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Protein kinase A (PKA) signaling is essential for numerous processes but the subcellular localization of specific PKA regulatory (R) and catalytic (C) subunits has yet to be explored comprehensively. Additionally, the localization of the Cβ subunit has never been spatially mapped in any tissue even though ∼50% of PKA signaling in neuronal tissues is thought to be mediated by Cβ. Here we used human retina with its highly specialized neurons as a window into PKA signaling in the brain and characterized localization of PKA Cα, Cβ, RIIα, and RIIβ subunits. We found that each subunit presented a distinct localization pattern. Cα and Cβ were localized in all cell layers (photoreceptors, interneurons, retinal ganglion cells), while RIIα and RIIβ were selectively enriched in photoreceptor cells where both showed distinct patterns of co-localization with Cα but not Cβ. Only Cα was observed in photoreceptor outer segments and at the base of the connecting cilium. Cβ in turn, was highly enriched in mitochondria and was especially prominent in the ellipsoid of cone cells. Further investigation of Cβ using RNA BaseScope technology showed that two Cβ splice variants (Cβ4 and Cβ4ab) likely code for the mitochondrial Cβ proteins. Overall, our data indicates that PKA Cα, Cβ, RIIα, and RIIβ subunits are differentially localized and are likely functionally non-redundant in the human retina. Furthermore, Cβ is potentially important for mitochondrial-associated neurodegenerative diseases previously linked to PKA dysfunction.

For improving the production efficiency of connecting rods by optimizing the shot peening process,the arc height values of Almen test pieces under different processes were tested,the saturation curves of the shot peening processes were drawn,and finally,the optimum shot peening process was determined according to the Almen 10% theory.The microhardness,surface roughness and residual compressive stress of the sample under the optimal peening process were investigated.Results showed that after shot peening,the hardness of the sample was improved from the original 334 HV to 408 HV,the surface roughness increased from 0.26 μm to 2.68 μm,the residual compressive stress gradually decreased from the surface to the core,and the highest residual compressive stress on the surface was-554 MPa.When shot peened under the optimal process conditions,the connecting rod could meet the technical requirements.

Background: Benzene and its metabolite hydroquinone (HQ) are widely used in daily life, and long‐term exposure to benzene or HQ can induce acute myeloid leukemia (AML). Circular RNAs (circRNAs) are mostly produced by reverse splicing of gene exon mRNA precursors. The modulation of circRNA expression is connected to leukemia progression; however, the molecular mechanism is still unknown. Materials and methods: In this study, the cells were divided into four groups: PBS control group (PBS‐TK6), TK6 malignantly transformed cells induced by 10.0 μmol/L HQ (HQ‐TK6), and HQ‐TK6 cells treated with 5 μmol/L 5‐AzaC (DNA methyltransferase inhibitor) for 24 h (HQ + 5‐AzaC). HQ‐TK6 cells were treated with 200 nmol/L TSA (histone deacetylation inhibitor) for 24 h (HQ + TSA). qRT–PCR was used to identify the differential hsa_circ_401351 expression between the four groups. We further determined the hsa_circ_401351 promoter methylation level with methylation‐specific PCR. DNMT1 and DNMT3b were knocked down by CRISPR/Cas9 to elucidate the specific molecular mechanism of hsa_circ_401351 in HQ‐TK6 cells. CCK‐8 and flow cytometry detected cell proliferation and apoptosis, respectively, after hsa_circ_401351 was overexpressed in HQ‐TK6 cells. Results: Compared with the PBS‐TK6 group, the expression of hsa_circ_401351 was found to be lower in the HQ‐TK6 group. Nevertheless, treatment with 5‐AzaC or TSA increased hsa_circ_401351 expression, with the upregulation being more pronounced in the TSA group. The expression of hsa_circ_401351 in the DNMT1 knockdown group was dramatically increased by 50% compared to that in the control group, and the DNA methylation level of the hsa_circ_401351 promoter region was decreased. When hsa_circ_401351 was overexpressed, HQ‐TK6 cell proliferation was significantly slowed after 48 h compared with the control group. Flow cytometry showed that cells were mainly arrested in G1 phase, and apoptosis was significantly enhanced. Similarly, qRT–PCR and Western blot data showed significant reductions in Caspase‐3 mRNA and protein production, and Bcl‐2 mRNA levels were also elevated. Conclusions: Overall, our research showed that elevated DNMT1 expression in HQ‐TK6 cells increased methylation levels and decreased expression of the hsa_circ_401351 promoter region, limiting its ability to suppress HQ‐TK6 cell growth and enhance apoptosis. [ABSTRACT FROM AUTHOR]

Cyclic AMP/protein kinase A (cAMP/PKA) and glucocorticoids promote the death of many cell types, including cells of hematopoietic origin. In wild-type (WT) S49 T-lymphoma cells, signaling by cAMP and glucocorticoids converges on the induction of the proapoptotic B-cell lymphoma-family protein Bim to produce mitochondria-dependent apoptosis. Kin(-), a clonal variant of WT S49 cells, lacks PKA catalytic (PKA-Cα) activity and is resistant to cAMP-mediated apoptosis. Using sorbitol density gradient fractionation, we show here that in kin(-) S49 cells PKA-Cα is not only depleted but the residual PKA-Cα mislocalizes to heavier cell fractions and is not phosphorylated at two conserved residues (Ser(338) or Thr(197)). In WT S49 cells, PKA-regulatory subunit I (RI) and Bim coimmunoprecipitate upon treatment with cAMP analogs and forskolin (which increases endogenous cAMP concentrations). By contrast, in kin(-) cells, expression of PKA-RIα and Bim is prominently decreased, and increases in cAMP do not increase Bim expression. Even so, kin(-) cells undergo apoptosis in response to treatment with the glucocorticoid dexamethasone (Dex). In WT cells, glucorticoid-mediated apoptosis involves an increase in Bim, but in kin(-) cells, Dex-promoted cell death appears to occur by a caspase 3-independent apoptosis-inducing factor pathway. Thus, although cAMP/PKA-Cα and PKA-R1α/Bim mediate apoptotic cell death in WT S49 cells, kin(-) cells resist this response because of lower levels of PKA-Cα and PKA-RIα subunits as well as Bim. The findings for Dex-promoted apoptosis imply that these lymphoma cells have adapted to selective pressure that promotes cell death by altering canonical signaling pathways.

Insulin resistance plays a major role in the development of type 2 diabetes and obesity and affects a number of biological processes such as mitochondrial biogenesis. Though mitochondrial dysfunction has been linked to the development of insulin resistance and pathogenesis of type 2 diabetes, the precise mechanism linking the two is not well understood. We used high fat diet (HFD)-induced obesity dependent diabetes mouse models to gain insight into the potential pathways altered with metabolic disease, and carried out quantitative proteomic analysis of liver mitochondria. As previously reported, proteins involved in fatty acid oxidation, branched chain amino acid degradation, tricarboxylic acid cycle, and oxidative phosphorylation were uniformly up-regulated in the liver of HFD fed mice compared with that of normal diet. Further, our studies revealed that retinol metabolism is distinctly down-regulated and the mitochondrial structural proteins-components of mitochondrial inter-membrane space bridging (MIB) complex (Mitofilin, Sam50, and ChChd3), and Tim proteins-essential for protein import, are significantly up-regulated in HFD fed mice. Structural and functional studies on HFD and normal diet liver mitochondria revealed remodeling of HFD mitochondria to a more condensed form with increased respiratory capacity and higher ATP levels compared with normal diet mitochondria. Thus, it is likely that the structural remodeling is essential to accommodate the increased protein content in presence of HFD: the mechanism could be through the MIB complex promoting contact site and crista junction formation and in turn facilitating the lipid and protein uptake.

Abstract Background Accumulation of aberrant proteins to form Lewy bodies (LBs) is a hallmark of Parkinson's disease (PD). Ubiquitination-mediated degradation of aberrant, misfolded proteins is critical for maintaining normal cell function. Emerging evidence suggests that oxidative/nitrosative stress compromises the precisely-regulated network of ubiquitination in PD, particularly affecting parkin E3 ligase activity, and contributes to the accumulation of toxic proteins and neuronal cell death. Results To gain insight into the mechanism whereby cell stress alters parkin-mediated ubiquitination and LB formation, we investigated the effect of oxidative stress. We found significant increases in oxidation (sulfonation) and subsequent aggregation of parkin in SH-SY5Y cells exposed to the mitochondrial complex I inhibitor 1-methyl-4-phenlypyridinium (MPP + ), representing an in vitro cell-based PD model. Exposure of these cells to direct oxidation via pathological doses of H2O2 induced a vicious cycle of increased followed by decreased parkin E3 ligase activity, similar to that previously reported following S-nitrosylation of parkin. Pre-incubation with catalase attenuated H2O2 accumulation, parkin sulfonation, and parkin aggregation. Mass spectrometry (MS) analysis revealed that H2O2 reacted with specific cysteine residues of parkin, resulting in sulfination/sulfonation in regions of the protein similar to those affected by parkin mutations in hereditary forms of PD. Immunohistochemistry or gel electrophoresis revealed an increase in aggregated parkin in rats and primates exposed to mitochondrial complex I inhibitors, as well as in postmortem human brain from patients with PD with LBs. Conclusion These findings show that oxidative stress alters parkin E3 ligase activity, leading to dysfunction of the ubiquitin-proteasome system and potentially contributing to LB formation.

With the massive quantification of networked data and the development of geo-social networks (GSNs), group activities are prevalent in people's life. The objects of recommendation systems are extended from individuals to user groups. Point-of-interest (POI) group recommendation problem is also gradually known as a hot research topic. However, the traditional methods are not suitable for group recommendation in geographic social networks, due to the multifactorial influence of user preferences in GSNs and the complexity of the group decisionmaking process. To reveal user preferences and the effect of the group decision process on group recommendation, this paper proposes a neural network-based model for dynamic POI group recommendation by leveraging multidimensional user preference. Firstly, the proposed model combines temporal and spatial factors to calculate user preferences based on user behavior activity records and builds a group-point-of-interest perception graph with group as unit. Next, this paper adds the influence of collaborative users to model group preferences, which fully considers the characteristics of GSNs, to ensure the accuracy of POI group recommendation. Finally, a neural network-based model can be constructed to simulate group decision-making, which can ensure the accuracy of POI recommendations. This paper conducts extensive experiments by comparing the existing group recommendation algorithms on the real datasets to demonstrate the performance of the method proposed in this paper. Experimental results show that the proposed method is significantly better than the existing algorithms in terms of the hit rate of POI, which proves the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

The strategic importance of lithium in global development has become increasingly prominent due to the rapid growth of the new energy automotive industry and the continuous advancements in controllable nuclear fusion technology. Lithium minerals in salt lakes possess advantageous characteristics, such as abundant reserves, environmental sustainability, and economic viability. Furthermore, with ongoing improvements in the lithium extraction process, the availability of lithium minerals in salt lakes is expected to further increase. The Qaidam Basin Salt Lake in China has served as the location for the establishment of numerous lithium carbonate production enterprises, resulting in a lithium carbonate production volume of 7 × 104 t/yr in 2022. How to meet the growing need for lithium resources has become an enterprise focus. Nevertheless, there are large amounts of clay minerals in and around the bottom and periphery of the salt lake in the Qaidam Basin, and whether these minerals are of exploitable value, regardless of the state of the occurrence of lithium resources, remains unexplored. To ascertain the attributes, extent, and distribution of the lithium occurrence within the clayey layer of the Qaidam Basin, as well as to assess its resource potential, a total of 87 drill holes were conducted within a designated area of the Mahai Basin, which is a secondary basin in the Qaidam Basin. The subsequent analysis encompassed the examination of the lithium content within the clay minerals, the mineral composition of the clay, and, ultimately, the evaluation of the resource potential within the region. Compared with Quaternary salt lake deposits, brine deposits in gravel pores, and the Paleogene–Neogene Li-bearing salt deposits that have been studied, it is suggested that this is a novel form of a clay-type sedimentary Li deposit within the Qaidam Basin. The findings of this research will serve as a fundamental basis for future endeavors pertaining to the exploration and exploitation of lithium deposits within salt lake areas. [ABSTRACT FROM AUTHOR]

The Named Data Network (NDN) enables efficient content dissemination through interest-based retrieval, name-based routing, and content caching. In the industrial Internet architecture based on NDN, device identity distribution, identification, resolution, and routing rely on identification resolution technology. However, this approach presents challenges such as cache poisoning, interest packet flood attacks, and black hole attacks. Existing security schemes primarily focused on routing forwarding and verification fail to address critical concerns, including routing environment credibility and data leakage, while exhibiting poor time and space efficiency. To address these challenges, this paper proposes a lightweight behavior auditing scheme using blockchain technology. The scheme utilizes an improved Bloom filter to compress behavioral information like interest and data packets during the identification transmission process. The compressed data are subsequently uploaded to a blockchain for auditing, achieving efficient space and time utilization while maintaining feasibility. [ABSTRACT FROM AUTHOR]

Through the physical model cross-section experiment, the effects of the relative width and groove depth on the transmission coefficient, horizontal wave force and vertical wave force of the new comb-type floating breakwater (FBW) model under fixed condition are observed. The results show that the hydrodynamic parameters of the new comb-type FBW are mainly influenced by its relative width under the action of regular wave, and the transmission coefficient decreases with the increase of its relative width. Especially when the relative width is 0.139 to 0.188, the transmission coefficient of the new comb-type FBW decreases rapidly with the increase of the relative width, and the horizontal wave force and the vertical wave force change slowly. This indicates that the new comb-type FBW has obvious effect on wave dissipation about short and medium waves. In addition, numerical investigations of selected experiment cases are conducted using RANS based commercial CFD code Flow3D. The numerical results show a good ability to capture the hydrodynamic interaction effect of the fixed FBW.

For solving the problem of the inevitable decline in the accuracy of cross-subject emotion recognition via Electroencephalograph (EEG) signal transfer learning due to the negative transfer of data in the source domain, this paper offers a new method to dynamically select the data suitable for transfer learning and eliminate the data that may lead to negative transfer. The method which is called cross-subject source domain selection (CSDS) consists of the next three parts. 1) First, a Frank-copula model is established according to Copula function theory to study the correlation between the source domain and the target domain, which is described by the Kendall correlation coefficient. 2) The calculation method for the Maximum Mean Discrepancy is improved to determine the distance between classes in a single source. After normalization, the Kendall correlation coefficient is superimposed, and the threshold is set to identify the source-domain data most suitable for transfer learning. 3) In the process of transfer learning, on the basis of Manifold Embedded Distribution Alignment, the Local Tangent Space Alignment method is used to provide a low-dimensional linear estimation of the local geometry of nonlinear manifolds, which maintains the local characteristics of the sample data after dimensionality reduction. Experimental results show that compared with the traditional methods, the CSDS increases the accuracy of emotion classification by approximately 2.8% and reduces the runtime by approximately 65%. [ABSTRACT FROM AUTHOR]