Capn2 Correlates With insulin Resistance States in Pcos as Evidenced By Multi-Dataset analysis

OBJECTIVE: IR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies. METHODS: We retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR scores as a phenotypic marker. Gene refinement was executed through the LASSO, SVM, and Boruta feature selection algorithms. qPCR was carried out on selected samples to confirm findings. We predicted both miRNA and lncRNA targets using the ENCORI database, which facilitated the construction of a ceRNA network. Lastly, a drug-target network was derived from the CTD. RESULTS: Thirteen genes related to insulin resistance in PCOS were identified via WGCNA analysis. LASSO, SVM, and Boruta algorithms further isolated CAPN2 as a notably upregulated gene, corroborated by biological verification. The ceRNA network involving lncRNA XIST and hsa-miR-433-3p indicated a possible regulatory link with CAPN2, supported by ENCORI database. Drug prediction analysis uncovered seven pharmacological agents, most being significant regulators of the endocrine system, as potential candidates for addressing insulin resistance in PCOS. CONCLUSIONS: This study highlights the pivotal role of CAPN2 in insulin resistance within the context of PCOS, emphasizing its importance as both a critical biomarker and a potential therapeutic target. By identifying CAPN2, our research contributes to the expanding evidence surrounding the CAPN family, particularly CAPN10, in insulin resistance studies beyond PCOS. This work enriches our understanding of the mechanisms underlying insulin resistance, offering insights that bridge gaps in the current scientific landscape

Clinicopathological Significance and Prognostic Value of DNA Methyltransferase 1, 3a, and 3b Expressions in Sporadic Epithelial Ovarian Cancer

Altered DNA methylation of tumor suppressor gene promoters plays a role in human carcinogenesis and DNA methyltransferases (DNMTs) are responsible for it. This study aimed to determine aberrant expression of DNMT1, DNMT3a, and DNMT3b in benign and malignant ovarian tumor tissues for their association with clinicopathological significance and prognostic value. A total of 142 ovarian cancers and 44 benign ovarian tumors were recruited for immunohistochemical analysis of their expression. The data showed that expression of DNMT1, DNMT3a, and DNMT3b was observed in 76 (53.5%), 92 (64.8%) and 79 (55.6%) of 142 cases of ovarian cancer tissues, respectively. Of the serious tumors, DNMT3a protein expression was significantly higher than that in benign tumor samples (P = 0.001); DNMT3b was marginally significant down regulated in ovarian cancers compared to that of the benign tumors (P = 0.054); DNMT1 expression has no statistical difference between ovarian cancers and benign tumor tissues (P = 0.837). Of the mucious tumors, the expression of DNMT3a, DNMT3b, and DNMT1 was not different between malignant and benign tumors. Moreover, DNMT1 expression was associated with DNMT3b expression (P = 0.020, r = 0.195). DNMT1 expression was associated with age of the patients, menopause status, and tumor localization, while DNMT3a expression was associated with histological types and serum CA125 levels and DNMT3b expression was associated with lymph node metastasis. In addition, patients with DNMT1 or DNMT3b expression had a trend of better survival than those with negative expression. Co-expression of DNMT1 and DNMT3b was significantly associated with better overall survival (P = 0.014). The data from this study provided the first evidence for differential expression of DNMTs proteins in ovarian cancer tissues and their associations with clinicopathological and survival data in sporadic ovarian cancer patients

New Design for Efficient Diesel Particulate Trap Regeneration

Using numerical simulations shows that particulate trap regeneration does not occur below a certain critical inlet temperature, 679 K, for a typical diesel exhaust mass flow rate of 0.0523 kg/s. A new bypass design for particulate trap regeneration has been studied, where the exhaust flow is divided into several channels, which results in a smaller flow rate in each particulate filter. This reduces the critical inlet temperature by 20 K to 40 K, depending on the number of channels, and allows for improved regeneration efficiency with low electric energy consumption. In addition, a zero-order analytical estimate for the ignition time is also developed, given by u ig = 2.50/ξ + ln|ri| - 0.344, where uig is a dimensionless ignition time, ri is a reduced temperature, and ξ depends upon feed temperature, flow rate, oxygen concentration, and initial deposit thickness. An optimal design using three bypass channels is obtained by theory and simulation

Stimulus-entrained oscillatory activity propagates as waves from area 18 to 17 in cat visual cortex.

Previous studies in cat visual cortex reported that area 18 can actively drive neurons in area 17 through cortico-cortical projections. However, the dynamics of such cortico-cortical interaction remains unclear. Here we used multielectrode arrays to examine the spatiotemporal pattern of neuronal activity in cat visual cortex across the 17/18 border. We found that full-field contrast reversal gratings evoked oscillatory wave activity propagating from area 18 to 17. The wave direction was independent of the grating orientation, and could not be accounted for by the spatial distribution of receptive field latencies, suggesting that the waves are largely mediated by intrinsic connections in the cortex. Different from the evoked waves, spontaneous waves propagated along both directions across the 17/18 border. Together, our results suggest that visual stimulation may enhance the flow of information from area 18 to 17

Ignition analysis of wall-flow monolith diesel particulate filters

During regeneration the diesel particulate filter (DPF) is a dynamic system whose trajectory depends on various parameters, especially the inlet gas temperature. Parametric sensitivity signifies large changes in the DPF trajectory induced by small changes in parameters across threshold values. This is a form of critical behavior and can lead to ignition conditions, which is necessary for complete regeneration. In this paper a transient one-phase model is used to derive analytical ignition criteria for a wall-flow monolith diesel particulate filter, which defines the ignition boundaries. The ignition criterion is a function of three parameters: α (a ratio of reaction time to convection time), B (a ratio of adiabatic temperature rise to the characteristic temperature for reaction), and γ (a ratio of total heat capacities of the soot bed to the substrate wall) and is given by α/ β \u3c e when reactant consumption is unimportant (B ≫ 10) and α/β +f(γ)B-g(γ) \u3c e when reactant consumption is important. For most practical cases of the DPF f(γ) = 6.0074 and g(γ) = 0.6411. The validity of the ignition criteria is verified by numerical simulations using the transient one-phase model. The effect of several parameters, i.e., the wall thickness, the total filtration area, the initial loading, the gas flow rate, the oxygen feed concentration, and on the critical inlet gas temperature are also discussed. It is shown that a thin channel wall, a high total filtration area, a high initial loading, a low gas flow rate and a high oxygen feed concentration are desirable for an efficient regeneration. © 2004 Elsevier B.V. All rights reserved

Comparison of the gradient between 2^nd harmonic phase map and RF latency map.

<p>(A) Upper, phase maps computed from the 2^nd harmonic responses of two experiments measured with 4-Hz contrast reversal gratings. Lower, RF latency maps measured in the same two experiments. Broken channels were marked with ‘*’. (B) Gradient directionality of the phase map was significantly larger than that of the RF latency map (P<0.01, n = 10, Wilcoxon signed rank test).</p

LFP responses to contrast reversal gratings and frequency analysis of the responses.

<p>(A) Left panel, raw LFP signal from a single channel during a single trial of visual stimulation by 4-Hz contrast reversal grating. Right panel, the black curve is the z-score signal for the trace shown in the left panel, and the red curve is the signal band-pass filtered at 6–10 Hz (2^nd harmonic response). (B) Upper panel, unfiltered LFP signals averaged over all trials in response to a 4-Hz contrast reversal grating (orientation = 135°) for 7 recording sites distributed along the medial-lateral axis. Lower panel, the z-score signal for the responses shown in the upper panel. (C) Power spectra for responses to 4-Hz contrast reversal gratings in all usable channels of the array from one experiment. Log power is presented. (D) Spatial coherence as a function of frequency computed from a space-frequency SVD analysis, averaged over 10 experiments. Shaded region: standard error of the mean.</p

Waves in single-trial responses and evoked responses to 4-Hz contrast reversal gratings.

<p>(A) Left, schematic drawing of areas 17 and 18 (right hemisphere) and the recording sites of the 8×8 array. A, anterior; P, posterior; L, lateral; M, medial. Middle, Single-trial LFPs band-pass filtered at 6–10 Hz during one cycle of oscillation for the 7 recording sites indicated in the left panel. Each red circle marks the trough of response in each site. Right, phase map obtained by averaging the instantaneous phases over the time points within one cycle of oscillation shown in the middle panel for each recording site across the array. Broken channels were marked with ‘*’. Since the electrodes on the rightmost column of the array were not properly inserted into the cortex because the electrodes were near the lateral sulcus, only 8×7 of the recording sites were used for the analysis. (B) Left, time snapshots of two wave-like events from single-trial responses. The data for the first event was the same as those shown in (A). Right, two phase maps for the two wave-like events, respectively. The phase data were interpolated for display purpose. (C) Responses averaged over all trials (i.e., evoked responses) for the 7 recording sites indicated in the left panel of (A). Systematic phase shift can be observed in every cycle of the responses. (D) Left, snapshots of 2 cycles of evoked responses measured from one experiment in the right hemisphere. Upper right, a phase map computed by the method of Hilbert transform, Lower right, a phase map containing the phase of 2^nd harmonic component computed by Fourier analysis. The two phase maps were computed from the same data set. Data were interpolated for display purpose.</p