Visualization of Endolymphatic Hydrops in Patients With Unilateral Idiopathic Sudden Sensorineural Hearing Loss With Four Types According to Chinese Criterion

Objective: The aim of this study is to evaluate the possible value of endolymphatic hydrops (EH) in patients with unilateral idiopathic sudden sensorineural hearing loss (UISSNHL) with four types according to audiometry.Methods: Seventy-two patients (40 men and 32 women; age range, 28–78 years; mean age: 50.0 ± 12.9 years) with UISSNHL were admitted retrospectively into this study. Based on the pure tone audiometry before treatment, the hearing loss of all these patients were categorized into four types: low-frequency group (LF-G), high-frequency group (HF-G), flat group (F-G), and total deafness group (TD-G). The average time from symptom onset to the first examination was 6.9 ± 4.4 days (1–20 days). 3D-FLAIR MRI was performed 24 h after intratympanic injection of gadolinium (Gd) within 1 week after the UISSNHL onset. The incidence of EH in the affected ears based on four types of hearing loss were analyzed using the Chi-square test, and the possible relationship with vertigo and prognosis were also assessed.Results: Eleven of 21 patients (52.4%) in LF-G had the highest EH-positive rate, followed by 18.2% in HF-G, 11.8% in F-G, and 17.4% in TD-G. The significant difference was found in the four groups (P = 0.018). The EH rate of LF-G was statistically significantly higher than that of F-G and TD-G (P = 0.009, P =0.014), respectively. After being valued by the volume-referencing grading system (VR scores), the EH level was represented by the sum scores of EH. In LF-G, no statistically significant difference was found in the prognosis of ISSNHL patients between with the EH group and the no EH group (P = 0.586). The symptom “vertigo” did not correlate with EH and prognosis.Conclusions: EH was observed in UISSNHL patients by 3D-FLAIR MRI. EH may be responsible for the pathology of LF-G but not related to prognosis. It might be meaningless to assess EH in other hearing loss types, which might be more related to the blood-labyrinth dysfunction

FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses

Ribbon synapses are important structures in transmitting auditory signals from the inner hair cells (IHCs) to their corresponding spiral ganglion neurons (SGNs). Over the last few decades, deafness has been primarily attributed to the deterioration of cochlear hair cells rather than ribbon synapses. Hearing dysfunction that cannot be detected by the hearing threshold is defined as hidden hearing loss (HHL). The relationship between ribbon synapses and FGF22 deletion remains unknown. In this study, we used a 6-week-old FGF22 knockout mice model (Fgf22–/–) and mainly focused on alteration in ribbon synapses by applying the auditory brainstem response (ABR) test, the immunofluorescence staining, the patch-clamp recording, and quantitative real-time PCR. In Fgf22–/– mice, we found the decreased amplitude of ABR wave I, the reduced vesicles of ribbon synapses, and the decreased efficiency of exocytosis, which was suggested by a decrease in the capacitance change. Quantitative real-time PCR revealed that Fgf22–/– led to dysfunction in ribbon synapses by downregulating SNAP-25 and Gipc3 and upregulating MEF2D expression, which was important for the maintenance of ribbon synapses’ function. Our research concluded that FGF22 deletion caused HHL by affecting the function of IHC ribbon synapses and may offer a novel therapeutic target to meet an ever-growing demand for deafness treatment

Regulatory Effect of Quaternized Cellulose Nanofiber/Zein Nanoparticles on the Steady-State Performance of Fucoxanthin

This study innovatively constructed a quaternized cellulose nanofiber (QCNF)/zein core-shell delivery system. By precisely controlling the concentration of QCNF (0.05–0.25 g/100 mL), the regulatory mechanisms of this system on the steady-state performance and targeted delivery of fucoxanthin (FUC) were elucidated. Fourier transform infrared (FTIR) spectroscopy revealed that electrostatic interactions between zein and nanofibers led to the formation of a stable interface. Transmission electron microscopy (TEM) images demonstrated that at a QCNF concentration of 0.2 g/100 mL, a distinct layer-by-layer self-assembled core-shell structure was formed, and the encapsulation efficiency of FUC was (95.64 ± 0.06) %. Moreover, 0.2 g/100 mL QCNF/zein@FUC was more stable to heat, light, pH and ions during storage at 4 ℃ compared with the control group (zein@FUC). Furthermore, the addition of QCNF as a coating on the zein surface was found to trigger passive targeted release of the encapsulated fucoxanthin, thereby enhancing its intestinal bioaccessibility. During in vitro simulated digestion, the cumulative release of 0.2 g/100 mL QCNF/zein@FUC was (85.32 ± 0.46) % with a bioaccessibility of (58.77 ± 3.84) %, indicating programmed and sustained release of fucoxanthin. The findings of this study offer theoretical support for exploring the formation mechanism and the steady-state targeted release performance of natural bio-based self-assembled nanodelivery carriers

Association between maternal blood lipids levels during pregnancy and risk of small-for-gestational-age infants.

Dyslipidemia in pregnancy are associated with risk of adverse outcomes. As an adverse pregnancy outcome, small-for-gestational-age has been extensively studied in Western countries. However, similar studies have rarely been conducted in Asian countries. Data were derived from 5695 pairs of non-diabetic mothers and neonates between 1 Jan 2014 and 31 Dec 2014. 5.6% neonates in our study were SGA. Serum samples were collected during second and third trimesters for evaluation on fasting lipids levels. The present study intended to explore the associations between maternal lipid profile and small-for-gestational-age neonates. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and adjusted via logistic regression analysis. After adjustments for confounders, third-trimester total cholesterol levels were associated with a decreased risk for small-for-gestational-age (aOR = 0.622, 95% CI 0.458-0.848, P = 0.002), and third-trimester high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were associated with an increased risk for small-for-gestational-age (aOR = 1.955, 95% CI 1.465-2.578, P < 0.001; aOR = 1.403, 95% CI 1.014-1.944, P = 0.041).In the highest gestational weight gain strata, especially the third-trimester, the effect of high-density lipoprotein cholesterol levels on the risk for small-for-gestational-age is larger. High high-density lipoprotein cholesterol level during third trimester could be considered as indicators of a high-risk of small-for-gestational-age, regardless of gestational weight gain

oneDNN Graph Compiler: A Hybrid Approach for High-Performance Deep Learning Compilation

With the rapid development of deep learning models and hardware support for dense computing, the deep learning workload characteristics changed significantly from a few hot spots on compute-intensive operations to a broad range of operations scattered across the models. Accelerating a few compute-intensive operations using the expert-tuned implementation of primitives does not fully exploit the performance potential of AI hardware. Various efforts have been made to compile a full deep neural network (DNN) graph. One of the biggest challenges is to achieve high-performance tensor compilation by generating expert level performance code for the dense compute-intensive operations and applying compilation optimization at the scope of DNN computation graph across multiple compute-intensive operations. We present oneDNN Graph Compiler, a tensor compiler that employs a hybrid approach of using techniques from both compiler optimization and expert-tuned kernels for high performance code generation of the deep neural network graph. oneDNN Graph Compiler addresses unique optimization challenges in the deep learning domain, such as low-precision computation, aggressive fusion of graph operations, optimization for static tensor shapes and memory layout, constant weight optimization, and memory buffer reuse. Experimental results demonstrate significant performance gains over existing tensor compiler and primitives library for performance-critical DNN computation graphs and end-to-end models on Intel Xeon Scalable Processors.Comment: 10 pages excluding reference, 9 figures, 1 tabl

Analysis of scene-guided camera assistance in transaxillary gasless endoscopic thyroidectomy: a minor improvement in operative technique

BackgroundTransaxillary gasless endoscopic thyroidectomy (TGET) is a widely performed operation, but its side view angle and instrument interference have caused concerns for most surgical groups. The aim of this study was to introduce scene-guided camera assistance (SGA) and analyze its role in facilitating TGET.MethodsWe put forward key points for camera holders, including one pivot, two positions, and three planes, and separated TGET operations into five parts. We also established the view angle for each part of the operation for the camera holder to follow. Then, we reviewed 416 patients who underwent TGET with or without SGA and analyzed their demographic characteristics, operative outcomes, pathologic outcomes, and early complications.ResultsThe TGET and TGET-SGA groups were similar in terms of age, sex ratio, height, weight, tumor size, Hashimoto’s thyroiditis ratio, and cN1 ratio. The operation time and postoperative hospital stay were significantly longer in the TGET group than in the TGET-SGA group (114.43 ± 17.20 minutes vs. 101.82 ± 19.39 minutes and 3.16 ± 0.77 days vs. 2.16 ± 0.55 days, respectively, P &lt; 0.001). The account of retrieved lymph nodes was less in the TGET group than in the TGET-SGA group (5.61 ± 4.27 vs. 6.57 ± 4.96, P = 0.038).ConclusionSGA provided guidance for camera holders, and the data showed that it was an improvement for TGET operations

Methylene Blue Attenuates Lung Injury Induced by Hindlimb Ischemia Reperfusion in Rats

Objective. This study was aimed to investigate the protective effect of methylene blue against lung injury induced by reperfusion of ischemic hindlimb in a rat model. Methods. Twenty-four healthy adult male Sprague-Dawley rats were equally randomized into three groups: sham (SM) group, ischemia reperfusion (IR) group, and methylene blue (MB) group. Rats in both IR and MB groups were subjected to 4 h of ischemia by clamping the left femoral artery and then followed by 4 h of reperfusion. Treatment with 1% methylene blue (50 mg/kg) was administrated intraperitoneally at 10 min prior to reperfusion in the MB group. After 4 h of reperfusion, malondialdehyde (MDA) level, myeloperoxidase (MPO), and superoxide dismutase (SOD) activities in lung tissue were detected; inflammatory cytokines, including IL-1β and IL-6, were measured in bronchoalveolar lavage fluid (BALF); correspondingly, the morphological changes and water content in both gastrocnemius muscle and lung samples were evaluated. Results. Hindlimb IR caused remarkable morphological abnormalities and edema in both muscle and lung tissues. SOD activity was decreased, both the MPO activity and MDA level in lung tissue, as well as IL-1β and IL-6 levels in BALF, were increased in the IR group (p<0.05). Compared with the IR group, SOD activity was increased, whereas MPO activity and MDA level in lung tissue and IL-1β and IL-6 levels in BALF were decreased in the MB group (p<0.05). Also, the histological damage and edema in both lung and muscle tissues were significantly attenuated by the treatment of methylene blue. Conclusion. Methylene blue attenuates lung injury induced by hindlimb IR in rats, at least in part, by inhibiting oxidative stress

Cartilage oligomeric matrix protein is a novel notch ligand driving embryonic stem cell differentiation towards the smooth muscle lineage

Cartilage oligomeric matrix protein (COMP), a protective component of vascular extracellular matrix (ECM), maintains the homeostasis of mature vascular smooth muscle cells (VSMCs). However, whether COMP modulates the differentiation of stem cells towards the smooth muscle lineage is still elusive. Firstly, purified mouse COMP directly induced mouse embryonic stem cell (ESC) differentiation into VSMCs both in vitro and in vivo, while the silencing of endogenous COMP markedly inhibited ESC-VSMC differentiation. RNA-Sequencing revealed that Notch signaling was significantly activated by COMP during ESC-VSMC differentiation, whereas the inhibition of Notch signaling attenuated COMP-directed ESC-VSMC differentiation. Furthermore, COMP deficiency inhibited Notch activation and VSMC differentiation in mice. Through silencing distinct Notch receptors, we identified that Notch1 mainly mediated COMP-initiated ESC-VSMC differentiation. Mechanistically, COMP N-terminus directly interacted with the EGF11-12 domain of Notch1 and activated Notch1 signaling, as evidenced by co-immunoprecipitation and mammalian two-hybrid assay. In conclusion, COMP served as a potential ligand of Notch1, thereby driving ESC-VSMC differentiation

Structural insights into molecular mechanism for N6-adenosine methylation by MT-A70 family methyltransferase METTL4

METTL4 belongs to a subclade of MT-A70 family members of methyltransferase (MTase) proteins shown to mediate N6-adenosine methylation for both RNA and DNA in diverse eukaryotes. Here, we report that Arabidopsis METTL4 functions as U2 snRNA MTase for N6−2’-O-dimethyladenosine (m6Am) in vivo that regulates flowering time, and specifically catalyzes N6-methylation of 2’-O-methyladenosine (Am) within a single-stranded RNA in vitro. The apo structures of full-length Arabidopsis METTL4 bound to S-adenosyl-L-methionine (SAM) and the complex structure with an Am-containing RNA substrate, combined with mutagenesis and in vitro enzymatic assays, uncover a preformed L-shaped, positively-charged cavity surrounded by four loops for substrate binding and a catalytic center composed of conserved residues for specific Am nucleotide recognition and N6-methylation activity. Structural comparison of METTL4 with the mRNA m6A enzyme METTL3/METTL14 heterodimer and modeling analysis suggest a catalytic mechanism for N6-adenosine methylation by METTL4, which may be shared among MT-A70 family members