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This study investigated the role of insulin-like growth factor-1/insulin-like growth factor-1 receptor (IGF-1/IGF-1R) in the genesis and progression of diabetic kidney disease (DKD) in a streptozotocin (STZ)-induced mouse diabetes model. We showed elevated IGF-1 expression in the DKD kidneys after 16 wk of diabetic onset. Intraperitoneal administration of IGF-1R inhibitor (glycogen synthase kinase-3β, GSK4529) from week 8 to week 16 postdiabetes induction ameliorated urinary albumin excretion and kidney histological changes due to diabetes, including amelioration of glomerulomegaly, inflammatory infiltration, and tubulointerstitial fibrosis. The GSK4529 treatment also attenuated alterations in renal tubular expression of E-cad and matrix protein fibronectin. Moreover, renal fibrosis in DKD (without treatment) was associated with Snail1 overexpression that was effectively prevented by IGF-1R inhibition. Further experiments in cultured renal epithelial cells (NRK) showed that IGF-1 silencing reproduced in vivo effects of IGF-1R inhibition with markedly attenuated Snail1 expression and near normalization of the Ecad1 and fibronectin expression pattern. Further Snail1 silencing prevented high-glucose-induced changes without affecting IGF-1 expression, consistent with Snail1 acting downstream to IGF-1. The antifibrotic effects were also shown with benazepril or insulin treatment but to a much lesser degree. In summary, in STZ-induced diabetic mice, activation of IGF-1 in diabetic kidneys induces fibrogenesis through Snail1 upregulation. The diabetes-related histological and functional changes, as well as fibrogenesis, can be attenuated by IGF-1/IGF-1R inhibition. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors can stimulate antitumor immunity but can also induce toxicities termed immune-related adverse events (irAEs). Colitis is a common and severe irAE that can lead to treatment discontinuation. Mechanistic understanding of gut irAEs has been hampered because robust colitis is not observed in laboratory mice treated with checkpoint inhibitors. We report here that this limitation can be overcome by using mice harboring the microbiota of wild-caught mice, which develop overt colitis following treatment with anti-CTLA-4 antibodies. Intestinal inflammation is driven by unrestrained activation of IFNg-producing CD4+ T cells and depletion of peripherally induced regulatory T cells through Fcγ receptor signaling. Accordingly, anti-CTLA-4 nanobodies that lack an Fc domain can promote antitumor responses without triggering colitis. This work suggests a strategy for mitigating gut irAEs while preserving antitumor stimulating effects of CTLA-4 blockade. [ABSTRACT FROM AUTHOR]

This paper deals with the initial boundary value problem for the nonlinear beam equation with double damping terms ... whereΩ= (0, 1), and g(s) is a given nonlinear function. We derive sufficient conditions for the blow-up of the solution to the problem by virtue of an adapted concavity method. In addition, global existence of weak solutions as well as exponential and uniform decay rates of the solution energy are established by the use of an integral inequality. [ABSTRACT FROM AUTHOR]

\A continuous attractor of a recurrent neural network (RNN) is a set of connected stable equilibrium points. Continuous attractors have been used to describe the encoding of continuous stimuli in neural net-works. Dynamic behaviors of continuous attractors of RNNs exhibit interesting properties. This brief desires to derive explicit representations of continuous attractors of RNNs. Representations of continuous attractors of linear RNNs as well as linear-threshold (LT) RNNs are obtained under some conditions. These representations could be looked at as solutions of continuous attractors of the networks. Such results provide clear and complete descriptions to the continuous attractors. [ABSTRACT FROM AUTHOR]

The authors propose explicit analytical results for energy eigenstates and eigenvalues for a class of models describing four-mode mixing with multiphoton processes that can be described resorting to a single parameter. The value of such parameter is determined by the roots of a polynomial and can be determined either analytically or numerically. [ABSTRACT FROM AUTHOR]

Objective: Immune inflammatory cells and cytokines play an important role in the occurrence and development of diabetic nephropathy (DN). Acteoside has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of acteoside on the expressions of MCP-1 and TGF-β1 on nephropathy in diabetic mice. Methods: C57BL/6J mice in the model group were given a single intraperitoneal injection of STZ (150 mg/kg). Model mice were divided randomly into two groups: 5 without treatment, 5 treated with acteoside. After continuous administration for 8 weeks, serum, urine, and kidney tissue were collected, then, ralated biochemical parameters, pathological characteristics and MCP-1 and TGF-β1 mRNA or protein were detected. The NRK-52E cells were divided into three groups as follows: the normal control group (NC group), the high glucose group (HS group), the high glucose+acteoside group (HS+ACT group). The expressions of MCP-1 and TGF-β1 in the mRNA and protein levels were assessed with RT-PCR, western blot and ELISA. Results: The expressions of MCP-1 and TGF-β1 were significantly enhanced in DN group and dramatically reduced after acteoside treatment. Compared with those in NC group, the expressions of MCP-1 and TGF-β1 in NRK-52E cell of HS group were sizgnificantly enhanced, while both were significantly decreased in HS+ACT group compared with HS group. Conclusion: Our findings indicate that Acteoside has protective effects on DNvia inhibiting the expressions of MCP-1 and TGF-β1. [ABSTRACT FROM AUTHOR]

The concepts of permitted and forbidden sets enable a new perspective of the memory in neural networks. Such concepts exhibit interesting dynamics in recurrent neural networks. This paper studies the basic theories of permitted and forbidden sets of the linear threshold discrete-time recurrent neural networks. The linear threshold transfer function has been regarded as an adequate transfer function for recurrent neural networks. Networks with this transfer function form a class of hybrid analog and digital networks which are especially useful for perceptual computations. Networks in discrete time can directly provide algorithms for efficient implementation in digital hardware. The main contribution of this paper is to establish foundations of permitted and forbidden sets. Necessary and sufficient conditions for the linear threshold discrete-time recurrent neural networks are obtained for complete convergence, existence of permitted and forbidden sets, as well as conditionally multiattractivity, respectively. Simulation studies explore some possible interesting practical applications. [ABSTRACT FROM AUTHOR]

This paper studies multiperiodicity and attractivity for a class of recurrent neural networks (RNNs) with unsaturating piecewise linear transfer functions and variable delays. Using local inhibition, conditions for boundedness and global attractivity are established. These conditions allow coexistence of stable and unstable trajectories. Moreover, multiperiodicity of the network is investigated by using local invariant sets. It shows that under some interesting conditions, there exists one periodic trajectory in each invariant set which exponentially attracts all trajectories in that region correspondingly. Simulations are carried out to illustrate the theories. [ABSTRACT FROM AUTHOR]

Here, polyaniline (PANI) is reported loaded on carbon paper to modify the carbon paper-PANI-Pt electrode surface, tailoring the electrocatalytic capability towards the hydrogen evolution reaction and ethanol oxidation reaction. The reasons for the enhancement by the PANI layer are attributed to the hydrophilic electrode surface, uniform dispersion of Pt, and large electrochemical active surface. [ABSTRACT FROM AUTHOR]

Objective(s): To explore the effect of verbascoside on renal fibrosis in unilateral ureteral obstruction (UUO) rats. Materials and Methods: Twenty Sprague-Dawley rats were randomly distributed into sham-operated, UUO, and UUO+Verbascoside groups. After two weeks of rat model construction, urine and blood samples were collected for biochemical analysis while kidney tissues were harvested for hematoxylin and eosin (H&E), Masson's Trichrome, and immunohistochemistry staining. Pearson coefficient was used to analyze the correlation between the two proteins. Results: Verbascoside improved UUO-induced renal dysfunction as detected by decreased serum creatinine, urea nitrogen, and urinary protein excretion rate. In UUO rats, H&E staining result revealed increased total nucleated cell number, and Masson's Trichrome staining results showed tubular interstitial fibrosis with the deposition of collagen fibrils. Besides, expressions of fibrosis-related proteins including collagen type I (COL-I), α-smooth muscle actin (a-SMA), and tissue inhibitor of metalloproteinase 2 (TIMP2) expressed higher in the UUO group. Moreover, macrophage infiltration-related factors such as CD68+, F4/80+ cells, and suppressor of cytokine signaling-3 (SOCS3) were significantly higher in the UUO group than in sham-operated rats. However, after administration with verbascoside, the accumulation of collagen fibrils and total nucleated cell numbers were mitigated. Likewise, macrophage infiltration was extenuated and fibrosis-related proteins were down-regulated in the UUO+Verbascoside rats. Correlation analysis indicated that macrophage infiltration-related markers were related to fibrosis-related factors. Conclusion: Verbascoside could alleviate renal fibrosis in UUO rats probably through ameliorating macrophage infiltration. [ABSTRACT FROM AUTHOR]

Mammalian SWI/SNF family chromatin remodelers, BRG1/BRM-associated factor (BAF) and polybromo-associated BAF (PBAF), regulate chromatin structure and transcription, and their mutations are linked to cancers. The 3.7-angstrom-resolution cryo–electron microscopy structure of human BAF bound to the nucleosome reveals that the nucleosome is sandwiched by the base and the adenosine triphosphatase (ATPase) modules, which are bridged by the actin-related protein (ARP) module. The ATPase motor is positioned proximal to nucleosomal DNA and, upon ATP hydrolysis, engages with and pumps DNA along the nucleosome. The C-terminal a helix of SMARCB1, enriched in positively charged residues frequently mutated in cancers, mediates interactions with an acidic patch of the nucleosome. AT-rich interactive domain-containing protein 1A (ARID1A) and the SWI/SNF complex subunit SMARCC serve as a structural core and scaffold in the base module organization, respectively. Our study provides structural insights into subunit organization and nucleosome recognition of human BAF complex. [ABSTRACT FROM AUTHOR]

Nonsense-mediated RNA decay (NMD) is a crucial post-transcriptional regulatory mechanism that recognizes and eliminates aberrantly processed transcripts, and mediates the expression of normal gene transcripts. In this study, we report that in the filamentous fungus Neurospora crassa, the NMD factors play a conserved role in regulating the surveillance of NMD targets including premature termination codon (PTC)-containing transcripts and normal transcripts. The circadian rhythms in all of the knockout strains of upf1-3 genes, which encode the Up-frameshift proteins, were aberrant. The upf1 knockout strain displays a shortened circadian period, which can be restored by constantly expressing exogenous Up-frameshift protein 1 (UPF1). UPF1 regulates the circadian clock by modulating the splicing of the core clock gene frequency (frq) through spliceosome and spliceosome-related arginine/serine-rich splicing factors, which partly account for the short periods in the upf1 knockout strain. We also demonstrated that the clock genes including White Collar (WC)-1, WC-2, and FRQ are involved in controlling the diurnal growth rhythm, and UPF1 may affect the growth rhythms by mediating the FRQ protein levels in the daytime. These findings suggest that the NMD factors play important roles in regulating the circadian clock and diurnal growth rhythms in Neurospora. [ABSTRACT FROM AUTHOR]