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Introduction: Our objective was to explore the clinical features, pregnancy complications, and outcomes of subchorionic hematomas (SCHs) in the third trimester. Material and methods: This was a retrospective analysis and evaluation of 1112 cases diagnosed with SCHs from January 2014 to December 2020. Comparisons were performed according to the clinical features (e.g., number of pregnancies, parity, gestational weeks, and age), pregnancy complications, and outcomes associated with SCHs. Results: In total, 71.85% (799/1112) of the patients were diagnosed with different pregnancy complications. The overall rates of gestational diabetes mellitus (GDM), hypertensive disorder complicating pregnancy (HDCP), premature rupture of membranes (PROM), and IVF were 12.14%, 7.55%, 17.27%, and 10.34%, respectively. The positive rates for newborn outcomes such as premature birth and low birth weight (LBW) were 9.35% and 6.47%, respectively. There was a significant relationship between repeated pregnancies and the incidence of GDM (p < 0.05), but not HDCP, PROM, or IVF. The proportion of SCH patients who conceived through IVF was significantly higher among primiparas than among multiparas (p < 0.05), but was not significantly different in terms of GDM, HDCP, or PROM. Premature birth was not a high-risk factor for most SCH patients with HDCP, IVF, or PROM (p < 0.05), most of whom delivered at term. The rate of cesarean sections for SCH patients with GDM, HDCP, or IVF was significantly higher than that for vaginal deliveries (p < 0.05), but this was not affected by age. Conclusions: The coexistence of SCHs with HDCP, IVF, or PROM lacked an effective predictive value for premature birth, but increased the rate of a cesarean section. [ABSTRACT FROM AUTHOR]

We prepare metal films with various thicknesses on liquid substrates by thermal evaporation and investigate the annealing effect on these films. Gold films deposited on a silicone oil surface consist of a large number of branched aggregates, which contains plenty of gold nanoparticles. This characteristic morphology is mainly attributed to the isotropic and free-sustained liquid substrate. Thermal annealing results in the reintegration of nanoparticles; thus, the surface morphology and microstructure of gold films change significantly. The dependence of annealing conditions on the surface-enhanced Raman scattering performance of gold films is studied, in which gold films show favorable Raman activity when annealed at certain annealing temperature and the experimental results are verified by simulation analysis. The study on the optimal annealing temperature of surface-enhanced Raman scattering substrate will pave the way for the potential application of films deposited on liquid surfaces in microfluidics and enhanced Raman detection. [ABSTRACT FROM AUTHOR]

Abstract The present study was aimed to establish a simple and robust protocol that was more suitable for sorting discharges of the arterial baroreceptor. Oligo-unit (≤ 5) baroreceptor discharges were recorded in vitro from fine filaments of the rabbit carotid sinus nerve. Different time windows, covering the fast phase only or both the fast and slow phases of the spike were used to extract spike event data for sorting. Three measurements focusing on the fast phase of spikes—the maximum slope in the ascending limb from the half amplitude to the peak, the peak amplitude, and the width of the spike at the half amplitude—were selected as a feature set. The performance of this measurement-based analysis with subsequent K-means algorithm (MBAKM) in sorting oligo-unit discharges was compared with the performance of principal component analysis followed by K-means (PCAKM) and template matching (TM). The present study proved that: (1) MBAKM was more discriminative with less intervention than PCAKM and TM in determining the number of clusters and cluster attributions of spikes; (2) there was a higher consistency (larger intersection set) among the three algorithms with narrow windows of 0.45–0.65 ms than with 1.45 ms window. This study suggested that discriminative features were embodied in the fast phase of spikes and the oligo-unit discharges of baroreceptors could be sorted more robustly and accurately with less intervention by MBAKM than by PCAKM and TM. MBAKM with narrow time window would be promising in further studying baroreceptors and multiunit discharges from other neural structures. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Pinellia pedatisecta Schott extract (PE), a traditional Chinese medicine, has been used to reduce swelling, dry dampness and suppress cervical tumors. Aims To evaluate the roles of PE in the regulation of anti-tumor effects and the cellular immune response in the tumor microenvironment. Methods The immune microenvironment of HPV + TC-1 tumors was examined by immunohistochemistry, real-time PCR and flow cytometry. Results Our study demonstrated that PE in vitro could significantly increase the percentage of apoptosis and necrosis in HPV + TC-1 cells and block the cell cycle phase. In vivo treatment with PE eradicated established subcutaneous HPV + TC-1 tumors in wild-type C57BL/6 mice by infiltrating CD8 + T cells and CD4 + T cells and by directly suppressing tumor growth and resistance to avascular necrosis. The key factors in the canonical Wnt signaling pathway in the experimental group ( PE+mDC+naive CD4 + T cells ) were challenged, and the levels of beta-catenin, C-myc, cyclin D1 and PPAR1 were significantly enhanced at the 5 th day. In particular, the subset proportion of Th1 cells (characterized by IFNγ production and the transcription factor Tbet) increased significantly, and both Th2 cells (characterized by IL-4 production and the transcription factor GATA3) and Th17 cells (characterized by IL-17 production and the transcription factor RoRγt) decreased profoundly. Conclusions These findings linked the anti-tumor properties of PE with the immune microenvironment to present a reliable basis for the future practical application of PE in cervical cancer as a novel and pharmacologically safe immunotherapy strategy. [ABSTRACT FROM AUTHOR]

Convolutional neural networks (CNNs) have achieved significant success in the field of single image dehazing. However, most existing deep dehazing models are based on atmospheric scattering model, which have high accumulate errors. Thus, Cascaded Deep Residual Learning Network for Single Image Dehazing (CDRLN) with encoder-decoder structure is proposed, which can directly restore the clean image from hazy image. The proposed algorithm consists of a primary network which predicts a residual map based on the entire image, and a sub-network which restores the haze-free image based on the residual image and the original hazy image. The encoder part of CDRLN embeds a context feature extraction module to fuse information effectively. In addition, the two-stage cascaded strategy can avoid feature dilution and restore detailed information, which reduces the color distortion in the dehazing process and generates a more natural, more real and less artifacts dehazed image. Experimental results demonstrate that the CDRLN surpasses previous state-of-the-art single image dehazing methods by a large margin on the synthetic datasets as well as real-world hazy images, and the visual effect of dehazed image is better. [ABSTRACT FROM AUTHOR]

Differential evolution (DE) is a simple yet efficient evolutionary algorithm for real-world engineering problems. However, its search ability should be further enhanced to obtain better solutions when DE is applied to solve complex optimization problems. This paper presents an enhanced differential evolution with elite chaotic local search (DEECL). In DEECL, it utilizes a chaotic search strategy based on the heuristic information from the elite individuals to promote the exploitation power. Moreover, DEECL employs a simple and effective parameter adaptation mechanism to enhance the robustness. Experiments are conducted on a set of classical test functions. The experimental results show that DEECL is very competitive on the majority of the test functions. [ABSTRACT FROM AUTHOR]

Growing evidence indicates that transient receptor potential canonical (TRPC) channels play important roles in various Ca-mediated physiological and pathophysiological processes, including development. Many types of TRPC proteins are expressed in the heart. However, limited data are available comparing the expression and localization among TRPC proteins in the ventricular myocyte at various developmental stages. Our purpose is to investigate the expression and localization profile of TRPC proteins in ventricular myocytes of fetal (18.5 days), neonatal (< 24 h after birth) and adult (8 week old) rats. Western blotting, immunofluorescence and confocal laser scanning microscopy were employed. TRPC1/3-6 proteins were expressed in the rat ventricle throughout the three developmental stages. The expression profile of TRPC1/3/4 in the ventricle followed an upward trend from the fetus to the adult. By contrast, TRPC6 in the ventricle was expressed at the highest level in the fetal group and was sharply down-regulated immediately after birth. TRPC5 expression in the ventricle did not change significantly during the three stages. TRPC1/3/5/6 proteins were localized to the T-tubule and TRPC1/3/4/6 to intercalated disks in adult myocytes. The wide spatiotemporal overlap and dynamic regulation of TRPC expression in ventricular myocytes indicates potential complex combinations and redundancy of native TRPC proteins in the heart and gives important clues for further investigations into the exact subunit compositions and functional properties of native TRPC channels in the heart. [ABSTRACT FROM AUTHOR]

Mutations that lead to muscular dystrophy often create deficiencies in cytoskeletal support of the muscle sarcolemma causing hyperactive mechanosensitive cation channel (MSC) activity and elevated intracellular Ca2+. Caveolae are cholesterol-rich microdomains that form mechanically deformable invaginations of the sarcolemma. Mutations to caveolin-3, the main scaffolding protein of caveolae in muscle, cause Limbe-Girdle muscular dystrophy. Using genetic and acute chemical perturbations of developing myotubes we investigated whether caveolae are functionally linked to MSCs. MSC sensitivity was assayed using suction application to patches and probe-induced indentation during whole-cell recordings. Membrane mechanical stress in patches was monitored using patch capacitance/impedance. Cholesterol depletion disrupted caveolae and caused a large increase in MSC current. It also decreased the membrane mechanical relaxation time, likely reflecting cytoskeleton dissociation from the bilayer. Reduction of Cav3 expression with miRNA also increased MSC current and decreased patch relaxation time. In contrast Cav3 overexpression produced a small decrease in MSC currents. To acutely and specifically inhibit Cav3 interactions, we made a chimeric peptide containing the antennapedia membrane translocation domain and the Cav3 scaffolding domain (A-CSD3). A-CSD3 action was time dependent initially producing a mild Ca2+ leak and increased MSC current, while longer exposures decreased MSC currents coinciding with increased patch stiffening. Images of GFP labeled Cav3 in patches showed that Cav3 doesn’t enter the pipette, showing patch composition differed from the cell surface. However, disruption via cholesterol depletion caused Cav3 to become uniformly distributed over the sarcolemma and Cav3 appearance in the patch dome. The whole-cell indentation currents elicited under the different caveolae modifying conditions mirror the patch response supporting the role of caveolae in MSC function. These studies show that normal expression levels of Cav3 are mechanoprotective to the sarcolemma through multiple mechanisms, and Cav3 upregulation observed in some dystrophies may compensate for other mechanical deficiencies. [ABSTRACT FROM AUTHOR]

Cardiac KATP channels link metabolism with electrical activity. They are implicated in arrhythmias, secretion of atrial natriuretic peptide and protection of the heart from hypertrophy and failure. These processes may involve mechanosensitivity. KATP channels can be activated by mechanical stimulation and disrupting the cortical actin increases the activity. We propose that KATP channels are modulated by local bilayer tension and this tension is affected by cortical F-actin. Here we measured KATP background activity and stretch sensitivity with inside-out patches of rat ventricular myocytes before and after disrupting F-actin. Disrupting F-actin potentiated background activity but did not influence the slope sensitivity in the semilog relationship of NPo vs. suction that is a measure of the change in dimensions between closed and open states. Thus actin alters prestress on the channel probably by parallel elastic sharing of mean cortical tension with the bilayer. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a pregnancy complication with high maternal and fetal morbidity and mortality rates. During pregnancy, the concentration of exosomes in the maternal blood circulation would increase, establishing that plasma exosomes play a role in the development of pregnancy. Our previous study implied the important role of exosomal miR-199a-5p in preeclampsia with severe features (sPE). This study aims to reveal the role of exosomal miR-199a-5p in contribution to the development of sPE. The results showed that the expression of miR-199a-5p was significantly higher in plasma exosomes and placenta tissue from patients with sPE than that in normal pregnant women. Additionally, hydrogen peroxide (H2O2) could upregulate the expression of miR-199a-5p in BeWo cells and cell-derived exosomes. In terms of the regulatory effect, exosomal miR-199a-5p was observed to inhibit the expression of SIRT1 in human umbilical venous endothelial cells (HUVECs). Moreover, the treatment of both miR-199a-5p-overexpressed exosomes and SIRT1 inhibitor EX527 could decrease the nitric oxide production, elevate the intracellular reactive oxygen species level, and enhance the expressions of ICAM-1 and VCAM-1 of HUVECs. Thus, our findings suggest that the upregulated plasma exosomal miR-199a-5p in sPE might result from the trophoblast of the impaired placenta under oxidative stress. Furthermore, exosomal miR-199a-5p could impair the endothelial cell function via targeting SIRT1, contributing to the development of preeclampsia. [ABSTRACT FROM AUTHOR]

Stress in the lipids of the cell membrane may be responsible for activating stretch-activated channels (SACs) in nonspecialized sensory cells such as cardiac myocytes, where they are likely to play a role in cardiac mechanoelectric feedback. We examined the influence of the mechanical microenvironment on the gating of stretch-activated potassium channels (SAKCs) in rat atrial myocytes. The goal was to examine the role of the cytoskeleton in the gating process. We recorded from blebs that have minimal cytoskeleton and cells treated with cytochalasin B (cyto-B) to disrupt filamentous actin. Histochemical and electron microscopic techniques confirmed that the bleb membrane was largely free of F-actin. Channel currents showed mechanosensitivity and potassium selectivity and were activated by low pH and arachidonic acid, similar to properties of TREK-1. Some patches showed a time-dependent decrease in current that may be adaptation or inactivation, and since this decrease appeared in control cells and blebs, it is probably not the result of adaptation in the cytoskeleton. Cyto-B treatment and blebbing caused an increase in background channel activity, suggesting a transfer of stress from actin to bilayer and then to the channel. The slope sensitivity of gating before and after cyto-B treatment was similar to that of blebs, implying the characteristic change of dimensions associated with channel gating was the same in the three mechanical environments. The mechanosensitivity of SAKCs appears to be the result of interaction with membrane lipids and not of direct involvement of the cytoskeleton. [ABSTRACT FROM AUTHOR]

The present study was undertaken to investigate the protective effect of H2S against myocardial ischemia–reperfusion (I/R) injury and its possible mechanism by using isolated heart perfusion and patch clamp recordings. Rat isolated hearts were Langendorff-perfused and subjected to a 30-minute ischemia insult followed by a 30-minute reperfusion. The heart function was assessed by measuring the LVDP, ±dP/dtmax, and the arrhythmia score. The results showed that the treatment of hearts with a H2S donor (40 μmol/L NaHS) during reperfusion resulted in significant improvement in heart function compared with the I/R group (LVDP recovered to 85.0% ± 6.4% vs. 35.0% ± 6.1%, +dP/dtmax recovered to 80.9% ± 4.2% vs. 43.0% ± 6.4%, and –dP/dtmax recovered to 87.4% ± 7.3% vs. 53.8% ± 4.9%; p < 0.01). The arrhythmia scores also improved in the NaHS group compared with the I/R group (1.5 ± 0.2 vs. 4.0 ± 0.4, respectively; p < 0.001). The cardioprotective effect of NaHS during reperfusion could be blocked by an ATP-sensitive potassium channel (KATP) blocker (10 μmol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of KATP channels from 0.07 ± 0.03 to 0.15 ± 0.08 after application of 40 μmol/L NaHS and from 0.07 ± 0.03 to 0.36 ± 0.15 after application of 100 μmol/L NaHS. These findings provide the first evidence that H2S increases the open probability of KATP in cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion. [ABSTRACT FROM AUTHOR]

In order to further improve the identification efficiency of tobacco mildew, a rapid identification model of tobacco mildew based on random forest algorithm was proposed in this study. In order to ensure the feasibility and pertinence of the model study, this study takes redried leaf tobacco as the research object, selects high-temperature and high-humidity environment as the experimental conditions, and obtains the sample data of the degree of tobacco mildew under different experimental conditions. At the same time, this paper constructs a rapid identification model of tobacco mildew with the help of random forest algorithm. Through the model experimental results, it is found that the accuracy of the model for the rapid identification of training samples can reach 93.82%, while the accuracy of independent testing is 94.84%. The experimental results fully reflect the availability and efficiency of the random forest algorithm model in the rapid identification of tobacco mildew. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation has been identified as biomarkers for breast cancer detection. Coiled-coil domain containing 12 gene (CCDC12) implicated in tumorigenesis. This study aims to investigate the potential of blood-based CCDC12 methylation for breast cancer detection. DNA methylation level of CpG sites (Cytosine-phosphate Guanine dinucleotides) in CCDC12 gene was measured by mass spectrometry in 255 breast cancer patients, 155 patients with benign breast nodules and 302 healthy controls. The association between CCDC12 methylation and breast cancer risk was evaluated by logistic regression and receiver operating characteristic curve analysis. A total of eleven CpG sites were analyzed. The CCDC12 methylation levels were higher in breast cancer patients. Compared to the lowest tertile of methylation level in CpG_6,7, CpG_10 and CpG_11, the highest quartile was associated with 82, 91 and 95% increased breast cancer risk, respectively. The CCDC12 methylation levels were associated with estrogen receptor (ER) and human epidermal growth factor 2 (HER2) status. In ER-negative and HER2-positive (ER-/HER2+) breast cancer subtype, the combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER−/HER2+ breast cancer from the controls (AUC = 0.727). The hypermethylation levels of CCDC12 in peripheral blood could be used for breast cancer detection. Breast cancer detection could be facilitated by novel blood-based DNA methylation biomarkers. The methylation levels of CpG sites in CCDC12 were higher in breast cancer than those in controls. The combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER-/HER2+ breast cancer subtype from the controls. [ABSTRACT FROM AUTHOR]

Pinellia pedatisecta Schott (PPS)is a traditional Chinese medicine functioning as reducing swelling and drying dampness. Pinellia pedatisecta Schott extract (PE) has been confirmed to suppress cervical tumor growth and modulate the antitumor CD4+T helper immunity towards Th1. To explore the roles of PE in modulating tumor-associated dendritic cell (TADC) activation and function. For in vivo studies, HPV+TC-1 mouse tumor models were conducted and treated with PE for 3 weeks (10 mg/kg/d or 20 mg/kg/day). The immune profiles of spleen, tumor-draining lymph nodes (TDLNs), tumor and serum were analyzed by flow cytometry and multiplexed bead-based immunoassay. For in vitro studies, TADCs were generated by tumor-conditioned medium and treated with PE solution. The maturation and function of TADCs were evaluated by flow cytometry, ELISA, mixed lymphocyte reaction (MLR) and cytotoxic T lymphocyte (CTL) assay. Furthermore, the effect of PE on SOCS1 pathway was examined by western blotting and real time PCR. PE upregulated the expression of major histocompatibility complex class II (MHCII) and costimulatory molecules CD80 and CD86 on TADCs and promoted IL-12 secretion from TADCs. In addition, PE-treated TADCs promoted the proliferation of CD4+ and CD8+ T cells and induced the differentiation of IFN-γ+CD4+ and GZMB+CD8+ T cells. PE-treated TADCs also elicited a more powerful antigen-specific cytotoxic T lymphocyte (CTL) response. Furthermore, PE treatment in vivo enhanced the proliferation, activated the functional ability (increased Ki67, CD137, GZMB or IFN-γ, TNF-α expression) and reversed the exhaustion (impaired CD95 or PD-1 expression) of antitumor T cells. Mechanistically, PE inhibited SOCS1-restrained JAK2 activation in TADCs. PE efficiently restored the immature status of TADCs and enhanced their function as antigen-presenting cells to further elicit antitumor Th1 and CTL responses, suggesting that PE may be a potential immunomodulatory drug for cancer treatment. Image 1 [ABSTRACT FROM AUTHOR]

Pulmonary lobe segmentation is an important prerequisite for accurately quantifying pulmonary damage in many pulmonary diseases and planning treatment. However, due to the incomplete lobar structures and morphological changes caused by diseases, the lobe segmentation still encounters great challenges. In this study, a Learnable Interpolation and Extrapolation Network (LIE‐Net) is proposed to form complete and consecutive fissure surfaces by learning to extract information of the fissures from existing fissure points and absent points (unsegmented points belonging to fissures) to predict the z coordinate of the absent fissure points. The completed pulmonary fissures are further used for accurate pulmonary lobe segmentation. Specifically, LIE‐Net takes the coordinate information of existing fissure points (their (x, y, z) coordinates) and absent fissure points (their (x, y) coordinates) as two independent inputs, and predicts the z coordinates of absent points. The proposed LIE‐Net makes voxel‐wise predictions based on the spatial structure characteristics of the lung fissure, and is able to provide a consecutive fissure surface in space. According to the evaluation of radiologists, the lobe segmentation performance was remarkably enhanced in approximately 76% of patients in our additional dataset after the application of LIE‐Net, especially for those cases with large‐scale missing fissures. [ABSTRACT FROM AUTHOR]

Superheated steam (SS), far-infrared radiation (FIR), and microwave treatment (Mw) are emerging stabilization treatments to improve the shelf life of black rice. However, their effects on the digestibility of cooked black rice remain unclear. Therefore, the structural characteristics of cooked black rice influenced by the above treatments and their effects on in vitro digestibility were compared. Results indicated that cooked SS stabilized black rice (CBR-SS) had the highest crystallinity (9.17%), the lowest porosity, and the completest protein network. Besides, the lowest level of rapidly digestible starch (31.02%) and the highest level of resistant starch (32.75%) were observed in CBR-SS. Consequently, CBR-SS showed the lowest equilibrium hydrolysis rate, kinetic constant, and expected glycemic index during in vitro starch digestion among the cooked stabilized black rice samples. Furthermore, the level of total bioaccessible phenolic compounds and antioxidant activity was the highest in CBR-SS. Therefore, SS stabilization treatment is the most valued as it grants cooked black rice the slowest starch digestibility and the highest level of bioaccessible phenolic compounds. [ABSTRACT FROM AUTHOR]

• The sea urchin-like Fe 3 O 4 @C wave absorber was obtained through a simple hydrothermal combined with calcination process. • The Fe 3 O 4 @C absorber exhibited −57.1 dB reflection loss at 5.10 mm thickness and an effective absorption bandwidth of 4.0 GHz. • The carbon content in Fe 3 O 4 @C obviously affected the electromagnetic parameters and wave-absorbing properties of the product. • The growth mechanism of Fe 3 O 4 @C with sea urchin-like morphology was proposed. The development of electromagnetic wave absorbing materials is crucial for various applications. Carbon materials and ferrite materials were recognized as ideal candidates of absorbing agents due to their respective dielectric loss and magnetic loss capabilities. In this study, Fe 3 O 4 @C were prepared using hydrothermal carbonization coupling method. The microstructure and morphology of Fe 3 O 4 @C were studied using SEM, TEM, XRD and TG. The results showed that Fe 3 O 4 @C exhibited a hollow sea urchin-like structure. The molar ratio of carbon to iron sources in the raw materials significantly influenced the crystal structure of the product. The growth mechanism of sea urchin-like Fe 3 O 4 @C was proposed. The carbon content in Fe 3 O 4 @C increased with the increase of molar ratio of glucose and iron (III) sulfate. The Fe 3 O 4 @C with carbon content of 31.10 % exhibited optimal absorption performance, with a minimum reflection loss of −57.1 dB at a matching thickness of 5.10 mm and effective absorption bandwidth (EAB) of 4 GHz. Electromagnetic parameters and absorption performance could be adjusted by varying the molar ratio of glucose and iron (III) sulfate. The unique sea urchin-like structure enhanced multiple reflection of electromagnetic waves. Interface polarization, conductivity loss and synergistic effect between carbon and Fe 3 O 4 also contributed to the favorable absorption properties. [ABSTRACT FROM AUTHOR]

General cognitive status (GCS) is a composite of cognitive abilities reflecting full function. The literature suggests a relationship between cognitive processing speed and GCS, as well as age-related changes of processing speed on cognitive performance. Therefore, this study recruited 34 younger and 39 older adults to verify age-related differences in relationships between cognitive processing speed and GCS. We measured cognitive processing speed with the Processing Speed Index of the Wechsler Adult Intelligence Scale. Findings indicated that cognitive processing speed predicted GCS in older but not younger adults. Future research may be needed to verify the training effect of processing speed on GCS. This study also further examined cognitive factors related to processing speed in aging and the relationships between cognitive processing speed and verbal fluency, cognitive inhibition, and divided attention. A stepwise regression analysis indicated that only verbal fluency contributed significantly to cognitive processing speed in older adults, accounting for 21% of the variance. These observations suggest that age-related changes of prefrontal regions may not fully explain age-related decline in cognitive processing speed. [ABSTRACT FROM PUBLISHER]

Storing energy in the form of triglyceride (TG) is one of the basic functions of adipose tissue. Large‐conductance calcium‐activated potassium channels (BKCa channels) are expressed in adipose tissue and adipocyte‐specific BKCa deficiency resists obesity in mice, but the role of BKCa channels in lipid deposition and the underlying mechanisms have not been elucidated. In the present study, we generated BKCa knockout (KO) rats and performed a transcriptome analysis of adipose tissue. We found that the phosphoinositide 3‐kinase (PI3K)–protein kinase B (Akt) signaling pathway, which is important for lipid deposition, exhibited the most notable reduction among various signaling pathways in BKCa KO rats compared to wild‐type rats. Insulin‐induced TG deposition, glucose uptake, and Akt (Ser473) phosphorylation were significantly reduced in cultured adipocytes differentiated from adipose‐derived stem cells of BKCa KO rats. Furthermore, we found that the insulin‐induced increase of intracellular calcium resulting from extracellular calcium influx was significantly impaired in BKCa KO adipocytes. Finally, insulin activated BKCa currents through PI3K, which was independent of Akt and intracellular calcium. The results of this study suggested that BKCa channels participate in the insulin signaling pathway and promote TG deposition by increasing extracellular calcium influx in adipocytes. [ABSTRACT FROM AUTHOR]

Background: Neuronal hyperactivity related to β-amyloid (Aβ) is considered an early warning sign of Alzheimer disease (AD). Although increasing evidence supports this opinion, the underlying mechanisms are still unknown. Methods: Here, we recorded whole-cell synaptic currents and membrane potentials using patch clamping of acute hippocampal slices from human amyloid precursor protein (APP)/presenilin-1 transgenic (5XFAD) mice and their wild-type littermates. Biochemical methods, electron microscopic imaging, behavioral tests, and intraventricular drug delivery applied with osmotic pumps were used in this study. Results: We confirmed hyperactivity of hippocampal CA1 pyramidal neurons in 5XFAD mice using whole-cell electrophysiological recording at 2.5 months old, when local Aβ-positive plaques had not developed and only mild cognitive dysfunction occurred. We further discovered attenuated inhibitory postsynaptic currents and unchanged excitatory postsynaptic currents in CA1 pyramidal neurons, in which the intrinsic excitability was unchanged. Moreover, the density of both γ-aminobutyric acid A (GABAA) receptor subunits, α1 and γ2, was reduced in synapses of the hippocampus in transgenic mice. Intriguingly, early intervention with the GABAA receptor agonist gaboxadol reversed the hippocampal hyperactivity and modestly ameliorated cognitive performance in 5XFAD mice under our experimental conditions. Conclusions: Inhibitory postsynaptic disruption critically contributes to abnormalities in the hippocampal network and cognition in 5XFAD mice and possibly in AD. Therefore, strengthening the GABAergic system could be a promising therapy for AD in the early stages. [ABSTRACT FROM AUTHOR]

Pinellia pedatisecta Schott extract (PE) is generated from Pinellia pedatisecta Schott, a traditional Chinese medicinal plant. PE suppresses cervical tumor growth and exhibits effects on dendritic cells (DCs) that lead to modulation of antitumor CD4+ and CD8+ responses. To explore the underlying mechanisms by which PE modulates tumor-associated dendritic cell (TADC) activation and function. DCs and TADCs were generated from murine bone marrow and exposed to PE solutions at different doses, as well as to repeated doses separated at different time intervals. Quantitative PCR, Western blot analysis, flow cytometry, and gene silencing were used to analyze the modulatory effects of PE on the SOCS1/JAK2/STAT pathways. Furthermore, we separated human cervical tumor-infiltrated DCs (TIDCs) and conducted an ex-vivo stimulation model to observe the effect of PE. For phenotypic analysis of cultured DCs and ex vivo human specimens, we used flow cytometry to detect the molecular markers associated with cell function. In cultured TADCs and human cervical TIDCs, maturation- and functional markers (MHCII, CD80, CD83, CD86, and IL-12) were downregulated, whereas SOCS1 was upregulated. PE enhanced the expression of CD80, CD86, and IL-12 in cervical TIDCs, which induced increased expression of CD107a, GZMB, and perforin in CTLs, and furthermore induced apoptosis in a larger number of tumor cells. In cultured TADCs, PE downregulated SOCS1 expression and activated the phosphorylation of JAK2, STAT1, STAT4, and STAT5 in both dose- and time-dependent manners. The effects of PE upregulating MHCII, CD80, CD86, IL-12 on TADCs were blocked after SOCS1 silencing. In this study, PE restored the impaired function of cervical TIDCs, thereby eliciting further antitumor CTL responses. The effects of PE on TADCs were mediated through inhibition of SOCS1 and activation of downstream JAK2-STAT1/STAT4/STAT5 pathways. PE may be a potent and effective immunomodulatory drug for antitumor treatment via the blockade of SOCS1 signaling in DCs. Image 1 • Human cervical cancer infiltrated dendritic cells exhibited dampened activating phenotype and SOCS1 hyperexpression. • PE restored the impaired function of cervical cancer infiltrated dendritic cells and enhanced antitumor T cell responses. • The effects of PE are mediated through inhibition of SOCS1 and activation of downstream JAK/STAT signalling. [ABSTRACT FROM AUTHOR]

Groundwater is generally important water resource for islands. Groundwater recharge source and its hydrochemical characteristics are vital issues for the sustainable development and management of island groundwater resources. In this study, taking Donghai island which is featured with multi-layer aquifer structure as an example, by comprehensive using of statistical analysis, stable isotope (2H-18O), Gibbs diagram and ion ratio graph, we conducted a comprehensive hydrochemistry investigation for the groundwater in the shallow aquifer (i.e., phreatic and feeble confined aquifers) and middle confined aquifer of this island. And the hydrochemical characteristics, recharge sources, hydrogeochemical processes and source of element components of groundwater in different aquifers of Donghai island were identified. The results show that the major ions and TDS of the shallow groundwater are higher than those of the confined groundwater, and that those aquifers have not suffered significant seawater intrusion. The main hydrochemical types of shallow groundwater and confined groundwater are Cl·SO 4 -Ca·Na and HCO 3 -Na·Mg, respectively. Different hydrochemical types and chemical component concentrations between these two aquifers indicate that the hydraulic relationship between aquifers is relatively weak. The results of 2H-18O stable isotope and deuterium excess indicate that the shallow groundwater originated from local precipitation and that the recharge period of the confined groundwater is different from the shallow groundwater. Results of ion ratio reveal that the island groundwater hydrochemistry is mainly controlled by the water-rock interaction, featuring with dissolution of silicate rocks (such as sodium feldspar, potassium feldspar, calcium feldspar and biotite). In addition, cation exchange is also an important hydrogeochemical process controlling the hydrochemical composition of the confined groundwater. The results will be helpful for understanding of the local island hydrogeology and be supportive for the groundwater resources quantitative research such as numerical modeling for Donghai island. • Hydrogeochemical and isotopic characteristics identified the hydrogeology conditions. • d and oxygen shift distinguished the hydrogeochemical evolutions in two aquifers. • Confined groundwater occurred intense water-rock interaction than shallow groundwater. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (PCa) is a widespread urinary neoplasm and one of the most prevalent and second most frequent malignancies diagnosed in males worldwide. This study aimed to identify a candidate marker and explore its molecular mechanism in PCa. Methods: Gene expression datasets, GSE55945 (n=21) and GSE46602 (n=50), were downloaded from the Gene Expression Omnibus database. Bioinformatic approaches were applied to identify potential markers. Effects of the candidate marker on proliferation, migration, invasion, and ferroptosis (ferrous iron and malondialdehyde (MDA)) in PCa cells and its mechanism were assessed after performing cell transfection. Results: A total of 1435 common differentially expressed genes were identified in GSE55945 and GSE46602. Five key gene modules were listed based on a protein–protein interaction network, containing five hub genes. Pannexin 2 (PANX2), a candidate marker was identified, and findings revealed substantial upregulation of its expression levels in PCa cell lines. Blocking expression of PANX2 resulted in suppression of proliferation, migration, and invasion in PCa cells, while increasing ferrous iron and MDA levels. However, these effects were rescued by Nrf2 activator, oltipraz. The Nrf2 signaling pathway was consequently applied to determine underlying mechanism of PANX2 in PCa cells. We established that silencing PANX2 remarkably reduced protein expression levels in members of Nrf2 signaling pathway (Nrf2, HO-1, and FTH1). Conclusion: Our study demonstrated that PANX2 is implicated in the pathogenesis of PCa, which regulates malignant phenotypes and ferroptosis through Nrf2 signaling pathway, and maybe a potential therapeutic target for PCa. [ABSTRACT FROM AUTHOR]

We report a facile approach for the wettability control of copper (Cu) films grown on a silicone oil surface by thermal evaporation. Characteristic aggregation of deposited Cu atoms was obtained due to the isotropic and free-sustained liquid substrates. Through the fine adjustment of deposition parameters in the growth process, Cu films with controlled morphology from ramified aggregates to continuous films can be prepared. Accompanied with the evolution of morphology, water wettability was effectively reduced and the hydrophilic-to-hydrophobic transition can be achieved. The relationship between the wettability and microstructure of Cu films was investigated. These films with characteristic morphology and controlled wettability may open lots of application avenues in the development of devices with modified surface properties. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: We have previously reported that high glucose impairs coronary vasodilation by reducing voltage-gated K+ (Kv) channel activity. However, the underlying mechanisms remain unknown. Advanced glycation end products (AGEs) are potent factors that contribute to the development of diabetic vasculopathy. The aim of this study was to investigate the role of AGEs in high glucose-induced impairment of Kv channels-mediated coronary vasodilation. Methods: Patch-clamp recording and molecular biological techniques were used to assess the function and expression of Kv channels. Vasodilation of isolated rat small coronary arteries was measured using a pressurized myograph. Treatment of isolated coronary vascular smooth muscle cells (VSMCs) and streptozotocin-induced diabetic rats with aminoguanidine, the chemical inhibitor of AGEs formation, was performed to determine the contribution of AGEs. Results: Incubation of VSMCs with high glucose reduced Kv current density by 60.4 ± 4.8%, and decreased expression of Kv1.2 and Kv1.5 both at the gene and protein level, whereas inhibiting AGEs formation or blocking AGEs interacting with their receptors prevented high glucose-induced impairment of Kv channels. In addition, diabetic rats manifested reduced Kv channels-mediated coronary dilation (9.3 ± 1.4% vs. 36.9 ± 1.4%, P < 0.05), which was partly corrected by the treatment with aminoguanidine (24.4 ± 2.2% vs. 9.3 ± 1.4%, P < 0.05). Conclusions: Excessive formation of AGEs impairs Kv channels in VSMCs, then leading to attenuation of Kv channels-mediated coronary vasodilation. [ABSTRACT FROM AUTHOR]

• Variability of GW-SW exchange was dominantly affected by lake level and rainfall. • Monthly groundwater discharge is inversely related to lake level and rainfall. • GW-SW exchange increases while net groundwater discharge decreases in rainy year. • Groundwater is more likely to discharge into rivers during a rainy year. For areas possessing both regional-scale floodplain lakes and complex river system, the allocation pattern of water interchange between the groundwater and the lakes and rivers, as well as its temporal variations under year-scale climate changes, are important issues in regard to water resources and ecology environment but are rarely revealed. This study presented a numerical groundwater modeling of the Poyang Lake area to reveal the difference of the temporal variation patterns of the groundwater-lake water interchange and that of the groundwater-river water interchange, and to assess the potential effects of year-scale climate on the temporal-spatial variability of water interchange and on the allocation pattern of the net groundwater discharges into rivers and lake. It is found that the monthly groundwater discharge into surface water exhibits significant temporal variability, which reveals an inverse correlation between monthly groundwater discharge and lake water levels and precipitation amounts. Rainy months can lead to groundwater recharge from the Poyang Lake. Our simulated results reveal that, in the dry year of 2018, the variable monthly groundwater discharge into Poyang Lake and the monthly groundwater recharge from Poyang Lake were 0.97–9.67 × 108 m3/month and 0.07–2.54 × 108 m3/month, respectively. Additionally, the annual water interchange amount between groundwater and the Poyang Lake was 9.44 × 108 m3/year, and the annual net groundwater discharge into Poyang Lake was 6.76 × 108 m3/year. However, the hydraulic interaction between groundwater and the five rivers only features groundwater discharge into rivers with variable monthly groundwater discharge into the five rivers of 0.20–0.72 × 108 m3/month and an annual total groundwater discharge amount of 5.32 × 108 m3/year in 2018. Additionally, our water interchange results of the rainy year of 2010 indicate that the annual water interchange amount between groundwater and the Poyang Lake was 22.74 × 108 m3/year, the annual net groundwater discharge into the Poyang Lake was 1.26 × 108 m3/year, and the annual groundwater discharge into the five rivers was 8.10 × 108 m3/year. These comparisons between the results of the rainy year of 2010 and dry year of 2018 can reveal the effects of the year-scale climate on water exchange between groundwater and surface water and imply that a rainy year can increase the total water interchange amount but decrease the total net groundwater discharge into surface water and that groundwater is more likely to discharge into rivers during a rainy year. Furthermore, it is found that a rainy year can significantly alter the spatial distribution of the water interchange between groundwater and lake water and that the backward particle tracking simulation could be helpful in regard to identifying the spatial distribution of water exchange between groundwater and regional-scale lake. These findings can contribute to a deeper understanding of climate effects on the spatial–temporal variability of water interchange between groundwater and surface water in regional floodplain lake areas and provide useful information for the evaluation of local water resources and the estimation of pollutant transportation. [ABSTRACT FROM AUTHOR]

Epigenetics mainly refers to covalent modifications to DNA or histones without affecting genomes, which ultimately lead to phenotypic changes in cells or organisms. Given the abundance of regulatory targets in epigenetic pathways and their pivotal roles in tumorigenesis and drug resistance, the development of epigenetic drugs holds a great promise for the current cancer therapy. However, lack of potent, selective, and clinically tractable small-molecule compounds makes the strategy to target cancer epigenetic pathways still challenging. Therefore, this review focuses on epigenetic pathways, small molecule inhibitors targeting DNA methyltransferase (DNMT) and small molecule inhibitors targeting histone modification (the main regulatory targets are histone acetyltransferases (HAT), histone deacetylases (HDACs) and histone methyltransferases (HMTS)), as well as the combination strategies of the existing epigenetic therapeutic drugs and more new therapies to improve the efficacy, which will shed light on a new clue on discovery of more small-molecule drugs targeting cancer epigenetic pathways as promising strategies in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a self-perpetuating method of disease prevention but requires a gene drive mechanism to spread these traits to high frequency [1–3]. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread are attractive because they bring about local but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals [4–6]. These features are likely to be important in many social and regulatory contexts [7–10]. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal-effect lethal underdominance (UDMEL), in which two maternally expressed toxins, located on separate chromosomes, are each linked with a zygotic antidote able to rescue maternal-effect lethality of the other toxin. We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. Models suggest that transgene spread can often be limited to local environments. They also show that in a population in which single-locus UDMEL has been carried out, repeated release of wild-type males can result in population suppression, a novel method of genetic population manipulation. [ABSTRACT FROM AUTHOR]

Abstract: Advances in insect transgenesis and our knowledge of insect physiology and genomics are making it possible to create transgenic populations of beneficial or pest insects that express novel traits. There are contexts in which we may want the transgenes responsible for these traits to spread so that all individuals within a wild population carry them, a process known as population replacement. Transgenes of interest are unlikely to confer an overall fitness benefit on those who carry them. Therefore, an essential component of any population replacement strategy is the presence of a drive mechanism that will ensure the spread of linked transgenes. We discuss contexts in which population replacement might be desirable and the requirements a drive system must satisfy to be both effective and safe. We then describe the creation of synthetic Medea elements, the first selfish genetic elements synthesized de novo, with the capability of driving population replacement, in this case in Drosophila. The strategy used to create Drosophila Medea is applicable to a number of other insect species and the Medea system satisfies key requirements for scientific and social acceptance. Finally, we highlight several challenges to implementing population replacement in the wild. [ABSTRACT FROM AUTHOR]

α-Synuclein (α-syn) overload is strongly associated with Parkinson disease (PD), and reduction of the α-syn level by targeting the peptide-based system through the autophagy-lysosomal pathway (ALP) is a promising strategy to delay PD progression. However, if the ALP is comprised, targeting the peptide-based proteasomal degradation system would be a good alternative. In this study, we designed a fusion peptide containing an α-syn-binding domain and a short strong proteasome-targeting motif. Our results reveal that this peptide could specifically bind to α-syn, and direct it to the proteasomes for degradation in a recombinant expression system. Furthermore, by adding a membrane-penetrating motif to this fusion peptide, we demonstrated that it could penetrate into cells and consequently suppress the cellular α-syn level through proteasome degradation in a dose- and time-dependent manner. Functionally, these effects rescued the mitochondrial dysfunction and cellular defects caused by α-syn overexpression in the cultured cells and primary neurons. • A targeting peptide-based system is developed for specific knockdown of α-syn • Synthesized peptide effectively induces α-syn degradation through proteasome pathway • Peptide protects cells from α-syn-induced mitochondria dysfunction • Decrement of α-syn induced by peptide attenuates its neurotoxicity in primary neurons α-Syn is an intrinsically disordered protein that is associated with the core pathology in PD. Qu et al. designed a peptide, composed of a cell-penetrating domain, an α-syn protein-binding domain, and a proteasome-targeting motif, to induce α-syn degradation. Partial reduction of α-syn induced by the peptide prevents its associated cytotoxicity. [ABSTRACT FROM AUTHOR]

Hyperspectral image (HSI) acquisitions are degraded by various noises, among which additive Gaussian noise may be the worst-case, as suggested by information theory. In this paper, we present a novel tensor-based HSI denoising approach by fully identifying the intrinsic structures of the clean HSI and the noise. Specifically, the HSI is first divided into local overlapping full-band patches (FBPs), then the nonlocal similar patches in each group are unfolded and stacked into a new third order tensor. As this tensor shows a stronger low-rank property than the original degraded HSI, the tensor weighted nuclear norm minimization (TWNNM) on the constructed tensor can effectively separate the low-rank clean HSI patches. In addition, a regularization strategy with spatial–spectral total variation (SSTV) is utilized to ensure the global spatial–spectral smoothness in both spatial and spectral domains. Our method is designed to model the spatial–spectral non-local self-similarity and global spatial–spectral smoothness simultaneously. Experiments conducted on simulated and real datasets show the superiority of the proposed method. [ABSTRACT FROM AUTHOR]