Anti-Staphylococcus aureus effects of natural antimicrobial peptides and the underlying mechanisms.

Staphylococcus aureus can cause localized infections such as abscesses and pneumonia, as well as systemic infections such as bacteremia and sepsis. Especially, methicillin-resistant S. aureus often presents multidrug resistance, which becomes a major clinical challenge. One of the most common reasons for methicillin-resistant S. aureus antibiotic resistance is the presence of biofilms. Natural antimicrobial peptides derived from different species have shown effectiveness in combating S. aureus biofilms. In this review, we summarize the inhibitory activity of antimicrobial peptides against S. aureus planktonic cells and biofilms. We also summarize the possible inhibitory mechanisms, involving cell adhesion inhibition, membrane fracture, biofilm disruption and DNA disruption. We believe this can provide the basis for further research against S. aureus biofilm-associated infections.

When a bacterial infection is treated, sometimes not all bacteria are killed. This is because they have ways to evade the treatment's action. Therefore, it is important to develop new drugs, although this is difficult, expensive and time-consuming. This paper summarizes new types of natural antimicrobials that could be used against bacteria, how they work and how well.

Prognostic value and potential mechanism of cellular senescence and tumor microenvironment in hepatocellular carcinoma: Insights from bulk transcriptomics and single-cell sequencing analysis.

The high mortality rate and postoperative recurrence of hepatocellular carcinoma (HCC) contribute to the burden on society and healthcare. The prognostic value and underlying mechanisms of cellular senescence and tumor microenvironment (TME) in HCC remain unclear. Bulk transcriptomic data were obtained from 368 HCC samples in The Cancer Genome Atlas-liver hepatocellular carcinoma cohort and 64 samples from the GSE116174 dataset. Single-cell RNA sequencing (scRNA-seq) data of HCC were obtained from the GSE149614 dataset, including 18 tumor samples from 10 patients. Prognosis-related cellular senescence genes and immune cells were identified through univariate analysis. Least absolute shrinkage and selection operator regression analysis was performed to construct the CellAge score and TME score, both of which were identified as independent prognostic factors for HCC based on multivariate Cox analysis. The combined CellAge and TME scores showed improved prognostic stratification for HCC patients, as confirmed by multivariate Cox analysis (p < .001). The gene set enrichment analysis (GSEA) revealed enrichment of the extracellular matrix receptor interaction signaling pathway in the group with high CellAge scores and low TME scores, which exhibited a worse prognosis. Single-cell sequencing results revealed higher expression activity of the cAMP response element modulator (CREM) extended transcription factor in HCC cells and most immune cells, indicating its involvement in TME remodeling. Finally, the tumor immune dysfunction and exclusion (TIDE) analysis demonstrated that the combined scores could predict the outcomes of immune therapy in patients with HCC. In conclusion, cellular senescence contributes to TME remodeling in HCC, and the developed CellAge and TME scores serve as independent prognostic factors and predictors of immune therapy in HCC.

Ore improver additions alter livestock manure compost ecosystem C:N:P stoichiometry.

Deciphering the pivotal components of nutrient metabolism in compost is of paramount importance. To this end, ecoenzymatic stoichiometry, enzyme vector modeling, and statistical analysis were employed to explore the impact of exogenous ore improver on nutrient changes throughout the livestock composting process. The total phosphorus increased from 12.86 to 18.72 g kg-1, accompanied by a marked neutralized pH with ore improver, resulting in the Carbon-, nitrogen-, and phosphorus-related enzyme activities decreases. However, the potential C:P and N:P acquisition activities represented by ln(ßG + CB): ln(ALP) and ln(NAG): ln(ALP), were increased with ore improver addition. Based on the ecoenzymatic stoiometry theory, these changes reflect a decreasing trend in the relative P/N limitation, with pH and total phosphorus as the decisive factors. Our study showed that the practical employment of eco stoichiometry could benefit the manure composting process. Moreover, we should also consider the ecological effects from pH for the waste material utilization in sustainable agriculture.

Chiral-Achiral Cations Intercalation Induced Lead-Free Chiral-Polar Hybrid Perovskites Enable Self-Powered X-Ray and Ultraviolet-Visible-Near-Infrared Photo Detection.

Lead halide hybrid perovskites have made great progress in direct X-ray detection and broadband photodetection, but the existence of toxic Pb and the demand for external operating voltage have severely limited their further applications and operational stability improvements. Therefore, exploring "green" lead-free hybrid perovskite that can both achieve X-ray detection and broadband photodetection without external voltage is of great importance, but remains severely challenging. Herein, using centrosymmetric (BZA)3BiI6 (1, BZA = benzylamine) as a template, a pair of chiral-polar lead-free perovskites, (BZA)2(R/S-PPA)BiI6 (2-R/S, R/S-PPA = (R/S)-1-Phenylpropylamine) are successfully obtained by introducing chiral aryl cations of (R/S)-1-Phenylpropylamine. Compared to 1, chiral-polar 2-R presents a significant irradiation-responsive bulk photovoltaic effect (BPVE) with an open circuit photovoltage of 0.4 V, which enables it with self-powered X-ray, UV-vis-NIR broadband photodetection. Specifically, 2-R device exhibits an ultralow detection limit of 18.5 nGy s-1 and excellent operational stability. Furthermore, 2-R as the first lead-free perovskite achieves significant broad-spectrum (377-940 nm) photodetection via light-induced pyroelectric effect. This work sheds light on the rational crystal reconstruction engineering and design of "green" hybrid perovskite toward high-demanded self-powered radiation detection and broadband photodetection.

SIK2-positive tumor epithelial cells in breast cancer maybe potential anti-cancer messengers: A systematic analysis from a single-cell perspective.

Breast cancer is the most common malignancy in the world and one of the leading causes of cancer death, which is a heterogeneous disease involving genetic and environmental factors. Breast cancer stem cells (BCSCs) are the main players in the aggressiveness of different tumors, at the same time, these cells are the main challenge for cancer treatment. There are multiple treatment options for breast cancer (BC) patients and the lack of understanding of prognostic and predictive biomarkers for breast cancer is a potential research direction for us to develop better treatments in the future. In this paper, we conducted a correlation analysis between SIK2 and clinical traits by searching numerous BRCA datasets in the GEO database. The model was constructed and validated by incorporating tumor samples from the TCGA-BRCA cohort. Surprisingly, we found differential expression of SIK2 gene in individual tumor samples from the UCSC database. Subsequently, we found significantly high expression of SIK2 in epithelial cells by comparing the differential expression of SIK2 in different cell subpopulations and performed subsequent immune infiltration and pathway correlation analysis. Differential genes in SIK2+ epithelial cells, which may be potential therapeutic targets for breast cancer. In conclusion, our results suggest that SIK2 may be a potential prognostic and predictive biomarker that could serve as an oncogenic messenger for breast cancer. This discovery of SIK2 may provide more valuable references for potential therapeutic tools for breast cancer.

Corydaline binds to a druggable pocket of hEAG1 channel and inhibits hepatic carcinoma cell viability.

Ether-à-go-go (EAG) potassium channels play a crucial role in the regulation of neuronal excitability and cancer progression, rendering them potential drug targets for cancer therapy. However, the scarcity of information regarding the selection sites on hEAG1 has posed a challenge in the discovery of new hEAG1 inhibitors. In this study, we introduced a novel natural product, corydaline, which selectively inhibits the hEAG1 channel without sensitivity to other KCNH channels. The IC50 of corydaline for the hEAG1 channel was 11.3 ± 0.6 µM, whereas the IC50 for hEAG2 and hERG1 were 73.6 ± 9.9 µM and 111.4 ± 8.5 µM, respectively. Molecular dynamics simulations together with site-directed mutagenesis, have unveiled that the site corydaline forms interactions with Lys217, Phe273, Pro276, Trp295 and Arg366, situated within the intracellular transmembrane segments S1-S4 of the voltage-sensor domain, be considered a novel drug pocket for hEAG1. Additionally, the intergaration of sequence alignment and 3D structural modeling revealed differences between the voltage sensor domain of hEAG1 channel and other EAG channels, suggesting the feasibility of a VSD modulation approach that could potentially lead to the selective inhibition of hEAG1 channels. Furthermore, antitumor experiments demonstrated that corydaline can inhibit the proliferation and migration of hepatic carcinoma cells by targeting hEAG1. The identification of this novel druggable pocket offers the possibility for drug screening against diseases linked to abnormal hEAG1 channels.

Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol.

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

CDK13 promotes lipid deposition and prostate cancer progression by stimulating NSUN5-mediated m5C modification of ACC1 mRNA.

Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.

Polymer Packaging through the Blending of Biowaste Oyster Shell and Low-Density Polyethylene: A Sustainable Approach for Enhanced Food Preservation.

This research delves into the impact of incorporating thermally treated oyster shell powder (TOS), a biowaste filler, into low-density polyethylene (LDPE) to develop a LDPE/TOS blend, aiming at enhancing food packaging materials. The LDPE/TOS blend portrays advantageous characteristics such as augmented mechanical strength, thermostability, crystallinity, water absorption, and improved hydrophobicity with TOS content up to 50%. Microstructure analysis reveals a transition from a sparse to a more interconnected structure, contributing to the amplified tensile strength. The blend demonstrates increased barrier properties against water vapor transmission, which is attributed to elongated diffusion paths induced by the TOS particles. Application of the blend material in vegetable preservation trials manifested a substantial reduction in water loss compared to pure LDPE or no packaging. This biowaste-based blend film extends the shelf-life of chicken significantly when compared to that of pure LDPE. Importantly, the LDPE/TOS blend exhibits excellent antibacterial properties against both Escherichia coli and Staphylococcus aureus.

Self-Assembled nanoparticles Combining Berberine and Sodium Taurocholate for Enhanced Anti-Hyperuricemia Effect.

Propose: Berberine (BBR) is extensively studied as an outstanding anti-hyperuricemia drug. However, the clinical application of BBR was limited due to its poor absorption and low bioavailability. Therefore, there is an urgent necessity to find a novel drug formulation to address the issues of BBR in clinical application. Methods: Herein, we conducted the solubility, characterization experiments to verify whether BBR and sodium taurocholate (STC) self-assembled nanoparticles (STC@BBR-SANPs) could form. Furthermore, we proceeded the release experiment in vitro and in vivo to investigate the drug release effect. Finally, we explored the therapeutic effect of STC@BBR-SANPs on hyperuricemia (HUA) through morphological observation of organs and measurement of related indicators. Results: The solubility, particle size, scanning electron microscopy (SEM), and stability studies showed that the stable STC@BBR-SANPs could be formed in the BBR-STC system at ratio of 1:4. Meanwhile, the tissue distribution experiments revealed that the STC@BBR-SANPs could accelerate the absorption and distribution of BBR. In addition, the pharmacology study demonstrated that both BBR and STC@BBR-SANPs exhibited favorable anti-HUA effects and nephroprotective effects, while STC@BBR-SANPs showed better therapeutic action than that of BBR. Conclusion: This work indicated that STC@BBR-SANPs can be self-assembly formed, and exerts excellent uric acid-lowering effect. STC@BBR-SANPs can help to solve the problems of poor solubility and low absorption rate of BBR in clinical use, and provide a new perspective for the future development of BBR.

Improving Mechanical and Barrier Properties of Antibacterial Poly(Phenylene Sulfide) Nanocomposites Reinforced with Nano Zinc Oxide-Decorated Graphene.

Nano zinc oxide-decorated graphene (G-ZnO) was blended with polyphenylene sulfide (PPS) to improve its tensile, thermal, crystalline, and barrier properties. The properties of neat PPS and PPS/G-ZnO nanocomposites were characterized and compared using various tests, including tensile tests, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, evaluation of Escherichia coli inhibition, and barrier performance. The results demonstrated that G-ZnO played a crucial role in heterogeneous nucleation and reinforcement. When the concentration of G-ZnO was 0.3%, the tensile strength, elongation at break, thermostability, crystallinity, and water vapor permeability coefficients (WVPC) approached their maximum values, and the microscopic morphology changed from the original brittle fracture to a relatively tough fracture. In addition, when G-ZnO was added to PPS at a ratio of 0.3%, the tensile strength, elongation at break, and WVPC of PPS were increased by 129%, 150%, and 283%, respectively, compared to pure PPS. G-ZnO endowed the nanocomposites with antibacterial properties. The improvement in barrier performance can be attributed to three reasons: (1) the presence of G-ZnO extended the penetration path of molecules; (2) the coordination and hydrogen bonds between PPS polymer matrix and G-ZnO nanofiller narrowed the H2O transmission path; and (3) due to its more hydrophobic surface, water molecules were less likely to enter the interior of PPS/G-ZnO nanocomposites. This study provides valuable insights for developing high-performance PPS-based nanocomposites for various applications.

Single hormone or synthetic agonist induces Gs/Gi coupling selectivity of EP receptors via distinct binding modes and propagating paths.

To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to the same hormone-receptor pair [R.P. Xiao, Sci STKE 2001, re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, Nature 402, 181-184 (1999); Y. Daaka, L. M. Luttrell, R. J. Lefkowitz, Nature 390, 88-91 (1997)]. Not only these questions lie in the heart of hormone actions and receptor signaling but also dissecting mechanisms underlying these questions could offer therapeutic routes for refractory diseases, such as kidney injury (KI) or X-linked nephrogenic diabetes insipidus (NDI). Here, we identified that Gs-biased signaling, but not Gi activation downstream of EP4, showed beneficial effects for both KI and NDI treatments. Notably, by solving Cryo-electron microscope (cryo-EM) structures of EP3-Gi, EP4-Gs, and EP4-Gi in complex with endogenous prostaglandin E2 (PGE2)or two synthetic agonists and comparing with PGE2-EP2-Gs structures, we found that unique primary sequences of prostaglandin E2 receptor (EP) receptors and distinct conformational states of the EP4 ligand pocket govern the Gs/Gi transducer coupling selectivity through different structural propagation paths, especially via TM6 and TM7, to generate selective cytoplasmic structural features. In particular, the orientation of the PGE2 ω-chain and two distinct pockets encompassing agonist L902688 of EP4 were differentiated by their Gs/Gi coupling ability. Further, we identified common and distinct features of cytoplasmic side of EP receptors for Gs/Gi coupling and provide a structural basis for selective and biased agonist design of EP4 with therapeutic potential.

[Arsenic speciation and valence].

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.

[Varieties systematization and standards status analysis of fermented Chinese medicine].

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.

Characteristics of small pancreatic neuroendocrine tumors and risk factors for invasion and metastasis.

Background: The number of people with small pancreatic neuroendocrine tumors (pNETs) (tumors with a diameter less than or equal to 2 cm) is gradually increasing, but the selection of treatment strategy is still controversial. Our aim was to characterize small pNETs with a poor prognosis and to define the impact of aggressive small pNETs on survival and the risk factors for the development of invasive disease. Methods: Patients with pNETs diagnosed between 2004 and 2019 and a tumor diameter of 2 cm or less were selected from the SEER Registry. Kaplan-Meier survival analysis was used to identify the factors affecting patient survival, and binary logistic regression was used to identify the associated risk factors. Results: A total of 3261 patients with pNETs were enrolled in the study. Both older and younger patients benefited from surgery. Regional invasion occurred in 10% of the patients, and distant metastases occurred in 9% of the patients, but in both categories, those who underwent surgery had better survival outcomes than those who did not. There was no difference in survival between patients with a tumor diameter of 1-2 cm and those with a tumor diameter of less than 1 cm, and there was no difference in survival between patients with functional and nonfunctional small pNETs. However, the survival of patients with pNETs in the head of the pancreas was worse than that of patients with tumors in other parts of the pancreas. Survival was worse in elderly patients and in those with poorly differentiated and undifferentiated tumors. Lymphatic metastasis, regional invasion, and distant metastasis all worsened the prognosis of patients. The presence or absence of neuroendocrine function, the degree of tumor differentiation, and the location of the tumor were associated with the risk of lymphatic metastasis and regional invasion; the risk factors for distant metastasis were associated with the degree of differentiation and tumor location. Conclusion: The pNETs ≤ 2 cm in diameter could be still aggressive, and patient prognosis worsens after invasive disease develops. Attention to the characteristics of aggressive tumors can improve patient survival.

PCGF6/MAX/KDM5D facilitates MAZ/CDK4 axis expression and pRCC progression by hypomethylation of the DNA promoter.

Polycomb group RING finger protein 6 (PCGF6) plays an important role as a regulator of transcription in a variety of cellular processes, including tumorigenesis. However, the function and expression of PCGF6 in papillary RCC (pRCC) remain unclear. In the present study, we found that PCGF6 expression was significantly elevated in pRCC tissues, and high expression of PCGF6 was associated with poor survival of patients with pRCC. The overexpression of PCGF6 promoted while depletion of PCGF6 depressed the proliferation of pRCC cells in vitro. Interestingly, myc-related zinc finger protein (MAZ), a downstream molecular of PCGF6, was upregulated in pRCC with hypomethylation promoter. Mechanically, PCGF6 promoted MAZ expression by interacting with MAX and KDM5D to form a complex, and MAX recruited PCGF6 and KDM5D to the CpG island of the MAZ promoter and facilitated H3K4 histone demethylation. Furthermore, CDK4 was a downstream molecule of MAZ that participated in PCGF6/MAZ-regulated progression of pRCC. These results indicated that the upregulation of PCGF6 facilitated MAZ/CDK4 axis expression and pRCC progression by hypomethylation of the MAZ promoter. The PCGF6/MAZ/CDK4 regulatory axis may be a potential target for the treatment of ccRCC.

TREM2 as an independent predictor of poor prognosis promotes the migration via the PI3K/AKT axis in prostate cancer.

OBJECTIVE: Prostate adenocarcinoma (PRAD) is one of the most common cancers, with high morbidity and mortality. Triggering receptors expressed on myeloid cells 2 (TREM2) is upregulated in various malignancies, however its effect on PRAD remains unknown. This study aimed to investigate the prognostic value of TREM2 in PRAD. METHODS: PRAD samples were collected from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), Oncomine, and the Human Protein Atlas (HPA) to analyze the differences in TREM2 expression between normal and tumor tissues. The influence of TREM2 on the clinicopathological characteristics and its prognostic value were evaluated using the Kaplan-Meier curve, Cox regression analysis, ROC (receiver operating characteristic) plot, and nomogram. Gene Ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) were conducted to screen biological functions and pathways. The relationship between TREM2 and tumor microenvironment (TME) characteristics was explored. The TREM2 expression in PRAD specimens and cell lines was assessed by immunohistochemistry staining and western blot. TREM2-specific siRNAs were used to evaluate the effects of TREM2 on cell function. RESULTS: TREM2 was upregulated and positively associated with poor clinicopathologic characteristics. Overexpression of TREM2 is an independent biomarker for the prognosis of PFI (progression-free interval). Moreover, TREM2 expression was positively correlated with various TME characteristics. Knockdown of TREM2 inhibited the migration of PRAD cell lines via the PI3K/AKT axis. CONCLUSION: High TREM2 expression may represent a novel diagnostic and prognostic biomarker and serve as a potential target gene for PRAD therapy.

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC). Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites. Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07). Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

Synergistic effect of Ag and Cu on improvingin vitrobiological properties of K2Ti6O13nanowires for potential biomedical applications.

The development of novel antibacterial nano-materials with synergistic biological effects has attracted extensive interest of the researchers. In the study, 0.5 mol% Ag and 0.5 mol% Cu co-doped K2Ti6O13(0.5 Ag-0.5 Cu-KTO) nanomaterial was successfully synthesized using two-step method of sol-gel and hydrothermal synthesis. The crystal structure of 0.5 Ag-0.5 Cu-KTO was the same as that of monoclinic K2Ti6O13. Ag ions and Cu ions were uniformly loaded on K2Ti6O13by replacing partial Ti ions, so that these antibacterial ions could be slowly released. High specific surface area of 0.5 Ag-0.5 Cu-KTO (337.6 m2g-1) provided more surface active sites for Ag-Cu doping and adsorption. More negative surface zeta potential (-32.83 mV in phosphate buffer solution and -21.45 mV in physiological saline solution, respectively) would be beneficial to prevent the aggregation of the nanowires in physiological environment. Under the same doping amount, compared to 1.0 mol% Cu doped K2Ti6O13, 0.5 Ag-0.5 Cu-KTO exhibited better antibacterial performance against gram-positive and gram-negative bacteria at only 100 µg ml-1dose concentration, near to 1.0 mol% Ag doped K2Ti6O13(1.0 Ag-KTO). And 0.5 Ag-0.5 Cu-KTO showed more excellent biocompatibility than 1.0 Ag-KTO, which was attribute to the introduction of Cu ions effectively decreasing the hemolytic and cytotoxic risks from Ag ions. As expected, the synthesized 0.5 Ag-0.5 Cu-KTO nanowires demonstrated excellent structural stability, high antibacterial activity, good hemocompatibility and cytocompatibility owing to the synergistic effects of Cu and Ag ions. 0.5 Ag-0.5 Cu-KTO nanowires will be a promising antimicrobial candidate for biomedical applications.

SF3B4 promotes Twist1 expression and clear cell renal cell carcinoma progression by facilitating the export of KLF 16 mRNA from the nucleus to the cytoplasm.

Splicing factor 3B subunit 4 (SF3B4) plays important functional roles not only in pre-mRNA splicing, but also in the regulation of transcription, translation, and cell signaling, and its dysregulation contributes to various diseases including Nager syndrome and tumorigenesis. However, the role of SF3B4 and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain obscure. In the present study, we found that the expression of SF3B4 was significantly elevated in ccRCC tissues and negatively correlated with the overall survival of ccRCC patients. Upregulation of SF3B4 promotes migration and invasion of ccRCC cells in vitro and in vivo. The promoting effect of SF3B4 on cell migration and invasion is mediated by Twist1, a key transcription factor to mediate EMT. Interestingly, SF3B4, a component of the pre-mRNA spliceosome, is able to promote KLF16 expression by facilitating the transport of KLF16 mRNA into the cytoplasm. Mechanistically, SF3B4 promotes the export of KLF16 mRNA from the nucleus to the cytoplasm and thus enhances KLF16 expression, and in turn elevated KLF16 directly binds to the Twist1 promoter to activate its transcription, leading to EMT and ccRCC progression. Our findings provide evidence that the SF3B4-KLF16-Twist1 axis plays important functional roles in the development and progression of ccRCC, and manipulating this pathway may be a novel therapeutic target for the treatment of ccRCC.