Sodium halide solid state electrolyte of Na3YBr6 with low activation energy.

Halide solid-state electrolytes (SSEs) are considered promising candidates for practical applications in all-solid-state batteries (ASSBs), due to their outstanding high voltage stability and compatibility with electrode materials. However, Na+ halide SSEs suffer from low ionic conductivity and high activation energy, which limit their applications in sodium all-solid-state batteries. Here, sodium yttrium bromide solid-state electrolytes (Na3YBr6) with a low activation energy of 0.15 eV is prepared via solid state reaction. Structure characterization using X-ray diffraction reveals a monoclinic structure (P21/c) of Na3YBr6. First principle calculations reveal that the low migration activation energy comes from the larger size and vibration of Br- anions, both of which expand the Na+ ion migration channel and reduce its activation energy. The electrochemical window of Na3YBr6 is determined to be 1.43 to 3.35 V vs. Na/Na+, which is slightly narrower than chlorides. This work indicates bromides are a good catholyte candidate for sodium all solid-state batteries, due to their low ion migration activation energy and relatively high oxidation stability.

Macromolecular Nano-Assemblies for Enhancing the Effect of Oxygen-Dependent Photodynamic Therapy Against Hypoxic Tumors.

In oxygen (O2)-dependent photodynamic therapy (PDT), photosensitizers absorb light energy, which is then transferred to ambient O2, and subsequently cytotoxic singlet oxygen (1O2) is generated. Therefore, the availability of O2 and the utilization efficiency of generated 1O2 are two significant factors that influence the effectiveness of PDT. However, tumor microenvironments (TMEs) characterized by hypoxia and limited utilization efficiency of 1O2 resulting from its short half-life and short diffusion distance significantly restrict the applicability of PDT for hypoxic tumors. To address these challenges, numerous macromolecular nano-assemblies (MNAs) have been designed to relieve hypoxia, utilize hypoxia or enhance the utilization efficiency of 1O2. Herein, we provide a comprehensive review on recent advancements achieved with MNAs in enhancing the effectiveness of O2-dependent PDT against hypoxic tumors.

Downregulation of VEGFA accelerates AGEs-mediated nucleus pulposus degeneration through inhibiting protective mitophagy in high glucose environments.

Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD.

The RING Domain of Rice HEI10 is Essential for Male, But Not Female Fertility.

HEI10 is a conserved E3 ubiquitin ligase involved in crossover formation during meiosis, and is thus essential for both male and female gamete development. Here, we have discovered a novel allele of HEI10 in rice that produces a truncated HEI10 protein missing its N-terminal RING domain, namely sh1 (shorter hei10 1). Unlike previously reported hei10 null alleles that are completely sterile, sh1 exhibits complete male sterility but retains partial female fertility. The causative sh1 mutation is a 76 kb inversion between OsFYVE4 and HEI10, which breaks the integrity of both genes. Allelic tests and complementation assays revealed that the gamete developmental defects of sh1 were caused by disruption of HEI10. Further studies demonstrated that short HEI10 can correctly localise to the nucleus, where it could interact with other proteins that direct meiosis; expressing short HEI10 in hei10 null lines partially restores female fertility. Our data reveal an intriguing mutant allele of HEI10 with differential effects on male and female fertility, providing a new tool to explore similarities and differences between male and female meiosis.

Curcuminoids Modulated the IL-6/JAK/STAT3 Signaling Pathway in LoVo and HT-29 Colorectal Cancer Cells.

BACKGROUND: Curcuminoids, including curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin, are natural polyphenolic compounds that exhibit various biological properties, such as antioxidant, anti-inflammatory, and anticancer activities. Dysregulation of the interleukin (IL)-6-mediated Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway is closely associated with the development of colorectal cancer (CRC). METHODS: Here, we have evaluated the modulation of the IL-6/JAK/STAT3 pathway of curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin in LoVo and HT-29 colorectal cancer cells with a single molecular array (Simoa), western blot analysis, real-time polymerase chain reaction (PCR), and pathway analysis system. RESULTS: The study showed that curcuminoids suppressed the amount of IL-6 in LoVo and HT-29 colorectal cancer cells. Meanwhile, curcuminoids inhibited the expression of inflammation regulator-related microRNA (miRNA). We also found that the expression of total STAT3 was downregulated by curcuminoids. Moreover, the pathway analysis system showed that curcuminoids inactivated the JAK/STAT3 signaling pathway. Taken together, we demonstrated that the anti-cancer activities of curcuminoids against colorectal cancer are due to the modulation of the IL-6/JAK/STAT3 cascade. CONCLUSION: Curcuminoids could be a promising anti-cancer agent for the treatment of human colorectal cancer.

Single-Cell Diagnosis of Cancer Drug Resistance through the Differential Endocytosis of Nanoparticles between Drug-Resistant and Drug-Sensitive Cancer Cells.

Single-cell diagnosis of cancer drug resistance is highly relevant for cancer treatment, as it can be used to identify the subpopulations of drug-resistant cancer cells, reveal the sensitivity of cancer cells to treatment, and monitor the progress of cancer drug resistance. However, simple and effective methods for cancer drug resistance detection at the single-cell level are still lacking in laboratory and clinical studies. Inspired by the fact that nanoparticles with diverse physicochemical properties would generate distinct and specific interactions with drug-resistant and drug-sensitive cancer cells, which have distinctive molecular signatures, here, we have synthesized a library of fluorescent nanoparticles with various sizes, surface charges, and compositions (SiO2 nanoparticles (SNPs), organic PS-co-PAA nanoparticles (ONPs), and ZIF-8 nanoparticles (ZNPs)), thus demonstrating that the composition has a critical influence on the interaction of nanoparticles with drug-resistant cancer cells. Furthermore, the clathrin/caveolae-independent endocytosis of ZNPs together with the P-glycoprotein-related decreased cell membrane fluidity resulted in a lower cellular accumulation of ZNPs in drug-resistant cancer cells, consequently causing the distinct cellular accumulation of ZNPs between the drug-resistant and drug-sensitive cancer cells. This difference was further quantified by detecting the fluorescence signals generated by the accumulation of nanoparticles at the single-cell level via flow cytometry. Our findings provide another insight into the nanoparticle-cell interactions and offer a promising platform for the diagnosis of cancer drug resistance of various cancer cells and clinical cancer samples at the single-cell level.

Roles of MT-ND1 in Cancer.

The energy shift toward glycolysis is one of the hallmarks of cancer. Complex I is a vital enzyme complex necessary for oxidative phosphorylation. The mitochondrially encoded NADH: ubiquinone oxidoreductase core subunit 1 (MT-ND1) is the largest subunit coded by mitochondria of complex I. The present study summarizes the structure and biological function of MT-ND1. From databases and literature, the expressions and mutations of MT-ND1 in a variety of cancers have been reviewed. MT-ND1 may be a biomarker for cancer diagnosis and prognosis. It is also a potential target for cancer therapy.

Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles.

Knee osteoarthritis (KOA) is one of the most commonly encountered degenerative diseases of the joints in people over 45 years of age. Currently, there are not any effective therapeutics for KOA,and the only end-point strategy is total knee arthroplasty (TKA); therefore, KOA is associated with economic burdens and societal costs. The immune inflammatory response is involved in the occurrence and development of KOA. We previously established a mouse model of KOA using type II collagen. Hyperplasia of the synovial tissue was present in the model, alongside a large number of infiltrated inflammatory cells. Silver nanoparticles have substantial anti-inflammatory effects and have been widely used in tumor therapy and surgical drug delivery. Therefore, we evaluated the therapeutic effects of silver nanoparticles in a collagenase II-induced KOA model. The experimental results showed that silver nanoparticles significantly reduced synovial hyperplasia and the infiltration of neutrophils in the synovial tissue. Hence, this work demonstrates the identification of a novel strategy for OA and provides a theoretical basis for preventing the progress of KOA.

Poly-l-lactide-co-ε-caprolactone (PLCL) and poly-l-lactic acid (PLLA)/gelatin electrospun subacromial spacer improves extracellular matrix (ECM) deposition for the potential treatment of irreparable rotator cuff tears.

Biodegradable subacromial spacer implantation has become practicable for the treatment of irreparable rotator cuff tears (IRCT). However, the relative high degradation rate and inferior tissue regeneration properties of current subacromial spacer may lead to failure regards to long-term survival. It is reported that satisfactory clinical results lie in the surrounding extracellular matrix (ECM) deposition after implantation. This study aims to develop a biological subacromial spacer that would enhance tissue regeneration properties and results in better ECM deposition. Physicochemical properties were characterized on both poly-l-lactide-co-ε-caprolactone (PLCL) dip-coating spacer (monolayer spacer, MS) and PLCL dip-coating + Poly-l-Lactic Acid (PLLA)/Gelatin electrospun spacer (Bilayer Spacer, BS). Cytocompatibility, angiogenesis, and collagen inducibility were evaluated with tendon fibroblasts and endothelial cells. Ultrasonography and histomorphology were used to analyze biodegradability and surrounding ECM deposition after the implantation in vivo. BS was successfully fabricated with the dip-coating and electrospinning technique, based on the human humeral head data. In vitro studies demonstrated that BS showed a greater cytocompatibility, and increased secretion of ECM proteins comparing to MS. In vivo studies indicated that BS promoted ECM deposition and angiogenesis in the surrounding tissue. Our research highlights that BS exhibits better ECM deposition and reveals a potential candidate for the treatment of IRCT in future.

Molecular fingerprints of nuclear genome and mitochondrial genome for early diagnosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with high morbidity and mortality rates. Due to the heterogeneity of LUAD, its characteristics remain poorly understood. Exploring the clinical and molecular characteristics of LUAD is challenging but vital for early diagnosis. METHODS: This observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed. RESULTS: This study identified a spectrum of nuclear and mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with diagnosis. The correlation coefficient for somatic mutations in cfDNA and patient-matched tumor tissues was high in nuclear and mitochondrial genomes. The mutation number of highly mutated genes was evaluated, and the Least Absolute Shrinkage and Selection Operator (LASSO) established a diagnostic model. Receiver operating characteristic (ROC) curve analysis explored the diagnostic ability of the two panels. All models were verified in the testing cohort, and the mtDNA panel demonstrated excellent performance. This study identified somatic mutations in the nuclear and mitochondrial genomes, and detecting mutations in cfDNA displayed good diagnostic performance for early-stage LUAD. Moreover, detecting somatic mutations in the mitochondria may be a better tool for diagnosing early-stage LUAD. CONCLUSIONS: This study identified specific and sensitive diagnostic biomarkers for early-stage LUAD by focusing on nuclear and mitochondrial genome mutations. This also further developed an early-stage LUAD-specific mutation gene panel for clinical utility. This study established a foundation for further investigation of LUAD molecular pathogenesis.

Electrochemical behaviors of Li-B alloys in a LiCl-LiBr-KBr molten salt system.

Li-B alloys present higher voltages and better power performances than those of conventional Li-Al and Li-Si anodes for thermal batteries. Herein, the electrochemical characteristics of the Li-B alloy in the LiCl-LiBr-KBr electrolyte, including the discharge mechanism, charge transfer coefficient and exchange current density, were investigated in the temperature range of 623-823 K by open circuit potential (OCP), cyclic voltammetry (CV), chronopotentiometry (CP), linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) techniques. Consequently, the OCP of the Li-B alloy in the LiCl-LiBr-KBr electrolyte is close to that of pure lithium at the investigated temperatures. The discharge of the Li-B alloy electrode includes electrochemical dissolution of free lithium (Li → Li+) and compounded lithium (LiB → Li+ + B). The charge transfer coefficient in the anodic direction (Li → Li+) is about 0.63 at 623 K, which slightly increases as the temperature increases. The exchange current density of the Li (Li-B)/Li+ couple determined by the EIS method increases from 3.84 A cm-2 to 8.40 A cm-2 when the temperature increases from 623 to 823 K, corresponding to an activation energy of 16.4 kJ mol-1. These results suggest that the Li-B anode allows ultrahigh-rate discharge in thermal batteries.

Codon usage bias regulates gene expression and protein conformation in yeast expression system P. pastoris.

BACKGROUND: Protein synthesis is one of the extremely important anabolic pathways in the yeast expression system Pichia pastoris. Codon optimization is a commonly adopted strategy for improved protein expression, although unexpected failures did appear sometimes waiting for further exploration. Recently codon bias has been studied to regulate protein folding and activity in many other organisms. RESULTS: Here the codon bias profile of P. pastoris genome was examined first and a direct correlation between codon translation efficiency and usage frequency was identified. By manipulating the codon choices of both endogenous and heterologous signal peptides, secretion abilities of N-terminal signal peptides were shown to be tolerant towards codon changes. Then two gene candidates with different levels of structural disorder were studied, and full-length codon optimization was found to affect their expression profiles differentially. Finally, more evidences were provided to support possible protein conformation change brought by codon optimization in structurally disordered proteins. CONCLUSION: Our results suggest that codon bias regulates gene expression by modulating several factors including transcription and translation efficiency, protein folding and activity. Because of sequences difference, the extent of affection may be gene specific. For some genes, special codon optimization strategy should be adopted to ensure appropriate expression and conformation.

Gene expression profiling of early Parkinson's disease patient reveals redox homeostasis.

Parkinson's disease (PD) is slowly progressive. Due to the lack of specific and sensitive biomarkers, the majority of PD patients are in the advanced stages when diagnosed. This study aimed to investigate biomarkers for early PD diagnosis. We first selected differential mRNAs by analysis of a Gene Expression Omnibus (GEO) data set. Next, we performed RNA sequencing to select differential mRNAs. After an integrated analysis of GEO and RNAseq data, we identified the PD early diagnosis biomarkers associated with oxidative stress. By function analysis, cellular response to hormone stimulus and response to the oxygen-containing compound was involved in the top Gene Set Enrichment Analysis (GSEA)s of the two cohorts. Moreover, SOCS7 was included in these GSEAs coincidentally. Further, by analyzing SOCS7 and its physical interactors, we found they mainly participate in immunity and redox homeostasis related processes, which might play a significant role in PD. Thus, our results suggest SOCS7 might be the potential diagnostic marker for PD.

Quantitative detection of circulating MT-ND1 as a potential biomarker for colorectal cancer.

Liquid biopsy represents a diagnostic and monitoring tool and the circulating cell-free mitochondrial DNA (mtDNA) plays a vital role in tumor diagnosis and dynamic assessment. Colorectal cancer (CRC) is one of the most common fatal cancers worldwide. Mitochondrially encoded NADH dehydrogenase subunit 1 (MT-ND1) encodes the biggest subunit of respiratory complex I of mtDNA, and mutations in the MT-ND1 are common in CRC. We sought to determine if mutations in circulating MT-ND1 could be a potential biomarker for colorectal cancer. In this study, twenty-two CRC patients at Zhujiang Hospital were included. We mainly used droplet digital PCR to determine the mutation status of MT-ND1, combined with clinical data. In the experiment in vivo, cell-free mtDNA generally presented high concordance with tumor tissues. By quantitative PCR, the MT-ND1 content of plasma in CRC patients was significantly higher than that in healthy individuals (58.01 vs. 0.64, p=0.027). The detection of circulating MT-ND1 content and variants (m.3606 A>G, m.3970 C>T, m.4071 C>T, m.4086 C>T) in cfDNA showed a good correlation with predicted tumor response and progression to chemotherapy. In conclusion, the content and variants of circulating MT-ND1 may become a versatile tool for the diagnosis and monitoring of colorectal cancer.

Dual-probe fluorescent biosensor based on T7 exonuclease-assisted target recycling amplification for simultaneous sensitive detection of microRNA-21 and microRNA-155.

Effective and simultaneous monitoring of the abnormal expression of certain microRNAs (miRNAs), especially for miRNA-21 and miRNA-155, can indicate drug resistance in lung cancer. In this work, T7 exonuclease (T7 Exo)-assisted target recycling amplification coupled with the extensive fluorescence quenching of graphene oxide (GO) was designed for the simultaneous detection of miRNA-21 and miRNA-155 using FAM- and ROX-labeled single-strand DNA probes. Through this method, the variable emission intensities of FAM and ROX caused by the introduction of miRNA-21 and miRNA-155, respectively, were obtained with high sensitivity. The method exhibited excellent analytical performance for simultaneous detection of miRNA-21 and miRNA-155 without cross-interference. The linear range was from 0.005 nM to 5 nM over three orders of magnitude, with detection limits as low as 3.2 pM and 4.5 pM for miRNA-21 and miRNA-155, respectively. Furthermore, the recovery (92.49-103.67%) and relative standard deviation (RSD < 4.8%) of the standard addition test of miRNA-21 and miRNA-155 in human plasma suggested the potential for drug resistance warning in clinical practice via this simple strategy. A homogeneous T7 Exo-assisted signal amplification combined with GO quenching platform was developed for accurate, sensitive and simultaneous analysis of miRNA-21 and miRNA-155 for drug resistance warning in lung cancer. This simple method exhibited a wide linear range and low LODs for miR-21 and miR-155.

Investigation of the dissolution and diffusion properties of interstitial oxygen at grain boundaries in body-centered-cubic iron by the first-principles study.

Oxidation corrosion of steel is a universal problem in various industries and severely accelerated in nuclear reactors. First-principles calculations are performed to explore the dissolution and diffusion properties of interstitial oxygen in the body-centered-cubic iron grain boundaries Σ3〈110〉(111) and Σ5〈001〉(310). Solution energies indicate that interstitial oxygen atoms prefer to dissolve in body-centered-cubic iron, and energetically segregate to grain boundaries. Energy barriers show that oxygen atoms would segregate towards Σ3〈110〉(111) with a low energy barrier. However, they concentrate to the transition region of Σ5〈001〉(310) due to the high-energy barrier in the transition zone. When O atoms arrive at grain boundaries, they would stay there due to the larger solution energy and diffusion energy barrier in grain boundaries compared to that in the defect-free Fe bulk. These results indicate that O atoms would prefer to diffuse through the bulk, and oxidize grain boundaries. This study provides insight into oxidation phenomena in experiments and necessary parameters for future studies on the oxidation of steel under irradiation in nuclear reactors.

Rapid Determination of 7-Hydroxycoumarin Using a Nanogold/Poly-thionine Modified Glass Carbon Electrode.

This paper presents a novel voltametric procedure for 7-hydroxycoumarin determination by using a nanogold/poly-thionine modified electrode. The characterization of nanomaterials has been conducted by scanning electron microscopy (SEM) and electrochemical methods. The electrochemical sensing of 7-hydroxycoumarin was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). By combining the excellent electrocatalytic property of nanogold and polymer materials, this sensor shows an improved electrochemical response for 7-hydroxycoumarin detection with a good linear relationship in the range of 5.0 × 10-6 - 3.0 × 10-5 mol L-1; the detection limit was 1.0 × 10-6 mol L-1. This method solves the problem that 7-hydroxycoumarin cannot be accurately quantified on a bare glassy carbon electrode, and also improves the detection sensitivity. This is expected to play a huge potential in the quantitative analysis of quality control, plasma concentration monitoring and mechanism research in vivo of this drug.

Immune-associated biomarkers for early diagnosis of Parkinson's disease based on hematological lncRNA-mRNA co-expression.

Early stage diagnosis of Parkinson's disease (PD) is challenging without significant motor symptoms. The identification of effective molecular biomarkers as a hematological indication of PD may help improve the diagnostic timeliness and accuracy. In this paper, we analyzed and compared the blood samples of PD and control (CTR) patients to identify the disease-related changes and determine the putative biomarkers for PD diagnosis. Based on the RNA sequencing analysis, differentially expressed genes (DEGs) were identified, and the co-expression network of DEGs was constructed using the weighted correlation network analysis (WGCNA). The analysis leads to the identification of 87 genes that were exclusively regulated in the PD group, whereas 66 genes were significantly increased and 21 genes were significantly decreased in contrast to the control group. The results indicate that the core lncRNA-mRNA co-expression network greatly changes the immune response in PD patients. Specifically, the results showed that PWAR6, LINC00861, AC83843.1, IRF family, IFIT family and CaMK4 may play important roles in the immune system of PD. Based on the findings from this the present study, future research aims at identify novel therapeutic strategies for PD.

Baicalin Represses C/EBPß via Its Antioxidative Effect in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the gradual loss of dopaminergic (DA) neurons in the substantia nigra (SN) and the formation of intracellular Lewy bodies (LB) in the brain, which aggregates α-synuclein (α-Syn) as the main component. The interest of flavonoids as potential neuroprotective agents is increasing due to its high efficiency and low side effects. Baicalin is one of the flavonoid compounds, which is a predominant flavonoid isolated from Scutellaria baicalensis Georgi. However, the key molecular mechanism by which Baicalin can prevent the PD pathogenesis remains unclear. In this study, we used bioinformatic assessment including Gene Ontology (GO) to elucidate the correlation between oxidative stress and PD pathogenesis. RNA-Seq methods were used to examine the global expression profiles of noncoding RNAs and found that C/EBPß expression was upregulated in PD patients compared with healthy controls. Interestingly, Baicalin could protect DA neurons against reactive oxygen species (ROS) and decreased C/EBPß and α-synuclein expression in pLVX-Tet3G-α-synuclein SH-SY5Y cells. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model, the results revealed that treatment with Baicalin improved the PD model's behavioral performance and reduced dopaminergic neuron loss in the substantia nigra, associated with the inactivation of proinflammatory cytokines and oxidative stress. Hence, our study supported that Baicalin repressed C/EBPß via redox homeostasis, which may be an effective potential treatment for PD.