characterized by uncontrolled high levels of calcium in the blood, which suggests the monoclonal or oligoclonal proliferation of parathyroid cells. However, the molecular abnormalities leading to THPT have not yet been fully understood. Methods: In this study, we analyzed DNA samples from hyperplastic parathyroid and corresponding blood cells of 11 patients with THPT using whole-exome sequencing (WES). We identified somatic single nucleotide variants (SNV) and insertions or deletions variants (INDEL) and performed driver mutation analysis, KEGG pathway, and GO functional enrichment analysis. To confirm the impact of selected driver mutated genes, we also tested their expression level in these samples using qRT-PCR. Results: Following quality control and mutation filtering, we identified 17,401 mutations, comprising 6690 missense variants, 3078 frameshift variants, 2005 stop-gained variants, and 1630 synonymous variants. Copy number variants (CNV) analysis showed that chromosome 22 copy number deletion was frequently observed in 6 samples. Driver mutation analysis identified 179 statistically significant mutated genes, including recurrent missense mutations on TBX20, ATAD5, ZNF669, and NOX3 genes in 3 different patients. KEGG pathway analysis revealed two enriched pathways: non-homologous end-joining and cell cycle, with a sole gene, PRKDC, involved. GO analysis demonstrated significant enrichment of various cellular components and cytobiological processes associated with four genes, including GO items of positive regulation of developmental growth, protein ubiquitination, and positive regulation of the apoptotic process. Compared to blood samples, THPT samples exhibited lower expression levels of PRKDC, TBX20, ATAD5, and NOX3 genes. THPT samples with exon mutations had relatively lower expression levels of PRKDC, TBX20, and NOX3 genes compared to those without mutations, although the difference was not statistically significant. Conclusion: This study provides a comprehensive landscape of the genetic characteristics of hyperplastic parathyroids in THPT, highlighting the involvement of multiple genes and pathways in the development and progression of this disease. The dominant mutations identified in our study depicted new insights into the pathogenesis and molecular characteristics of THPT.

Detecting fa leptin receptor mutation in Zucker rats with tetra-primer amplification-refractory mutation system (ARMS)-PCR.

Due to the genetic mutation (fa) in the gene encoding for leptin receptor, homozygous Zucker rats (fa-/-) develop excessive adiposity and become an experimental animal model in obesity and metabolic-related diseases research. Based on tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), we developed a method to quickly genotype Zucker rats with a mutated fa allele from their wildtype littermates. The three genotypes are clearly discriminated on 2.0% agarose gel. Our method can be used as a reliable tool to set up and maintain the breeding colony in animal facilities as well as assign animals to control and treatment groups based on their genotypes for animal studies.

Reciprocal Effect of Environmental Stimuli to Regulate the Adipogenesis and Osteogenesis Fate Decision in Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs).

Mesenchymal stem cells derived from bone marrow (BM-MSCs) can differentiate into adipocytes and osteoblasts. Various external stimuli, including environmental contaminants, heavy metals, dietary, and physical factors, are shown to influence the fate decision of BM-MSCs toward adipogenesis or osteogenesis. The balance of osteogenesis and adipogenesis is critical for the maintenance of bone homeostasis, and the interruption of BM-MSCs lineage commitment is associated with human health issues, such as fracture, osteoporosis, osteopenia, and osteonecrosis. This review focuses on how external stimuli shift the fate of BM-MSCs towards adipogenesis or osteogenesis. Future studies are needed to understand the impact of these external stimuli on bone health and elucidate the underlying mechanisms of BM-MSCs differentiation. This knowledge will inform efforts to prevent bone-related diseases and develop therapeutic approaches to treat bone disorders associated with various pathological conditions.

Prognosis of post-neoadjuvant therapy patients who underwent immediate breast reconstruction: a SEER-based, propensity-matched study.

OBJECTIVE: The application of immediate breast reconstruction (IBR) for post-neoadjuvant therapy (NAT) patients was controversial. The aim of this study was to investigate the long-term survival outcomes of IBR for these patients. METHODS: Data between January 2010 and November 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce the influence of confounding factors between the mastectomy alone group (MA) and the mastectomy with IBR group (IBR). The rates of 5 year breast cancer-specific survival (BCSS) were compared by Kaplan-Meier curves with log-rank test. RESULTS: The IBR was associated with improved 5-year BCSS in the IBR group before PSM (88.5 vs. 79.1%, P < 0.001). The proportion of IBR increased from 21.5% in 2010 to 28.2% in 2017. After PSM, a total of 9,610 patients were enrolled for survival analysis (4,805 in each group). In the complete response (CR) group, the 5-year BCSS rates did not differ (93.4 vs. 95.6%, P = 0.16). In the non-CR group, the 5-year BCSS rate was higher in patients who received IBR (82.5% 79.4%, P = 0.034). CONCLUSION: In general, the application of IBR among post-NAT patients has steadily increased from 2010 to 2017. In the CR group, survival outcomes of post-NAT patients who received IBR were similar to those who received mastectomy alone. In the non-CR group, IBR was associated with potential survival benefits. More studies are expected to validate our findings.

HRD effects on first-line adjuvant chemotherapy and PARPi maintenance therapy in Chinese ovarian cancer patients.

Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526-0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423-0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201-0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029-0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.

Systematic Review of Descriptions and Justifications Provided for Single-Case Quantification Techniques.

There are currently a multitude of quantification techniques that have been developed for use with single-case designs. As a result, choosing an appropriate quantification technique can be overwhelming and it can be difficult for researchers to properly describe and justify their use of quantification techniques. However, providing clear descriptions and justifications is important for enhancing the credibility of single-case research, and allowing others to evaluate the appropriateness of the quantification technique used. The aim of this systematic literature review is to provide an overview of the quantification techniques that are used to analyze single-case designs, with a focus on the descriptions and justifications that are provided. A total of 290 quantifications occurred across 218 articles, and the descriptions and justifications that were provided for the quantification techniques that were used are systematically examined. Results show that certain quantification techniques, such as the non-overlap indices, are more commonly used. Descriptions and justifications provided for using the quantification techniques are sometimes vague or subjective. Single-case researchers are encouraged to complement visual analysis with the use of quantification techniques for which they can provide objective and appropriate descriptions and justifications, and are encouraged to use tools to guide their choice of quantification techniques.

Copper Increases the Sensitivity of Cholangiocarcinoma Cells to Tripterine by Inhibiting TMX2-Mediated Unfolded Protein Reaction Activation.

Chemotherapy-induced adaptive resistance is a significant factor that contributes to low therapeutic efficacy in tumor cells. The unfolded protein response (UPR) is a key mechanism in the development of drug resistance and serves as a critical reactive system for endoplasmic reticulum stress. Cu(II) can reduce the abundance of 60S ribosomal subunits and inhibit rRNA processing, leading to a decrease in the translation efficiency of the GRP78/BiP mRNA, which serves as a primary sensor for UPR activation. In this study, CuET-Lipid@Cela, composed of CuET and tripterine (Cela), demonstrates a significant synergistic antitumor effect on cholangiocarcinoma (CCA) cells. RNA-Seq is used to investigate the underlying mechanism, which suggests that the transmembrane protein 2 (TMX2) gene may be crucial in Cu(II) regulation of UPR by inhibiting the activation of GRP78/BiP and PERK/eIF2α. The synergistic antitumor efficacy of CuET-Lipid@Cela via inhibition of TMX2 is also confirmed in a myrAKT/YapS127A plasmid-induced primary CCA mouse model, providing new insights into the reversal of acquired chemotherapy-induced resistance in CCA.

Survival Nomogram for Patients With Locally Advanced Breast Cancer Undergoing Immediate Breast Reconstruction: A SEER Population-Based Study.

INTRODUCTION/BACKGROUND: This study aimed to construct a nomogram to provide prognostic references for patients with locally advanced breast cancer (LABC) to receive immediate breast reconstruction (IBR). MATERIALS AND METHODS: All data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and best subset regression (BSR), separately followed by backward stepwise multivariable Cox, were used to construct the nomogram. Risk stratification was established after validation. RESULTS: A total of 6,285 patients were enrolled to generate the training group (n = 3,466) and the test group (n = 2,819) by geographical split. Age, marital status, grade, T staging, N staging, radiotherapy, chemotherapy, estrogen receptor status (ER), progesterone receptor status (PR) and human epidermal growth factor receptor type 2 status (HER2) were used to fit the nomogram. The overall Harrell's concordance index (C-index) was 0.772 in the training group and 0.762 in the test group. The area under the receiver operator characteristic curves (AUC) at 3-year and 5-year were respectively 0.824 and 0.720 in the training group, 0.792 and 0.733 in the test group. The calibration curves showed great consistency in both groups. A dynamic nomogram (https://dcpanfromsh.shinyapps.io/NomforLABCafterIBR/) was developed. CONCLUSION: A nomogram was developed and validated that predicts prognosis more accurately than the AJCC 7th stage and can be used as a reference for decision-making in LABC patients receiving IBR.

Characteristics of Moderators in Meta-Analyses of Single-Case Experimental Design Studies.

Hierarchical linear modeling (HLM) has been recommended as a meta-analytic technique for the quantitative synthesis of single-case experimental design (SCED) studies. The HLM approach is flexible and can model a variety of different SCED data complexities, such as intervention heterogeneity. A major advantage of using HLM is that participant and-or study characteristics can be incorporated in the model in an attempt to explain intervention heterogeneity. The inclusion of moderators in the context of meta-analysis of SCED studies did not yet receive attention and is in need of methodological research. Prior to extending methodological work validating the hierarchical linear model including moderators at the different levels, an overview of characteristics of moderators typically encountered in the field is needed. This will inform design conditions to be embedded in future methodological studies and ensure that these conditions are realistic and representative for the field of SCED meta-analyses. This study presents the results of systematic review of SCED meta-analyses, with the particular focus on moderator characteristic. The initial search yielded a total of 910 articles and book chapters. After excluding duplicate studies and non peer-reviewed studies, 658 unique peer-reviewed studies were maintained and screened by two independent researchers. Sixty articles met the inclusion criteria and were eligible for data retrieval. The results of the analysis of moderator characteristics retrieved from these 60 meta-analyses are presented. The first part of the results section contains an overview of moderator characteristics per moderator level (within-participant level, participant level, and study level), including the types of moderators, the ratio of the number of moderators relative to the number of units at that level, the measurement scale, and the degree of missing data. The second part of the results section focuses on the metric used to quantify moderator effectiveness and the analysis approach. Based on the results of the systematic review, recommendations are given for conditions to be included in future methodological work.

Impact of Paraben Exposure on Adiposity-Related Measures: An Updated Literature Review of Population-Based Studies.

Parabens are alkyl esters of p-hydroxybenzoic acid that are commonly used in pharmaceutical and cosmetic products. Humans are exposed to parabens when they use these products and through diet. There are growing concerns that paraben exposure can adversely impact human health. The endocrine-disrupting and obesogenic properties of parabens have been observed in animal studies and in vitro, prompting the increase in population-based studies of paraben exposure and adiposity-related endpoints. In this review, we summarize epidemiological studies published between 2017 and 2022 that examined paraben exposure in utero, between birth and adolescence, and in adulthood, in relation to adiposity-related measures. Overall, these studies provide some evidence that suggests that paraben exposure, especially during critical development windows, is associated with adiposity-related measures. However, we have noted several limitations in these studies, including the predominance of cross-sectional studies, inconsistent sample collection procedures, and small sample sizes, which should be addressed in future studies.

Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma.

Identifying functional brown adipose tissue (BAT) has provided new hope for obesity treatment and prevention. Functional BAT includes classical BAT and brown-like adipose tissue converted from white adipose tissue. By promoting thermogenesis (i.e., heat production) via uncoupling protein 1 (UCP1), functional BAT can increase energy expenditure and aid obesity treatment and prevention. Naringenin (NAR) is a flavanone primarily found in citrus fruits. NAR has been reported to decrease body weight, increase energy expenditure in treated mice, and promote browning in human adipocytes. Here, we examined the effects of NAR on 3T3-L1 adipocytes' browning and ß-adrenergic agonist isoproterenol (ISO)-stimulated thermogenic activation and classical murine brown adipogenesis. In addition, we demonstrated the signaling pathways and involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in the process. We found that NAR did not increase Ucp1 mRNA expression at the basal (i.e., non-ISO stimulated) condition. Instead, it enhanced Ucp1 and Pgc-1α up-regulation and thermogenesis under ISO-stimulated conditions in 3T3-L1 adipocytes. NAR promoted protein kinase A (PKA) activation and phosphorylation of p38 MAPK downstream of ISO stimulation and activated PPARγ. Pharmacological inhibition of either PKA or p38 and PPARγ knockdown attenuated Ucp1 up-regulation by NAR. Moreover, NAR promoted brown adipogenesis by increasing lipid accumulation, brown marker expression, and thermogenesis in murine brown adipocytes, which was also attenuated by PPARγ knockdown. Together, our results suggest that NAR may promote the development of functional BAT in part through PPARγ activation. NAR's role in combating human obesity warrants further investigation.

Tetra-Primer Amplification-Refractory Mutation System (ARMS)-PCR for Genotyping Mouse Leptin Gene Mutation.

Due to spontaneous deficiency in leptin, ob/ob mice are one of the most commonly used experimental animal models in diabetes research. In this study, we reported a quick and easy-to-conduct genotyping method using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to differentiate mice with a mutated allele from the wild-type genotype. The amplicon patterns of different genotypes are clearly visible and distinguishable on 1.5% agarose gel. This method can serve as a valuable tool to differentiate genotypes for breeding purposes, to maintain animal colonies, control the available space in the animal facility, and identify appropriate individuals for animal experiments.

Polarized light compass-aided inertial navigation under discontinuous observations environment.

In recent years, integrated polarized light/inertial heading measurement systems have been widely used to obtain autonomous heading measurements of small unmanned combat platforms in the case of satellite navigation rejection. However, existing polarized light/inertial heading measurement systems have certain limitations. For example, they can only measure the heading angle in environments where continuous observations can be obtained. When encountering a complex environment with trees and/or tall buildings, the measured heading angle will contain sharp noise which greatly affects its accuracy. In particular, when encountering an underpass, it will lead to the complete loss of lock of the polarized light compass signal. Therefore, for the problem of sharp noise arising from a complex environment, a robust Cubature Kalman filter (CKF) data-fusion algorithm is proposed and verified by experiments. It is proved that the robust CKF algorithm has a certain ability to filter out the effects of poor measurements. After application of the robust CKF algorithm, the Root Mean Square Error (RMSE) of the heading angle reaches 0.3612°. This method solves the problem of low precision and poor stability of the polarized light/inertial system when high buildings and/or trees are contained in a complex environment. Next, in view of the problem that the polarized light compass signal is completely lost due to passing through an underground passage, a random forest regression (RFR) neural network model is established and introduced into the combined system. Simulated and outdoor experiments are carried out to verify the designed model using data obtained with a vehicle. The RMSE of the heading angle obtained in the experiment is 1.1894°, which solves the problem that the polarized light/inertial system cannot utilize discontinuous observations when attempting to detect the carrier heading angle.

Secondary coronary artery ostial lesions: Three case reports.

BACKGROUND: Atherosclerosis is one of the main causes of coronary artery ostial lesions seen clinically. Secondary coronary artery ostial lesions are rare, and cases reported previously were associated with syphilitic vasculitis and aortic dissection. Here, we report three rare cases of secondary coronary ostial lesions. Due to their rareness, these lesions can easily be neglected, which may lead to misdiagnosis and missed diagnosis. CASE SUMMARY: We present three patients with acute myocardial infarction and unstable angina caused by secondary coronary artery ostial lesions. In Case 1, coronary angiography (CAG) revealed 90% stenosis of the left main coronary ostium. Chest contrast computed tomography (CT) suggested thymic carcinoma invading the left main coronary ostium. Coronary artery bypass grafting and tumor resection were performed. In Case 2, echocardiography revealed a sinus of Valsalva aneurysm (SVA)-like dilatation. CAG showed a right coronary sinus giant aneurysm and complete obstruction of the right coronary artery (RCA) ostium. Aortic contrast CT confirmed these findings. The Bentall procedure was performed. In Case 3, CT CAG identified an anomalous origin of the right coronary artery (AORCA) from the left sinus of Valsalva coursing between the aorta and pulmonary trunk, causing severe RCA ostium stenosis by compression. Surgical correction of the AORCA was performed. CONCLUSION: The cases reported here suggest that we should consider other causes of coronary ostial lesions other than atherosclerosis.

Sequentially targeting and intervening mutual Polo-like Kinase 1 on CAFs and tumor cells by dual targeting nano-platform for cholangiocarcinoma treatment.

Rationale: Synergistic treatment strategies for two or more drugs have gradually developed as the main options in clinics for cholangiocarcinoma (CCA) owing to the complicated crosstalk between the tumor and stroma. However, the different synergetic mechanisms pose great challenges to the dosages and order of administration of drugs. Thus, a strategy for exploring and intervening in mutual targets derived from stromal cells and cholangiocarcinoma cells was proposed. Methods: Genes with overexpression patterns in tumors and displaying a significant association with overall survival were identified from RNA-seq data of human CCA patients and CCA mouse models. Western blotting, qRT-PCR, immunofluorescence (IF), colony formation and flow cytometry assays were conducted to determine the biological roles of the key oncogene in cholangiocarcinoma and stromal cells respectively. Additionally, a dual-targeting drug delivery system (AA-HA-ODA) for cancer-associated fibroblasts (CAFs) and tumor cells was constructed to verify the effectiveness of intervening the screened genes in vivo. Results: Polo-like kinase 1 (PLK1) was verified to play vital role in the malignant proliferation of CCA by regulating the cell cycle pathway. PLK1 also decreased stromal production by regulating the CAF phenotype. In addition, a PLK1 inhibitor (Ro3280) loaded dual-targeting drug delivery system (AA-HA-ODA) was prepared and exhibited high affinity for CAFs and cholangiocarcinoma cells. The in vivo distribution pattern and antitumor efficacy of AA-HA-ODA/Ro also verify the effectiveness of inhibiting PLK1 in CCA in vivo. Conclusion: In summary, PLK1 is a mutual target derived from tumor cells and stroma due to its crucial role in the proliferation of tumor cells and stroma regulation in CAFs, which might provide enlightenment for multitarget treatment strategies and guidance for clinical cholangiocarcinoma treatment.

Role of female-predominant MYB39-bHLH13 complex in sexually dimorphic accumulation of taxol in Taxus media.

Taxus trees are major natural sources for the extraction of taxol, an anti-cancer agent used worldwide. Taxus media is a dioecious woody tree with high taxol yield. However, the sexually dimorphic accumulation of taxoids in T. media is largely unknown. Our study revealed high accumulation of taxoids in female T. media trees using a UPLC-MS/MS method. Thereafter, many differential metabolites and genes between female and male T. media trees were identified using metabolomic and transcriptomic analyses, respectively. Most of the taxol-related genes were predominantly expressed in female trees. A female-specific R2R3-MYB transcription factor gene, TmMYB39, was identified. Furthermore, bimolecular fluorescence complementation and yeast two-hybrid assays suggested the potential interaction between TmMYB39 and TmbHLH13. Several taxol biosynthesis-related promoter sequences were isolated and used for the screening of MYB recognition elements. The electrophoretic mobility shift assay indicated that TmMYB39 could bind to the promoters of the GGPPS, T10OH, T13OH, and TBT genes. Interaction between TmMYB39 and TmbHLH13 transactivated the expression of the GGPPS and T10OH genes. TmMYB39 might function in the transcriptional regulation of taxol biosynthesis through an MYB-bHLH module. Our results give a potential explanation for the sexually dimorphic biosynthesis of taxol in T. media.