VPS34 Acetylation Controls Its Lipid Kinase Activity and the Initiation of Canonical and Non-canonical Autophagy.

The class III phosphoinositide 3-kinase VPS34 plays a key role in the regulation of vesicular trafficking and macroautophagy. So far, we know little about the molecular mechanism of VPS34 activation besides its interaction with regulatory proteins to form complexes. Here, we report that VPS34 is specifically acetylated by the acetyltransferase p300, and p300-mediated acetylation represses VPS34 activity. Acetylation at K771 directly diminishes the affinity of VPS34 for its substrate PI, while acetylation at K29 hinders the VPS34-Beclin 1 core complex formation. Inactivation of p300 induces VPS34 deacetylation, PI3P production, and autophagy, even in AMPK-/-, TSC2-/-, or ULK1-/- cells. In fasting mice, liver autophagy correlates well with p300 inactivation/VPS34 deacetylation, which facilitates the clearance of lipid droplets in hepatocytes. Thus, p300-dependent VPS34 acetylation/deacetylation is the physiological key to VPS34 activation, which controls the initiation of canonical autophagy and of non-canonical autophagy in which the upstream kinases of VPS34 can be bypassed.

Chiral Assembly of Perovskite Nanocrystals: Sensitive Discrimination of Amino Acid Enantiomers.

Chirality is a widespread phenomenon in nature and in living organisms and plays an important role in living systems. The sensitive discrimination of chiral molecular enantiomers remains a challenge in the fields of chemistry and biology. Establishing a simple, fast, and efficient strategy to discriminate the spatial configuration of chiral molecular enantiomers is of great significance. Chiral perovskite nanocrystals (PNCs) have attracted much attention because of their excellent optical activity. However, it is a challenge to prepare perovskites with both chiral and fluorescence properties for chiral sensing. In this work, we synthesized two chiral fluorescent perovskite nanocrystal assembly (PNA) enantiomers by using l- or d-phenylalanine (Phe) as chiral ligands. PNA exhibited good fluorescence recognition for l- and d-proline (Pro). Homochiral interaction led to fluorescence enhancement, while heterochiral interaction led to fluorescence quenching, and there is a good linear relationship between the fluorescence changing rate and l- or d-Pro concentration. Mechanism studies show that homochiral interaction-induced fluorescence enhancement is attributed to the disassembly of chiral PNA, while no disassembly of chiral PNA was found in heterochiral interaction-induced fluorescence quenching, which is attributed to the substitution of Phe on the surface of chiral PNA by heterochiral Pro. This work suggests that chiral perovskite can be used for chiral fluorescence sensing; it will inspire the development of chiral nanomaterials and chiral optical sensors.

Measurable residual disease monitoring by ddPCR in the early posttransplant period complements the traditional MFC method to predict relapse after HSCT in AML/MDS: a multicenter retrospective study.

BACKGROUND: Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously. METHODS: Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse. RESULTS: Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P < 0.001) and lower rates of relapse-free survival (RFS, 55.5% vs. 83.7%, P < 0.001) and overall survival (OS, 60.5% vs. 90.5%, P < 0.001). In multivariate analysis, ddPCR-MRD positivity of non-DTA genes was an independent adverse predictor for CIR (hazard ratio [HR], 4.02; P < 0.001), RFS (HR, 2.92; P = 0.002) and OS (HR, 3.12; P = 0.007). Moreover, the combination of ddPCR with multiparameter flow cytometry (MFC) can further accurately identify patients at high risk of relapse (F+/M+, HR, 22.44; P < 0.001, F+/M-, HR, 12.46; P < 0.001 and F-/M+, HR, 4.51; P = 0.003). CONCLUSION: ddPCR-MRD is a feasible approach to predict relapse after allo-HSCT in AML/MDS patients with non-DTA genes and is more accurate when combined with MFC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06000306. Registered 17 August 2023 -Retrospectively registered ( https://clinicaltrials.gov/study/NCT06000306?term=NCT06000306&rank=1 ).

Synthesis of a water-stable CsPbBr3 perovskite for selective detection of mercury ion in water.

By using the method of low-temperature crystallization, CsPbBr3 perovskite nanocrystals (PNCs) coated with trifluoroacetyl lysine (Tfa-Lys) and oleamine (Olam) were synthesized in aqueous solution. The structure of the CsPbBr3 PNCs was characterized by many methods, such as ultraviolet (UV)-visible absorption spectrophotometer, fluorescence spectrophotometer, transmission electron microscopy (TEM), and X-ray diffraction (XRD) pattern. The fluorescence emission of the CsPbBr3 PNCs is stable in water for about 1 day at room temperature. It was also found that the fluorescence of the PNCs could be obviously and selectively quenched after the addition of mercury ion (Hg2+ ), allowing a visual detection of Hg2+ by the naked eye under UV light illumination. The fluorescence quenching rate (I0 /I) has a good linear relationship with the addition of Hg2+ in the concentration range 0.075 to 1.5 mg/L, with a correlation coefficient (R2 ) of 0.997, and limit of detection of 0.046 mg/L. The fluorescence quenching mechanism of the PNCs was determined by the fluorescence lifetime and X-ray photoelectron spectroscopy (XPS) of the PNCs. Overall, the synthesis method for CsPbBr3 PNCs is simple and rapid, and the as-prepared PNCs are stable in water that could be conveniently used for selective detection of Hg2+ in the water environment.

Femtosecond Laser-Driven Phase Engineering of WS2 for Nano-Periodic Phase Patterning and Sub-ppm Ammonia Gas Sensing.

Laser-driven phase transition of 2D transition metal dichalcogenides has attracted much attention due to its high flexibility and rapidity. However, there are some limitations during the laser irradiation process, especially the unsatisfied surface ablation, the inability of nanoscale phase patterning, and the unexploited physical properties of new phase. In this work, the well-controlled femtosecond (fs) laser-driven transformation from the metallic 2M-WS2 to the semiconducting 2H-WS2 is reported, which is confirmed to be a single-crystal to single-crystal transition without layer thinning or obvious ablation. Moreover, a highly ordered 2H/2M nano-periodic phase transition with a resolution of ≈435 nm is achieved, breaking through the existing size bottleneck of laser-driven phase transition, which is attributed to the selective deposition of plasmon energy induced by fs laser. It is also demonstrated that the achieved 2H-WS2 after laser irradiation contains rich sulfur vacancies, which exhibits highly competitive ammonia gas sensing performance, with a detection limit below 0.1 ppm and a fast response/recovery time of 43/67 s at room temperature. This study provides a new strategy for the preparation of the phase-selective transition homojunction and high-performance applications in electronics.

Life's Essential 8 and Mortality in US Adults with Chronic Kidney Disease.

INTRODUCTION: The current prevalence of chronic kidney disease (CKD) is substantial, and CKD individuals face a heightened risk of mortality, encompassing both all-cause and cause-specific outcomes. The current study aims to investigate the potential impact of adhering to Life's Essential 8 (LE8) on reducing mortality among CKD individuals. METHODS: Using the National Health and Nutrition Survey (NHANES) data from 2005 to 2018, we analyzed 22,420 US adults (≥20 years old). CKD is defined by urinary albumin-to-creatinine ratio (≥30 mg/g or 3 mg/mmol) and estimated glomerular filtration rate (<60 mL/min/1.73 m2). The components of LE8, including diet, physical activity (PA), nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure (BP), were measured and given a score of 0-100. The total LE8 score was the unweighted average of all components and was divided into low cardiovascular health (CVH) (0-49), moderate CVH (50-79), and high CVH (80-100). A Cox proportional hazards regression model was used to explore the associations of LE8 with all-cause, cardiovascular disease (CVD), and cancer mortality, which were followed prospectively by the National Center for Health Statistics until December 31, 2019. RESULTS: In the overall population, individuals with moderate CVH had a 47% lower risk of CKD, while high CVH was linked to a 55% lower risk compared to low CVH. During a median follow-up of 7.58 years, CKD individuals had a 93% higher all-cause mortality rate and a 149% higher CVD mortality rate compared to those without CKD. Among the CKD individuals, every 10-point increase in the LE8 score was associated with reduced risks of 17% for all-cause mortality (especially PA, nicotine exposure, blood glucose, and BP), 18% for CVD mortality (especially PA), and 12% for cancer mortality (especially PA and sleep health). In additional and sensitivity analysis, the results remained significant after further consideration of potential confounding of renal function. Additionally, LE8 demonstrated superior risk stratification for CVD mortality among CKD patients compared with LS7. Interaction was observed between LE8 and age, education level, marital status, and drinking status. CONCLUSION: The current study demonstrates that adherence to higher LE8 levels within CKD individuals is associated with a reduced risk of both all-cause and cause-specific mortality.

Unconventional-Phase Crystalline Materials Constructed from Multiscale Building Blocks.

Crystal phase, an intrinsic characteristic of crystalline materials, is one of the key parameters to determine their physicochemical properties. Recently, great progress has been made in the synthesis of nanomaterials with unconventional phases that are different from their thermodynamically stable bulk counterparts via various synthetic methods. A nanocrystalline material can also be viewed as an assembly of atoms with long-range order. When larger entities, such as nanoclusters, nanoparticles, and microparticles, are used as building blocks, supercrystalline materials with rich phases are obtained, some of which even have no analogues in the atomic and molecular crystals. The unconventional phases of nanocrystalline and supercrystalline materials endow them with distinctive properties as compared to their conventional counterparts. This Review highlights the state-of-the-art progress of nanocrystalline and supercrystalline materials with unconventional phases constructed from multiscale building blocks, including atoms, nanoclusters, spherical and anisotropic nanoparticles, and microparticles. Emerging strategies for engineering their crystal phases are introduced, with highlights on the governing parameters that are essential for the formation of unconventional phases. Phase-dependent properties and applications of nanocrystalline and supercrystalline materials are summarized. Finally, major challenges and opportunities in future research directions are proposed.

Selective Epitaxial Growth of Rh Nanorods on 2H/fcc Heterophase Au Nanosheets to Form 1D/2D Rh-Au Heterostructures for Highly Efficient Hydrogen Evolution.

Phase engineering of nanomaterials (PEN) enables the preparation of metal nanomaterials with unconventional phases that are different from their thermodynamically stable counterparts. These unconventional-phase nanomaterials can serve as templates to construct precisely controlled metallic heterostructures for wide applications. Nevertheless, how the unconventional phase of templates affects the nucleation and growth of secondary metals still requires systematic explorations. Here, two-dimensional (2D) square-like Au nanosheets with an unconventional 2H/face-centered cubic (fcc) heterophase, composing of two pairs of opposite edges with 2H/fcc heterophase and fcc phase, respectively, and two 2H/fcc heterophase basal planes, are prepared and then used as templates to grow one-dimensional (1D) Rh nanorods. The effect of different phases in different regions of the Au templates on the overgrowth of Rh nanorods has been systematically investigated. By tuning the reaction conditions, three types of 1D/2D Rh-Au heterostructures are prepared. In the type A heterostructure, Rh nanorods only grow on the fcc defects including stacking faults and/or twin boundaries (denoted as fcc-SF/T) and 2H phases in two 2H/fcc edges of the Au nanosheet. In the type B heterostructure, Rh nanorods grow on the fcc-SF/T and 2H phases in two 2H/fcc edges and two 2H/fcc basal planes of the Au nanosheet. In the type C heterostructure, Rh nanorods grow on four edges and two basal planes of the Au nanosheet. Furthermore, the type C heterostructure shows promising performance toward the electrochemical hydrogen evolution reaction (HER) in acidic media, which is among the best reported Rh-based and other noble-metal-based HER electrocatalysts.

Ferromagnetism and optical properties of SnS2 doped with two impurities: first-principles calculations.

Based on the first principles of the GGA method, the magnetic and optical properties of intrinsic SnS2; Fe, Cr mono-doped SnS2; and (Fe, Cr) co-doped SnS2 are studied. The results show that the ground states of Fe, Cr mono-doped SnS2 are spin polarized, and the magnetic moments caused are 1.99 µB and 3.00 µB, respectively. The magnetic moment of Fe mono-doped SnS2 is mainly produced by Fe:3d orbitals, and the magnetic moment of Cr mono-doped SnS2 is mainly produced by Cr:3d and Sn:4d orbitals. We calculate that in the (Fe, Cr) co-doped SnS2 system, Fe, Cr and the adjacent S atoms form a strong hybrid, that is, the closest S atom between Fe and Cr atoms mediates the spin polarization and ferromagnetic (FM) coupling. This promotes the formation of a Fe:3d-S:3p-Cr:3d coupling chain, so that (Fe, Cr) co-doped SnS2 obtains FM stability. In addition, with the introduction of Fe and Cr atoms, the absorption coefficient is the largest in the long-wavelength infrared region of 0.23-1.63 eV. This shows that Fe and Cr doping can make up for the lack of absorption of intrinsic materials in the infrared region. In summary, Fe, Cr doped SnS2 dilute magnetic semiconductors may be a good candidate in the field of spintronic devices.

Chronological Changes of Viral Shedding in Adult Inpatients With COVID-19 in Wuhan, China.

BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan. Epidemiological and clinical characteristics of patients with COVID-19 have been reported, but the relationships between laboratory features and viral load has not been comprehensively described. METHODS: Adult inpatients (≥18 years old) with COVID-19 who underwent multiple (≥5 times) nucleic acid tests with nasal and pharyngeal swabs were recruited from Renmin Hospital of Wuhan University, including general patients (n = 70), severe patients (n = 195), and critical patients (n = 43). Laboratory data, demographic data, and clinical data were extracted from electronic medical records. The fitted polynomial curve was used to explore the association between serial viral loads and illness severity. RESULTS: Viral load of SARS-CoV-2 peaked within the first few days (2-4 days) after admission, then decreased rapidly along with virus rebound under treatment. Critical patients had the highest viral loads, in contrast to the general patients showing the lowest viral loads. The viral loads were higher in sputum compared with nasal and pharyngeal swab (P = .026). The positive rate of respiratory tract samples was significantly higher than that of gastrointestinal tract samples (P < .001). The SARS-CoV-2 viral load was negatively correlated with portion parameters of blood routine and lymphocyte subsets and was positively associated with laboratory features of cardiovascular system. CONCLUSIONS: The serial viral loads of patients revealed whole viral shedding during hospitalization and the resurgence of virus during the treatment, which could be used for early warning of illness severity, thus improve antiviral interventions.

Phase-Selective Epitaxial Growth of Heterophase Nanostructures on Unconventional 2H-Pd Nanoparticles.

Heterostructured, including heterophase, noble-metal nanomaterials have attracted much interest due to their promising applications in diverse fields. However, great challenges still remain in the rational synthesis of well-defined noble-metal heterophase nanostructures. Herein, we report the preparation of Pd nanoparticles with an unconventional hexagonal close-packed (2H type) phase, referred to as 2H-Pd nanoparticles, via a controlled phase transformation of amorphous Pd nanoparticles. Impressively, by using the 2H-Pd nanoparticles as seeds, Au nanomaterials with different crystal phases epitaxially grow on the specific exposed facets of the 2H-Pd, i.e., face-centered cubic (fcc) Au (fcc-Au) on the (002)h facets of 2H-Pd while 2H-Au on the other exposed facets, to achieve well-defined fcc-2H-fcc heterophase Pd@Au core-shell nanorods. Moreover, through such unique facet-directed crystal-phase-selective epitaxial growth, a series of unconventional fcc-2H-fcc heterophase core-shell nanostructures, including Pd@Ag, Pd@Pt, Pd@PtNi, and Pd@PtCo, have also been prepared. Impressively, the fcc-2H-fcc heterophase Pd@Au nanorods show excellent performance toward the electrochemical carbon dioxide reduction reaction (CO2RR) for production of carbon monoxide with Faradaic efficiencies of over 90% in an exceptionally wide applied potential window from -0.9 to -0.4 V (versus the reversible hydrogen electrode), which is among the best reported CO2RR catalysts in H-type electrochemical cells.

Necessity for detection of SARS-CoV-2 RNA in multiple types of specimens for the discharge of the patients with COVID-19.

BACKGROUND: The SARS-CoV-2 RNA was detected positive again after discharged from hospital in some COVID-19 patients, with or without clinical symptoms such as fever or dry cough. METHODS: 1008 severe COVID-19 patients, with SARS-CoV-2 RNA positive detected with the mixed specimen of nasopharyngeal swab and oropharyngeal swab by real-time fluorescence quantitative PCR (RT-qPCR), were selected to monitor SARS-CoV-2 RNA with the 12 types of specimens by RT-qPCR during hospitalization. All of 20 discharged cases with COVID-19 were selected to detect SARS-CoV-2 RNA in isolation period with 7 types of specimens by RT-qPCR before releasing the isolation period. RESULTS: Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn't be detected in other types of specimen in this study. Of the 20 discharged cases during the isolation period, the positive rate of SARS-CoV-2 RNA was 30% (6/20): 2 cases were positive in sputum at the eighth and ninth day after discharge, respectively, 1 case was positive in nasopharynx swab at the sixth day after discharge, 1 case was positive in anal swab at the eighth day after discharge, and 1 case was positive in 3 specimens (nasopharynx swab, oropharynx swab and sputum) simultaneously at the fourth day after discharge, and no positive SARS-CoV-2 RNA was detected in other specimens including stool, urine and blood at the discharged patients. CONCLUSIONS: SARS-CoV-2 RNA should be detected in multiple specimens, such as nasopharynx swab, oropharynx swab, sputum, and if necessary, stool and anal swab specimens should be performed simultaneously at discharge when the patients were considered for clinical cure and before releasing the isolation period.

The obstructive sleep apnoea syndrome in adolescents.

BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) results from a combination of structural and neuromotor factors; however, the relative contributions of these factors have not been studied during the important developmental phase of adolescence. We hypothesised that adenotonsillar volume (ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway electromyographic response to subatmospheric pressure and the ventilatory response to CO2 during sleep would be major predictors of OSAS risk. METHODS: 42 obese adolescents with OSAS and 37 weight-matched controls underwent upper airway MRI, measurements of Pcrit, genioglossal electromyography and ventilatory response to CO2 during wakefulness and sleep. RESULTS: ATV, NPAV, activated and hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO2 during sleep were all associated with OSAS risk. Multivariate models adjusted for age, gender, body mass index and race indicated that ATV, NPAV and activated Pcrit each independently affected apnoea risk in adolescents; genioglossal electromyography was independently associated in a reduced sample. There was significant interaction between NPAV and activated Pcrit (p=0.021), with activated Pcrit more strongly associated with OSAS in adolescents with larger NPAVs and NPAV more strongly associated with OSAS in adolescents with more negative activated closing pressure. CONCLUSIONS: OSAS in adolescents is mediated by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated Pcrit). This may have important implications for the management of OSAS in adolescents.

Systematic Review and Meta-Analysis: Circulating miRNAs for Diagnosis of Hepatocellular Carcinoma.

Because early-stage hepatocellular carcinoma (HCC) is difficult to diagnose using the existing techniques, identifying better biomarkers would likely improve the patients' prognoses. We performed a systematic review and meta-analysis of published studies to appraise the utility of microRNAs (miRNAs) for the early diagnosis of HCC. Pertinent literature was collected from the Medline, Embase, and Chinese National Knowledge Infrastructure databases. We analyzed 50 studies that included 3423 cases of HCC, 2403 chronic hepatic disease (CH) patients, and 1887 healthy controls in 16 articles. Summary receiver operating characteristic analyses of all miRNAs showed an area under the curve (AUC) of 0.82, with 75.8% sensitivity and 75.0% specificity in discriminating patients with HCC from healthy controls. miR-21 and miR-122 individually distinguished patients with HCC from healthy controls, with an AUC of 0.88 for miR-21 and 0.77 for miR-122. The sensitivity and specificity for miR-21 were 86.6% and 79.5%, respectively, those for miR-122 were 68.0% and 73.3%. We conclude that circulating miRNAs, particularly miR-21, and miR-122, are promising biomarkers for the early diagnosis of HCC.

Selective visual attention based clutter metric with human visual system adaptability.

Most existing clutter metrics are proposed based on fixed structural features and experienced weight measures. In this paper, we identify the clutter as selective visual attention effects and propose a type of clutter metric. First, adaptive structural features are extracted from the blocks with an edge-structure similarity to the target. Next, the confusing blocks are selected by the similarity threshold based on the attention guidance map. The clutter is estimated by quantifying the effects of confusing blocks on target acquisition performance. The comparative field experiments, with a Search_2 dataset, show that the proposed metric is consistent with the adaptability of the human visual system (HVS) and outperforms other metrics.

Next generation digital PCR measurement of hepatitis B virus copy number in formalin-fixed paraffin-embedded hepatocellular carcinoma tissue.

BACKGROUND: Hepatocellular carcinoma (HCC) is strongly associated with hepatitis B virus (HBV) infection. False-negative results are common in routine serological tests and quantitative real-time PCR because of HBV surface antigen (HBsAg) variation and low HBV copy number. Droplet digital PCR (ddPCR), a next generation digital PCR, is a novel, sensitive, and specific platform that can be used to improve HBV detection. METHODS: A total of 131 HCC cases with different tumor stages and clinical features were initially classified with a serological test as HBsAg positive (n = 107) or negative (n = 24) for HBV infection. Next, DNA templates were prepared from the corresponding formalin-fixed paraffin-embedded (FFPE) tissues to determine HBV copy number by ddPCR. RESULTS: HBV copy numbers, successfully determined for all clinical FFPE tissues (n = 131), ranged from 1.1 to 175.5 copies/µL according to ddPCR. The copy numbers of HBV were positively correlated with tumor-nodes-metastasis (P = 0.008) and Barcelona-Clinic Liver Cancer (P = 0.045) classification. Moreover, serum cholinesterase correlated with hepatitis B viral load (P = 0.006). CONCLUSIONS: HBV infection is a key factor that influences tumorigenesis in HCC by regulating tumor occurrence and development. ddPCR improves the analytical sensitivity and specificity of measurements in nucleic acids at a single-molecule level and is suitable for HBV detection.

Reliable Quantitative SERS Analysis Facilitated by Core-Shell Nanoparticles with Embedded Internal Standards.

Quantitative analysis is a great challenge in surface-enhanced Raman scattering (SERS). Core-molecule-shell nanoparticles with two components in the molecular layer, a framework molecule to form the shell, and a probe molecule as a Raman internal standard, were rationally designed for quantitative SERS analysis. The signal of the embedded Raman probe provides effective feedback to correct the fluctuation of samples and measuring conditions. Meanwhile, target molecules with different affinities can be adsorbed onto the shell. The quantitative analysis of target molecules over a large concentration range has been demonstrated with a linear response of the relative SERS intensity versus the surface coverage, which has not been achieved by conventional SERS methods.

High-resolution melting analysis reveals genetic polymorphisms in microRNAs confer hepatocellular carcinoma risk in Chinese patients.

BACKGROUND: Although several single-nucleotide polymorphisms in microRNA (miRNA) genes have been associated with primary hepatocellular carcinoma, published findings regarding this relationship are inconsistent and inconclusive. METHODS: The high-resolution melting (HRM) analysis was used to determine whether the occurrence of the SNPs of miR-146a C > G (rs2910164), miR-196a2 C > T (rs11614913), miR-301b A > G (rs384262), and miR-499 C > T (rs3746444) differs in frequency-matched 314 HCC patients and 407 controls by age and sex. RESULTS: The groups' genotype distributions of miR-196a2 C > T and miR-499 C > T differed significantly (P < 0.01), both of them increased the risk of HCC in different dominant genetic models (P < 0.01); compared with individuals carrying one or neither of the unfavorable genotypes, individuals carrying both unfavorable genotypes (CT + CC) had a 3.11-fold higher HCC risk (95% confidence interval (CI), 1.89-5.09; P = 7.18 × 10-6). Moreover, the allele frequency of miR-499 C > T was significantly different between the two groups, and the HCC risk of carriers of the C allele was higher than that of carriers of the T allele (odds ratio, 1.53; 95% CI, 1.15-2.03; P = 0.003). Further, we found that the activated partial thromboplastin time (APTT) in HCC patients with miR-196a2 CC genotype was longer than patients with TT genotypes (P < 0.05), and HCC patients with miR-499 C allele had higher serum levels of direct bilirubin, globulin, γ-glutamyltranspeptidase, alkaline phosphatase, and lower serum cholinesterase (P < 0.05). CONCLUSIONS: Our findings suggest that the SNPs in miR-196a2 C > T and miR-499 C > T confer HCC risk and that affect the clinical laboratory characteristics of HCC patients.

Respiratory and auditory cortical processing in children with obstructive sleep apnea syndrome.

RATIONALE: Children with obstructive sleep apnea syndrome (OSAS) have impaired cortical processing of respiratory afferent stimuli, manifested by blunted sleep respiratory-related evoked potentials (RREP). However, whether this impairment is limited to respiratory stimuli, or reversible after successful treatment, is unknown. We hypothesized that, during sleep, children with OSAS have (1) abnormal RREP, (2) normal cortical processing of nonrespiratory stimuli, and (3) persistence of abnormal RREP after treatment. OBJECTIVES: To measure sleep RREP and auditory evoked potentials in normal control subjects and children with OSAS before and after treatment. METHODS: Twenty-four children with OSAS and 24 control subjects were tested during N3 sleep. Thirteen children with OSAS repeated testing 4-6 months after adenotonsillectomy. MEASUREMENTS AND MAIN RESULTS: RREP were blunted in OSAS compared with control subjects (N350 at Cz -27 ± 15.5 vs. -47.4 ± 28.5 µV; P = 0.019), and did not improve after OSAS treatment (N350 at Cz pretreatment -25.1 ± 7.4 vs. -29.8 ± 8.1 post-treatment). Auditory evoked potentials were similar in OSAS and control subjects at baseline (N350 at Cz -58 ± 33.1 vs. -66 ± 31.1 µV), and did not change after treatment (N350 at Cz -67.5 ± 36.8 vs. -65.5 ± 20.3). CONCLUSIONS: Children with OSAS have persistent primary or irreversible respiratory afferent cortical processing deficits during sleep that could put them at risk of OSAS recurrence. OSAS does not seem to affect the cortical processing of nonrespiratory (auditory) afferent stimuli during sleep.