The American cockroach (Periplaneta americana) residue could partially replace the dietary puffed soybean meal in the Three-yellow chickens.

Periplaneta americana residue is a byproduct of using Periplaneta americana in pharmaceutical research and development for extracting active ingredients. Three hundred Three-yellow chickens were selected for the experiment and randomly divided into 6 groups (5 replications per group, 10 chickens per replicate): the control group (group A) was fed a basal ration, and the experimental groups (groups B, C, D, E, and F) were fed experimental diets in which P. americana residue replaced puffed soybean meal at proportions of 20, 40, 60, 80, and 100%, respectively, for a period of 42 d. The aim was to assess the impact of different levels of P. americana residue on the growth, survival, intestinal morphology, digestive enzyme activity, intestinal flora, and intestinal transcriptional responses of Three-yellow chickens. The results indicated that the increase in P. americana residue levels had a linear and quadratic impact on the average daily gain (ADG) and feed conversion ratio (FCR), respectively. The ADG was notably greater in the 40% group than in the 100% group, while the FCR was significantly lower in the 20% and 40% groups than in the 100% group (P < 0.05). Protease, lipase, and amylase activities exhibited a quadratic increase with increasing concentrations of P. americana residue (P < 0.05). Protease and lipase activities were notably greater in the 20% and 40% groups than in the 0% group (control group), amylase activity was significantly greater in the 40% group than in the 0% group (control group) (P < 0.05). Duodenal crypt depth (CD) decreased quadratically with increasing P. americana residue (P < 0.05). The duodenal villus height/crypt depth ratio (V/C) was significantly lower in the 100% group than in the 60% group (P < 0.05). The intestinal villus height (VH) increased quadratically with increasing levels of P. americana residue. The VH in the 60% group was significantly greater than that in the 0% (control group), 20, 80, and 100% groups (P < 0.05). The Chao and Ace indices demonstrated linear and quadratic increases with increasing levels of P. americana residue, while the Pd index showed a quadratic increase with increasing levels of P. americana residue (P < 0.05). The relative abundance profile of Lactobacillus exhibited a linear and quadratic decrease with increasing levels of P. americana residue, with the 100% group showing a significantly lower abundance than the 0% (control group) and 40% groups (P < 0.05). The transcriptome results showed that P. americana residue could enhance the digestive system by promoting vitamin, fat, carbohydrate digestion and absorption, cholesterol metabolism, etc. In conclusion, P. americana residue can replace puffed soybean meal without negatively affecting the growth performance of three-yellow chickens. The low and medium groups had positive effects on the growth performance, digestive enzyme activity, intestinal morphology, intestinal flora, and substance digestion and absorption of three-yellow chickens. The recommended replacement of P. americana residue for puffed soybean meal in the diets of three-yellow chickens ranged from 20% to 60%.

A near-infrared aggregation-induced emission photosensitizer targeting mitochondria for depleting Cu2+ to trigger light-activated cancer cells oncosis.

Abnormally high levels of copper in tumors stimulate malignant proliferation and migration of cancer cells, which proposes a formidable challenge for the thorough therapy of malignant tumors. In this work, we developed a reliable, mitochondria-targeted near-infrared aggregation-induced emission fluorescent probe, TTQ-Th, whose thiourea moiety specifically could recognize mitochondria even both upon loss of mitochondrial membrane potential or in fixated cells, and can capture copper overexpressed by tumor cells, leading to severe copper deficiency. In parallel, TTQ-Th can generate sufficient reactive oxygen species (ROS) upon photoexcitation, while copper deficiency inhibits expression of related copper-based enzymes, resulting in a decline in ATP production. Such energy deficiency, combined with reduced MMP and elevated oxidative stress can lead to critical cell oncosis. Both in vitro and intracellular experiments can illustrate that the elevated ROS has remarkable damage to tumor cells and contributes to the elimination of the primary tumor, while copper deficiency further hinder tumor cell migration and induces G0/G1 cell cycle arrest in a dose-dependent manner, which is an efficacious strategy for the treatment of malignant tumors.

A near-infrared AIE fluorescent probe for accurate detection of sulfur dioxide derivatives and visualization of fingerprints.

In most biophysiological processes, sulfur dioxide (SO2) is an important intracellular signaling molecule that plays an important role. The change of SO2 in cells are closely related to various diseases such as neurological disorders and lung cancer, so it is necessary to develop fluorescent probes with the ability to accurately detect SO2 during physiological processes. In this work, we designed and synthesized a multifunctional fluorescent probe TIS. TIS has excellent properties such as near-infrared emission, large stokes shift, excellent SO2 detection capabilities, low detection limit, high specificity and visualization of color change before and after reaction. Simultaneously, TIS has low cytotoxicity, good biocompatibility, clear cell imaging capability and mitochondrial targeting ability. In addition, the ability of TIS to be applied to different material surfaces for latent fingerprint fluorescence imaging was also explored. TIS provides an excellent method for the accurate detection of SO2 derivatives and shows great potential applications in near-infrared cellular imaging and latent fingerprint fluorescence imaging.

Biomechanical effects of iatrogenic muscle-ligaments complex damage on adjacent segments following posterior lumbar interbody fusion: A finite element analysis.

OBJECTIVE: To analyze the biomechanical effects of proximal iatrogenic muscle-ligaments complex (MLC) damage on adjacent segments following posterior lumbar interbody fusion (PLIF) by finite element (FE) analysis. METHODS: The multifidus muscle force was loaded in the validated intact lumbosacral finite element model. Based on whether undergoing PLIF or the proximal MLC damage, three models were established. Range of motion (ROM) and the maximum von Mises (VM) stress of adjacent segments were analyzed, as well as the average muscle force and work capacity in four loading directions. RESULTS: PLIF results in significant changes in ROM and stress. ROM changed significantly in the upper adjacent segment, the PLIF model changed the most in extension, and the largest change in the lower adjacent segment occurred after MLC damage. The VM stress of the upper adjacent segment occurred in extension of the PLIF model, and that of the lower adjacent segment occurred in rotation after MLC damage. In flexion, ROM, and stress of the damaged MLC fusion model were significantly increased compared with the normal and PLIF models, there was a stepwise amplification. The average muscle force comparison of three models was 5.8530, 12.3185, and 13.4670 N, respectively. The total work capacity comparison was close to that of muscle force. CONCLUSION: PLIF results in increased ROM and the VM stress of adjacent segments, the proximal MLC damage will aggravate this change. This may increase the risk of ASD and chronic low back pain. Preserving the proximal MLC reduces the biomechanical effects on adjacent segments.

Biomechanical effect of proximal multifidus injury on adjacent segments during posterior lumbar interbody fusion: a finite element study.

BACKGROUND: Adjacent segment degeneration (ASD) is a common complication of lumbar interbody fusion; the paraspinal muscles significantly maintain spinal biomechanical stability. This study aims to investigate the biomechanical effects of proximal multifidus injury on adjacent segments during posterior lumbar interbody fusion (PLIF). METHODS: Data from a lumbosacral vertebral computed tomography scan of a healthy adult male volunteer were used to establish a normal lumbosacral vertebral finite element model and load the muscle force of the multifidus. A normal model, an L4/5 PLIF model (PFM) based on a preserved proximal multifidus, a total laminectomy PLIF model (TLPFM), and a hemi-laminectomy PLIF model based on a severed proximal multifidus were established, respectively. The range of motion (ROM) and maximum von Mises stress of the upper and lower adjacent segments were analyzed along with the total work of the multifidus muscle force. RESULTS: This model verified that the ROMs of all segments with four degrees of freedom were similar to those obtained in previous research data, which validated the model. PLIF resulted in an increased ROM and maximum von Mises stress in the upper and lower adjacent segments. The ROM and maximum von Mises stress in the TLPFM were most evident in the upper adjacent segment, except for lateral bending. The ROM of the lower adjacent segment increased most significantly in the PFM in flexion and extension and increased most significantly in the TLPFM in lateral bending and axial rotation, whereas the maximum von Mises stress of the lower adjacent segment increased the most in the TLPFM, except in flexion. The muscle force and work of the multifidus were the greatest in the TLPFM. CONCLUSIONS: PLIF increased the ROM and maximum von Mises stress in adjacent cranial segments. The preservation of the proximal multifidus muscle contributes to the maintenance of the physiological mechanical behavior of adjacent segments, thus preventing the occurrence and development of ASD.

LY103, a pomalidomide derivative, alleviates taxol resistance in NSCLC via energy metabolism crosstalk and tumor microenvironment intervention.

In this study, we identified HIF 1α as a potential target for reversing taxol resistance in lung cancer by combining bioinformatics analysis with pharmacological analysis. Furthermore, pomalidomide derivative LY103 was also be synthesized by introducing an isatin analogue into the amino terminal ofpomalidomide, and it has a broad antitumor spectrum and showed excellent activity against A549/Taxol cells (IC50 = 6.33 ± 0.51 µM). The results of molecular docking showed that not only LY103 was inclined to bind to HIF 1α stably, it could also form multiple hydrogen bonds with VAL376, ASP256, ILE454, and GLU455 of HIF 1α even was reduced to LY103-NH2 by nitroreductase, which was further stabilized the complex formed by them, thereby inhibiting the activity of HIF 1α. LY103 was able to significantly induce DNA damage and inhibit angiogenesis. Concurrently, LY103 activated the immune response, reduced the expression of cytokines TNF-α, IL-6, and IL-1ß, thus might be inhibit the proliferation and metastasis of tumor cells. Pharmacological analysis proved that LY103 led to cell apoptosis through the mitochondrial pathway, and its combination with taxol significantly promoted this process. In general, the consumption of glutathione, the crosstalk of energy metabolism, and the improvement of the tumor microenvironment caused by LY103 eventually led to the decrease of ABCC1 protein expression and the drug resistance was reversed. The rational design of LY103 provided a basis for the application of nitro compounds in the treatment of hypoxic tumors and the reversal of taxol resistance.

Biological and physiological responses of two Bradysia pests, Bradysia odoriphaga and Bradysia difformis, to Dinotefuran and Lufenuron.

Bradysia odoriphaga and Bradysia difformis are destructive root maggots that cause severe losses to vegetables, flowers and edible fungi. Due to the long-term dependence on single pesticides, Bradysia resistance to insecticides has increased, and field control efficacy has decreased obviously. To screen alternative insecticides, and compare the insecticide susceptibility of these two species, we tested the toxicity of eight insecticides to B. odoriphaga and B. difformis, and measured the sublethal effects of Dinotefuran and Lufenuron on life-history parameters and detoxification enzyme activities. Bioassay results indicated that Dinotefuran and Lufenuron had relatively higher toxicity to B. odoriphaga and B. difformis compared to other neonicotinoid and insect growth regulator insecticides, respectively. Significant adverse impacts caused by sublethal concentrations (LC20) of Dinotefuran and Lufenuron on the life-history parameters of F0 and F1 generations of B. odoriphaga and B. difformis were observed. These included reduced survival, prolonged larval development and reduced adult longevity and fecundity. B. odoriphaga had greater resistance and adaptation to insecticides than B. difformis, and an LC20 concentration of Dinotefuran stimulated the reproduction of B. odoriphaga F1 generation and increased the life table parameters. Detoxifying enzymes (CarE and GSTs) and P450 activities fluctuated after a sublethal concentration (Dinotefuran and Lufenuron) treatment, and at the peak value of enzyme activities, the enhancement of detoxifying enzymes of B. odoriphaga was significantly higher than that of B. difformis. These results indicated that Dinotefuran and Lufenuron should be considered as alternatives to other insecticides for control of root maggots. B. odoriphaga exhibited stronger adaptation to insecticides than B. difformis. These data provide guidance for control of root maggots, and the basic information presented here can help reveal the differences in adaptive mechanisms between B. odoriphaga and B. difformis.

Trans-intervertebral osteotomy classification of posterior spinal corrective osteotomy procedures via the intervertebral space.

•This is a diagnostic study for a classification for posterior spinal osteotomy procedures via the intervertebral space.•Proposed â€‹a novel classification â€‹with â€‹excellent reliability â€‹and â€‹validity, differ from the SRS-Schwab osteotomy classification.•Give a novel definition of "trans-intervertebral osteotomy" (TIO) for posterior spinal osteotomy procedures.•Thoroughly discussed about the histories of posterior spinal osteotomy procedures via the intervertebral space.•Systematically introduced the TIO technique with fine original schematics.

An AIE luminogen targeting the endoplasmic reticulum inhibits cancer cell growth via multicellular organelle oxidative stress.

Organelle-targeted photodynamic therapy has been increasingly investigated in recent decades, but little attention has been paid to the damage caused to other non-primary target organelles during the course of action, even though these non-primary target organelles may play a substantial role in inhibiting the growth of cancer cells. In this contribution, we report an AIE-type strong endoplasmic reticulum-targeted luminogen (MTOQS) with a distorted structure, which is efficient in producing ROS both in cellular and non-cellular environment, causing an effective reduction of high levels of GSH and MDA in cancer cells through the efficient accumulation of intracellular ROS, and the levels of ATP, l-lactic acid, anti-apoptotic factor Bcl-2 and apoptotic protein caspase-3 were determined. Through the identification of these markers, it was evidenced that MTOQS-induced dual organelle oxidative stress could diminish the degree of oxidative phosphorylation and glycolysis in cancer cells and trigger an alteration in the culture environment of cancer cells, while causing damage to the endoplasmic reticulum and mitochondria through multiorganelle oxidative stress, turning on the pathway of apoptosis and consequently driving cancer cells to apoptosis.

A Modified Langmuir Model for Moisture Diffusion in UGFRE of Composite Insulator Considering the Composite Degradation.

Water invasion induced aging and degradation of the unidirectional glass fiber reinforced epoxy resin (UGFRE) rod is inferred as the primary reason for the decay-like fracture of the composite insulator. In this paper, the moisture diffusion processes in the UGFRE from different directions at various test humidities and temperatures are studied. The moisture diffusion of the UGFRE sample obeys the Langmuir diffusion law under the humidity conditions of 53%, 82% and 100% at 40 °C. In deionized water, the moisture diffusion of the UGFRE sample also obeys the Langmuir diffusion law when the invading direction is vertical to the glass fiber. However, when the water invades the UGFRE sample, parallel with the glass fiber, the weight loss caused by composite degradation should not be neglected. A modified Langmuir model, taking Arrhenius Theory and the nonlinear aging characteristic of the composite into consideration, is proposed and can successfully describe the moisture diffusion process. Both the glass fibers and epoxy resin will degrade in the deionized water. The glass fibers show better resistance to degradation than the epoxy resin. The epoxy resin degrades from the glass fiber/epoxy resin interface and become fragments. For composite insulators, the water invasion through the ends should be avoided as far as possible, or the degradation of the UGFRE rod will result in decay-like fracture.

Identification and Pathogenicity of a New Entomopathogenic Fungus, Mucor hiemalis (Mucorales: Mucorales), on the Root Maggot, Bradysia odoriphaga (Diptera: Sciaridae).

Bradysia odoriphaga Yang and Zhang (Diptera: Sciaridae), the Chinese chive root maggot, is a destructive pest of Allium vegetables and flowers that causes severe losses in northern China. Novel biological control technologies are needed for controlling this pest. We identified a new entomopathogenic fungus isolated from infected B. odoriphaga larvae and evaluated the susceptibility of the biological stages of B. odoriphaga and the effects of temperature on fungus growth and pathogenicity. Based on morphological characteristics and molecular phylogeny, the fungus was identified as Mucor hiemalis BO-1 (Mucorales: Mucorales). This fungus had the strongest virulence to B. odoriphaga larvae followed by eggs and pupae, while B. odoriphaga adults were not susceptible. A temperature range of 18-28°C was optimum for the growth and sporulation of M. hiemalis BO-1 and virulence to B. odoriphaga larvae. At 3 and 5 d after inoculation with 105 spores/ml at 23°C, the survival rates were 24.8% and 4.8% (2nd instar larvae), respectively, and 49.6% and 12.8% (4th instar larvae), respectively. The potted plant trials confirmed that M. hiemalis BO-1 exerted excellent control efficiency against B. odoriphaga larvae, and the control exceeded 80% within 5 d when the spore concentration applied exceeded 107 spores/ml. In conclusion, these findings supported the hypotheses that this fungus could serve as an effective control agent against B. odoriphaga larvae and is worth being further tested to determine its full potential as a biocontrol agent.

The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis.

Previous studies show that 3ß-hydroxysterol-Δ24 reductase (DHCR24) has a remarked decline in the brain of AD patients. In brain cholesterol synthetic metabolism, DHCR24 is known as the heavily key synthetase in cholesterol synthesis. Moreover, mutations of DHCR24 gene result in inhibition of the enzymatic activity of DHCR24, causing brain cholesterol deficiency and desmosterol accumulation. Furthermore, in vitro studies also demonstrated that DHCR24 knockdown lead to the inhibition of cholesterol synthesis, and the decrease of plasma membrane cholesterol and intracellular cholesterol level. Obviously, DHCR24 could play a crucial role in maintaining cholesterol homeostasis via the control of cholesterol synthesis. Over the past two decades, accumulating data suggests that DHCR24 activity is downregulated by major risk factors for AD, suggesting a potential link between DHCR24 downregulation and AD pathogenesis. Thus, the brain cholesterol loss seems to be induced by the major risk factors for AD, suggesting a possible causative link between brain cholesterol loss and AD. According to previous data and our study, we further found that the reduced cholesterol level in plasma membrane and intracellular compartments by the deficiency of DHCR24 activity obviously was involved in ß-amyloid generation, tau hyperphosphorylation, apoptosis. Importantly, increasing evidences reveal that the brain cholesterol loss and lipid raft disorganization are obviously linked to neuropathological impairments which are associated with AD pathogenesis. Therefore, based on previous data and research on DHCR24, we suppose that the brain cholesterol deficiency/loss might be involved in the pathogenesis of AD.

Optimization of Copper Electroforming Process Parameters Based on Double Hidden Layer BP Neural Network.

In order to optimize the pulse electroforming copper process, a double hidden layer BP (back propagation) neural network was constructed. Through sample training, the mapping relationship between electroforming copper process conditions and target properties was accurately established, and the prediction of microhardness and tensile strength of the electroforming layer in the pulse electroforming copper process was realized. The predicted results were verified by electrodeposition copper test in copper pyrophosphate solution system with pulse power supply. The results show that the microhardness and tensile strength of copper layer predicted by "3-4-3-2" structure double hidden layer neural network are very close to the experimental values, and the relative error is less than 2.82%. In the parameter range, the microhardness of copper layer is between 100.3~205.6 MPa and the tensile strength is between 165~485 MPa. When the microhardness and tensile strength are optimal, the corresponding range of optimal parameters are as follows: current density is 2-3 A·dm-2, pulse frequency is 1.5-2 kHz and pulse duty cycle is 10-20%.

The effects of vertebral rotation on the position of the aorta relative to the spine in patients with adult degenerative scoliosis.

AIMS: This study aimed to explore the effects of vertebral rotation on the position of the aorta relative to the thracolumbar and lumbar spine, and to identify risk factors for vertebral rotation in patients with adult degenerative scoliosis (ADS). METHODS: A total of 71 patients with ADS were divided into left scoliosis (LS) group (n = 40 cases) and right scoliosis (RS) group (n = 31cases) with well-matched demographics. Apical vertebrae, Cobb angle (°), coronal horizontal movement, thoracolumbar kyphosis (TLK) and Nash-Moe rotation classification were measured on X-ray. The Cartesian coordinate system was established on T2-MRI for each level of intervertebral disc on thracolumbar and lumbar spine, where aorta-vertebrae angle (α), aorta-vertebrae distance (d), and vertebral rotation angle (γ) for each level of T12-L1 to L3-L4 on MRI were defined within the Cartesian coordinate system. RESULTS: There was no statistical difference in the distribution of apical vertebrae between LS and RS groups. Nash-Moe classification was of no significance between the two groups. When there was a larger Cobb angle and coronal horizontal movement, a greater γ in LS group and a lower γ in RS group were noted (both p < 0.001). There was no correlation among γ, α, and d in LS group (p = 0.908 and 0.661, respectively) nor in RS group (p = 0.738 and 0.289, respectively). In LS group, Nash-Moe classification correlated to Cobb angle, coronal movement and TLK. In RS group, it correlated to Cobb angle and coronal movement. Cobb angle was the risk factor for Nash-Moe classification in RS group while no factors were identified in LS group. Coronal movement was independent risk factor for γ (p = 0.003) in LS group. Moreover, γ was affected by Cobb angle (p = 0.001) and coronal horizontal movement (p = 0.006) in RS group. CONCLUSION: Vertebral rotation could be predicted by Cobb angle or coronal horizontal movement measured on X-ray in ADS patients and aorta maintained in a relatively normal position in patients with ADS.

DHCR24 Knock-Down Induced Tau Hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, Ser396 Epitopes and Inhibition of Autophagy by Overactivation of GSK3ß/mTOR Signaling.

Accumulating evidences supported that knock-down of DHCR24 is linked to the pathological risk factors of AD, suggesting a potential role of DHCR24 in AD pathogenesis. However, the molecular mechanism link between DHCR24 and tauopathy remains unknown. Here, in order to elucidate the relationship between DHCR24 and tauopathy, we will focus on the effect of DHCR24 on the tau hyperphosphorylation at some toxic sites. In present study, we found that DHCR24 knock-down significantly lead to the hyperphosphorylation of tau sites at Thr181, Ser199, Thr231, Ser262, Ser396. Moreover, DHCR24 knock-down also increase the accumulation of p62 protein, simultaneously decreased the ratio of LC3-II/LC3-I and the number of autophagosome compared to the control groups, suggesting the inhibition of autophagy activity. In contrast, DHCR24 knock-in obviously abolished the effect of DHCR24 knock-down on tau hyperphosphrylation and autophagy. In addition, to elucidate the association between DHCR24 and tauopathy, we further showed that the level of plasma membrane cholesterol, lipid raft-anchored protein caveolin-1, and concomitantly total I class PI3-K (p110α), phospho-Akt (Thr308 and Ser473) were significantly decreased, resulting in the disruption of lipid raft/caveola and inhibition of PI3-K/Akt signaling in silencing DHCR24 SH-SY5Y cells compared to control groups. At the same time, DHCR24 knock-down simultaneously decreased the level of phosphorylated GSK3ß at Ser9 (inactive form) and increased the level of phosphorylated mTOR at Ser2448 (active form), leading to overactivation of GSK3ß and mTOR signaling. On the contrary, DHCR24 knock-in largely increased the level of membrane cholesterol and caveolin-1, suggesting the enhancement of lipid raft/caveola. And synchronously DHCR24 knock-in also abolished the effect of DHCR24 knock-down on the inhibition of PI3-K/Akt signaling as well as the overactivation of GSK3ß and mTOR signaling. Collectively, our data strongly supported DHCR24 knock-down lead to tau hyperphosphorylation and the inhibition of autophagy by a lipid raft-dependent PI3-K/Akt-mediated GSK3ß and mTOR signaling. Taking together, our results firstly demonstrated that the decrease of plasma membrane cholesterol mediated by DHCR24 deficiency might contribute to the tauopathy in AD and other tauopathies.

MicroRNA-936 Targets JAG1 and Inhibits the Proliferation of Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Investigating the underlying molecular mechanism is essential for the treatment and prognosis of HCC. Emerging evidence suggests that microRNAs (miRNAs) play pivotal roles in cancer progression. Down-regulation of miR-936 has been found in several cancers, which serves as a tumor suppressor to inhibit the development of cancers. However, the clinical significance and functional roles of miR-936 in HCC have not been determined. To explore this, the expression of miR-936 in HCC tissues and cells was detected by RT-qPCR. Cell Counting Kit-8 (CCK-8) assay, cell migration and cell cycle analysis were performed to evaluate the effects of miR-936 on the growth of HCC cells. The targets of miR-936 were predicted using the miRDB database and confirmed by luciferase reporter experiments. The protein expression of targets was determined by western blot. The results showed that miR-936 was significantly decreased in HCC tissues and cell lines. Low expression of miR-936 was associated with the advance progression and poor survival of HCC patients (P = 0.0036). Functional study revealed that overexpression of miR-936 inhibited the proliferation, migration (decreased to ∼0.26 fold) and induced cell cycle arrested in G1 phase (from 35.3% to 44.7%) of HCC cells. Additionally, miR-936 targeted the 3'-untranslated region (UTR) of jagged-1 (JAG1) and reduced the expression of JAG1 (decreased to ∼0.35 fold). JAG1 was found to be up-regulated in HCC tissues and was inversely correlated with the expression of miR-936 (Pearson r = -0.4633; P = 0.0007). The anti-cancer effects of miR-936 on the proliferation of HCC cells were partially reversed by the rescue of JAG1. Therefore, these results suggested that miR-936 might be a potential target for HCC treatment.

Agomelatine Prevents Amyloid Plaque Deposition, Tau Phosphorylation, and Neuroinflammation in APP/PS1 Mice.

Agomelatine, an agonist of melatonergic MT1 and MT2 receptors and a selective 5-hydroxytryptamine 2C receptor antagonist, is widely applied in treating depression and insomnia symptoms in several neurogenerative diseases. However, the neuroprotective effect of agomelatine in Alzheimer's disease (AD) is less known. In this study, a total of 30 mice were randomly divided into three groups, namely, wild type (WT), APP/PS1, and agomelatine (50 mg/kg). After 30 days, the Morris water maze was performed to test the cognitive ability of mice. Then, all mice were sacrificed, and the hippocampus tissues were collected for ELISA, Western blot, and immunofluorescence analysis. In this study, we found that agomelatine attenuated spatial memory deficit, amyloid-ß (Aß) deposition, tau phosphorylation, and neuroinflammation in the hippocampus of APP/PS1 mice. Further study demonstrated that agomelatine treatment upregulated the protein expression of DHCR24 and downregulated P-Akt, P-mTOR, p-p70s6k, Hes1, and Notch1 expression. In summary, our results identified that agomelatine could improve cognitive impairment and ameliorate AD-like pathology in APP/PS1 mice via activating DHCR24 signaling and inhibiting Akt/mTOR and Hes1/Notch1 signaling pathway. Agomelatine may become a promising drug candidate in the therapy of AD.

A hybrid therapeutic approach for decreasing postoperative complications in patients with adult lumbar degenerative scoliosis.

To decrease postoperative complications in patients with adult lumbar degenerative scoliosis (ALDS), short-segment fusion surgery was used in this study. However, the incidence of adjacent segment disease was found to be remarkable. Therefore, we applied the hybrid treatment (short-segment fusion for responsibility levels plus nonfusion stabilization of lumbar segments, which was called the Wallis system, for the proximal level) to patients enrolled into this study. The purpose of this study was to investigate the feasibility of a novel hybrid therapeutic approach for treating patients with ALDS.From January 2011 to January 2017, a retrospective study was conducted consisting of 16 patients with ALDS who were treated with hybrid treatment. All patients were treated with short-segment decompression and fusion for responsibility levels and nonfusion stabilization of lumbar segments for the proximal levels. The imaging outcomes were evaluated preoperatively and at the time of follow-up.The mean visual analog score for back pain decreased from 6.1 ±â€Š2.0 preoperatively to 2.1 ±â€Š0.7 at 2-year follow-up (P < .05), and the mean visual analog score for leg pain reduced from 8.1 ±â€Š0.6 preoperatively to 1.3 ±â€Š0.8 at 2-year follow-up (P < .05). The Oswestry disability index scores improved from 65.4 ±â€Š16.3% preoperatively to 18.3 ±â€Š5.6% at 2-year follow-up (P < .05). The mean Cobb angle was 22.1 ±â€Š6.2° preoperatively, and 13.8 ±â€Š6.8° at 2-year follow-up (P < .05). The lumbar lordosis changed from -40.4 ±â€Š14.8° to -43.5 ±â€Š11.2° at 2-year follow-up (P < .05). Solid fusion was achieved in all the patients, and no incidence of adjacent segment disease was noted as well.The proposed hybrid treatment for patients with ALDS can achieve favorable clinical outcomes and a lower incidence of ALDS. However, the correction of deformity is still limited that highlights the necessity of further study.

Limited correction of lumbar lordosis in the treatment of degenerative scoliosis.

BACKGROUND: Patients suffering from degenerative scoliosis (DS) were commonly associated with coronal and sagittal imbalance which made deformity correction surgery necessary. The study aimed to explore the efficacy and feasibility of the limited correction of lumbar lordosis (LL) in the treatment of patients with DS. METHODS: This was a retrospective study including 58 DS patients who underwent spinal deformity correction surgery and were followed up at least 2 years between January 2013 and January 2017. According to the difference of postoperative LL, the patients were divided into 2 groups: the limited correction group: Pelvic incidence(PI)-18°≤ LL .05). In terms of surgery, the limited group had less intra-operative blood loss and operation time (P < .05). At the last follow-up, significant differences were found in terms of LL(-38.2 ±â€Š4.7° and -46.9 ±â€Š4.7°), PT (18.8 ±â€Š5.2° and 11.1 ±â€Š3.6°), sacrum slope (33.7 ±â€Š7.0° and 41.4 ±â€Š6.1°) (P < .05), while there were no significant differences in terms of lumbar Cobb angle (10.5 ±â€Š9.3°and 8.3 ±â€Š6.7°), Oswestry Disability Index scores (25.6 ±â€Š10.2 and 26.4 ±â€Š12.1), and JOA scores (23.6 ±â€Š5.2 and 22.3 ±â€Š5.7) (P > .05). CONCLUSION: Limited correction of LL in the treatment of DS patients can achieve favorable clinical outcomes including effective Cobb angle correction with less blood loss and operative time.

Effects of Different Orientations of Cage Implantation on Lumbar Interbody Fusion.

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) via a fusion cage is widely carried out to treat degenerative lumbar spinal disease, and cage implantation plays a pivotal role in buttressing the vertebrae and promoting fusion. Clinically, the cage implantation is commonly placed in 2 different orientations: oblique and traverse. Therefore, this study aimed to explore the effects of different orientations of cage implantation on lumbar interbody fusion. METHODS: From January 2016 to January 2018, a retrospective study of 98 patients with lumbar degenerative disease who were treated with lumbar interbody fusion with at least 2-year follow-up was performed. According to the different positions of cage implantation, the patients were divided into 2 groups: oblique group (OG) and traverse group (TG). The clinical and radiographic outcomes were compared preoperatively, postoperatively, and at last follow-up evaluation. Radiographic measurements included the height of intervertebral (HOI) disk, segment lordosis (SL), lumbar lordosis (LL), the distance between the posterior of cage and vertebrae postoperatively (D1), the distance at final follow-up (D2), and the distance of cage move (D3). Radiographic evaluation of fusion integrity was performed based on the Bridwell interbody fusion grading system at the final follow-up. RESULTS: There was no significant difference between the 2 groups in terms of sex, age, surgical levels, operative time, intraoperative blood loss, time to ambulation, and length of hospital stay (P > 0.05). The HOI disk, SL, and LL in the 2 groups were noticeably improved postoperatively compared with preoperatively (P > 0.05), and there was no significant difference between the 2 groups (P > 0.05). However, at the final follow-up, HOI disk, SL, and LL in the TG were larger than those in the OG (P < 0.05). D1 and D2 in the TG were larger than those in the OG, and there was a significant difference between the 2 groups (P < 0.05). D3 in the OG was larger than that in the TG (P < 0.05). All patients achieved grade I fusion at the final evaluation. CONCLUSIONS: The traverse cage implantation in TLIF had the same clinical effect as oblique cage implantation, but is superior in improving sagittal alignment. Therefore, we advise that the cage should be placed in traverse orientation in TLIF.