Hierarchical Structure with Microcrater Covered with Nanograss Enhancing Condensation and Its Antifrosting/Anti-Icing Performance Inspired by Euphorbia helioscopia L.

Over an extended period of evolution and natural selection, a multitude of species developed a diverse array of biological interface features with specific functions. These biological structures provide a rich source of inspiration for the design of bionic structures on superhydrophobic surfaces. Understanding the functional mechanism of plant leaves is of paramount importance for the advancement of new engineering materials and the further promotion of engineering applications of bionic research. The hierarchical structure of microcrater-covered nanograss (MCNG) on the surface of E. helioscopia L. leaf provided the inspiration for the bionic MCNG surface, which was successfully prepared on a copper substrate by hybrid laser micromachining technology and chemical etching. The combined action of texture structure and surface chemistry resulted in a contact angle of 169° ± 1° for MCNG surface droplets and a rolling angle of less than 1°. Notably, the condensation-induced adhesion force does not augment with the increase of the temperature difference, which facilitated the shedding of hot droplets from the surface. The microscope observation revealed a high density of condensed droplets on the MCNG surface and the tangible jumping behavior of the droplets. The fabricated MCNG also demonstrated excellent antifrost/anti-icing abilities in low-temperature and high-humidity environments. Finally, the study confirmed the exceptional mechanical durability and reusability of the MCNG surface through various tests, including scratch damage, sandpaper wear, water flow impact and flushing, and condensation-drying cycle tests. The nanograss can be effectively protected within the microcrater structure. This research presents a promising approach for preventing and/or removing unwanted droplets in numerous engineering applications.

Superhydrophobic Surfaces with Excellent Ice Prevention and Drag Reduction Properties Inspired by Iridaceae Leaf.

The anti-icing and drag-reduction properties of diverse microstructured surfaces have undergone extensive study over the past decade. Nonetheless, tough environments enforce stringent demands on the composite characteristics of superhydrophobic surfaces (SHS). In this study, fresh composite structures were fabricated on a metal substrate by nanosecond laser machining technology, drawing inspiration from the hardy plant Iridaceae. The prepared sample surface mainly consists of a periodic microrhombus array and irregular nanosheets. To comprehensively investigate the effect of its special structure on surface properties, three surfaces with different sizes of rhombic structures were used for comparative analysis, and the results show that the SH-S2 sample is optimal. This can significantly delay the freezing time by an impressive 1404 s at -10 °C while revealing the sample surface anti-icing strategy. In addition, the rheological experiments determined over 300 µm of slip length for the SH-S2 sample, and the drag reduction rate of the surface reaches nearly 40%, which is well aligned with the results of the delayed icing experiments. Finally, the mechanical durability of the SH-S2 surface was investigated through scratch damage, sandpaper abrasion, reparability trials, and icing and melting cycle tests. This research presents a new approach and methodology for the application of SHS on polar ship surfaces.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Life events and parent style for mental health in children: a cross-sectional study.

BACKGROUND: Life events and parenting styles might play an important role in children's mental health. AIMS: This study aims to explore how life events and parenting styles influence children's mental health based on a Chinese sample. METHODS: A total of 3535 participants had at least one mental disorder (positive group), while a total of 3561 participants had no mental disorders (negative group). The Child Behavior Checklist (CBCL), Adolescent Self-Rating Life Events Check List (ASLEC) and Egna Minnen Beträffande Uppfostran (EMBU) were used for screening these two groups. RESULTS: CBCL total scores differed significantly by sex in the Positive group according to the Mann-Whitney tests (Z = -5.40, p < 0.001). Multiple regression analyses showed that the dimensions of punishment (p = 0.014) and other (p = 0.048) in the ASLEC scale can significantly predict CBCL total scores in the Positive group. Sex, age and overprotection from the father were risk factors (p < 0.001) according to binary logistic regression. CONCLUSIONS: Life events and parenting styles may have impacts on mental health. Fathers play a very important role in children's growth. Punitive education and fathers' overprotection might be risk factors for children's mental health. IMPACT: It is a large sample (3535) study of Chinese children and adolescents It provides evidence that life events and parenting styles have impacts on mental health and that fathers play a very important role in children's growth. It is conducive to the development of interventions for the mental health of children and adolescents.

Ultrafast Self-Healing Superhydrophobic Surface for Underwater Drag Reduction.

The self-healing superhydrophobic surfaces have attracted great interest owing to restoring superhydrophobicity without preparation crafts. However, the self-healing superhydrophobic surface still faces the dilemma of long repairing time. Especially in aqueous environments, superhydrophobic surfaces are highly susceptible to contamination and damage. In the current study, a superhydrophobic surface with ultrafast repairability was developed, which apply for drag reduction in aqueous medium. The prepared superhydrophobic surface can recover superhydrophobicity in only 30 s after severe physical and chemical damage. In addition, this research pioneered the combination of superhydrophobicity and porous structures for underwater drag reduction. The study of drag reduction confirms that the superhydrophobic surface can reduce the frictional drag by about 43% in the water. However, the drag reduction rate of the superhydrophobic surface with the porous structure can be improved to 76% due to increased stability of the air layer. More importantly, the porous structure with the average pore size of 50 µm has the most excellent stability through further experiments on the underwater air layer. This is attributed to the proper size of the pore to effectively balance the capillary force and resist wetting in the marginal region. This study will bring inspiration for the large-scale application of superhydrophobic surfaces and long-term drag reduction.

EPHA5 mediates trastuzumab resistance in HER2-positive breast cancers through regulating cancer stem cell-like properties.

Trastuzumab is a successful, rationally designed therapy that provides significant clinical benefit for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients. However, about half of individuals with HER2-positive breast cancer do not respond to trastuzumab treatment because of various resistance mechanisms, including but not limited to: 1) shedding of the HER2 extracellular domain, 2) steric hindrance ( e.g., MUC4 and MUC1), 3) parallel pathway activation (this is the general mechanism cited in the quote above), 4) perturbation of downstream signaling events ( e.g., PTEN loss or PIK3CA mutation), and 5) immunologic mechanisms (such as FcR polymorphisms). EPHA5, a receptor tyrosine kinase, has been demonstrated to act as an anticancer agent in several cancer cell types. In this study, deletion of EPHA5 can significantly increase the resistance of HER2-positive breast cancer patients to trastuzumab. To investigate how EPHA5 deficiency induces trastuzumab resistance, clustered regularly interspaced short palindromic repeat technology was used to create EPHA5-deficient variants of breast cancer cells. EPHA5 deficiency effectively increases breast cancer stem cell (BCSC)-like properties, including NANOG, CD133+, E-cadherin expression, and the CD44+/CD24-/low phenotype, concomitantly enhancing mammosphere-forming ability. EPHA5 deficiency also caused significant aggrandized tumor malignancy in trastuzumab-sensitive xenografts, coinciding with the up-regulation of BCSC-related markers and intracellular Notch1 and PTEN/AKT signaling pathway activation. These findings highlight that EPHA5 is a potential prognostic marker for the activity of Notch1 and better sensitivity to trastuzumab in HER2-positive breast cancer. Moreover, patients with HER2-positive breast cancers expressing high Notch1 activation and low EPHA5 expression could be the best candidates for anti-Notch1 therapy.-Li, Y., Chu, J., Feng, W., Yang, M., Zhang, Y., Zhang, Y., Qin, Y., Xu, J., Li, J., Vasilatos, S. N., Fu, Z., Huang, Y., Yin, Y. EPHA5 mediates trastuzumab resistance in HER2-positive breast cancers through regulating cancer stem cell-like properties.

Expression pattern of microRNAs related with response to trastuzumab in breast cancer.

BACKGROUND: Although an immense effort has been made to develop a novel biomarker for response to trastuzumab, no reliable biomarkers are available to guide management, expect for HER2. The aim of this study was to examine the relationship between microRNA (miRNA) expression and resistance to trastuzumab. METHODS: Differentially expressed miRNAs between trastuzumab-resistant and trastuzumab-sensitive cell lines were analyzed using microarrays. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to determine the functions of differentially expressed miRNA and their targeted genes. Furthermore, the protein-protein interactions (PPI) network was analyzed. Serum samples were collected from patients with HER2-positive breast cancer who were treated with trastuzumab. We validated the miRNAs expression levels by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in these serums. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the miRNA. RESULTS: Using miRNA microarrays, 151 miRNAs that significant differentially expressed between the trastuzumab-resistant and sensitive cells were identified, including 46 upregulated and 105 downregulated miRNAs. Results of real-time PCR confirmed seven miRNAs in cell lines. PI3K-Akt signaling pathway was involved in regulating biological function according to KEGG analysis. Compared with the serums of trastuzumab-sensitive patients, three miRNAs, namely miR-200b, miR-135b, and miR-29a, were identified to be upregulated, and miR-224 was downregulated in the trastuzumab-resistant serums. ROC analysis showed that four miRNAs were correlated with trastuzumab resistance. Furthermore, three subnetwork modules of PPI network were obtained. CONCLUSION: The results indicated that miRNAs were reliable predictive biomarkers for response to trastuzumab.

Silencing FUNDC1 alleviates chronic obstructive pulmonary disease by inhibiting mitochondrial autophagy and bronchial epithelium cell apoptosis under hypoxic environment.

Chronic obstructive pulmonary disease (COPD) is a major global epidemic with increasing incidence worldwide. The pathogenesis of COPD is involved with mitochondrial autophagy. Recently, it has been reported that FUN14 domain containing 1 (FUNDC1) is a mediator of mitochondrial autophagy. Therefore, we hypothesized that FUNDC1 was involved in cigarette smoke (CS)-induced COPD progression by regulating mitochondrial autophagy. In vitro cigarette smoke extract (CSE)-treated human bronchial epithelial cell (hBEC) Beas-2B cell line and in vivo CS-induced COPD mouse models were developed, in which FUNDC1 expression was measured. Next, whether FUNDC1 interacted with dynamin-related protein 1 (DRP1) in COPD was investigated. The functional mechanism of FUNDC1 in COPD was evaluated through gain- or loss-of-function studies. Then, pulmonary function, mitochondrial transmembrane potential (MTP) and mucociliary clearance (MCC) were examined. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and expression of autophagy-specific markers (light chain 3 [LC3] II, LC3 I, and Tom20) were measured. Finally, apoptosis and mitochondrial autophagy were assessed. FUNDC1 was highly expressed in CSE-treated hBECs and COPD mice. Meanwhile, FUNDC1 was proved to interact with DRP1 in CSE-treated cells. Moreover, in CSE-treated hBECs, silencing FUNDC1 was observed to reduce levels of IL-6 and TNF-α, and MTP but increase MCC, and inhibit CSE-induced mitochondrial autophagy and Beas-2B cell apoptosis, which was consistent with the trend in COPD mouse models. In addition, pulmonary function of COPD mouse models was increased in response to FUNDC1 silencing. Finally, silencing of DRP1 also inhibited mitochondrial autophagy and Beas-2B cell apoptosis. Collectively, FUNDC1 silencing could suppress the progression of COPD by inhibiting mitochondrial autophagy and hBEC apoptosis through interaction with DRP1, highlighting a potential therapeutic target for COPD treatment.

Functional role of PLCE1 intronic insertion variant associated with susceptibility to esophageal squamous cell carcinoma.

Genome-wide association studies (GWAS) have consistently identified PLCE1 as esophageal squamous cell carcinoma (ESCC) susceptibility gene; however, the functional role of PLCE1 variants remains to be verified. In this study, we performed fine mapping of the PLCE1 region using our previous ESCC GWAS data and identified 33 additional risk variants in this susceptibility locus. Here, we report the functional characterization of a four-nucleotide insertion/deletion variation (rs71031566 C----/CATTT) in PLCE1 that was associated with risk of developing ESCC. We demonstrate for the first time that rs71031566[CATTT] insertion creates a silencer element, repressing PLCE1 transcription via long-range interaction with PLCE1 promoter mediated by OCT-2 binding. PLCE1 is down-regulated in majority of clinical ESCC samples and overexpression of PLCE1 in ESCC cells suppresses cell growth in vitro and in vivo, suggesting a tumor suppressor role of this gene. Therefore, repression of PLCE1 transcription may be the underlying mechanism for the rs71031566[CATTT] variant to be susceptible to ESCC.

BRCA1-Associated Protein Increases Invasiveness of Esophageal Squamous Cell Carcinoma.

BACKGROUND & AIMS: We performed a screen for genes whose expression correlates with invasiveness of esophageal squamous cell carcinoma (ESCC) cells. We studied the effects of overexpression and knockdown of these genes in cell lines and expression levels in patient samples. METHODS: We selected genes for analysis from 11 loci associated with risk of ESCC. We analyzed the effects of knocking down expression of 47 of these genes using RNA interference on-chip analysis in ESCC cells and HeLa cells. Cells with gene overexpression and knockdown were analyzed in migration and invasion assays or injected into nude mice and metastasis of xenograft tumors was quantified. We collected ESCC and non-tumor esophageal tissues from 94 individuals who underwent surgery in China from 2010 and 2014; clinical information was collected and survival time was measured from the date of diagnosis to the date of last follow-up or death. Levels of messenger RNAs (mRNAs) were quantified by RNA sequencing, and levels of proteins were determined from immunoblot analyses. Patient survival was compared with mRNA levels using Kaplan-Meier methods and hazard ratios were calculated by Cox models. RESULTS: We identified 8 genes whose disruption increased migration and 10 genes whose disruption reduced migration. Knockdown of BRCA1-associated protein gene (BRAP) significantly reduced migration of KYSE30, KYSE150, and HeLa cells. In patient tumors, 90% of ESCCs examined had higher levels of BRAP protein than paired non-tumor tissues, and 63.8% had gains in BRAP DNA copy number. Levels of BRAP mRNA in ESCC tissues correlated with patient survival time, and high expression increased risk of death 2.4-fold compared with low expression. ESCCs that had metastasized to lymph node had significantly higher levels of BRAP mRNA than tumors without metastases. Knockdown of BRAP in ESCC and HeLa cell lines significantly reduced migration and invasiveness; these cell lines formed less metastases in mice than control cells. Nuclear translocation of the nuclear factor-κB (NF-κB) P65 subunit and phosphorylation of inhibitor of NF-κB kinase subunit ß (IKBKB or IKKß) increased in cells that overexpressed BRAP and decreased in cells with BRAP knockdown. In immunoprecipitation assays, BRAP interacted directly with IKKß. Expression of matrix metalloproteinase 9 and vascular epithelial growth factor C, which are regulated by NF-κB, was significantly reduced in cells with knockdown of BRAP and significantly increased in cells that overexpressed BRAP. CONCLUSIONS: Expression of BRAP is increased in ESCC samples compared with non-tumor esophageal tissues; increased expression correlates with reduced patient survival time and promotes metastasis of xenograft tumors in mice. BRAP overexpression leads to increased activity of NF-κB and expression of matrix metalloproteinase 9 and vascular epithelial growth factor C.

MiR-4319 Suppress the Malignancy of Triple-Negative Breast Cancer by Regulating Self-Renewal and Tumorigenesis of Stem Cells.

BACKGROUND/AIMS: High levels of cancer stem cells (CSCs) in patients with triple-negative breast cancer (TNBC) correlate with risk of poor clinical outcome and possibly contribute to chemoresistance and metastasis in patients with highly malignant TNBC. Aberrant microRNA expression is associated with the dysfunction of self-renewal and proliferation in cancer stem cells, while there is little information about the TNBC-specific microRNAs in regulating CSC ability. METHODS: Solexa deep sequencing was performed to detect the expression levels of TNBC or non-TNBC stem cells (CSCs) microRNAs. Mammosphere formation assay, qRT-PCR and the xenograft model in nude mice were performed. Bioinformatic analysis and microarray were used to select the target gene, and luciferase reporter assays were used to confirm the binding sites. RESULTS: Solexa sequencing data exhibited differential expression of 193 microRNAs between TNBC and non-TNBC stem cells. The gene ontology analysis and pathways analyses showed that genes were involved in the maintenance of stemness. MiR-4319 could suppress the self-renewal and formation of tumorspheres in TNBC CSCs through E2F2, and also inhibited tumor initiation and metastasis in vivo. Moreover, increased E2F2 could reverse the effect of miR-4319 on the self-renewal in TNBC CSCs. CONCLUSIONS: MiR-4319 suppresses the malignancy of TNBC by regulating self-renewal and tumorigenesis of stem cells and might be a remarkable prognostic factor or therapeutic target for patients with TNBC.

tRNA-Derived Fragments as Novel Predictive Biomarkers for Trastuzumab-Resistant Breast Cancer.

BACKGROUND/AIMS: Resistance to trastuzumab remains a common challenge to HER-2 positive breast cancer. Up until now, the underlying mechanism of trastuzumab resistance is still unclear. tRNA-derived small non-coding RNAs, a new class of small non-coding RNA (sncRNAs), have been observed to play an important role in cancer progression. However, the relationship between tRNA-derived fragments and trastuzumab resistance is still unknown. METHODS: We detected the levels of tRNA-derived fragments expression in normal breast epithelial cell lines, trastuzumab-sensitive and -resistant breast cancer cell lines using high-throughput sequencing. qRT-PCR was conducted to validate the differentially expressed fragments in serums from trastuzumab-sensitive and -resistant patients. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the power of specific tRNA-derived fragments. Progression-free survival (PFS) was analyzed using Cox-regression. RESULTS: Our sequence results showed that tRNA-derived fragments were differentially expressed in the HBL-100, SKBR3, and JIMT-1 cell lines. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were found significantly upregulated in trastuzumab-resistant patients compared to sensitive individuals, and the ROC analysis showed that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were correlated with trastuzumab resistance. In a multivariate analysis, higher levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression were associated with significantly shorter PFS in patients with metastatic HER-2 positive breast cancer. CONCLUSION: Our results suggest that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN play important roles in trastuzumab resistance. Patients with high levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression benefitted less from trastuzumab-based therapy than those that express lower-levels of these molecules. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN may be potential biomarkers and intervention targets in the clinical treatment of trastuzumab-resistant breast cancer.

MiR-129-5p Sensitizes the Response of Her-2 Positive Breast Cancer to Trastuzumab by Reducing Rps6.

BACKGROUND/AIMS: Trastuzumab is an important treatment used for patients with Her-2-positive breast cancer, but an increasing incidence of trastuzumab resistance has been observed clinically during the past decade. Aberrant microRNA (miR) expression levels are correlated with prognosis and response to trastuzumab in breast cancer. MiR-129-5p is downregulated in trastuzumab-resistant human breast cancer cells (JIMT-1), but its potential function and underlying mechanism remain unclear. METHODS: Quantitative RT-PCR (qRT-PCR) was used to determine the expression levels of miR-129-5p and its potential target genes. The effects of miR-129-5p on cell responses to trastuzumab were analyzed by CCK-8 and flow cytometry assays in Her-2-positive breast cancer cells (SKBR-3 and JIMT-1). Bio-informatics analyses were performed to predict target genes of miR-129-5p, and luciferase assays were carried out to confirm the binding of miR-129-5p and rpS6. RESULTS: MiR-129-5p, which was downregulated and predicted to target rpS6 in trastuzumab-resistant breast cancer cells, enhanced the sensitivity of breast cancer cells to trastuzumab by reducing the expression of rpS6. Moreover, the overexpression of rpS6 reversed the sensitivity of cells to trastuzumab induced by miR-129-5p. CONCLUSIONS: MiR-129-5p sensitized Her-2-positive breast cancer to trastuzumab by downregulating rpS6. These findings provide novel insights into the common role of rpS6 and its related molecular mechanisms in mediating trastuzumab-resistance in Her-2-positive breast cancers.

Des-gamma-carboxy prothrombin (DCP) antagonizes the effects of gefitinib on human hepatocellular carcinoma cells.

BACKGROUND/AIMS: Des-gamma-carboxy prothrombin (DCP), an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells, is known as a marker for HCC. Recent studies indicated that high levels of DCP are associated with the malignant potential of HCC. In this study, we aimed to investigate the association of DCP with gefitinib treatment failure in HCC and whether DCP counteracts gefitinib-induced growth inhibition and apoptosis of HCC. METHODS: The experiments were performed in HCC cell lines HepG2 and PLC/PRF/5. The effects of gefitinib on HCC in the presence or absence of DCP were evaluated by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptotic cells were identified by Annexin V-FITC/PI staining. Western blotting was performed to analyze the expressions of molecules related to the apoptotic caspase-dependent pathway and epidermal growth factor receptor (EGFR) pathway. RESULTS: Gefitinib inhibited HCC cell proliferation and induced apoptosis in HCC cells. The effects of gefitinib on HCC cells were antagonized by DCP. In the presence of DCP, HCC cells were resistant to the gefitinib-induced inhibition of proliferation and stimulation of apoptosis. DCP prevented the activation of the apoptotic caspase-dependent pathway induced by gefitinib. These antagonistic effects of DCP also arose from its ability to up-regulate EGFR, c-Met and hepatocyte growth factor (HGF) in HCC cells. CONCLUSION: DCP antagonized gefitinib-induced HCC cell growth inhibition by counteracting apoptosis and up-regulating the EGFR pathway. High levels of DCP might thus lead to low response rates or possibly no response to gefitinib in patients with HCC.

Des-γ-carboxy prothrombin (DCP) as a potential autologous growth factor for the development of hepatocellular carcinoma.

Des-γ-carboxy prothrombin (DCP) is a prothrombin precursor produced in hepatocellular carcinoma (HCC). Because of deficiency of vitamin K or γ-glutamyl carboxylase in HCC cells, the 10 glutamic acid (Glu) residues in prothrombin precursor did not completely carboxylate to γ-carboxylated glutamic acid (Gla) residues, leaving some Glu residues remained in N-terminal domain. These prothrombin precursors with Glu residues are called DCPs. DCP displays insufficient coagulation activity. Since Liebman reported an elevated plasma DCP in patients with HCC, DCP has been used in the diagnosis of HCC. Recently, its biological malignant potential has been specified to describe DCP as an autologous growth factor to stimulate HCC growth and a paracrine factor to integrate HCC with vascular endothelial cells. DCP was found to stimulate HCC growth through activation of the DCP-Met-JAK1-STAT3 signaling pathway. DCP might increase HCC invasion and metastasis through activation of matrix metalloproteinase (MMPs) and the ERK1/2 MAPK signaling pathway. DCP has also been found to play a crucial role in the formation of angiogenesis. DCP could increase the angiogenic factors released from HCC and vascular endothelial cells. These effects of DCP in angiogenesis might be related to activation of the DCP-KDR-PLC-γ-MAPK signaling pathway. In this article, we summarized recent studies on DCP in biological roles related to cancer progression and angiogenesis in HCC.

Efficacy and safety of Trastuzumab Emtansine in treating human epidermal growth factor receptor 2-positive metastatic breast cancer in Chinese population: a real-world multicenter study.

Background: Trastuzumab emtansine (T-DM1) has been approved worldwide for treating metastatic breast cancer (mBC) in patients who have received first-line therapy, shown disease progression, and are human epidermal growth factor receptor 2 (HER2)-positive. T-DM1 received approval in China to treat early-stage breast cancer (BC) in 2020 and for mBC in 2021. In March 2023, T-DM1 was included in medical insurance coverage, significantly expanding the eligible population. Materials and methods: This post-marketing observational study aimed to assess the safety and effectiveness of T-DM1 in real-world clinical practice in China. This study enrolled 31 individuals with HER2-positive early-stage BC and 70 individuals with HER2-positive advanced BC from 8 study centers in Shandong Province, China. The T-DM1 dosage was 3.6 mg/kg injected intravenously every 3 weeks until the disease advanced or the drug toxicity became uncontrollable, whichever occurred earlier. Additionally, efficacy and safety information on T-DM1 were collected. Results: During the 7-month follow-up period, no recurrence or metastases were observed in patients who had early-stage BC. The disease control rate was 31.43% (22/70) in patients with advanced BC. The most common adverse effect of T-DM1 was thrombocytopenia, with an incidence of 69.31% (70/101), and the probability of Grade ≥ 3 thrombocytopenia was 11.88% (12/101). Conclusion: This real-world study demonstrated that T-DM1 had good efficacy and was well tolerated by both HER2-positive early-stage BC and mBC patients.

Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade.

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy. METHODS: We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno-collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in-house samples. Additionally, novel therapeutic targets were identified based on these established immuno-collagenic subtypes. RESULTS: Our categorization divided tumors into three subtypes: "soft & hot" (low collagen activity and high immune infiltration), "armored & cold" (high collagen activity and low immune infiltration), and "quiescent" (low collagen activity and immune infiltration). Notably, "soft & hot" tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7-H3), an available drug target, as strongly expressed in "armored & cold" tumors, relating with poor prognosis. CONCLUSION: This study introduces histopathology-based universal immuno-collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

Recent advances in prevailing antifogging surfaces: structures, materials, durability, and beyond.

In past decades, antifogging surfaces have drawn more and more attention owing to their promising and wide applications such as in aerospace, traffic transportation, optical devices, the food industry, and medical and other fields. Therefore, the potential hazards caused by fogging need to be solved urgently. At present, the up-and-coming antifogging surfaces have been developing swiftly, and can effectively achieve antifogging effects primarily by preventing fog formation and rapid defogging. This review analyzes and summarizes current progress in antifogging surfaces. Firstly, some bionic and typical antifogging structures are described in detail. Then, the antifogging materials explored thus far, mainly focusing on substrates and coatings, are extensively introduced. After that, the solutions for improving the durability of antifogging surfaces are explicitly classified in four aspects. Finally, the remaining big challenges and future development trends of the ascendant antifogging surfaces are also presented.

Phyllostachys Viridis-Leaf-like MLMN Surfaces Constructed by Nanosecond Laser Hybridization for Superhydrophobic Antifogging and Anti-Icing.

In nature, many species commonly evolve specific functional surfaces to withstand harsh external environments. In particular, structured wettability of surfaces has attracted tremendous interest due to its great potential in antifogging and anti-icing properties. Phyllostachys Viridis is a resistant low-temperature (-18 °C) plant with superhydrophobicity and ice resistivity behaviors. In this work, with inspiration from the representative cold-tolerant plants leaves, a unique multilevel micronano (MLMN) surface was fabricated on copper substrate by ultrafast laser process, which exhibited superior superhydrophobic characteristics with the water contact angle > 165° and rolling angle< 2°. In the dynamic wettability experiment, the rebound efficiency of the droplet on the MLMN surface reached 20.6%, and the contact time was only 10.6 ms. In the condensation experiment, the nucleation, growth, merging, and bouncing of fog drops on the surface was distinctly observed, indicating that rational texture structures can improve the antifogging performance of the surface. In the anti-icing experiment, the freezing time was delayed to 921 s at -10 °C, and the freezing time of salt water reached a staggering 1214 s. Moreover, the mechanical durability of MLMN surfaces was confirmed by scratch damage, sandpaper abrasion, and icing and melting cycle tests, and their repairability was evaluated for product applications in practice. Finally, the underlying antifogging/anti-icing strategy of the MLMN surface was also revealed. We anticipate that the investigations offer a promising way to handily design and fabricate multiscale hierarchical structures with reliable antifogging and anti-icing performance, especially in saltwater-related applications.