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Polarization‐sensitive photodetectors have garnered significant interest due to their promising applications in navigation, remote sensing, and optical communication. However, conventional polarized light detectors relying on optical filters face challenges due to intricate fabrication and calibration procedures. While structures based on in‐plane anisotropic 2D materials have the potential to offer viable solutions for polarization detection, achieving both low power consumption and high performance remains challenging. Herein, a self‐powered anisotropic/isotropic ReS2/SnSe2 van der Waals (vdWs) heterojunction detector with high‐performance features is constructed. This device exhibits outstanding photovoltaic (PV) performance across a wide spectral range from 405 to 850 nm without bias, featuring excellent responsivity (0.966 A W−1) and specific detectivity (1.47 × 1010 Jones) under 650 nm laser illumination. Moreover, benefiting from the built‐in electric field that promotes carrier separation and extremely low dark current, the device shows fast response time (230/240 µs) with an on/off ratio of up to 104. Furthermore, the ReS2/SnSe2 photodetector demonstrates exceptional polarization encoding performance, with a polarization ratio of 1.56 under 650 nm illumination, opening up new possibilities in optical communication technology development. This research provides a novel and viable option for developing energy‐efficient and high‐performance polarization‐sensitive detectors. [ABSTRACT FROM AUTHOR]

In order to investigate the viability of carbon dioxide (CO2) storage in seawater, molecular dynamics techniques were employed to study the dynamic evolution of CO2 hydrate in saline water. The simulation was conducted under specific conditions: a temperature of 275 K, a pressure of 10 MPa and a simulated marine environment achieved using a 3.4 wt% sodium chloride (NaCl) solution. The total simulation time was 1000 ns. The results of the simulation indicate that the pre‐existence of CO2 hydrate crystals as seeds leads to rapid growth of CO2 hydrate. However, analysis of the F3 and F4 order parameters reveals that the hydrate does not meet the standard values of the perfect structure I (sI) type, confirming the existence of an imperfect structure during the simulation. Additionally, the changes in the number of different phase states of water molecules during the hydrate growth process shows that there are always some liquid water molecules, which means some water molecules fail to form solid water cages. Further investigation suggests that the presence of Na+ and Cl− hampers the hydrogen bonds between water molecules, resulting in incomplete cage structures. By analyzing the density variations in the system, it is observed that CO2 hydrate, with a density of around 1.133 g cm−3, forms rapidly, surpassing the average density of seawater. This density increase facilitates the efficient and swift containment of CO2 on the seabed, thereby supporting the feasibility of the CO2 storage theory. [ABSTRACT FROM AUTHOR]

A water-soluble nonionic surfactant hydrophobic monomer (AT100) was synthesized by esterification of acryloyl chloride with Triton X-100, after that, a nonionic hydrophobically associating polyacrylamide P(AM-AT100) was synthesized and used as drag reducer. They were characterized by IR and NMR. In fresh water, when the concentration of drag reducer reached 0.3 g·L−1 (so called slick water), the viscosity was 3.86 mm2·s−1 with a drag reduction rate up to 74.7%. After sodium dodecyl sulfate (SDS) was added into the slick water, hydrophobic chains of SDS and hydrophobic units in P(AM-AT100) aggregated and micelles were likely formed, and this process was just like hydrophobic association. The viscosity of the slick water increased significantly, while the drag reduction rate of the mixed system decreased. With SDS concentration at 1.5 g·L−1 and the drag reducer concentration at 0.3 g·L−1, the drag reduction rate was 71.72% and viscosity was 6.25 mm2·s−1, indicating that increasing viscosity had a significantly adverse effect on drag reduction performance. The proppant layup experiment confirmed that the sand-carrying capacity of low-viscosity slick water is limited, so proppant will settle inevitably. [ABSTRACT FROM AUTHOR]

• Enthesitis-related arthritis (ERA) has a poor prognosis and often progresses to adult ankylosing spondylitis , which need a simple, non-invasive biomarker with high diagnostic efficacy urgently for early screening and diagnosis. • tRNA-derived fragments (tRFs) play crucial roles in the progression of various diseases, we identify tRF-21-LNK8KEP1B as a promising novel biomarker for ERA diagnosis. tRNA-derived fragments (tRFs) play crucial roles in the progression of various diseases, and widely distribute in human tissues, including blood and urine. The diagnosis of enthesitis-related arthritis (ERA) is based on the observation of clinical manifestations. Therefore, we aimed to investigate whether serum tRFs can be used as diagnostic markers for ERA. Serum was collected from children admitted to the Children's Hospital Affiliated with Nanjing Medical University between February 2022 to October 2022. The expression profiles of tRFs in the serum of ERA patients (n = 5) and healthy controls (HCs; n = 5) were investigated using small RNA high-throughput sequencing. The level and diagnostic value of tRF-21-LNK8KEP1B were evaluated by real-time quantitative PCR in serum samples from 30 ERA patients and 31 HCs. The specificity and sensitivity of tRFs were determined using receiver operating characteristic analyses. Bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs. Ninety-eight upregulated and 63 downregulated tRFs were identified in the serum. We selected tRF-21-LNK8KEP1B as a candidate marker using KEGG pathway enrichment and PCR validation. tRF-21-LNK8KEP1B was substantially increased in the serum of ERA patients compared with that in HCs. The area under the curve (AUC) for tRF-21-LNK8KEP1B in the ERA group was 0.7849. Collectively, we demonstrated the promising role of serum tRF-21-LNK8KEP1B -levels as a diagnostic biomarker for ERA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Folate supplementation is recommended before and during early pregnancy to prevent neural tube defects, but the effect of red blood cell (RBC) folate on large for gestational age (LGA) is still unknown. We performed a nested case‐control study including 542 LGA cases and 1,084 appropriate for gestational age (AGA) controls to examine the association of RBC folate concentrations with risk of LGA. Then, male offspring of dams fed basic folic acid (2 mg/kg, control) or 10‐fold folic acid (20 mg/kg, HFol) diet before and during pregnancy were used to explore the effect of high folate intake on birth weight and long‐term effects. We observed higher RBC folate concentrations in the cases compared to controls (p = 0.039). After adjustment for maternal age, BMI at enrollment, gestational weeks at enrollment, gestational weeks at delivery and infant gender, higher RBC folate levels were significantly associated with increased risk of LGA (Ptrend = 0.003). Interestingly, male offspring of HFol dams showed the higher birth weight, elevated levels of post loading blood glucose at 9 and 13 weeks post‐weaning and increased triglyceride (TG) and total cholesterol (TC) levels at 17 weeks post‐weaning. Furthermore, we observed that high folate intake increased the proliferation and differentiation of adipose cells. Our results suggest that maternal high folate intake confers the risk of LGA birth and accelerates the development of obesity in male offspring. Our results suggest that maternal high folate intake confers the risk of LGA birth and accelerates the development of obesity in male offspring. [ABSTRACT FROM AUTHOR]

Breast cancer is a serious health problem worldwide. Acquisition of multi-drug resistance (MDR) during the treatment of breast cancer is still considered a major clinical obstacle. Despite the biological functions of miRNAs becoming increasingly apparent, the function of miRNAs in regulating drug resistance of breast cancer remains under investigation. Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-132/-212 (miR-132 and miR-212) in doxorubicin (DOX)-resistant and -sensitive breast cancer tumors and cells. The function of miR-132/-212 in drug resistance was investigated in vitro (MTT assay, TUNEL assay, fluorescence, immunohistochemistry, luciferase reporter assay, Western blotting). We found that miR-132/-212 were commonly overexpressed in DOX-resistant breast cancer tumors and cells. Silenced miR-132/-212 expression induced DOX accumulation in MCF-7/ADR cells, while overexpression of miR-132/-212 led to breast cancer resistance protein (BCRP)-based DOX efflux in MCF-7 cells. Further study showed that up-regulation of miR-132/-212 in MCF-7/ADR cells suppressed the expression of PTEN, a target gene of miR-132/-212, which activated AKT phosphorylation and the NF-κB pathway and led to increased BCRP expression. Down-regulation of miR-132/-212 sensitized MCF-7/ADR cells to DOX. Mechanistic investigations suggested that miR-132/-212 enhancement was a result of NF-κB-mediated transactivation of the pri-miR-132/-212 gene. Taken together, our findings are among the first to demonstrate a novel aspect of the miR-132/-212-PTEN-AKT/NF-κB-BCRP pathway in the generation of breast cancer resistance and provides a potential method to reverse drug resistance. [ABSTRACT FROM AUTHOR]

Tongue squamous epithelial cells are the main component of tongue coating, with proliferation, differentiation and apoptosis being the root cause of the formation and maintenance of tongue coating. The present study aimed to explore the molecular mechanism by which serum influences tongue coating, to enable a better understanding for future investigations. Tongue carcinoma squamous cells were exposed to serum‑starvation in vitro. Cellular proliferation and apoptosis were observed by using 3‑[4,5‑dimethyl‑2‑thiazolyl]‑2,5‑ diphenyl‑2‑H‑tetrazolium bromide (MTT) assay, flow cytometry, Hoechst staining, scanning electron microscope (SEM), transmission electron microscope (TEM), and by measuring the expression ratio of B‑cell lymphoma 2 apoptosis regulator (Bcl‑2)/Bcl‑2 associated protein X apoptosis regulator (Bax) mRNA and protein by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting, respectively. MTT assays revealed that serum‑starvation results in suppression of cellular proliferation, while flow cytometry data revealed that serum‑starvation induces cell cycle arrest at G1 phase and increases apoptosis. In addition, chromatin condensation and membrane blebbing were observed through Hoechst staining, TEM and SEM. The Bcl‑2/Bax ratio was found to be significantly decreased in cells that had undergone serum‑starvation by both RT‑qPCR and western blotting analysis, further indicating that serum‑starvation induces apoptosis. Therefore, tongue carcinoma squamous cells in a serum‑free medium can simulate apoptosis related to the formation of tongue coating, which may offer guidance for future investigations about other factors. [ABSTRACT FROM AUTHOR]

Transfer RNAs (tRNAs) were traditionally considered to participate in protein translation. Recent studies have identified a novel class of small non-coding RNAs (sncRNAs), produced by the specific cleavage of pre- and mature tRNAs, which have been named tRNA-derived fragments. tRNA-derived fragments are classified into diverse subtypes based on the different cleavage positions of the pre- and mature tRNAs. Recently, accumulated evidence has shown that these tRNA-derived fragments are frequently dysregulated in several cancers. Several tRNA-derived fragments were found to participate in cell proliferation, apoptosis, and invasive metastasis in several malignant human tumors. These dysregulated fragments are able to bind both Argonaute proteins and Piwi proteins to regulate gene expression. Some of the newly identified tRNA-derived fragments have been considered as the new biomarkers and therapeutic targets for the treatment of cancer. This review summarizes the biogenesis and biological functions of different subtypes of tRNA-derived fragments and discusses their molecular mechanisms in cancer progression. [ABSTRACT FROM AUTHOR]

Heat and water transfers for the frost heave behavior of freezing graded soil as affected by fine content, cooling temperature, and water supply were investigated in this study. Results showed that, the total frost heave mainly came from the external water supply, and higher fine content and lower cooling temperature led to higher frost heave and more water intake (e.g., 14.62 mm and 186.48 ml for sample under −7.5 °C with 50% fine content). The sample experienced shorter temperature cooling stage with higher fine content (e.g., 8.7 h for sample with 50% fine content), and longer temperature cooling stage under lower cooling temperature (e.g., 13.2 h for sample under −7.5 °C). Higher fine content and lower cooling temperature resulted in higher maximum volumetric water content above the frozen fringe (e.g., 52.33% and 55.63% for samples under −5 °C and − 7.5 °C with 50% fine content, respectively). The thickness of visible ice lenses was proportional to the frost heave and "invisible" ice lenses contributed more to the frost heave. Theoretical predictions of frost heave based on the modified formula showed good agreement with the experiment results with relative error of 2.7%. [ABSTRACT FROM AUTHOR]

The human uterine cervix carcinoma is one of the most well-known malignancy reproductive system cancers, which threatens women health globally. However, the mechanisms of the oncogenesis and development process of cervix carcinoma are not yet fully understood. Long non-coding RNAs (lncRNAs) have been proved to play key roles in various biological processes, especially development of cancer. The function and mechanism of lncRNAs on cervix carcinoma is still rarely reported. We selected 3 cervix cancer and normal cervix tissues separately, then performed lncRNA microarray to detect the differentially expressed lncRNAs. Subsequently, we explored the potential function of these dysregulated lncRNAs through online bioinformatics databases. Finally, quantity real-time PCR was carried out to confirm the expression levels of these dysregulated lncRNAs in cervix cancer and normal tissues. We uncovered the profiles of differentially expressed lncRNAs between normal and cervix carcinoma tissues by using the microarray techniques, and found 1622 upregulated and 3026 downregulated lncRNAs (fold-change > 2.0) in cervix carcinoma compared to the normal cervical tissue. Furthermore, we found HOXA11-AS might participate in cervix carcinogenesis by regulating HOXA11, which is involved in regulating biological processes of cervix cancer. This study afforded expression profiles of lncRNAs between cervix carcinoma tissue and normal cervical tissue, which could provide database for further research about the function and mechanism of key-lncRNAs in cervix carcinoma, and might be helpful to explore potential diagnosis factors and therapeutic targets for cervix carcinoma. [ABSTRACT FROM AUTHOR]

Background/Aims Chemoresistance of breast cancer is a growing problem and still a major clinical obstacle to successful treatment in clinical patients. miR-760 was significantly downregulated in chemoresistance breast cancer tissues compared to chemo-sensitive tissues in our previous study. However, the role of miR-760 in modulating drug resistance remains largely unexplored. In this study, we sought to determine the expression pattern of miR-760 targeted mRNAs, and explore their potential functions and participated-pathways in breast cancer drug resistance cells. Results Compared to parental cell line MCF-7, miR-760 was downregulated by 6.15 folds in MCF-7/Adr cells. The qRT-PCR result showed that compared to miR-760 negative control cells group, miR-760 was up-regulated 15.817 folds after miR-760 lentiviral transfection in miR-760 mimics group. The microarray data showed that 270 genes were dysregulated over 2-fold change in MCF-7/Adr cells after miR-760 overexpressed, including 241 up-regulated and 29 downregulated genes. GO analysis result appeared that the predicted target genes of miR-760 mainly regulated DNA binding, protein binding, molecular function, nucleic acid binding, and so on; the pathway analysis data demonstrated that these target genes mainly involved in cell cycle, TGF-beta signaling pathway, mRNA processing reactome, G protein signaling, apoptosis, Wnt signaling pathway, and other signaling pathways. There were 3 predicted target genes ( RHOB , ANGOTL4 , ABCA1 ) of miR-760 were selected at a P value < 0.05 and the fold enrichment was > 40. Conclusion Our study explored the genes expression pattern after miR-760 overexpresssed, and confirmed 3 dominantly dysregulated genes, which could expand the insights into the miR-760 function and molecular mechanisms in drug resistance of breast cancer. This study might afford a comprehensive understanding of miR-760 as prognostic biomarkers during clinical treatment, and we supposed that the miR-760 expression levels in drug resistance carcinoma tissues could be pursued to develop new strategies for targeted therapies in chemoresistant breast cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Experimental study has been performed on nanosecond (ns) laser ablation of silicon at 1064nm, through which a so-called “multi-pulse enhancement effect” has been revealed, which has been rarely reported in literature. The major features of this effect are: (1) for multi-pulse laser ablation at the same spatial location, the ablation efficiency increases as the pulse number increases and the pulse-to-pulse temporal distance decreases; (2) for multi-pulse ablation performed sequentially at a group of locations, the ablation quality and efficiency starting from the second location can be significantly enhanced if the distance between adjacent locations is sufficiently small. Further study is needed to confirm and understand the underlying physical mechanism for the multi-pulse enhancement effect, which can be utilized to significantly improve the quality and efficiency of laser silicon micromachining using the low-cost and low-energy-consumption infrared ns lasers. This may decrease the cost and energy consumption of many relevant areas, such as the solar cell industry. [Copyright &y& Elsevier]

• Aimed to identify serum biomarkers for predicting the efficacy of trastuzumab-based therapy to HER2-positive breast cancer. • TMT label-based quantitative proteomics discovered 18 differentially expressed proteins in the serum. • MRM approach-based targeted proteomics identified SRGN, LDHA and CST3 as candidate biomarkers. • Trastuzumab-based therapy resistance diagnostic score was established based on the level of SRGN, LDHA and CST3. Human epidermal growth factor receptor 2 (HER2)-positive is a particularly aggressive type of the breast cancer. Trastuzumab-based therapy is a standard treatment for HER2-positive breast cancer, but some patients are resistant to the therapy. Serum proteins have been used to predict therapeutic benefit for various cancers, but whether serum proteins can serve as biomarkers for HER2-positive breast cancer remains unclear. Using an isobaric Tandem Mass Tag (TMT) label-based quantitative proteomic, we discovered 18 differentially expressed proteins in the serum of trastuzumab-based therapy resistant patients before therapy. Then, four proteins were selected and validated using an LC–MS/MS-based multiple reaction monitoring quantification method, and it was confirmed that three proteins (SRGN, LDHA and CST3) were correlated with trastuzumab-based therapy resistance. Finally, the trastuzumab-based therapy resistance diagnostic score was calculated and acquired by means of a logistic regression pattern based on the level of these three proteins. In summary, we develop a serum-based protein signature that potentially predicts the therapeutic effects of trastuzumab-based therapy for HER2-positive breast cancer patients. [ABSTRACT FROM AUTHOR]

• Understanding the impact of H 2 S concentrations on hydrate formation, a small amount of H 2 S can promote the formation of CH 4 hydrates. • Although H 2 S can indeed promote the formation and growth of hydrates, a very small amount of H 2 S cannot maintain the stability of hydrates. • Rapidly forming and growing hydrates are not standard structure I or II hydrates. We used molecular dynamics method to simulate the formation and growth of CH 4 hydrates with different concentrations of H 2 S. At the large scale of simulation time, 10000 ns, it is unlikely to form hydrates at 10 MPa and 260 K if there are only CH 4 and water; and if there was a small proportion of H 2 S in the gas, hydrates would easily form. When the molar concentration of H 2 S in the gas is 1 %, the formed hydrate is unstable and will eventually disintegrate, leaving the box in a two-phase state of gaseous and liquid. In contrast, at molar concentrations of 5 % or higher of H 2 S, hydrate formation is accelerated, and the hydrate will grow continuously. However, it is not structure I type as expected. These views are supported by the changes in F3 and F4 order parameters, numbers of different cage types, and the number of water molecules belonging to different states. Moreover, since the formation of hydrates is an energy reduction process, we can easily develop inhibitors targeted at hydrates in actual production and gas transportation. According to IGMH analysis, only van der Waals interactions occur between gas molecules inside the cages and the water cage. [ABSTRACT FROM AUTHOR]

Secondary trastuzumab resistance represents an evolutionary adaptation of HER2‐positive breast cancer during anti‐HER2 treatment. Most current studies have tended to prioritize HER2 and its associated signaling pathways, often overlooking broader but seemingly less relevant cellular processes, along with their associated genetic and epigenetic mechanisms. Here, transcriptome data is not only characterized but also examined epigenomic and 3D genome architecture information in both trastuzumab‐sensitive and secondary‐resistant breast cancer cells. The findings reveal that the global metabolic reprogramming associated with trastuzumab resistance may stem from genome‐wide alterations in both histone modifications and chromatin structure. Specifically, the transcriptional activities of key genes involved in lipid metabolism appear to be regulated by variant promoter H3K27me3 and H3K4me3 modifications, as well as promoter‐enhancer interactions. These discoveries offer valuable insights into how cancer cells adapt to anti‐tumor drugs and have the potential to impact future diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

The aim of the present work is to prepare polymeric materials and to be used as drag reducer. In this paper, a new type of drag reducer was synthesized with polymeric materials. Technically, N, N-dimethyl-N-hexadecyl allylammonium bromide (DHAB) was synthesized with 3-bromopropene and N, N-dimethylcetyl tertiary amine, and then cationic hydrophobically associating polyacrylamide P(AM-DHAB), the desired drag reducer, was synthesized. The chemical structures of the products were confirmed by IR and NMR. The molecular weight of the drag reducer was found to be 2.66 × 106 g/mol as measured by laser light scattering method. In fresh water, when the concentration of drag reducer is 0.03%, the highest drag reduction rate is reached up to 73.05%. However, when the concentration of drag reducer is further increased, the viscosity is increased and drag reduction rate is decreased; indicating high viscosity has a significant negative effect on drag reduction rate. While in brine, with a viscosity obviously lower than that in fresh water, the drag reduction rate was slightly lower than 70% when the concentration of drag reducer was 0.03%; increasing the concentration of P(AM-DHAB) did not lead to a significant increase in viscosity, instead, it caused the drag reduction rate to be higher than 70%. Therefore, low viscosity facilitates drag reduction performance. Potassium persulfate makes the viscosity of slick water decrease sharply, which helps promote the polymer degradation and thus prevent polymer damage to the reservoir. Scanning electron microscope (SEM) showed that the drag reducer featured an obvious network structure in fresh water before gel breaking, and that there was almost no network structure but a small number of crystallites after gel breaks. In contrast, in brine, no matter before and after gel breaking, only salt crystals were cleanly seen under electron microscope due to high concentration of salt. [ABSTRACT FROM AUTHOR]

Vacuum ultraviolet (VUV) light plays a crucial role in various scientific and technological fields, such as nanolithography and biomedical treatments. However, the inherent nonlinear optical coefficient of nonlinear optical crystals is typically very low, and increasing the action length is often necessary to improve the nonlinear conversion efficiency. This makes it challenging for these materials to achieve high-density optoelectronic integration at the micro-/nano-scale. In this study, we propose a design for generating coherent VUV radiation close to 175 nm using second harmonic generation (SHG) with an absolute efficiency exceeding 1.2‰ mW−1. This is achieved by merging multiple bound state in the continuum modes in a free-standing photonic crystal slab. Even with fabrication imperfections at a level lower than 10% disorder, the SHG efficiency of the samples remains robust, maintaining an efficiency of at least 2‰. This research provides a beneficial platform for generating efficient VUV light in the nanoscale. [ABSTRACT FROM AUTHOR]

Simple Summary: tRF-27 has been identified as upregulated in both naïve trastuzumab-resistant HER2-positive breast cancer cells and patient samples, positioning it as a potential biomarker. However, the underlying mechanisms of this upregulation remain unclear. This study proposes that the abnormal transcription of specific tRNA-Cys-GCA isodecoders in naïve trastuzumab-resistant cells might contribute to the accumulation of tRF-27. Additionally, the reduction in H3K27me3 modifications at these tRNA genes, attributed to imbalances in histone modification enzymes, appears to influence tRNA transcription alterations. Building upon these findings, our research demonstrates that the application of a demethylase inhibitor may offer a potential strategy to overcome trastuzumab resistance. tRNA-derived fragments (tRFs) play crucial roles in cancer progression. Among them, tRF-27 has been identified as a key factor in promoting naïve trastuzumab resistance in HER2-positive breast cancer. However, the origin of tRF-27 remains uncertain. In this study, we propose that the upregulated expression of specific cysteine tRNAs may lead to the increased accumulation of tRF-27 in trastuzumab-resistant JIMT1 cells. Mechanistically, the reduced inhibitory H3K27me3 modification at the promoter regions of tRF-27-related tRNA genes in JIMT1 cells, potentially resulting from decreased EZH2 and increased KDM6A activity, may be a critical factor stimulating the transcriptional activity of these tRNA genes. Our research offers fresh insights into the mechanisms underlying elevated tRF-27 levels in trastuzumab-resistant breast cancer cells and suggests potential strategies to mitigate trastuzumab resistance in clinical treatments. [ABSTRACT FROM AUTHOR]

Interest in the high folate status of pregnant women has increased due to its role in the prevention of neural tube defects (NTDs). The effect of increased red blood cell (RBC) folate status during the second trimester of pregnancy on gestational diabetes mellitus (GDM) remains unclear. We measured RBC folate concentrations by competitive protein‐binding assay and obtained clinical information from electronic medical records. Logistic regression analysis was used to explore the associations of RBC folate concentrations with risks of gestational diabetes mellitus (GDM). We further assessed the potential nonlinear relations between continuous log‐transformed RBC folate concentrations and GDM risk by using the restricted cubic splines. We observed high RBC folate concentrations in GDM patients compared to control group [median (interquartile range, IQR), GDM vs. controls: 1,554.03 (1,240.54–1,949.99) vs. 1,478.83 (1,124.60–1,865.71) nmol/L, p = .001]. Notably, high folate concentrations were significantly associated with an increased risk of GDM [RR per 1‐SD increase: 1.16 (1.03, 1.30), p = .012] after adjustment for maternal age, parity, and body mass index (BMI) at enrollment. In the restricted cubic spline model, a test of the null hypothesis of the linear relationship was rejected (p = .001). Our study firstly showed that maternal RBC folate concentrations during the second trimester of pregnancy increase the risk of GDM in a Chinese population. Further randomized clinical trials (RCTs) are warranted to confirm the adverse effect. [ABSTRACT FROM AUTHOR]

Background: BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU‐sourced reference bevacizumab (EU‐bevacizumab) in patients with advanced nonsquamous non‐small cell lung cancer (NSCLC). Methods: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU‐bevacizumab plus paclitaxel and carboplatin (EU‐bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU‐bevacizumab. The primary endpoint was overall response rate at week 18 (ORR18). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU‐bevacizumab ORR18 risk ratio was contained within the predefined equivalence margins of 0.75–1.33 (China National Medical Products Administration requirements), or 0.73–1.36 (US Food and Drug Administration), or if the 95% CI of the ORR18 risk difference between treatments was contained within the predefined equivalence margin of −0.12 to 0.15 (EMA requirements). Results: In total, 649 randomized patients (BAT1706, n = 325; EU‐bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR18 was comparable between the BAT1706 and EU‐bevacizumab arms (48.0% and 44.5%, respectively). The ORR18 risk ratio of 1.08 (90% CI: 0.94–1.24) and the ORR18 risk difference of 0.03 (95% CI: −0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU‐bevacizumab. The safety profile of BAT1706 was consistent with that of EU‐bevacizumab and no new safety signals were observed. Conclusion: In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU‐bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity. [ABSTRACT FROM AUTHOR]

Background: NME1 has been exploited as a potential translational target for decades. Substantial efforts have been made to upregulate the expression of NME1 and restore its anti-metastasis function in metastatic cancer. Methods: Cycloheximide (CHX) chase assay was used to measure the steady-state protein stability of NME1 and HSP90α. The NME1-associating proteins were identified by immunoprecipitation combined with mass spectrometric analysis. Gene knockdown and overexpression were employed to examine the impact of HSP90AA1 on intracellular NME1 degradation. The motility and invasiveness of breast cancer cells were examined in vitro using wound healing and transwell invasion assays. The orthotopic spontaneous metastasis and intra-venous experimental metastasis assays were used to test the formation of metastasis in vivo, respectively. Results: HSP90α interacts with NME1 and increases NME1 lifetime by impeding its ubiquitin-proteasome-mediated degradation. HSP90α overexpression significantly inhibits the metastatic potential of breast cancer cells in vitro and in vivo. A novel cell-permeable peptide, OPT22 successfully mimics the HSP90α function and prolongs the life span of endogenous NME1, resulting in reduced metastasis of breast cancer. Conclusion: These results not only reveal a new mechanism of NME1 degradation but also pave the way for the development of new and effective approaches to metastatic cancer therapy. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNA) has been recognized as a regulator of gene expression, and the dysregulation of lncRNAs is involved in the progression of many types of cancer, including epithelial ovarian cancer (EOC). To explore the potential roles of lncRNAs in EOC, we performed lncRNA and mRNA microarray profiling in malignant EOC, benign ovarian cyst and healthy control tissues. In this study, 663 transcripts of lncRNAs were found to be differentially expressed in malignant EOC compared with benign and normal control tissues. We also selected 18 altered lncRNAs to confirm the validity of the microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, especially the cell cycle. Furthermore, Series Test of Cluster (STC) and lncRNA-mRNA co-expression network analyses were conducted to predict lncRNA expression trends and the potential target genes of lncRNAs. We also determined that two antisense lncRNAs (RP11-597D13.9 and ADAMTS9-AS1) were associated with their nearby coding genes (FAM198B, ADAMTS9), which participated in cancer progression. This study offers helpful information to understand the initiation and development mechanisms of EOC. [ABSTRACT FROM AUTHOR]

Tamoxifen is a drug used for treating breast cancer (BC), especially for individuals diagnosed with estrogen receptor-positive (ER+) BC. Its prolonged use could reduce the risk of recurrence and significantly lengthen the survival rate of BC patients. However, an increasing number of patients developed resistance to tamoxifen treatment, which reduced therapeutic efficiency and caused substandard prognosis. Therefore, the exploration of the molecular processes involved in tamoxifen resistance (TR) is urgently required. This investigation aimed to elucidate the relationship of microRNA-330 (miR-330-3p) with the TR of BC. There is little information on miR-330-3p′s link with drug-resistant BC, although it is well known to regulate cell proliferation and apoptosis. Primarily, miR-330-3p expression in parental BC (MCF7/T47D), TR (MCF7-TR), and T47D/TR cell lines was detected by qRT-PCR. Then, the impact of miR-330-3p on the TR of BC cells was assessed by a cell proliferation assay. Lastly, dual-luciferase reporter, qRT-PCR, and western blot assessments were carried out to identify histone deacetylase 4 (HDAC4) as the potential miR-330-3p target gene. The data indicated that miRNA-330 was overexpressed in TR ER+ BC cells and its overexpression could induce TR. Furthermore, miRNA-330 could also reduce the expression of HDAC4, which is closely linked to TR, and overexpression of HDAC4 could reverse miRNA-330-induced drug resistance. In summary, miR-330-3p could induce TR of ER+ BC cells by downregulating HDAC4 expression, which might be a novel marker of TR and a possible treatment target against BC patients who are tamoxifen-resistant. [ABSTRACT FROM AUTHOR]

Anti‐angiogenic therapy has long been considered a promising strategy for solid cancers. Intrinsic resistance to hypoxia is a major cause for the failure of anti‐angiogenic therapy, but the underlying mechanism remains unclear. Here, it is revealed that N4‐acetylcytidine (ac4C), a newly identified mRNA modification, enhances hypoxia tolerance in gastric cancer (GC) cells by promoting glycolysis addiction. Specifically, acetyltransferase NAT10 transcription is regulated by HIF‐1α, a key transcription factor of the cellular response to hypoxia. Further, acRIP‐sequencing, Ribosome profiling sequencing, RNA‐sequencing, and functional studies confirm that NAT10 in turn activates the HIF‐1 pathway and subsequent glucose metabolism reprogramming by mediating SEPT9 mRNA ac4C modification. The formation of the NAT10/SEPT9/HIF‐1α positive feedback loop leads to excessive activation of the HIF‐1 pathway and induces glycolysis addiction. Combined anti‐angiogenesis and ac4C inhibition attenuate hypoxia tolerance and inhibit tumor progression in vivo. This study highlights the critical roles of ac4C in the regulation of glycolysis addiction and proposes a promising strategy to overcome resistance to anti‐angiogenic therapy by combining apatinib with ac4C inhibition. [ABSTRACT FROM AUTHOR]

Human gastric cancer is a common malignant neoplasm of the digestive system and represents a threat to human health worldwide. The mechanisms underlying gastric cancer germination and development are not yet fully understood. Circular RNAs (circRNAs) serve crucial roles in various physiological and pathological processes, particularly cancer. However, few studies have focused on the mechanisms involving circRNAs in gastric cancer. Therefore the present study set out to identify the differentially expressed circRNAs in gastric cancer. Three specimens of gastric cancer and normal gastric tissue were selected and circRNA microarray analysis was performed to detect the differentially expressed circRNAs. The changes in circRNAs were confirmed by reverse transcription‑quantitative polymerase chain reaction analysis. A total of 347 upregulated and 603 downregulated circRNAs (fold‑change, >2.0) were identified in gastric cancer compared with the normal gastric tissue. A total of 20 selected circRNAs were dysregulated during gastric cancer, which suggests their potential role in gastric cancer. The present study identified circRNAs in the expression profile of human gastric cancer that were potentially involved in the underlying molecular mechanisms of its development. [ABSTRACT FROM AUTHOR]

Simple Summary: While the prognosis of hormone receptor-positive (HR+) breast cancer has been significantly improved, tamoxifen resistance remains a challenge in the treatment of HR+ breast cancer. This study identified that tRF-16-K8J7K1B, a novel small ncRNA derived from the 3′-end of tRNAAla-TGC, was highly expressed in tamoxifen-resistant cells compared to parental cells. Moreover, extracellular tRF-16-K8J7K1B confers tamoxifen resistance via incorporation into exosomes and then degrades the expression of apoptosis-related proteins, reducing the proportion of drug-induced cell apoptosis. Therefore, we propose that exosomal tRF-16-K8J7K1B could be a potential predictive biomarker and therapeutic target for overcoming tamoxifen resistance. Tamoxifen resistance remains a challenge in hormone receptor-positive (HR+) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments and tamoxifen resistance remains unclear. In this study, we found that the expression of tRF-16-K8J7K1B was upregulated in tamoxifen-resistant cells in comparison with tamoxifen-sensitive cells. Higher levels of tRF-16-K8J7K1B were associated with shorter disease-free survival in HR+ breast cancer. Overexpression of tRF-16-K8J7K1B promotes tamoxifen resistance. Moreover, extracellular tRF-16-K8J7K1B could be packaged into exosomes and could disseminate tamoxifen resistance to recipient cells. Mechanistically, exosomal tRF-16-K8J7K1B downregulates the expression of apoptosis-related proteins, such as caspase 3 and poly (ADP-ribose) polymerase, by targeting tumor necrosis factor-related apoptosis-inducing ligand in receptor cells, thereby reducing drug-induced cell apoptosis. Therapeutically, the inhibition of exosomal tRF-16-K8J7K1B increases the sensitivity of breast cancer cells to tamoxifen in vivo. These data demonstrate that exosomal tRF-16-K8J7K1B may be a novel therapeutic target to overcome tamoxifen resistance in HR+ breast cancer. [ABSTRACT FROM AUTHOR]

Introduction Our previous study showed that the expression of miR-197 in leiomyoma was down-regulated compared with myometrium. Further, miR-197 has been identified to affect uterine leiomyoma cell proliferation, apoptosis, and metastasis ability, though the responsible molecular mechanism has not been well elucidated. In this study, we sought to determine the expression patterns of miR-197 targeted genes and to explore their potential functions, participating Pathways and the networks that are involved in the biological behavior of human uterine leiomyoma. Methods After transfection of human uterine leiomyoma cells with miR-197, we confirmed the expression level of miR-197 using quantitative real-time PCR (qRT-PCR), and we detected the gene expression profiles after miR-197 over-expression through DNA microarray analysis. Further, we performed GO and Pathway analysis. The dominantly dys-regulated genes, which were up- or down-regulated by more than 10-fold, compared with parental cells, were confirmed using qRT-PCR technology. Result Compared with the control group, miR-197 was up-regulated by 30-fold after miR-197 lentiviral transfection. The microarray data showed that 872 genes were dys-regulated by more than 2-fold in human uterine leiomyoma cells after miR-197 overexpression, including 537 up-regulated and 335 down-regulated genes. The GO analysis indicated that the dys-regulated genes were primarily involved in response to stimuli, multicellular organ processes, and the signaling of biological progression. Further, Pathway analysis data showed that these genes participated in regulating several signaling Pathways, including the JAK/STAT signaling Pathway, the Toll-like receptor signaling Pathway, and cytokine–cytokine receptor interaction. The qRT-PCR results confirmed that 17 of the 66 selected genes, which were up- or down-regulated more than 10-fold by miR-197, were consistent with the microarray results, including tumorigenesis-related genes, such as DRT7, SLC549, SFMBT2, FLJ37956, FBLN2, C10orf35, HOXD12, CACNG7, and LOC100134279. Conclusion Our study explored gene expression patterns after miR-197 overexpression and confirmed 17 dominantly dys-regulated genes, which could expand the insights into the function of miR-197 and the molecular mechanisms during the development and progression of uterine leiomyomas. This study might afford new clues for understanding the pathogenesis of uterine leiomyomas, and it could likely provide a unique method for diagnosing or predicting prognosis in the clinical treatment of leiomyoma. [ABSTRACT FROM AUTHOR]

Simple Summary: There are limited treatments for patients with HER2-negative breast cancer, especially for patients with metastatic breast cancer. This study aimed to observe the efficacy and safety of low-dose apatinib combined with chemotherapy in real-world clinical diagnosis and treatment of HER2-negative metastatic breast cancer. A total of 128 patients were treated with 250 mg apatinib, and we observed the median progression-free survival (PFS) and overall survival (OS) were 4.7 months and 15.3 months, respectively. This observation also indicated that the breast cancer susceptibility gene (BRCA) mutation predicted a better response to apatinib and that combination of immunotherapy or paclitaxel-platinum regimens might be an optimal treatment option. Importantly, a lower dose of apatinib showed mild side effects that improved the patients' life quality. Treatment options for human epidermal growth factor receptor (HER2)-negative breast cancer patients are limited in comparison to the HER2-positive patients, particularly for metastatic breast cancer patients. Apatinib is a small-molecule tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we reported the apatinib-based therapy data in HER2-negative metastatic breast cancer. Apatinib was taken at a dose of 250 mg orally once per day and combined with standard chemotherapy regimens. The PFS and OS of 128 patients were 4.7 months and 15.3 months, respectively. The objective response rate (ORR) and the disease control rate (DCR) were 22.7% and 80.5%, respectively. Patients with breast cancer susceptibility gene (BRCA) mutations were found to have a longer PFS and OS. Moreover, combination immunotherapy or paclitaxel-platinum regimens shared an improved response to other regimens. Most of the adverse effects (hypertension, anaemia, and hand-foot syndrome) were grade 1 to 2. Metastatic breast cancer patients could benefit from apatinib therapy at a low dosage, and the adverse effects are mild in real-world clinical practice. Furthermore, BRCA may be a putative biomarker for apatinib in HER2-negative breast cancer. Immunotherapy or paclitaxel-platinum regimens may be recommended to combine with apatinib therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study was to investigate microRNA (miRNA) expression profiles in CD44+ ovarian cancer stem cells (ovarian CSCs). Methods: In this study, we enriched CD44+ ovarian CSCs using magnetic activated cell sorting (MACS). A combination of real-time quantitative PCR (qRT-PCR), western blot and sphere formation assays was used to demonstrate stem cell-like properties. RNA sequencing was used to detect the miRNA expression profiles in CD44+ ovarian CSCs. Transient transfection, qRT-PCR, western blot and sphere formation assays were further used to test the function of miR-181a-2-3p. Results: We found that CD44+ ovarian CSCs showed enhanced sphere formation and expression of stemness-associated genes (NANOG, OCT4, SOX2) compared to ovarian cancer cells. The RNA sequencing results showed that the miRNA expression profiles of CD44+ ovarian CSCs were different from those of ovarian cancer cells. GO and KEGG pathway analyses indicated that these miRNAs regulate stem cell-like properties in CD44+ ovarian CSCs. In addition, miR-181a-2-3p negatively regulates the stem cell-like properties of CD44+ ovarian CSCs by targeting EGR1. Conclusion: Our data suggest that miRNAs play important roles in regulating the stem cell-like properties of CD44+ ovarian CSCs. [ABSTRACT FROM AUTHOR]

Background/aims Uterine leiomyoma is the ahead benign tumor of the female genital tract, which resulted in menstrual abnormalities, recurrent pregnancy loss, and other serious gynecological disorders in women. Recently, as the process of exploring the brief molecular mechanisms of tumorgenesis, microRNAs (miRNAs) have attracted much more attention. Methods In this study, we first confirmed that microRNA-197 (miR-197) was down-regulated significantly in human uterus leiomyoma by quantity real-time polymerase chain reaction, compared to normal uterus myometrium. Then we observed the potential effects of miR-197 overexpression on human uterus leiomyoma cells by cell counting kit 8, wound healing assay, and flow cytometric assessment separately. Results The data showed that miR-197 could inhibit cell proliferation, induce cell apoptosis, and block cell migration in vitro. Coincidently, levonorgestrel (LNG), a well-known uterus leiomyoma therapy, could induce miR-197 expression in human uterus leiomyoma cells, and over-expression of miR-197 showed a synergy effect on human uterus leiomyoma cell proliferation and apoptosis with LNG. Conclusion In this study, the data showed that miR-197 could play an anti-oncogenic role in human uterus leiomyoma cells, and cooperate with LNG on the cell proliferation and apoptosis, which suggested that miR-197 might be a potential target and provided database for clinical treatment. [ABSTRACT FROM AUTHOR]

The growth of carbon dioxide (CO2) hydrate in CO2 aqueous solution (box A), and in CO2 aqueous solution with structure I (sI) CO2 hydrate cell as seed (box B) under the same conditions of 275 K and 10 MPa, were simulated respectively. The total simulation time is 5000 ns. The nucleation process is very slow, so it is difficult to observe CO2 hydrate growth in box A without CO2 hydrate seed, CO2 just accumulates to form bubbles, while H2O still remains liquid, the F4 order parameter remains about –0.1. By contrast, beautiful CO2 hydrate in box B grows rapidly, CO2 is trapped in the cages formed by H2O molecules, F4 rises from 0.12 to 0.7 due to the formation of sI hydrate. The density of CO2 hydrate in box B is as high as 1.25 g/cm3, higher than that of seawater, which is beneficial to its permanent sealing on the seabed. In box B, in accordance with the independent gradient model based on Hirshfeld partition (IGMH) analysis, a H2O molecule forms four hydrogen bonds with surrounding H2O molecules, CO2 only has van der Waals interaction with surrounding water cages. In the actual large-scale CO2 storage process, especially for the rapid storage of CO2 in the form of hydrate, it is strongly recommended to pre-add CO2 hydrate crystals into the solution to achieve the purpose of rapid growth of CO2 hydrate. [ABSTRACT FROM AUTHOR]

Breast cancer has been considered to be a multifactorial disease with a wide array of well-characterized gene mutations and chromosomal abnormalities. However, it is becoming evident that the onset or development of breast cancer also depends on epigenetic factors, although the mechanisms have not been fully elucidated. We performed a genome-wide analysis of DNA methylation of breast carcinomatous tissues and paired normal tissues to examine the differences in methylation between them. Methylation-specific polymerase chain reaction (MSP) was used to validate the hypermethylated genes screened out by DNA methylation microarray. We found that hypomethylation and hypermethylation occurred in 2753 and 1795 genes, respectively, in breast carcinomatous tissues. Meanwhile, gene ontology analysis and ingenuity pathway analysis revealed the function and pathway of several genes whose methylation status was altered in breast carcinomatous tissues. In addition, we investigated the promoter methylation status of four genes in breast carcinomatous tissue and paired normal tissues ( n = 30) by MSP. Promoter hypermethylation of CRABP1 , HOXB13 , IFNGR2 , and PIK3C3 was found in 37% (11/30), 23% (7/30), 17% (5/30), and 2% (2/30) of the carcinomas, respectively. Mutation of these four important genes was critical to many types of cancer. Our results suggest that DNA methylation mechanisms may be involved in regulating the occurrence and development of breast cancer. [ABSTRACT FROM AUTHOR]

Background/Aims: Obesity and the related metabolic syndrome have emerged as major public health issues in modern society. miRNAs have been shown to play key roles in regulating obesity-related metabolic syndrome, and some miRNAs regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. miR-378 is a candidate target that was shown to be involved in adipose differentiation, mitochondrial metabolism and systemic energy homeostasis. However, little is known about the regulatory mechanisms of miR-378 expression. To better understand the physiological role of miR-378 in obesity and metabolic syndrome, it is crucial that we understand the regulation of miR-378 gene expression in human adipocytes. Methods: In this study, we investigated the effects of adipokines and inflammatory cytokines on miR-378 expression using Real-time PCR and the potential regulatory mechanisms using luciferase reporter assays and electrophoretic mobility shift assay (EMSA). Results: We found that adipokines and cytokines upregulated miR-378 expression primarily through SREBP and C/EBP binding sites in the miR-378 promoter region. Conclusion: Our findings showed that adipokines induced miR-378 expression and revealed the most likely mechanism of adipokine-induced miR-378 dysregulation in human adipocytes. miRNAs have been shown to function in regulating obesity-related metabolic syndrome, and miR-378 may be a novel target for controlling adipose tissue inflammation. This study offers a theoretical basis for understanding systemic adipose tissue inflammation and may provide new strategies for clinical treatment. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: In order to investigate the potential effects of microcystin-LR (MC-LR) on the expression of metalloproteinases (MMPs), Mice were orally administered with MC-LR in drinking water (0, 1, 40 and 80μg/L) for 180d, and hepatic MMP-2/-9 expression was evaluated at the levels of enzyme activity, protein level and mRNA expression. Histopathologic observation showed the obvious hepatic lymphocyte infiltration and fatty degeneration in the mice exposed to 40 and 80μg/L MC-LR. Immunohisto-chemical staining and enzyme-linked immunosorbent assay (ELISA) revealed that excess MMP-2/-9 proteins were produced in livers of the mice exposed to MC-LR at the higher concentrations. Hepatic MMP-9 level was elevated from 0.6ng/g liver weight in control to 1.4ng/g liver weight in 80-μg/L group, but a slight increase was found for MMP-2 level. Real time PCR showed that MMP-2/-9 mRNA expression was up-regulated by 6.9 fold and 5.0 fold after 80-μg/L-MC treatment, respectively. MMP-2/-9 expression showed a good dose-dependent manner at both protein and mRNA levels. ELISA demonstrated that MC-LR stimulated phosphorylation of mitogen-activated protein kinases, a potential signal transduction pathway of the MMP-2/-9 expression alteration. This study revealed a significant alteration in hepatic MMP-2/-9 expression induced by MC-LR, which might be involved in cell invasion and metastasis. [ABSTRACT FROM AUTHOR]

Background: With life span extending, breast cancer (BC) survivors may face the possibility of developing second primary cancer (SPC) and considerably shorten survivorship. However, little is known about multiple primary cancer (MPC) patients with nonmetastatic breast cancer as a first primary malignancy (BCFPM). Methods: Here, we retrospectively analyzed data on cancer survivors with BCFPM diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic factors for breast cancer‐specific survival (BCSS) were ascertained by the stepwise regression analysis and a competing risk model, and were integrated to the establishment of prognostic nomogram, of which the accuracy was measured by the calibration curve and the concordance index (C‐index). Results: In total, 8616 patients were identified with 4.6% of 3‐year breast cancer‐ specific death (BCSD) and 8.6% of 5‐year BCSD. The most common SPC among BCFPM patients were female BC and lung cancer. Besides, the median latency time between BC and SPC was 22 months. At a ratio of 7:3, all patients were randomly categorized into a training cohort (n = 6032) and a validation cohort (n = 2584). By a proportional subdistribution hazards regression analysis, the following factors were considered to own independent prognostic abilities of BCSS: subtypes, grade, T classification, N classification, radiation, and sites of SPC. The nomogram could accurately predict 3‐year and 5‐year breast cancer‐associated survival of BCFPM patients with high internal and external validated C‐index, 0.715 (95% CI, 0.691–0.739), and 0.683 (95% CI, 0.642–0.724), respectively. Conclusions: BC survivors remained a high risk of developing SPC and considerably shortened survival time. In this study, a favorable nomogram was constructed to as a prediction model for 3‐year and 5‐year BCSS of BCFPM patients, largely intending to prolong the life of these patients by assisting clinicians to make individualized follow‐up plans. [ABSTRACT FROM AUTHOR]

Objectives: Whether the maternal vitamin D deficiency is associated with preeclampsia is still an argument. We aimed to assess the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of preeclampsia in a Chinese population and systematically evaluate published evidence on this association.Methods: We conducted a nested case-control study involving 122 pregnant women with preeclampsia and 488 pregnant women whose blood pressure was within the normal range (as controls). For further meta-analysis, 20 studies and our study were included for the final pooled analysis, involving 39,031 participants and 3305 preeclampsia cases with various ethnicities.Results: The results showed that 65.6% of women with preeclampsia had serum 25(OH)D concentrations <50.0 nmol L-1 compared with 55.3% of women in controls. The 25(OH)D concentrations were significantly lower in women with preeclampsia than controls [Median (IQR), women with preeclampsia versus controls: 43.3 (35.5, 55.2) versus 47.5 (37.6, 60.4) nmol L-1, p = .014]. For women with 25(OH)D concentrations <50.0 nmol L-1, they had a 65% increase in preeclampsia risk (95% CI = 1.02-2.69), as compared with women with 25(OH)D concentrations from 50.0 to 74.9 nmol L-1. Further, meta-analysis showed that low 25(OH)D concentrations were associated with a significantly increased risk of preeclampsia by 62% (pooled OR = 1.62, 95%CI = 1.36-1.94), and the risk effect of low 25(OH)D concentrations existed in most subgroups.Conclusions: Low 25(OH)D concentration in pregnancy was significantly associated with preeclampsia risk, and it may serve as biomarkers for the surveillance of high-risk pregnant women. [ABSTRACT FROM AUTHOR]

Purpose: The long noncoding RNA (lncRNA) ZEB1-AS1 is reported overexpressed in sensitive ovarian cancer cells A2780 compared with paclitaxel (PTX)—and cisplatin (DDP)- resistant. However, the function and mechanism of ZEB1-AS1 in EOC cells still unknown. Methods: We used quantitative real-time PCR (qPCR) to detect ZEB1-AS1 expression in A2780 and A2780/R cells. A combination of siRNA, plasmids, CCK8 and flow cytometry was used to detect the effect of ZEB1-AS1 on ovarian cancer cell A2780 PTX and DDP resistance. Transcriptome sequencing, qPCR, and western blot were used for further mechanistic studies. Results: ZEB1-AS1 depletion using siRNA in chemosensitive A2780 cells significantly increased PTX and DDP resistance. In contrast, ZEB1-AS1 overexpression in PTX- and DDP-resistant A2780/resistant (A2780/R) cells reversed the observed drug resistance. Thus, ZEB1-AS1 plays an important role in PTX and DDP resistance in EOC cells. However, quantitative real-time PCR (qPCR) and western blot results suggested that ZEB1-AS1 did not regulate chemoresistance through regulation of ZEB1 protein. We used sequencing to detect mRNA expression changes in A2780 cells after ZEB1-AS1 silencing. The results indicated that MMP19 was the likely downstream factor of ZEB1-AS1. We further examined whether ZEB1-AS1 played an important role in chemoresistance by silencing MMP19 in ZEB1-AS1-overexpressing cells. CCK8 assay results suggested that MMP19 knockdown promoted ZEB1-AS1-induced chemoresistance to PTX and DDP in A2780 cells. Conclusion: This study is the first to reveal that ZEB1-AS1 plays a pivotal role in cancer chemoresistance. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease with a complex microenvironment consisting of tumor cells, immune cells, fibroblasts and vascular cells. These cancer-associated cells shape the tumor microenvironment (TME) and influence the progression of breast cancer and the therapeutic responses in patients. The exact composition of the intra-tumoral cells is mixed as the highly heterogeneous and dynamic nature of the TME. Recent advances in single-cell technologies such as single-cell DNA sequencing (scDNA-seq), single-cell RNA sequencing (scRNA-seq) and mass cytometry have provided new insights into the phenotypic and functional diversity of tumor-infiltrating cells in breast cancer. In this review, we have outlined the recent progress in single-cell characterization of breast tumor ecosystems, and summarized the phenotypic diversity of intra-tumoral cells and their potential prognostic relevance. [ABSTRACT FROM AUTHOR]

For advanced all-solid-state lithium batteries, the solid electrolyte is one of the most critical components that significantly affect battery performance. Herein, solid electrolytes 75Li2S·(25-x)P2S5·xP2O5 (mol%) are successfully prepared via wet chemistry method. Their XRD patterns show that only the crystalline phase β-Li3PS4 is detected for x = 0, 1, 2, 3, 5 mol% and the highest room-temperature ionic conductivity of 2.53 × 10−4 S cm−1 is obtained when x = 2. Next, effects of heat treatment on the structure and electrochemical performance of 75Li2S·23P2S5·2P2O5 are systematically studied. The thermal stability, morphology, structure, and crystal phase of the 75Li2S·23P2S5·2P2O5 electrolyte heated at different temperatures are characterized by thermogravimetric analysis and differential scanning calorimetry (TGA-DSC), SEM, N2 adsorption/desorption, Raman, and XRD. The 75Li2S·23P2S5·2P2O5 electrolyte heat-treated at 320 °C exhibits the highest ionic conductivity of 2.72 × 10−4 S cm−1, the lowest electronic conductivity of 4.8 × 10−9 S cm−1, and excellent electrochemical stability against the metallic lithium electrode. When the heat treatment temperature further increases from 320 to 500 °C, the electrolyte partially decomposes into Li4P2S6 and Li2S. Our results underscore the importance of heat treatment for the synthesis and performance optimization of solid electrolytes for the application of high-energy solid-state batteries. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of lapatinib plus capecitabine (LC or LX) versus trastuzumab plus chemotherapy in patients with HER-positive metastatic breast cancer who are resistant to trastuzumab is unknown.Methods: We retrospectively analyzed data from breast cancer patients who began treatment with regimens of lapatinib plus capecitabine (LC or LX) or trastuzumab beyond progression (TBP) at eight hospitals between May 2010 and October 2017.Results: Among 554 patients who had developed resistance to trastuzumab, the median PFS (progression free survival) was 6.77 months in the LX group compared with 5.6 months in the TBP group (hazard ratio 0.804; 95% CI, 0.67 to 0.96; P = 0.019). The central nervous system progression rate during treatment was 5.9% in the LX group and 12.5% in the TBP group (P = 0.018).Conclusion: The combination of lapatinib and capecitabine showed a prolonged PFS relative to TBP in patients who had progressed on trastuzumab. [ABSTRACT FROM AUTHOR]

Breast cancer has become the most common cancer in women, and nontriple negative breast cancer (non‐TNBC) accounts for 80–90% of all invasive breast cancers. Early detection, diagnosis, and treatment are considered key to a successful cure. Conventionally, breast imaging and needle core biopsy are used for detection and monitoring. However, small variations in volume might be ignored in imaging, and traditional biopsies are spatially and temporally limited, leading to a significant delay in cancer detection and thus prompting renewed focus on early and accurate diagnosis. In this article, we investigated whether there is an accurate molecule in peripheral blood that can help diagnose breast cancer. Similar to microRNAs, tRNA‐derived fragments (tRFs) have been reported to be involved in many pathological processes in breast cancer, but whether they can serve as candidate biomarkers for breast cancer remains unclear. Using high‐throughput sequencing technology, we identified 4,021 differentially expressed tRFs in normal and breast cancer cell lines, and eight tRFs were selected to establish a signature as a predictive biomarker of non‐TNBC. Furthermore, quantitative reverse‐transcriptase polymerase chain reaction was performed to verify the expression of the signature and analyze the correlation between dysregulated tRFs and breast cancer. The results indicated that tDR‐7816, tDR‐5334, and tDR‐4733 might be promising biomarkers. Through further bioinformatics analysis, we predicted that tDR‐7816 influences the xenobiotic metabolic processes that support the oncogenesis of breast cancer. In summary, our results provide a rationale for using circulating tDR‐7816 expression as a novel potential biomarker for the diagnosis of patients with early non‐TNBC. [ABSTRACT FROM AUTHOR]

Three kinds of amorphous ITO (a-ITO) films were deposited on chemically strengthened glass by DC magnetron sputtering at room temperature. A rapid infrared annealing (RIA) device was built, and an infrared fast crystallization process was developed. Not only the effects of RIA on the structural, optical, and electrical properties of ITO films, but also the effects of RIA on the mechanical properties of chemically strengthened glass substrates were investigated compared with those of conventional furnace annealing (CFA). The rules of the structural and physical properties during amorphous-crystalline transition are basically the same by RIA and CFA. However, the RIA time is only 10% of the CFA time, and the compressive stress reduction of chemically strengthened glass is only 4.2% at 500 °C, which is 38.5% by CFA. These results demonstrate that very effective RIA technology could replace the traditional annealing method (CFA), which can greatly reduce production costs and significantly improve production efficiency. [ABSTRACT FROM AUTHOR]

Abnormal development of embryonic conus arteriosus could lead to conotruncal defects in fetal heart, and increase the incidence of fetal congenital heart disease. Tetralogy of Fallot (TOF) is one of the most common forms of congenital heart disease. It may be helpful for us to solve this clinical problem through exploring the molecular mechanisms of development in embryonic congenital heart disease. Proteomics has attracted much attention in understanding the development of human diseases during the past decades. However, there is still little information about the relationship between protein expression pattern and TOF. In this study, we aimed to explore the potential linkage of proteomics and TOF development. Briefly, 121 differentially expressed proteins were identified from a TOF group, compared with a control group. The expression levels of 34 of these proteins were significantly different (>1.5 absolute fold change, p < 0.05) between the two groups. Gene ontology (GO) and pathway analysis showed that these proteins were mainly associated with carbon metabolism, biosynthesis of antibodies, positive regulation of transcription from RNA polymerase II promoter, nucleus, ATP binding, and so on. The ingenuity pathway analysis (IPA) results indicated that 435 of upstream regulators were identified of these differentially expressed proteins, which might be involved in the development of TOF. Data of string analysis showed the protein–protein interaction network among the differentially expressed proteins and regulators, which are related to TOF. In conclusion, our study explored the protein expression pattern of TOF, which might provide new insights into understanding the mechanism of TOF development and afford potential targets for TOF diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Objective: The aim was to investigate the lncRNA KB-1471A8.2 function in ovarian cancer progression and paclitaxel resistance. Methods: The expression and distribution of KB-1471A8.2 was detected by qRT-PCR. The cell proliferation, apoptosis, invasion, migration and chemoresistance were analyzed by CCK8 assay, flow cytometry and transwell assay. The expression of DEPTOR, whose sequence is reverse overlapped with KB-1471A8.2 was analyzed by qRT-PCR, western blot and immunofluorescence. The cell cycle and the cell cycle related gene expression were analyzed by flow cytometry and qRT-PCR, respectively. Results: KB-1471A8.2 was significantly downregulated in both ovarian cancer tissues and chemoresistant ovarian cancer cells. Overexpression of KB-1471A8.2 significantly inhibited the proliferation, invasion, migration, and paclitaxel resistance, and increased the apoptosis of ovarian cancer cells. KB-1471A8.2 was mainly distributed in the nucleus of ovarian cancer cells. KB-1471A8.2 overexpression significantly decreased the S phase cell ratio, increased the G0/G1 phase cell ratio, but not affected the expression and distribution of DEPTOR. However, cyclin-dependent kinase 4 (CDK4), which is an important regulator of G1/S transition, was significantly decreased in KB-1471A8.2-overexpressed ovarian cancer cells. Conclusion: KB-1471A8.2 could significantly inhibit the development and paclitaxel resistance of ovarian cancer cells, at least partly, by suppressing CDK4 expression. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is an aggressive subtype of epithelial breast malignancy, and chemoresistance is the major obstacle for cancer therapy. TNBC is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA‐derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. Here, we conducted a comparative analysis of the aberrant expression of tDRs in hypoxia‐treated TNBC cell lines through the use of high‐throughput sequencing technique. Quantitative real‐time polymerase chain reaction was used to validate the differently expressed tDRs between two samples. The results showed that tDR‐0009 [derived from transfer RNA (tRNA)Gly‐GCC‐1‐1] and tDR‐7336 (derived from tRNA Gly‐GCC‐1–2) were significantly upregulated when the SUM‐1315 cell lines were stimulated by hypoxia. Gene ontology (GO) and pathway analysis indicated that these two upregulated tDRs were mainly involved in maintenance of stem cell population and cellular response to interleukin (IL)‐6, which may be the underlying mechanism of hypoxia‐induced tDRs that facilitate the doxorubicin resistance in TNBC. The protein–protein interaction network for predicted target genes established by the STRING database manifested that tDR‐0009 (tDR‐7336) might be involved in the chemoresistance of TNBC via regulation of the activation of phosphorylation of STAT3. In summary, our study provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia‐treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia‐induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets. Triple negative breast cancer (TNBC) is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA‐derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. We provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia‐treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia‐induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC), an intrinsic subtype of breast cancer, is characterized by aggressive pathology and shorter overall survival. Yet there is no effective therapy for these patients. Breast cancer stem cells (BCSCs) in TNBC may account for treatment failure. It is urgent to identify new therapeutic targets for TNBC. tRNA‐derived small noncoding RNAs (tDRs) represent a new class of small noncoding RNAs (sncRNA), which have been reported in some human diseases and biological processes. However, there is no detailed information about the relationship between tDRs and BCSCs. In this study, a population of CD44+/CD24−/low cells was isolated and identified by reliable BCSC surface markers. tDR expression profiles in TNBC and non‐TNBC CSCs were performed by RNA sequencing. A total of 1327 differentially expressed tDRs contained 18 upregulated and 54 downregulated in TNBC group. Furthermore, the selected tDRs were validated by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). tDR‐000620 expression level was consistently lower in TNBC cell lines CSCs (all P < 0.05) and serum samples (t = 2.597, P = 0.013). tDR‐000620 expression was significant association with age (P = 0.018), node status (P = 0.026) and local recurrence (P = 0.019) by chi‐square test. Kaplan‐Meier method with log‐rank test for comparison of recurrence curves. The results showed that the tDR‐000620 expression (P = 0.002) and node status (P = 0.001) group were statistically significant with recurrence‐free survival. Furthermore, multivariate Cox regression demonstrated that lymphatic metastasis (HR, 3.616; 95% CI, 1.234‐10.596; P = 0.019) and low tDR‐000620 expression (HR, 0.265; 95% CI, 0.073‐0.959; P = 0.043) were two independent adverse predictive factors for recurrence‐free survival. Finally, we found that tDR‐000620 participated in some important biological processes though GO and KEGG analysis. Taken together, our study reveals the expression profiles of tDRs in TNBC and non‐TNBC CSCs. It offers helpful information to understand the tDR‐000620 expression is responsible for the aggressive phenotype of BCSCs. It may provide predictive biomarkers and therapeutic targets for TNBC recurrence. tDR‐000620 expression is responsible for the aggressive phenotype of BCSCs. tDR‐000620 may serve as predictive biomarkers and therapeutic targets for TNBC recurrence. [ABSTRACT FROM AUTHOR]

In the cover, the angiogenesis inhibitor Apatinib (Red Armillary Sash) combined with the N acetyltransferase 10 (NAT10, Dragon Tendon) inhibitor Remodelin attenuates the hypoxia tolerance of gastric cancer cells (Dragon) and inhibits tumor progression. In article number 2300898, Fengping Li, Gengtai Ye, Guoxin Li, and co-workers demonstrate that N4-acetylcytidine (ac4C) promotes glycolysis addiction through a NAT10/SEPT9/HIF-1 I i positive feedback loop in gastric cancer cells, leading to anti-angiogenic therapy resistance. N4-Acetylcytidine Drives Glycolysis Addiction in Gastric Cancer via NAT10/SEPT9/HIF-1 Positive Feedback Loop (Adv. Sci. 23/2023). [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

As a class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified to regulate tumourigenesis and progression in multiple malignancies. However, the expression profiles and function of circRNAs in breast cancer metastasis are largely unknown. Here, we determined that the expression of a novel circRNA, which we named circIRAK3, was increased in metastatic breast cancer (BC) cells and predictive of BC recurrence. Gain-of-function and loss-of-function studies in BC cells demonstrated that circIRAK3 promoted cell migration, invasion and metastasis in vitro and in vivo but did not affect cell proliferation, colony formation or cell cycle progression. Using circIRAK3 in vivo precipitation and luciferase reporter assays, we identified miR-3607 as a circIRAK3-associated miRNA. Furthermore, RNA sequencing and bioinformatics analysis showed that forkhead box C1 (FOXC1), the target of miR-3607, was downregulated in circIRAK3-silenced cells and mediated circIRAK3-induced BC cell migration. Intriguingly, FOXC1 could, in turn, bind to the IRAK3 promoter, triggering a positive-feedback loop that perpetuated the circIRAK3/miR-3607/FOXC1 signaling axis. Collectively, our findings indicated that circIRAK3 may exert regulatory roles in BC metastasis and may be a potential target for metastatic BC therapy. [ABSTRACT FROM AUTHOR]