Hearing loss has been recognized as a risk factor for dementia and non-motor features of Parkinson's disease (PD). The apolipoprotein E (APOE) protein contributes to maintenance and repair of ...neuronal cell membranes, causing age-related disorders. This study aimed to analyze the impact of hearing loss on cognitive impairment, PD severity, and APOE gene expression in these patients.
A total of 72 out-patients diagnosed with either PD or hearing loss were enrolled in this study. The hearing assessment included pure-tone audiometry, speech reception thresholds, and speech discrimination ability. Dementia was assessed by filling out the Clinical Dementia Rating and Mini-Mental State Examination questionnaires. The severity of PD was assessed using the Modified Hoehn and Yahr scale. Blood samples were tested for the gene expression of APOE.
Out of the 72 cases, there were 44 males and 28 females, with an average age of 64.4 ± 9.1 years. A total of 41 out of 72 cases had dementia and had a worse hearing threshold than those without dementia (47.1 ± 24.4 vs. 31.7 ± 22.1 dB,
= 0.006). A total of 58 patients were diagnosed with PD, with 14 of them classified as having severe symptoms (Modified Hoehn and Yahr scale > 2). Patients with severe PD were found to have a worse hearing threshold (49.6 ± 28.3 vs. 30.3 ± 17.8 dB,
= 0.028) and higher prevalence of dementia (12/14 vs. 18/44,
= 0.006). Among 10 individuals with the APOE ε4 gene, the prevalence of dementia was higher than those without the ε4 allele (9/10 vs. 32/62,
= 0.036).
Hearing loss is common in severe PD and in dementia patients. Severe PD has a negative impact on the hearing threshold and cognitive dysfunction. Patients with APOE ε4 have a higher prevalence of dementia.
A resistive random access memory (RRAM) device with a tunable switching window is demonstrated for the first time. The SET voltage can be continuously tuned from 0.27 to 4.5 V by electrical gating ...from −10 to +35 V. The gate‐controlled bilayer graphene‐electrode RRAM can function as 1D1R and potentially increase the RRAM density.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and current treatments exhibit limited efficacy against advanced HCC. The majority of cancer-related deaths are ...caused by metastasis from the primary tumor, which indicates the importance of identifying clinical biomarkers for predicting metastasis and indicating prognosis. Patient-derived cells (PDCs) may be effective models for biomarker identification. In the present study, a wound healing assay was used to obtain 10 fast-migrated and 10 slow-migrated PDC cultures from 36 HCC samples. MicroRNA (miRNA) signatures in PDCs and PDC-derived exosomes were profiled by microRNA-sequencing. Differentially expressed miRNAs between the low- and fast-migrated groups were identified and further validated in 372 HCC profiles from The Cancer Genome Atlas (TCGA). Six exosomal miRNAs were identified to be differentially expressed between the two groups. In the fast-migrated group, five miRNAs (miR-140-3p, miR-30d-5p, miR-29b-3p, miR-130b-3p and miR-330-5p) were downregulated, and one miRNA (miR-296-3p) was upregulated compared with the slow-migrated group. Pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were significantly enriched in the 'focal adhesion' pathway, which is consistent with the roles of these miRNAs in tumor metastasis. Three miRNAs, miR-30d, miR-140 and miR-29b, were significantly associated with patient survival. These findings indicated that these exosomal miRNAs may be candidate biomarkers for predicting HCC cell migration and prognosis and may guide the treatment of advanced HCC.
Background: Quality of life (QoL) attained before, during, or after treatments is recognized as a vital factor associated with therapeutic benefits in cancer patients. This nasopharyngeal cancer ...(NPC) patient longitudinal study assessed the relationship among QoL, cancer stage, and long-term mortality in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Patients and Methods: The European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the head and neck cancer-specific QoL questionnaire module (QLQ-HN35) were employed to evaluate four-dimensional QoL outcomes at five time points: pre- (n = 682), during (around 40 Gy) (n = 675), 3 months (n = 640), 1 year (n = 578) and 2 years post-IMRT (n = 505), respectively, for 682 newly diagnosed NPC patients treated between 2003 and 2017 at a single institute. The median followed-up time was 7.5 years, ranging from 0.3 to 16.1 years. Generalized estimating equations, multivariable proportional hazards models, and Baron and Kenny’s method were used to assess the investigated effects. Results: Advanced AJCC stage (III–IV) patients revealed a 2.26-fold (95% CI—1.56 to 3.27) higher covariate-adjusted mortality risk than early-stage (I–II) patients. Compared with during IMRT, advanced-stage patients had a significantly low global health QoL and a significantly high QoL-HN35 symptom by a large magnitude at pre-, 3 months, and 2 years post-IMRT. QoL scales at pre-IMRT, 1 year, and 2 years post-IMRT were significantly associated with mortality. The effect changes of mortality risk explained by global health QoL, QoL-C30, and QoL-HN35 symptom were 5.8–9.8% at pre-IMRT but at 2 years post-IMRT were 39.4–49.4% by global health QoL and QoL-HN35 symptoms. Conclusions: We concluded advanced cancer stage correlates with a long-term high mortality in NPC patients treated with IMRT and the association is partially intermediated by QoL at pre-IMRT and 2 years post-IMRT. Therefore, QoL-HN35 symptom and global health QoL-dependent medical support and care should be focused and tailored at 2 years post-IMRT.
Gastric cancer (GC) is still a major aggressive malignancy worldwide. While the importance of circular RNAs (circRNAs) involved in carcinogenesis has gradually been acknowledged, their role in human ...cancers is not largely understood, including in GC. Here, we focused on hsa_circ_0001368 in GC, a novel circRNA that has not been previously reported. In the current study, we found a broad downregulation of hsa_circ_0001368 in GC tissues and cells, which correlates with a worse prognosis in GC patients. Functional experiments suggested that the knockdown of hsa_circ_0001368 promoted cell viability and motility by cell proliferation and invasion assays. In addition, the knockdown of hsa_circ_0001368 led to accelerated tumor growth in vivo. Mechanically, we demonstrated that hsa_circ_0001368 served as a competing endogenous RNA (ceRNA) to sponge miR-6506–5p. Subsequently, FOXO3 may act as the functional target of miR-6506–5p, and the knockdown of hsa_circ_0001368 decreased the expression of the tumor-suppressive gene FOXO3. Taken together, our study revealed that hsa_circ_0001368 plays a tumor-suppression role in GC via the miR-6506–5p/FOXO3 axis and may serve as a potential target for GC therapy.
•In this study, we performed high-throughput circRNA microarray assays using gastric cancer (GC) patient samples to investigate the potential involvement of circRNAs in GC, and we revealed that lower levels of circRNA hsa_circ_0001368 were expressed in GC tissues than in normal adjacent tissues.•Functionally, knockdown of hsa_circ_0001368 dramatically promoted the ability of GC cells to proliferate and invasion in vitro and in vivo.•Regarding the mechanism, we found that hsa_circ_0001368 was mainly observed in the cytoplasm and was capable of sponging miR-6506–5p to increase the expression of the tumor-suppressive gene FOXO3.•Our study first revealed a novel signaling pathway of hsa_circ_0001368/miR-6506-5p/FOXO3 involved in GC progression.
This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell ...carcinoma (LAOSCC).
Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction.
There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI <97.8). In Cox models, low GNRI remained an independent negative prognosticator of OS (HR: 1.6; 95% CI: 1.124–2.277; p = 0.009) and CSS (HR: 1.907; 95% CI: 1.219–2.984; p = 0.005). The c-index of the proposed nomogram, incorporating assorted clinicopathological factors and GNRI, had a statistically significant increase compared with the predictive nomogram constructed by the TNM staging system alone (0.692 vs. 0.637, p < 0.001).”
Preoperative GNRI is an independent prognostic factor of OS and CSS in patients with LAOSCC. A multivariate nomogram that includes GNRI may better help us to accurately estimate individual survival outcomes.
This paper aims to improve the signal response in headspace (HS) analysis over than the GC analysis with a classical splitless injection mode, and this was achieved by the development of ...high-pressure headspace (HP-HS) analysis method. Based on the theoretical analysis on the sampling principle of HS, the HP-HS concept was proposed in section one, indicative of possibility to achieve excellent signal response. In the proposed HP-HS technology, the complete transfer of gas sample from HS to GC column is achieved in a very short purge-off time in the splitless injection of GC using the high-pressure carrier gas. The sampling size was increased by adopting high-pressure auxiliary gas. The dilution effect of venting process on detected substance was greatly reduced by controlling the terminal pressure of venting process at a high level. With the HP-HS analysis technology, the optimal equilibration temperature and signal response for analytes with high or medium volatility in ten common solvents was determined, and the results showed that the HP-HS-GC method can achieve very high signal response and very low solvent effect on GC. For aqueous samples, the signal response of HP-HS-GC can be up to three times than that of the splitless GC analysis. The present technology has a great potential, in particular, in high sensitivity analysis of complicated samples with serious substrate effect.
In this work, ZnO nanorods (ZnO NRs) with different sizes were hydrothermally grown on the surface of Whatman filter paper for the fabrication of a microfluidic paper-based device (μPAD) for the ...simultaneous detection of glucose and uric acid. As dual enzymatic reaction was employed for the colorimetric detection in this μPAD, the presence of ZnO NRs promoted the enzyme immobilization thus significantly enhancing the colorimetric signal. The coffee ring effect was effectively conquered by the uniform distribution of ZnO NR as well as a specialized double-layered μPAD design. Meanwhile, two color indicators with distinct colors were used to provide complementary results to better quantify the concentration of the analytes by naked eye. As a result, two linear calibration curves were obtained for the detection of glucose (0.01–10 mmol L−1) and uric acid (0.01–5 mmol L−1), along with a LOD of 3 μmol L−1 for glucose and 4 μmol L−1 for uric acid, respectively. The practical usefulness of the proposed μPAD was further validated by the simultaneous analysis of glucose and uric acid in serum samples and urine samples.
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•A microfluidic paper-based device (μPAD) for the simultaneous detection of glucose and uric acid was fabricated.•ZnO nanorods were grown in situ on the surface of μPAD using hydrothermal method.•After ZnO nanorods immobilization, the colorimetric signal was significantly enhanced with shorter reaction time.•Both the double-layered µPAD design and the immobilization of ZnO nanorods improved the color uniformity.
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•HP mafic granulite discovered from the Pingdu–Anqiu area, the Jiaobei terrane.•U–Pb age data reveal 1950–1900Ma peak and 1900–1800Ma retrogressive metamorphism.•HP mafic granulite ...defined a clockwise P–T–t path involving near-isothermal decompression and near-isobaric cooling.
High-pressure (HP) mafic granulites in the Pingdu–Anqiu area of the Jiaobei Terrane, in the southwestern segment of the Jiao–Liao–Ji Belt of the North China Craton, occur as irregular lenses or deformed dike swarms within the Paleoproterozoic graphite-bearing paragneisses and marbles. Petrographic examination has revealed three distinct metamorphic mineral assemblages: a peak HP granulite-facies assemblage (M1) that consists of garnet+clinopyroxene+plagioclase+quartz±amphibole±Fe–Ti oxides, a post-peak decompression assemblage (M2) that is characterized by symplectites of orthopyroxene+clinopyroxene+plagioclase±amphibole±Fe–Ti oxides, and a late cooling assemblage (M3) represented by symplectites of amphibole+plagioclase+Fe–Ti oxides. Pseudosection modeling using THERMOCALC in the NCFMASHTO system and conventional thermobarometers constrained the P–T conditions of the M1, M2 and M3 assemblages to P=1.28–1.44GPa and T=757–805°C, P=0.50–0.80GPa and T=780–840°C, and P=0.55–0.73GPa and T=665–730°C, respectively. An integrated study involving laser Raman spectroscopy and scanning electron microscope analysis of mineral inclusions, cathodoluminescence imaging, and in-situ U–Pb dating of zircons showed that the protolith ages of the HP mafic granulites are mainly 2200–2000Ma and that the timing of the peak HP granulite-facies metamorphism ranges from 1950 to 1900Ma, as recorded by the cores of metamorphic zircons. The medium- to low-pressure amphibolite- to granulite-facies retrogression occurred mainly at 1900–1800Ma, as recorded by the rims of some zircon grains as well as zircon grains that contain inclusions of clinopyroxene+orthopyroxene+plagioclase+amphibole+sphene. Comprehensive petrographic, mineralogical, and geochronological investigations of the HP mafic granulites defined a clockwise P–T–t path involving near-isothermal decompression and near-isobaric cooling, which further suggests that the Jiaobei Terrane had underwent initial crustal thickening during 1950–1900Ma, followed by relatively rapid exhumation, cooling, and retrogression in the period 1900–1800Ma. This P–T–t path was probably generated by the Paleoproterozoic collisional orogenesis of the North China Craton.
Currently, the early disease screening is still the most effective way to increase the survival rate of the HIV/HCV infected patients. However, the trace analysis remains a great challenge for early ...disease screening. Herein, a novel silver nanocluster (AgNCs) is in situ generated and served as fluorescence probes for the ultrasensitive HIV/HCV DNA detection by combing Exo III-assisted target recycling amplification (ERA) with rolling circle amplification (RCA). As an important key element of this sensor, the padlock probes (PLP) of RCA are exquisitely designed to compose of a guanine-rich (G-rich) region. Target DNA firstly hybridizes with the stem segment of the hairpin DNA (hp-DNA) and triggered the Exo III digestion, which releases and recycles the target and generate numerous ssDNA fragments. The generated ssDNA fragments act as ligation probes, which hybridize with PLP to trigger the RCA process, generating numerous periodically repeated cytosine-rich (C-rich) units. In the presence of NaBH4 and AgNO3, numerous AgNCs are in situ generated, thereby producing a strong fluorescent signal. Under optimal conditions, an ultrasensitive DNA machine is constructed for the detection of HIV DNA with a detection limit of 1.4 fM and a linear range of 10 fM to 100 pM. More fascinatingly, this DNA machine could intelligently distinguish multiple virus DNAs by the construction of analog AND and OR logic circuits.
•A novel silver nanocluster is in situ synthesized on rolling circle amplification products as a fluorescent output probe.•By using cascade amplification involving ERA and RCA, HIV/HCV DNA can be sensitively detected.•The DNA sensor could intelligently distinguish multiple DNA by the construction of analog AND and OR logic gates.
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