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In order to solve the problem that bearing vibration signal fault feature is difficult to extract effectively under noise, a fault diagnosis method based on Variational Mode Decomposition (VMD) optimized by Cuckoo Search (CS) and Particle Swarm Optimization (PSO) is proposed. The effect of VMD is affected by the number of modes and the penalty parameter. The Levy flight strategy and elimination mechanism of the CS algorithm is added to PSO algorithm and the position updating process is optimized. According to the correlation coefficient and envelope entropy of the Intrinsic Mode Function (IMF), the objective function is constructed to search for the optimal combination of VMD mode number and penalty parameter. The bearing fault type is determined by analyzing the IMF envelope spectrum of the optimal objective function. The fault diagnosis classification task upon the bearing sample data from Case Western Reserve University demonstrates that the proposed CS-PSO algorithm improves the model's classification performance by 5%, which is on average 7.3% higher than other state-of-the-art models. This model can provide an important reference for the accuracy of bearing fault diagnosis. [ABSTRACT FROM AUTHOR]

β(2) adrenergic receptor (β(2)AR) is a prototypical G-protein coupled receptor that stimulates the classic cAMP-protein kinase A (PKA) signaling pathway. Recent studies indicate that the cAMP-PKA activities are spatiotemporally regulated in part due to dynamic association of β(2)AR with phosphodiesterase 4D (PDE4D), a group of cAMP degradation enzymes. Here, we demonstrate that in cardiomyocytes, palmitoylation of β(2)AR, the covalent acylation of cysteine residue 341, plays a critical role in shaping subcellular cAMP-PKA activities in cardiomyocytes via regulating β(2)AR association with arrestin/PDE4D. Replacing cysteine 341 on β(2)AR with alanine (C341A) leads to an impaired binding to β arrestin 2. Surprisingly, the C341A mutant is able to internalize via an arrestin-independent pathway at saturated concentration of agonist stimulation; the internalization becomes caveolae-dependent and requires dynamin GTPase. However, the impaired binding to β arrestin 2 also leads to an impaired recruitment of PDE4D to the C341A mutant. Thus, the mutant C341A β(2)AR is transported alone from the plasma membrane to the endosome without recruiting PDE4D. This alteration leads to an enhanced cytoplasmic cAMP signal for PKA activation under β(2)AR stimulation. Functionally, Mutation of the C341 residue or inhibition of palmitoylation modification of β(2)AR enhances the receptor-induced PKA activities in the cytoplasm and increases in myocyte contraction rate. Our data reveal a novel function of palmitoylation in shaping subcellular cAMP-PKA signaling in cardiomyocytes via modulating the recruitment of β arrestin 2-PDE4D complexes to the agonist-stimulated β(2)AR.

Apolipoprotein L1 (APOL1) risk alleles in donor kidneys associate with graft loss, but whether recipient risk allele expression affects transplant outcomes is unclear. To test whether recipient APOL1 risk alleles independently correlate with transplant outcomes, we analyzed genome-wide SNP genotyping data on donors and recipients from 2 kidney transplant cohorts: Genomics of Chronic Allograft Rejection (GOCAR) and Clinical Trials in Organ Transplantation 01/17 (CTOT-01/17). We estimated genetic ancestry (quantified as the proportion of African ancestry, or pAFR) by ADMIXTURE and correlated APOL1 genotypes and pAFR with outcomes. In the GOCAR discovery set, we noted that the number of recipient APOL1 G1/G2 alleles (R-nAPOL1) associated with an increased risk of death-censored allograft loss (DCAL), independent of ancestry (HR = 2.14; P = 0.006), as well as within the subgroup of African American and Hispanic (AA/H) recipients (HR = 2.36; P = 0.003). R-nAPOL1 also associated with an increased risk of any T cell-mediated rejection (TCMR) event. These associations were validated in CTOT-01/17. Ex vivo studies of PMBCs revealed, unexpectedly, high expression levels of APOL1 in activated [CD4.sup.+]/[CD8.sup.+] T cells and NK cells. We detected enriched immune response gene pathways in risk allele carriers compared with noncarriers on the kidney transplant waitlist and among healthy controls. Our findings demonstrate an immunomodulatory role for recipient APOL1 risk alleles associated with TCMR and DCAL. We believe this finding has broader implications for immune-mediated injury to native kidneys., Introduction Patients with African ancestry have a significantly higher risk of non-Mendelian focal segmental glomerulosclerosis (FSGS) as well as end-stage renal disease (ESRD) (reviewed in ref. 1). Seminal work identified [...]

Proteins perform most cellular functions in macromolecular complexes. The same protein often participates in different complexes to exhibit diverse functionality. Current ensemble approaches of identifying cellular protein interactions cannot reveal physiological permutations of these interactions. Here we describe a single-molecule pull-down (SiMPull) assay that combines the principles of a conventional pull-down assay with single-molecule fluorescence microscopy and enables direct visualization of individual cellular protein complexes. SiMPull can reveal how many proteins and of which kinds are present in the in vivo complex, as we show using protein kinase A. We then demonstrate a wide applicability to various signalling proteins found in the cytosol, membrane and cellular organelles, and to endogenous protein complexes from animal tissue extracts. The pulled-down proteins are functional and are used, without further processing, for single-molecule biochemical studies. SiMPull should provide a rapid, sensitive and robust platform for analysing protein assemblies in biological pathways.

BACKGROUND: Phytosterol can improve its lipid solubility, lipophilic/hydrophilic balance and bioaccessibility by esterification with fatty acids, which increases its practical application range in the food industry. In the present study, small angle X‐ray scattering combined with the pH‐stat in vitro digestion model was applied to continuously monitor the molecular structure evolution of mixed micelles during digestion and investigate the effect of three edible oils (olive oil with 72.41 ± 0.57% oleic, sunflower seed oil with 63.45 ± 0.78% linoleic, refined linseed oil with 51.74 ± 0.34% linolenic) on bioaccessibility of stigmasterol oleate in vitro. RESULTS: The release degree and rate of fatty acids in the three edible oil systems (kOO+ST‐OA = 0.0501, kSO+ST−OA = 0.0357, kLO+ST‐OA = 0.0323) was compared. The three different edible oils had similar impact on the formation of dietary mixed micelles during the simulatedin vitro digestion of stigmasterol oleate, although there were significant differences in molecular morphology and composition of mixed micelles. The results showed that the vesicles formed by linoleic oil (SO system) or linolenic oil (LO system) were easy to dissociate. The largest average number and diameter of vesicles (5.55 × 1016 cm−3 and 2230.75 Å), the most stable vesicle structure and the fastest fatty acid release rate were observed in the OO system. CONCLUSION: Compared to linoleic (SO system) or linolenic (LO system), the oleic (OO system) could facilitate the transformation of micelles to vesicles and maintain the stability of its membrane, significantly promotin the dissolution of stigmasterol and improving bioaccessibility. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In this paper, ZnO/ g-C3N4 series composite photocatalysts were prepared by thermal polymerization and hydrothermal method. The structure, morphology and light absorption properties of the prepared samples were characterized and tested. The photocatalytic performance of these samples was evaluated by the photocatalytic degradation of methylene blue (MB) and the photolysis aquatic hydrogen under visible light irradiation. The experimental results indicate that the performances of the ZnO/ g-C3N4 composite photocatalysts are superior to those of ZnO and g-C3N4 . Moreover, when the molar ratio of ZnO and g-C3N4 is 1:1, the photocatalytic performance of the prepared ZnO/ g-C3N4 composite samples is the best. On the one hand, the degradation rate of the 1:1 composite sample reaches 94. 36% after only 30 min, and the degradation rate is 5. 6 and 6. 7 times that of ZnO and g-C3 N4, respectively. On the other hand, the photolysis aquatic hydrogen of the 1:1 sample after 6 h is 11. 75 mmol, and the photolysis aquatic hydrogen rate is 7 times that of g-C3N4 . The results show that the ZnO/ g-C3N4 composite photocatalyst has excellent performance in pollutant degradation and photolysis aquatic hydrogen. In addition, the photocatalytic degradation and photolysis aquatic hydrogen mechanism of ZnO/ g-C3N4 series composite photocatalyst are also studied. [ABSTRACT FROM AUTHOR]

The master cytokine TGF-[beta] mediates tissue fibrosis associated with inflammation and tissue injury. TGF-[beta] induces fibroblast activation and differentiation into myofibroblasts that secrete extracellular matrix proteins. Canonical TGF-[beta] signaling mobilizes Smad2 and Smad3 transcription factors that control fibrosis by promoting gene expression. However, the importance of TGF-[beta]-Smad2/3 signaling in fibroblast-mediated cardiac fibrosis has not been directly evaluated in vivo. Here, we examined pressure overload-induced cardiac fibrosis in fibroblast- and myofibroblast-specific inducible Creexpressing mouse lines with selective deletion of the TGF-[beta] receptors Tgfbr1/2, Smad2, or Smad3. Fibroblast-specific deletion of Tgfbr1/2 or Smad3, but not Smad2, markedly reduced the pressure overload-induced fibrotic response as well as fibrosis mediated by a heart-specific, latency-resistant TGF-[beta] mutant transgene. Interestingly, cardiac fibroblast-specific deletion of Tgfbr1/2, but not Smad2/3, attenuated the cardiac hypertrophic response to pressure overload stimulation. Mechanistically, loss of Smad2/3 from tissue-resident fibroblasts attenuated injury-induced cellular expansion within the heart and the expression of fibrosis-mediating genes. Deletion of Smad2/3 or Tgfbr1/2 from cardiac fibroblasts similarly inhibited the gene program for fibrosis and extracellular matrix remodeling, although deletion of Tgfbr1/2 uniquely altered expression of an array of regulatory genes involved in cardiomyocyte homeostasis and disease compensation. These findings implicate TGF-[beta]Smad2/3 signaling in activated tissue-resident cardiac fibroblasts as principal mediators of the fibrotic response., Introduction Heart failure is an increasingly prevalent disease characterized by reduced cardiac output resulting from a progressive loss of cardiomyocytes, ventricular chamber remodeling, and accumulation of interstitial fibrosis (1). Excessive [...]