LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling.

BACKGROUND: Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). METHODS: LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH+) and non-BCSC (ALDH-). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. RESULTS: LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. CONCLUSIONS: Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer.

Electromagnetic forming of AA1060 sheet based on mixed forces generated by a three-coil dual-power system.

The electromagnetic force used in electromagnetic forming is mainly divided into attraction and repulsion. Dual-coil attractive electromagnetic forming can be used in the field of sheet pit repair. However, the magnetic field and eddy current generated by the two coils compete with each other, and the energy utilization rate is low. Therefore, a compensation coil is introduced, and an electromagnetic forming scheme of a three-coil dual-power sheet based on mixed force is proposed and verified by simulation. It is found that the three-coil mixed force can effectively improve the competition between the magnetic field and eddy current. The loading of the mixing force is not a simple superposition of attraction and repulsion, but the mutual promotion of the two. The forming displacement of the three-coil mixed force forming scheme is 582% higher than that of the dual-coil attraction forming scheme, and 89% higher than that of the attract first and then repel forming scheme. The forming effect of the three-coil mixing force is related to the number of turns of the compensation coil. The research results can improve the energy utilization rate of electromagnetic forming and provide a new idea for the loading scheme of electromagnetic forming force field.

Target and Semitarget Analysis of Advanced Glycation End Products Using a New Pair of Permanently Positively Charged Stable Isotope Labeling Agents.

A pair of positively charged stable isotope labeling (SIL) agents, (4-carbonochloridoylphenyl)-trimethylazanium iodide (d0-CCPTA) and d6-CCPTA, were designed and synthesized. These agents were employed in the precolumn labeling of advanced glycation end products (AGEs) within 5 min under mild conditions. Through derivatization, the mass spectrometry response of the AGEs was enhanced by approximately 2 orders of magnitude. The detection and quantitation limits were in the ranges of 3.1-7.1 and 10.0-23.7 ng/kg, respectively. The recoveries were in the range of 90.1-94.3%, and the matrix effect ranged from -6.6 to -3.5%. CCPTA produced "CCPTA-specific production ions", and all analytes were analyzed by common multiple reaction monitoring (MRM) parameters. The common MRM parameters were applied to the semitarget analysis of 41 types of AGE candidates in the absence of standards, with 13 AGEs identified.

Covalent conjugation of Inca peanut albumin and polyphenols with different phenolic hydroxyl numbers through laccase catalysis to improve functional properties.

BACKGROUND: Enzymatic crosslinking is a method that can be used to modify Inca peanut albumin (IPA) using polyphenols, and provides desirable functionalities; however, the effect of polyphenol structures on conjugate properties is unclear. In this study, we selected four polyphenols with different numbers of phenolic hydroxyl groups [para-hydroxybenzoic acid (HBA), protocatechuic acid (PCA), gallic acid (GA), and epigallocatechin gallate (EGCG)] for covalent modification of IPA by enzymatic crosslinking, and explored the structure-function changes of the IPA-polyphenol conjugates. RESULTS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis showed that laccase successfully promoted covalent crosslinking of IPA with polyphenols, with the order of degree of conjugation as EGCG > GA > PCA > HBA, the IPA-EGCG conjugate showed the highest polyphenol binding equivalents (98.35 g kg-1 protein), and a significant reduction in the content of free amino, sulfhydryl, and tyrosine group. The oxidation of polyphenols by laccase forms quinone or semiquinone radicals that are covalently crosslinked to the reactive groups of IPA, leading to significant changes in the secondary and tertiary structures of IPA, with spherical structures transforming into dense lamellar structures. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability and emulsification stability of IPA-EGCG conjugates improved by almost 6-fold and 2.7-fold, respectively, compared with those of unmodified IPA. CONCLUSION: These data suggest that the higher the number of polyphenol hydroxyl groups, the higher the degree of IPA-polyphenol conjugation; additionally, enzymatic crosslinking can significantly improve the functional properties of IPA. © 2024 Society of Chemical Industry.

Recent advances in the authentication (geographical origins, varieties and aging time) of tangerine peel (Citri reticulatae pericarpium): A review.

The consumption of tangerine peel (Citri reticulatae pericarpium, CRP) has been steadily increasing worldwide due to its proven health benefits and sensory characteristics. However, the price of CRP varies widely based on its origin, variety, and aging time, which has led many manufacturers to offer inferior products by exploiting the sensory similarity of CRP, seriously undermining consumers' interests. Therefore, it is essential to identify the authenticity of the CRP. In this study, the research progress on the authenticity of CRP from different origins, years and varieties over the past 10 years and the application and prospects of the main technologies and techniques were reviewed. The advantages and disadvantages of the commonly used methods were also summarized and compared. Mass spectrometry-based and spectroscopy-based techniques are the most commonly used methods for analyzing CRP authenticity. However, designing fast, non-destructive and green methods for identifying CRP authenticity would be the future trend.

A stretchable wearable sensor with dual working electrodes for reliable detection of uric acid in sweat.

Wearable sweat sensors with stretch capabilities and robust performances are desired for continuous monitoring of human health, and it remains a challenge for sweat sensors to detect targets reliably in both static and dynamic states. Herein, a flexible sweat sensor was created using a cost-effective approach involving the utilization of three-dimensional graphene foam and polydimethylsiloxane (PDMS). The flexible electrochemical sensor was fabricated based on PDMS and Pt/Pd nanoparticles modified 3D graphene foam for the detection of uric acid in sweat. Pt/Pd nanoparticles were electrodeposited on the graphene foam to markedly enhance the electrocatalytic activity for uric acid detection. The graphene foam with excellent electrical property and high porosity, and PDMS with an ideal mechanical property endow the sensing device with high stretchability (tolerable strain up to 110 %), high sensitivity (0.87 µA µM-1 cm-2), and stability (remaining unchanged for more than 5000 cycles) for daily wear. To eliminate possible interferences, the wearable sensor was designed with dual working electrodes, and their response difference ensured reliable and accurate detection of targets. This strategy of constructing sweat sensors with dual working electrodes based on the flexible composite material represents a promising way for the development of robust wearable sensing devices.

In Situ Fe-Substituted Hexacyanoferrate for High-Performance Aqueous Potassium Ion Batteries.

The eco-friendliness, safety, and affordability of aqueous potassium batteries (AKIBs) have made them popular for large-scale energy storage devices. However, the cycling and rate performance of research materials, particularly cobalt hexacyanoferrate, have yet to meet satisfactory standards. Herein, a room-temperature drafted K1.66 Fe0.25 Co0.75 [Fe(CN)6 ]·0.83H2 O (KFCHCF) sample is reported using an in situ substitution strategy. A higher concentration of ferrocyanide ions decreases the water content and increases the potassium content, while citric acid works as a chelating agent and is responsible for Fe-substitution in the KFCHCF sample. The resultant KFCHCF sample exhibits good rate performance, and about 97% and 90.6% of discharge capacity are conserved after 400 and 1000 cycles at 100 and 200 mA g-1 , respectively. The full cell using the KFCHCF cathode and 1,4,5,8-naphthalenetetracarboxylic dianhydride-derived polyimide (PNTCDA) anode maintains ≈74.93% and 74.35% of discharge capacity at 200 mA g-1 and 1000 mA g-1 for 1000 and >10,000 cycles, respectively. Furthermore, ex situ characterizations demonstrate the high reversibility of K-ions and structural stability during the charge-discharge process. Such high performance is attributed to the fast K-ion migration and crystal structure stabilization caused by in situ Fe-substitution in the KFCHCF sample. Other hexacyanoferrates can be synthesized using this method and used in grid-scale storage systems.

Differences in the structural properties of three OSA starches and their effects on the performance of high internal phase Pickering emulsions.

The emulsifying properties of emulsions are significantly influenced by the structural properties of octenyl succinic anhydride (OSA) starch. The purpose of this work was to elucidate the effect of the structure of OSA starch on its performance as an emulsifier to stabilize Pickering high-internal-phase emulsions (HIPEs). The degrees of substitution (DS) of the three OSA starches were 0.0137, 0.0177 and 0.0236, and their degrees of branching (DB) were 13.96 %, 14.20 % and 14.32 % measured by 1H NMR, which were sequentially labeled as OSA1, OSA2, and OSA3. The OSA3 starch with higher DS and DB had a lower critical micelle concentration (CMC) (0.11 mg/mL). Its emulsification activity (EAI) and emulsion stability (ES) were 61.8 m2/g and 72.5 min, respectively, which were higher than OSA1 and OSA2 starches. The contact angle of the three OSA starches increased from 45.35° to 80.03° with increasing DS and DB. Therefore, it is hypothesized that OSA3 starches have better emulsification properties. The results of physical stability of HIPEs confirmed the above results. These results indicated that DS and DB have a synergistic effect on emulsion properties, and OSA starch with higher DS and DB values were more conducive to the construction of stable HIPEs systems.

Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain.

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.

Comparing the differences of physicochemical properties and volatiles in semi-dry Hakka rice wine and traditional sweet rice wine via HPLC, GC-MS and E-tongue analysis.

This study aimed to explore effects of indica rice addition, rice soaking time and rice soup addition on total sugar and alcohol content of semi-dry Hakka rice wine (HRW) and compare its difference in physicochemical properties and volatiles with traditional sweet rice wine (TSRW) via HPLC, GC-MS and E-tongue. The optimal fermentation conditions of semi-dry HRW were 50 % indica rice addition, 12 h rice soaking time and 85 % rice soup addition. The total sugar (16.13 mg/mL) of semi-dry HRW was significantly lower than that of TSRW (135.79 mg/mL), especially the trehalose, glucose, sucrose and maltose. Its alcohol content was significantly higher than that of TSRW. There were significant differences in volatile components between semi-dry HRW and TSRW, especially esters, alcohols and ketones, but no significant differences in organic acids and amino acids. Results obtained could provide reference data for improving the fermentation process and quality of semi-dry HRW.

The Numerical Analysis of Force and Comparison of Pulse Magnet and Electromagnetic Forming Coil.

As an important energy conversion component in electromagnetic-forming technology, the coil is subjected to great internal stress and is easy to break. The geometric structure and winding process of the forming coil draw on the research results of pulsed magnets. However, the two use conditions are different. It is very important to clarify the force difference between the two for the design of the forming coil. In this paper, the numerical model of an aluminum alloy (AA1060-O) is established, and the difference in force between the pulse magnet and forming coil with the same size in time and space under different working conditions is analyzed. A two-dimensional fully coupled finite element model consisting of circuit, magnetic field, and solid mechanics is established and used to determine the key parts of the coil force. It is found that the von Mises stress of the forming coil is greater than that of the pulsed magnet under the same circuit parameters and geometric structure. In the electromagnetic forming of the tube, the glass fiber is subjected to a large stress. In addition, the stress of glass fiber under the condition of tube necking is about 2 times that of pulsed magnet. When the voltage is increased, the failure of the middle part of the glass fiber causes the coil to break. In the electromagnetic forming of the sheet, the coil skeleton is subjected to large stress, and its upper end failure causes the coil to break. Therefore, new design ideas for forming coils under different working conditions are proposed.

Comparison Study of the Physicochemical Properties, Amino Acids, and Volatile Metabolites of Guangdong Hakka Huangjiu.

The physicochemical properties, amino acids, and volatile metabolites of 20 types of Guangdong Hakka Huangjiu were systematically compared in this study. Lower sugar contents were detected in LPSH, ZJHL-1, and GDSY-1, but the total sugar contents of the other types of Guangdong Hakka Huangjiu were more than 100 g/L (which belonged to the sweet type). Among them, a lower alcohol content was found in GDSY-1 (8.36 %vol). There was a significant difference in the organic acid and amino acid composition among the 20 Guangdong Hakka Huangjiu samples, especially the amino acid composition. However, bitter amino acids as the major amino acids accounted for more than 50% of the total amino acids. A substantial variation in volatile profiles was also observed among all types of Guangzhou Hakka Huangjiu. Interestingly, MZSK-1 had different volatile profiles from other Guangzhou Hakka Huangjiu samples. According to gas chromatography olfactometry (GC-O), most of the aroma-active ingredients identified in Guangdong Hakka Huangjiu were endowed with a pleasant aroma of "fruity".

sTRBC1 and cyTRBC1 Expression Distinguishes Indolent T-Lymphoblastic Proliferations From T-Lymphoblastic Leukemia/Lymphoma.

Indolent T-lymphoblastic proliferation (iT-LBP) consists of a proliferation of non-neoplastic TdT + T cells in extrathymic tissues, requiring no treatment. However, due to overlapping clinical and histologic features, distinguishing iT-LBP from T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) can be challenging. Recently, flow cytometry-based evaluation of TRBC1 has been used to detect of T-cell clonality in TCRαß + mature T-cell lymphomas and aid in the differential diagnosis between T-ALL and normal thymocytes. We present a case of iT-LBP with high-grade serous ovarian carcinoma (HGSOC). To investigate the potential utility of TRBC1 expression in distinguishing iT-LBP from T-ALL/LBL, we assessed both surface (s) and cytoplasmic (cy) TRBC1 expression patterns on blast cells from the patient with iT-LBP and HGSOC as well as 11 patients diagnosed with T-ALL/LBL. The results revealed that sTRBC1 and cyTRBC1 exhibited polytypic expression patterns in patient with iT-LBP and HGSOC, while cyTRBC1 showed monotypic expression in those with T-ALL/LBL. This suggests that evaluation of sTRBC1 and cyTRBC1 expression can serve as a simple, rapid, and effective approach to differentiate between iT-LBP and T-ALL/LBL.

Phosphorylation of Oligopeptides: Design of Ultra-Hydrophilic Zwitterionic Peptides for Anti-Fouling Detection of Nucleic Acids in Saliva.

The construction of low-fouling biosensors for assaying biomarkers in complex biological samples remains a challenge, and the key limitation is the lack of effective anti-fouling materials. Inspired by the biomimetic process of protein phosphorylation, we herein designed a new phosphorylated peptide modified with the dihydrogen phosphate (-PO4H2) group, which significantly increased the hydrophilicity and anti-fouling capability of the peptide when compared with natural and normal peptides. Molecular simulation (MS) illustrated that, compared with the -COOH and -NH2 groups, the -PO4H2 group formed the most numbers of hydrogen bonds and stronger hydrogen bonds with water molecules. As a result, the PO4H2-oligopeptide was proved by MS to be able to attract the greatest number of water molecules, so as to form a compact layer of H2O to resist further adsorption of nonspecific biomolecules. The modification of electrodes with the designed PO4H2-oligopeptides, in addition to the adoption of neutral peptide nucleic acids (PNAs) as the sensing probes, ensured the fabrication of anti-fouling electrochemical biosensors capable of detecting nucleic acids in complex saliva. The constructed anti-fouling biosensor was able to detect the nucleic acid of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in undiluted saliva, with a wide linear response range (0.01 pM-0.01 µM) and a low limit of detection (LOD) of 3.4 fM (S/N = 3). The phosphorylation of oligopeptides offers an effective strategy to designing ultra-hydrophilic peptides suitable for the construction of promising anti-biofouling biosensors and bioelectronics.

Targeting TRIM24 promotes neuroblastoma differentiation and decreases tumorigenicity via LSD1/CoREST complex.

PURPOSE: High-risk neuroblastoma (NB) still has an unfavorable prognosis and inducing NB differentiation is a potential strategy in clinical treatment, yet underlying mechanisms are still elusive. Here we identify TRIM24 as an important regulator of NB differentiation. METHODS: Multiple datasets and clinical specimens were analyzed to define the role of TRIM24 in NB. The effects of TRIM24 on differentiation and growth of NB were determined by cell morphology, spheres formation, soft agar assay, and subcutaneous xenograft in nude mice. RNA-Seq and qRT-PCR were used to identify genes and pathways involved. Mass spectrometry and co-immunoprecipitation were used to explore the interaction of proteins. RESULTS: Trim24 is highly expressed in spontaneous NB in TH-MYCN transgenic mice and clinical NB specimens. It is associated with poor NB differentiation and unfavorable prognostic. Knockout of TRIM24 in neuroblastoma cells promotes cell differentiation, reduces cell stemness, and inhibits colony formation in soft agar and subcutaneous xenograft tumor growth in nude mice. Mechanistically, TRIM24 knockout alters genes and pathways related to neural differentiation and development by suppressing LSD1/CoREST complex formation. Besides, TRIM24 knockout activates the retinoic acid pathway. Targeting TRIM24 in combination with retinoic acid (RA) synergistically promotes NB cell differentiation and inhibits cell viability. CONCLUSION: Our findings demonstrate that TRIM24 is critical for NB differentiation and suggest that TRIM24 is a promising therapeutic target in combination with RA in NB differentiation therapy.

Ion Pre-Embedding Engineering of δ-MnO2 for Chemically Self-Charging Aqueous Zinc Ions Batteries.

Aqueous zinc ion batteries (ZIBs), especially those with self-charging properties, have been promisingly developed in recent years. Yet, most inorganic materials feature high redox potential, which limit their development in the self-charging field. To achieve this target, by pre-embedding potassium ions into δ-MnO2 to reduce the energy barrier in oxygen adsorption, the first application of MnO2 in self-charging ZIBs is realized. The design features a facile two-electrode configuration with no excessively complex component to allow for energy storage and conversion. Due to the voltage difference between the oxygen in the air and the discharge products, a redox reaction can be carried out spontaneously to realize the self-charging process. After the chemical self-charging process, the Zn-K0.37 MnO2 ·0.54H2 O/C cell achieves an open circuit voltage of around 1.42 V and a discharge capacity of 201 mAh g-1 , reflecting the promising self-charging capability. Besides, the chemically self-charging ZIBs operate well in multiple modes of constant current charge/discharge/chemical charging. And decent cycling capability can also be achieved at extreme temperatures and high mass loading. This work promotes the development of ZIBs and further broadens the application of inorganic metal oxides in the self-charging systems.

Clinical Outcomes After Cranioplasty With Titanium Mesh, Polyetheretherketone, or Composite Bone Cement: A Retrospective Study.

Cranioplasty is a common neurosurgical procedure; however, the optimal material choice remains controversial. At the time of this writing, autologous bone, the preferred choice for primary cranioplasty, has a high incidence of complications such as infection and resorption, thus requiring frequent use of synthetic materials. Therefore, this study aimed to compare the clinical benefits of titanium mesh (Ti), polyetheretherketone (PEEK), and composite bone cement (CBC) in cranioplasty to provide a clear selection basis for clinicians and patients. This study retrospectively collected data from 207 patients who underwent cranioplasty with Ti (n=129), PEEK (n=54), and CBC (n=24) between January 2018 and December 2020 at Henan Provincial People's Hospital. Postoperative follow-up information after 6 months was used to compare the long-term effects of the 3 materials on the patients. There were no significant differences in the overall complication rate after cranioplasty among the 3 materials. However, subcutaneous effusion was more frequent with PEEK (24.07%) and CBC (20.83%) than with Ti (2.33%). Second, there were no significant differences in the increase in Glasgow Outcome Scale and Karnofsky Performance Status scores after cranioplasty among the 3 materials. Finally, we found that PEEK had the highest patient satisfaction and hospitalization cost, whereas the opposite was true for Ti. Although the surgical outcomes of the 3 implant materials were similar, an examination of clinical outcomes such as patient satisfaction showed significant differences, deepening people's perceptions of the 3 materials.

High Expression of Triggering Receptor Expressed on Myeloid Cells 1 Predicts Poor Prognosis in Glioblastoma.

Background: Glioblastoma (GBM) is a highly malignant tumor with poor prognosis, and new treatment strategies are urgently needed. Currently, the role of triggering receptor expressed on myeloid cells 1 (TREM-1) in tumors has been studied, but the role of TREM-1 in GBM remains unclear. Methods: Immunohistochemical staining for TREM-1 was performed in 91 patients diagnosed with GBM. Clinicopathological characteristics and survival times were recorded. TREM-1 expression and its effect on prognosis were analyzed using online Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA) databases. The expression profile of TCGA-GBM cohort was used to perform functional enrichment analysis. The CIBERSORT method and Tumor Immune Estimation Resource (TIMER) database were used to estimate the tumor-infiltrating immune cells (TIICs). The ESTIMATE algorithm was used to estimate the immune-stromal scores. Finally, the relationships of TREM-1 with TIICs, immune-stromal score, and immune checkpoint genes (ICGs) were analyzed. Results: The expression of TREM-1 was upregulated in GBM, and high TREM-1 expression predicted a poor prognosis. TREM-1, surgical resection, postoperative radiotherapy, and temozolomide (TMZ) chemotherapy were associated with the survival time of patients with GBM, but only surgical resection and TREM-1 expression were independent prognostic factors. GBM with high TREM-1 expression exhibited increased neutrophil and macrophage infiltration. TREM-1 was positively associated with the immune-stromal score and multiple ICGs, and most of which were involved in immunosuppressive responses. Conclusion: The present study revealed that high expression of TREM-1 in GBM is an independent poor prognosis factor and that TREM-1 is associated with the immunosuppressive microenvironment. Thus, blocking TREM-1 may be a strategy for enhancing the GBM immune response.