Genomic Profiling Reveals Immune-Related Gene Differences in Lung Cancer Patients Stratified by PD1/PDL1 Expression: Implications for Immunotherapy Efficacy.

Lung cancer remains a leading cause of global cancer-related mortality, and the exploration of innovative therapeutic approaches, such as PD1/PDL1 immunotherapy, is critical. This study leverages comprehensive data from the Cancer Genome Atlas (TCGA) to investigate the differential expression of PD1/PDL1 in lung cancer patients and explores its implications. Clinical data, RNA expression, somatic mutations, and copy number variations of 1017 lung cancer patients were obtained from TCGA. Patients were categorized into high (HE) and low (LE) PD1/PDL1 expression groups based on mRNA levels. Analyses included differential gene expression, functional enrichment, protein-protein interaction networks, and mutational landscape exploration. The study identified 391 differentially expressed genes, with CD4 and PTPRC among the upregulated genes in the HE group. Although overall survival did not significantly differ between HE and LE groups, enrichment analysis revealed a strong association with immunoregulatory signaling pathways, emphasizing the relevance of PD1/PDL1 in immune response modulation. Notably, TP53 mutations were significantly correlated with high PD1/PDL1 expression. This study provides a comprehensive analysis of PD1/PDL1 expression in lung cancer, uncovering potential biomarkers and highlighting the intricate interplay between PD1/PDL1 and the immune response. The identified upregulated genes, including CD4 and PTPRC, warrant further investigation for their roles in the context of lung cancer and immunotherapy. The study underscores the importance of considering molecular heterogeneity in shaping personalized treatment strategies for lung cancer patients. Limitations, such as the retrospective nature of TCGA data, should be acknowledged.

Efficacy and safety of atropine at different concentrations in prevention of myopia progression in Asian children: a systematic review and Meta-analysis of randomized clinical trials.

AIM: To assess the efficacy versus the adverse effects of various concentrations of atropine in the prevention of myopia in Asian children. METHODS: Databases (PubMed, EMBASE, the Cochrane Library and Web of science) were comprehensively searched from inception to April 2022. Types of studies included were randomized clinical trials (RCTs). The published languages were limited to English. Two researchers assessed the quality of included studies independently using Cochrane risk of bias tool based on the Cochrane Handbook for Systematic Reviews of Interventions. Funnel plots and Egger's test were used for detection of publication bias. Meta-analyses were conducted using STATA (version 15.0; StataCorp). RESULTS: A total of 15 RCTs involving 2268 patients were included in the study. In the atropine group, spherical equivalent progressed at a significantly lower rate [weighted mean difference (WMD)=0.39, 95% confidence interval (CI): 0.23, 0.54] than in the control group. A WMD of 0.15 mm was associated with less axial elongation (95%CI -0.19, -0.10). Different doses showed statistically significant differences (P<0.05) and an improved effect could result from a higher concentration. Changes in photopic pupil size and mesopic pupil size in atropine group is 0.70 mm (95%CI: 0.33, 1.06) and 0.38 mm (95%CI: 0.22, 0.54) more than the control group. In the present Meta-analysis, no changes in accommodative amplitude (AA) were associated with atropine administration. Atropine administration increased the risk of adverse effects by 1.37 times. CONCLUSION: Concentrations of less than 1% atropine are able to effectively retard diopter and axis growth of myopia in Asian children in a dose-dependent manner. Meanwhile, it caused pupil enlargement, but induced no change in the AA within this range. Further study is required to determine the dosage needed to achieve maximum efficacy and minimal side effects.

Integrated Transcriptomic and Metabolomic Analyses Uncover the Differential Mechanism in Saline-Alkaline Tolerance between Indica and Japonica Rice at the Seedling Stage.

Saline-alkaline stress is one of the major damages that severely affects rice (Oryza sativa L.) growth and grain yield; however, the mechanism of the tolerance remains largely unknown in rice. Herein, we comparatively investigated the transcriptome and metabolome of two contrasting rice subspecies genotypes, Luohui 9 (abbreviation for Chao2R under study, O. sativa ssp. indica, saline-alkaline-sensitive) and RPY geng (O. sativa ssp. japonica, saline-alkaline-tolerant), to identify the main pathways and important factors related to saline-alkaline tolerance. Transcriptome analysis showed that 68 genes involved in fatty acid, amino acid (such as phenylalanine and tryptophan), phenylpropanoid biosynthesis, energy metabolism (such as Glycolysis and TCA cycle), as well as signal transduction (such as hormone and MAPK signaling) were identified to be specifically upregulated in RPY geng under saline-alkaline conditions, implying that a series of cascade changes from these genes promotes saline-alkaline stress tolerance. The transcriptome changes observed in RPY geng were in high accordance with the specifically accumulation of metabolites, consisting mainly of 14 phenolic acids, 8 alkaloids, and 19 lipids based on the combination analysis of transcriptome and metabolome. Moreover, some genes involved in signal transduction as hub genes, such as PR5, FLS2, BRI1, and NAC, may participate in the saline-alkaline stress response of RPY geng by modulating key genes involved in fatty acid, phenylpropanoid biosynthesis, amino acid metabolism, and glycolysis metabolic pathways based on the gene co-expression network analysis. The present research results not only provide important insights for understanding the mechanism underlying of rice saline-alkaline tolerance at the transcriptome and metabolome levels but also provide key candidate target genes for further enhancing rice saline-alkaline stress tolerance.

Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion.

AIM: To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy (DR) or retinal vein occlusion (RVO). METHODS: This is a retrospective case control study. The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor (VEGF) for patients diagnosed with macular edema secondary to DR (DME) or RVO (RVO-ME) at Xijing Hospital from August 2021 to July 2022. Meanwhile, aqueous humor samples during vitrectomy from patients with idiopathic macular hole (IMH) were also collected and served as controls. The aqueous humor concentrations of VEGF, platelet-derived factor (PDGF), interleukin (IL)-6, IL-8, IL-18, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) were measured with Human Premixed Multi-Analyte Kit (Luminex). The difference of the aqueous cytokines and the correlation between the two diseases were analyzed. RESULTS: A total of 40 eyes of 38 patients were enrolled in the study, including 13 eyes of 11 DME patients (DME group), 16 eyes of 16 RVO-ME patients (RVO-ME group) and 11 eyes of 11 IMH patients (control group). The VEGF, PDGF, IL-6, IL-8, and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group (all P<0.05), the levels of TNF-α was higher in the DME group than in the control group (P<0.05). The VEGF, IL-6, MCP-1, and TNF-α levels in the aqueous humor were significantly higher in the DR group than those in the RVO group (all P<0.05). Correlation analyses revealed that there were complex positive correlations between IL-6, IL-8, IL-18, MCP-1, and TNF-α levels in the aqueous humor of eyes with two diseases. CONCLUSION: Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME, the roles of these factors are more significant or more likely to be activated in DR patients, suggesting different treatment strategies should be considered for the two diseases.

Single Exosome Amperometric Measurements Reveal Encapsulation of Chemical Messengers for Intercellular Communication.

In multicellular organisms, cells typically communicate by sending and receiving chemical signals. Chemical messengers involved in the exocytosis of neuroendocrine cells or neurons are generally assumed to only originate from the fusing of intracellular large dense core vesicles (LDCVs) or synaptic vesicles with the cellular membrane following stimulation. Accumulated evidence suggests that exosomes─one of the main extracellular vesicles (EVs)─carrying cell-dependent DNA, mRNA, proteins, etc., play an essential role in cellular communication. Due to experimental limitations, it has been difficult to monitor the real-time release of individual exosomes; this restricts a comprehensive understanding of the basic molecular mechanisms and the functions of exosomes. In this work, we introduce amperometry with microelectrodes to capture the dynamic release of single exosomes from a single living cell, distinguish them from other EVs, and differentiate the molecules inside exosomes and those secreted from LDCVs. We show that, similar to many LDCVs and synaptic vesicles, exosomes released by neuroendocrine cells also contain catecholamine transmitters. This finding reveals a different mode of chemical communication via exosome-encapsulated chemical messengers and a potential interconnection between the two release pathways, changing the canonical view of exocytosis of neuroendocrine cells and possibly neurons. This defines a new mechanism for chemical communication at the fundamental level and opens new avenues in the research of the molecular biology of exosomes in the neuroendocrine and central nervous systems.

Effect of exercise and antioxidant supplementation on cellular lipid peroxidation in elderly individuals: Systematic review and network meta-analysis.

Background: The viewpoints of previous studies on the correlation between exercise and cellular lipid peroxidation are contradictory from many perspectives and lack evidence for elder individuals. A new systematic review with network meta-analysis is necessary and will have significant practical value to provide high-quality evidence in the development of exercise protocols and an evidence-based guide for antioxidant supplementation for the elderly. Aims: To identify the cellular lipid peroxidation induced by different types of exercise, with or without antioxidant supplementation, in elderly individuals. Methods: Randomized controlled trials that recruited elderly participants and reported cellular lipid peroxidation indicators and were published in peer-reviewed journals in English were searched by a Boolean logic search strategy and screened in the databases PubMed, Medline, Embase, and Web of Science. The outcome measures were the biomarkers of oxidative stress in cell lipids in urine and blood, namely F2-isoprostanes, hydrogen peroxide (LOOH, PEROX, or LIPOX), malondialdehyde (MDA), and thiobarbituric acid reactive substances (TBARS). Result: 7 trials were included. A combination program of aerobic exercise (AE), low-intensity resistance training (LIRT), and a placebo intake (Placebo) and a combination program of aerobic exercise, low-intensity resistance training, and antioxidant supplementation (S) had the most and sub-most potential to dampen cellular lipid peroxidation (AE + LIRT + Placebo: 0.31 in Rank 1 and 0.2 in Rank 2; AE + LIRT + S: 0.19 in Rank 1 and 0.20 in Rank 2); A placebo intake (Placebo) and a blank intervention without exercise (NE) had the most and sub-most potential to induce an enhancement of cellular lipid peroxidation (Placebo: 0.51 in Rank 9 and 0.16 in Rank 8; NE: 0.16 in Rank 9 and 0.28 in Rank 8). All included studies had an unclear risk of selecting reporting. There were no high confidence ratings in all the direct and indirect comparisons, 4 comparisons in the direct evidence structure and 7 comparisons in the indirect evidence structure had moderate confidence. Conclusion: A combined protocol consisting of aerobic exercise and low-intensity resistance training is recommended to dampen cellular lipid peroxidation. Extra antioxidant supplementation might be unnecessary if an elderly individual has enough aerobic and resistance exercise. Systematic Review Registration: CRD42022367430.

Quantifying Intracellular Single Vesicular Catecholamine Concentration with Open Carbon Nanopipettes to Unveil the Effect of L-DOPA on Vesicular Structure.

Understanding the regulatory mechanisms of exocytosis is essential for uncovering the pathologies of neuronal disorders and developing related pharmaceuticals. In this work intracellular vesicle impact electrochemical cytometry (IVIEC) measurements with different-sized (50-500 nm radius) open carbon nanopipettes (CNPs) were performed to quantify the vesicular content and release kinetics of specific vesicle populations grouped by orifice sizes. Intracellular vesicles with radius below 100 nm were captured and narrowed between 50 and 100 nm. On the basis of this, single vesicular catecholamine concentrations in the intracellular environment were quantified as 0.23-1.1 M. Our results with L-3,4-dihydroxyphenylalanine (L-DOPA)-exposure indicate that L-DOPA regulates exocytosis by increasing the dense core size and vesicular content while catecholamine concentrations did not show obvious alterations. These were all achieved simultaneously and relatively noninvasively with open CNPs.

Potentiometric pH Nanosensor for Intracellular Measurements: Real-Time and Continuous Assessment of Local Gradients.

We present a pH nanosensor conceived for single intracellular measurements. The sensing architecture consisted of a two-electrode system evaluated in the potentiometric mode. We used solid-contact carbon nanopipette electrodes tailored to produce both the indicator (pH nanosensor) and reference electrodes. The indicator electrode was a membrane-based ion-selective electrode containing a receptor for hydrogen ions that provided a favorable selectivity for intracellular measurements. The analytical features of the pH nanosensor revealed a Nernstian response (slope of -59.5 mV/pH unit) with appropriate repeatability and reproducibility (variation coefficients of <2% for the calibration parameters), a fast response time (<5 s), adequate medium-term drift (0.7 mV h-1), and a linear range of response including physiological and abnormal cell pH levels (6.0-8.5). In addition, the position and configuration of the reference electrode were investigated in cell-based experiments to provide unbiased pH measurements, in which both the indicator and reference electrodes were located inside the same cell, each of them inside two neighboring cells, or the indicator electrode inside the cell and the reference electrode outside of (but nearby) the studied cell. Finally, the pH nanosensor was applied to two cases: (i) the tracing of the pH gradient from extra-to intracellular media over insertion into a single PC12 cell and (ii) the monitoring of variations in intracellular pH in response to exogenous administration of pharmaceuticals. It is anticipated that the developed pH nanosensor, which is a label-free analytical tool, has high potential to aid in the investigation of pathological states that manifest in cell pH misregulation, with no restriction in the type of targeted cells.

UDP-N-Acetylglucosamine Pyrophosphorylase 2 (UAP2) and 1 (UAP1) Perform Synergetic Functions for Leaf Survival in Rice.

Functional inactivation of UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1) induces defense response-related lesion-mimic spots and subsequent early senescence in every newly grown leaf of the rice mutant uap1 after a short period's normal growth. However, the molecular mechanism of these leaves sustaining the short period's survival is still unknown. Phenotypic and molecular studies show that defense response-related lesion-mimic spots and early leaf senescence appear on the normally grown uap1 leaf and aggravate with the growth time. Bioinformatic analysis reveals that UAP proteins are evolutionarily conserved among eukaryotes, and there exists UAP2 protein except UAP1 protein in many higher organisms, including rice. Rice UAP2 and UAP1 proteins present high sequence identities and very similar predicted 3D structures. Transcriptional expression profile of the UAP2 gene decreases with the appearance and aggravating of leaf spots and early senescence of uap1, implying the role of the UAP2 gene in maintaining the initial normal growth of uap1 leaves. Enzymatic experiments verified that the UAP2 protein performs highly similar UAP enzymatic activity with the UAP1 protein, catalyzing the biosynthesis of UDP-GlcNAc. And these two UAP proteins are found to have the same subcellular localization in the cytoplasm, where they most presumably perform their functions. Overexpression of the UAP2 gene in uap1 plants succeeds to rescue their leaf mutant phenotype to normal, providing direct evidence for the similar function of the UAP2 gene as the UAP1 gene. The UAP2 gene is mainly expressed in the young leaf stage for functions, while the UAP1 gene is highly expressed during the whole leaf developmental stages. Based on these findings, it is suggested that UAP2 and UAP1 play key roles in rice leaf survival during its development in a synergetic manner, protecting the leaf from early senescence.

Electrochemical Measurements Reveal Reactive Oxygen Species in Stress Granules*.

Stress granules (SGs) are membrane-less organelles that assemble in the cytoplasm to organize cellular contents and promote rapid adaptation during stress. To understand how SGs contribute to physiological functions, we used electrochemical measurements to detect electroactive species in SGs. With amperometry, we discovered that reactive oxygen species (ROS) are encapsulated inside arsenite-induced SGs, and H2 O2 is the main species. The release kinetics of H2 O2 from single SGs and the number of H2 O2 molecules were quantified. The discovery that SGs contain ROS implicates them as communicators of the cellular stresses rather than a simple endpoint. This may explain how SGs regulate cellular metabolism and stress responses. This may also help better understand their cytoprotective functions in pathological conditions associated with SGs such as neurodegenerative diseases (NDs), cancers and viral infections.

Thin layer cell behavior of CNT yarn and cavity carbon nanopipette electrodes: Effect on catecholamine detection.

Carbon nanotube yarn microelectrodes (CNTYMEs) are an alternative to carbon-fiber microelectrodes (CFMEs) with interesting electrochemical properties because analyte is momentarily trapped in cavities between the CNTs. Here, we compare fast-scan cyclic voltammetry (FSCV) detection of catecholamines, including dopamine, norepinephrine, and epinephrine, at CNTYMEs, CFMEs, as well as cavity carbon nanopipette electrodes (CNPEs). At CFMEs, current decreases dramatically at high FSCV repetition frequencies. At CNTYMEs, current is almost independent of FSCV repetition frequency because the analytes are trapped in the crevices between CNTs, and thus the electrode acts like a thin-layer cell. At CFMEs, small cyclization product peaks are observed due to an intramolecular cyclization reaction to form leucocatecholamine, which is electroactive, and these peaks are largest for the secondary amine epinephrine. At CNTYMEs, more of the leucocatecholamine cyclization product is detected for all catecholamines because of the enhanced trapping effects, particularly at higher repetition rates where the reaction occurs more frequently and more product is accumulated. For epinephrine, the secondary peaks have larger currents than the primary oxidation peaks at 100 Hz, and similar trends are observed with faster scan rates and 500 Hz repetition frequencies. Finally, we examined CNPEs, which also momentarily trap neurotransmitters. Similar to CNTYMEs, at CNPEs, catecholamines have robust cyclization peaks, particularly at high repetition rates. Thus, CNTYMEs and CNPEs have thin layer cell behavior that facilitates high temporal resolution measurements, but catecholamines CVs are complicated by cyclization reactions. However, those additional peaks could be useful in discriminating the analytes, particularly epinephrine and norepinephrine.

Correlating Molecule Count and Release Kinetics with Vesicular Size Using Open Carbon Nanopipettes.

In this work, open carbon nanopipettes (CNPs) with radius between 50 and 600 nm were used to control translocation of different-sized vesicles through the pipette orifice followed by nanoelectrochemical analysis. Vesicle impact electrochemical cytometry (VIEC) was used to determine the number of catecholamine molecules expelled from single vesicles onto an inner-wall carbon surface, where the duration of transmitter release was quantified and correlated to the vesicle size all in the same nanotip. This in turn allowed us to both size and count molecules for vesicles in a living cell. Here, small and sharp open CNPs were employed to carry out intracellular VIEC with minimal invasion and high sensitivity. Our findings with VIEC reveal that the vesicular content increases with vesicle size. The release kinetics of vesicular transmitters and dense core size have the same relation with the vesicle size, implying that the vesicular dense core size determines the speed of each release event. This direct correlation unravels one of the complexities of exocytosis.

In situ homogeneous formation of Au@AgNPs for the rapid determination of formaldehyde residues by surface-enhanced Raman spectroscopy coupled with microhydrodistillation.

The reaction of formaldehyde (HCHO) with the solution containing Au nanoparticles and [Ag(NH3)2]+ through Tollens' reaction is described to form Au@Ag nanoparticles (Au@AgNPs), which are used as a SERS enhancement material. A minimized hydrodistillation device with air condense is designed to obtain a clean aqueous background for SERS analysis and simplified pretreatment process. A good linear relationship is found between the SERS signals and the concentration of HCHO in the range 0.3 to 55 mg L-1 when p-aminothiophenol (p-ATP) is selected as the Raman signal molecule, and the detection limit is 0.08 mg L-1. Stable SERS signals could be achieved due to both homogeneous formation of Au@AgNPs and clean aqueous background. The relative standard deviation (RSD) of 15 batches samples is found to be 7.1%. The proposed approach has successfully been applied to the determination of HCHO residues in beer samples with low interferences. The recoveries of spiked samples are in the range 96 to 117% with RSDs lower than 5.9%. Graphical Abstract.

Resistive-Pulse Sensing Inside Single Living Cells.

Resistive-pulse sensing is a technique widely used to detect single nanoscopic entities such as nanoparticles and large molecules that can block the ion current flow through a nanopore or a nanopipette. Although the species of interest, e.g., antibodies, DNA, and biological vesicles, are typically produced by living cells, so far, they have only been detected in the bulk solution since no localized resistive-pulse sensing in biological systems has yet been reported. In this report, we used a nanopipette as a scanning ion conductance microscopy (SICM) tip to carry out resistive-pulse experiments both inside immobilized living cells and near their surfaces. The characteristic changes in the ion current that occur when the pipet punctures the cell membrane are used to monitor its insertion into the cell cytoplasm. Following the penetration, cellular vesicles (phagosomes, lysosomes, and/or phagolysosomes) were detected inside a RAW 264.7 macrophage. Much smaller pipettes were used to selectively detect 10 nm Au nanoparticles in the macrophage cytoplasm. The in situ resistive-pulse detection of extracellular vesicles released by metastatic human breast cells (MDA-MB-231) is also demonstrated. Electrochemical resistive-pulse experiments were carried out by inserting a conductive carbon nanopipette into a macrophage cell to sample single vesicles and measure reactive oxygen and nitrogen species (ROS/RNS) contained inside them.

Electrochemical Resistive-Pulse Sensing.

Resistive-pulse sensing with biological or solid-state nanopores and nanopipettes has been widely employed in detecting single molecules and nanoparticles. The analytical signal in such experiments is the change in ionic current caused by the molecule/particle translocation through the pipet orifice. This paper describes a new version of the resistive-pulse technique based on the use of carbon nanopipettes (CNP). The measured current is produced by electrochemical oxidation/reduction of redox molecules at the carbon surface and responds to the particle translocation. In addition to counting single entities, this technique enables qualitative and quantitative analysis of the electroactive material they contain. Using liposomes as a model system, we demonstrate the capacity of CNPs for (1) conventional resistive-pulse sensing of single liposomes, (2) electrochemical resistive-pulse sensing, and (3) electrochemical identification and quantitation of redox species (e.g., ferrocyanide, dopamine, and nitrite) contained in a single liposome. The small physical size of a CNP suggests the possibility of single-entity measurements in biological systems.

Biomimetic Hydroxyapatite on Graphene Supports for Biomedical Applications: A Review.

Hydroxyapatite (HA) has been widely used in fields of materials science, tissue engineering, biomedicine, energy and environmental science, and analytical science due to its simple preparation, low-cost, and high biocompatibility. To overcome the weak mechanical properties of pure HA, various reinforcing materials were incorporated with HA to form high-performance composite materials. Due to the unique structural, biological, electrical, mechanical, thermal, and optical properties, graphene has exhibited great potentials for supporting the biomimetic synthesis of HA. In this review, we present recent advance in the biomimetic synthesis of HA on graphene supports for biomedical applications. More focuses on the biomimetic synthesis methods of HA and HA on graphene supports, as well as the biomedical applications of biomimetic graphene-HA nanohybrids in drug delivery, cell growth, bone regeneration, biosensors, and antibacterial test are performed. We believe that this review is state-of-the-art, and it will be valuable for readers to understand the biomimetic synthesis mechanisms of HA and other bioactive minerals, at the same time it can inspire the design and synthesis of graphene-based novel nanomaterials for advanced applications.

Ultrasensitive Detection of Dopamine with Carbon Nanopipets.

Carbon fiber micro- and nanoelectrodes have been extensively used to measure dopamine and other neurotransmitters in biological systems. Although the radii of some reported probes were ≪1 µm, the lengths of the exposed carbon were typically on the micrometer scale, thus limiting the spatial resolution of electroanalytical measurements. Recent attempts to determine neurotransmitters in single cells and vesicles have provided additional impetus for decreasing the probe dimensions. Here, we report two types of dopamine sensors based on carbon nanopipets (CNP) prepared by chemical vapor deposition of carbon into prepulled quartz capillaries. These include 10-200 nm radius CNPs with a cavity near the orifice and CNPs with an open path in the middle, in which the volume of sampled solution can be controlled by the applied pressure. Because of the relatively large surface area of carbon exposed to solution inside the pipet, both types of sensors yielded well-shaped voltammograms of dopamine down to ca. 1 nM concentrations, and the unprecedented voltammetric response to 100 pM dopamine was obtained with open CNPs. TEM tomography and numerical simulations were used to model CNP responses. The effect of dopamine adsorption on the CNP detection limit is discussed along with the possibilities of measuring other physiologically important analytes (e.g., serotonin) and eliminating anionic and electrochemically irreversible interferences (e.g., ascorbic acid).

Correlation of MicroRNA 17-92 Cluster Host Gene (MIR17HG) Polymorphisms With Susceptibility and Prognosis for Multiple Myeloma.

PURPOSE: To explore the correlation of MIR17HG polymorphism with susceptibility and prognosis of multiple myeloma (MM). PATIENTS AND METHODS: A total of 217 MM patients treated with high-dose melphalan combined with autologous peripheral blood stem-cell transplantation at our hospital were enrolled as the case group, and 220 healthy people were included as the control group. Sequenom MassARRAY iPLEX Gold single nucleotide polymorphism genotyping was used to detect polymorphisms of MIR17HG, including rs7336610, rs17735387, rs4284505, and rs1428. RESULTS: An increased risk of MM was found in patients who carried the rs7336610 T allele and rs4284505 G allele, and the higher the Durie-Salmon and International Staging System stages were, the more MM patients carrying rs7336610 CT + TT genotype and rs4284505 AG + GG genotype (all P < .05). Haplotype AC (rs4284505-rs1428) and CA (rs7336610-rs4284505) evidently reduce MM risk, whereas haplotype GC (rs4284505-rs1428) significantly elevated MM risk (all P < .05). Kaplan-Meier curve analysis demonstrated that rs7336610 CC genotype carriers had higher 5-year survival rate than CT + TT genotype carriers (P = .034), and the AA genotype carriers of rs4284505 had higher 5-year survival rate than AG + GG genotype carriers (P < .001). CONCLUSION: Polymorphisms of MIR17HG rs7336610 and rs1428 were correlated with MM risk and prognosis.

Surface-Charge Effects on Voltammetry in Carbon Nanocavities.

Ion transport controlled by electrostatic interactions is an important phenomenon in biological and artificial membranes, channels, and nanopores. Here, we employ carbon-coated nanopipets (CNPs) for studying permselective electrochemistry in a conductive nanopore. A significant accumulation (up to 2000-fold) of cationic redox species and anion depletion inside a CNP by diffuse-layer and surface-charge effects in a solution of low ionic strength were observed as well as the shift of the voltammetric midpeak potential. Finite-element simulations of electrostatic effects on CNP voltammograms show permselective ion transport in a single conducting nanopore and semiquantitatively explain our experimental data. The reported results are potentially useful for improving sensitivity and selectivity of CNP sensors for ionic analytes.