Transmission of new CRF07_BC Strains with 7 amino acid deletion in Gag p6

A 7 amino acid deletion in Gag p6 (P6delta7) emerged in Chinese prevalent HIV-1 strain CRF07_BC from different epidemic regions. It is important to determine whether this mutation could be transmitted and spread. In this study, HIV-1 Gag sequences from 5 different epidemic regions in China were collected to trace the transmission linkage and to analyze genetic evolution of P6delta7 strains. The sequence analysis demonstrated that P6delta7 is a CRF07_BC specific deletion, different P6delta7 strains could be originated from different parental CRF07_BC recombinants in different epidemic regions, and the transmission of P6delta7 strain has occurred in IDU populations. This is for the first time to identify the transmission linkage for P6delta7 strains and serves as a wake-up call for further monitoring in the future; In addition, P6delta7 deletion may represent an evolutionary feature which might exert influence on the fitness of CRF07_BC strain

Salmon Calcitonin Exerts an Antidepressant Effect by Activating Amylin Receptors

Depressive disorder is defined as a psychiatric disease characterized by the core symptoms of anhedonia and learned helplessness. Currently, the treatment of depression still calls for medications with high effectiveness, rapid action, and few side effects, although many drugs, including fluoxetine and ketamine, have been approved for clinical usage by the Food and Drug Administration (FDA). In this study, we focused on calcitonin as an amylin receptor polypeptide, of which the antidepressant effect has not been reported, even if calcitonin gene-related peptides have been previously demonstrated to improve depressive-like behaviors in rodents. Here, the antidepressant potential of salmon calcitonin (sCT) was first evaluated in a chronic restraint stress (CRS) mouse model of depression. We observed that the immobility duration in CRS mice was significantly increased during the tail suspension test and forced swimming test. Furthermore, a single administration of sCT was found to successfully rescue depressive-like behaviors in CRS mice. Lastly, AC187 as a potent amylin receptor antagonist was applied to investigate the roles of amylin receptors in depression. We found that AC187 significantly eliminated the antidepressant effects of sCT. Taken together, our data revealed that sCT could ameliorate a depressive-like phenotype probably via the amylin signaling pathway. sCT should be considered as a potential therapeutic candidate for depressive disorder in the future

Chk1 Inhibition Ameliorates Alzheimer's Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling

Alzheimer's disease (AD) is the most common neurodegenerative disease with limited therapeutic strategies. Cell cycle checkpoint protein kinase 1 (Chk1) is a Ser/Thr protein kinase which is activated in response to DNA damage, the latter which is an early event in AD. However, whether DNA damage-induced Chk1 activation participates in the development of AD and Chk1 inhibition ameliorates AD-like pathogenesis remain unclarified. Here, we demonstrate that Chk1 activity and the levels of protein phosphatase 2A (PP2A) inhibitory protein CIP2A are elevated in AD human brains, APP/PS1 transgenic mice, and primary neurons with A beta treatment. Chk1 overexpression induces CIP2A upregulation, PP2A inhibition, tau and APP hyperphosphorylation, synaptic impairments, and cognitive memory deficit in mice. Moreover, Chk1 inhibitor (GDC0575) effectively increases PP2A activity, decreases tau phosphorylation, and inhibits A beta overproduction in AD cell models. GDC0575 also reverses AD-like cognitive deficits and prevents neuron loss and synaptic impairments in APP/PS1 mice. In conclusion, our study uncovers a mechanism by which DNA damage-induced Chk1 activation promotes CIP2A-mediated tau and APP hyperphosphorylation and cognitive dysfunction in Alzheimer's disease and highlights the therapeutic potential of Chk1 inhibitors in AD

Effects of Intestinal M Cells on Intestinal Barrier and Neuropathological Properties in an AD Mouse Model

Intestinal microfold cells (M cells) play a critical role in the immune response of the intestinal mucosa by actively taking up antigens, facilitating antigen presentation to immune cells, and promoting the production of secretory immunoglobulin A by B cells. Despite their known important functions in the gut, the effect of M cells on the central nervous system remains unclear. We investigated the expression of M cell-related factor genes and protein levels in Peyer's patches (PPs) of 3-month-old and 9-month-old APP/PS1 mice, as well as the expression of intestinal barrier proteins in the ileum and colon of these mice. Furthermore, we employed intestinal M cell conditional ablation mice (i.e., RankΔIEC mice) to assess the influence of M cells on the intestinal barrier and Alzheimer's disease (AD)-like behavioral and pathological features. Our findings revealed that compared to wild-type mice, APP/PS1 mice showed altered M cell-related genes and disrupted intestinal barriers. In addition, there is a significant decrease in glycoprotein 2 (GP2) mRNA levels in the PPs of 3-month-old APP/PS1 mice, with the relative expression of GP2 mRNA tending to zero. Parameters related to the intestinal barrier (IgA, MUC2, Claudin-5, ZO-1) were significantly downregulated in both 3-month-old and 9-month-old APP/PS1 mice compared to wild-type controls, and the differences were more pronounced in the 9-month-old mice. Moreover, M cell ablation in APP/PS1 mice (i.e., APP/PS1ΔMC mice) resulted in more severe intestinal barrier destruction. Notably, we observed through water maze experiments that APP/PS1ΔMC mice at 6 months of age exhibited significantly poorer spatial learning memory compared to APP/PS1 mice. And the neuropathological alterations were also observed in APP/PS1ΔMC mice at 6 months of age that when intestinal M cells are damaged in APP/PS1 mice, brain microglia are activated, Tau phosphorylation is exacerbated, and the number of neurons is reduced. Our results suggest for the first time that the absence of intestinal M cells might further aggravate intestinal leakage, lead to neuropathological damage, and subsequently cause the impairment of learning memory ability in AD mice. Our research highlights the impact of intestinal M cells on the intestinal barrier and AD neuropathogenesis in AD mouse model

A Novel Parallel Processing Model for Noise Reduction and Temperature Compensation of MEMS Gyroscope

To eliminate the noise and temperature drift in an Micro-Electro-Mechanical Systems (MEMS) gyroscope’s output signal for improving measurement accuracy, a parallel processing model based on Multi-objective particle swarm optimization based on variational modal decomposition-time-frequency peak filter (MOVMD–TFPF) and Beetle antennae search algorithm- Elman neural network (BAS–Elman NN) is established. Firstly, variational mode decomposition (VMD) is optimized by multi-objective particle swarm optimization (MOPSO); then, the best decomposition parameters [kbest,abest] can be obtained. Secondly, the gyroscope output signals are decomposed by VMD optimized by MOPSO (MOVMD); then, the intrinsic mode functions (IMFs) obtained after decomposition are classified into a noise segment, mixed segment, and drift segment by sample entropy (SE). According to the idea of a parallel model, the noise segment can be discarded directly, the mixed segment is denoised by time-frequency peak filtering (TFPF), and the drift segment is compensated at the same time. In the compensation part, the beetle antennae search algorithm (BAS) is adopted to optimize the network parameters of the Elman neural network (Elman NN). Subsequently, the double-input/single-output temperature compensation model based on the BAS-Elman NN is established to compensate the drift segment, and these processed segments are reconstructed to form the final gyroscope output signal. Experimental results demonstrate the superiority of this parallel processing model; the angle random walk of the compensated gyroscope output is decreased from 0.531076 to 5.22502 × 10−3°/h/√Hz, and its bias stability is decreased from 32.7364°/h to 0.140403°/h, respectively

A Novel Parallel Processing Model for Noise Reduction and Temperature Compensation of MEMS Gyroscope

To eliminate the noise and temperature drift in an Micro-Electro-Mechanical Systems (MEMS) gyroscope’s output signal for improving measurement accuracy, a parallel processing model based on Multi-objective particle swarm optimization based on variational modal decomposition-time-frequency peak filter (MOVMD–TFPF) and Beetle antennae search algorithm- Elman neural network (BAS–Elman NN) is established. Firstly, variational mode decomposition (VMD) is optimized by multi-objective particle swarm optimization (MOPSO); then, the best decomposition parameters [kbest,abest] can be obtained. Secondly, the gyroscope output signals are decomposed by VMD optimized by MOPSO (MOVMD); then, the intrinsic mode functions (IMFs) obtained after decomposition are classified into a noise segment, mixed segment, and drift segment by sample entropy (SE). According to the idea of a parallel model, the noise segment can be discarded directly, the mixed segment is denoised by time-frequency peak filtering (TFPF), and the drift segment is compensated at the same time. In the compensation part, the beetle antennae search algorithm (BAS) is adopted to optimize the network parameters of the Elman neural network (Elman NN). Subsequently, the double-input/single-output temperature compensation model based on the BAS-Elman NN is established to compensate the drift segment, and these processed segments are reconstructed to form the final gyroscope output signal. Experimental results demonstrate the superiority of this parallel processing model; the angle random walk of the compensated gyroscope output is decreased from 0.531076 to 5.22502 × 10−3°/h/√Hz, and its bias stability is decreased from 32.7364°/h to 0.140403°/h, respectively