Development and validation of machine learning models to predict frailty risk for elderly.

AIMS: Early identification and intervention of the frailty of the elderly will help lighten the burden of social medical care and improve the quality of life of the elderly. Therefore, we used machine learning (ML) algorithm to develop models to predict frailty risk in the elderly. DESIGN: A prospective cohort study. METHODS: We collected data on 6997 elderly people from Chinese Longitudinal Healthy Longevity Study wave 6-7 surveys (2011-2012, 2014). After the baseline survey in 1998 (wave 1), the project conducted follow-up surveys (wave 2-8) in 2000-2018. The osteoporotic fractures index was used to assess frailty. Four ML algorithms (random forest [RF], support vector machine, XGBoost and logistic regression [LR]) were used to develop models to identify the risk factors of frailty and predict the risk of frailty. Different ML models were used for the prediction of frailty risk in the elderly and frailty risk was trained on a cohort of 4385 elderly people with frailty (split into a training cohort [75%] and internal validation cohort [25%]). The best-performing model for each study outcome was tested in an external validation cohort of 6997 elderly people with frailty pooled from the surveys (wave 6-7). Model performance was assessed by receiver operating curve and F2-score. RESULTS: Among the four ML models, the F2-score values were similar (0.91 vs. 0.91 vs. 0.88 vs. 0.90), and the area under the curve (AUC) values of RF model was the highest (0.75), followed by LR model (0.74). In the final two models, the AUC values of RF and LR model were similar (0.77 vs. 0.76) and their accuracy was identical (87.4% vs. 87.4%). CONCLUSION: Our study developed a preliminary prediction model based on two different ML approaches to help predict frailty risk in the elderly. IMPACT: The presented models from this study can be used to inform healthcare providers to predict the frailty probability among older adults and maybe help guide the development of effective frailty risk management interventions. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Detecting frailty at an early stage and implementing timely targeted interventions may help to improve the allocation of health care resources and to reduce frailty-related burden. Identifying risk factors for frailty could be beneficial to provide tailored and personalized care intervention for older adults to more accurately prevent or improve their frail conditions so as to improve their quality of life. REPORTING METHOD: The study has adhered to STROBE guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Surgical methods influence on the risk of anastomotic fistula after pancreaticoduodenectomy: a systematic review and network meta-analysis.

BACKGROUND: Pancreaticoduodenectomy is the first choice surgical intervention for the radical treatment of pancreatic tumors. However, an anastomotic fistula is a common complication after pancreaticoduodenectomy with a high mortality rate. With the development of minimally invasive surgery, open pancreaticoduodenectomy (OPD), laparoscopic pancreaticoduodenectomy (LPD), and robotic pancreaticoduodenectomy (RPD) are gaining interest. But the impact of these surgical methods on the risk of anastomosis has not been confirmed. Therefore, we aimed to integrate relevant clinical studies and explore the effects of these three surgical methods on the occurrence of anastomotic fistula after pancreaticoduodenectomy. METHODS: A systematic literature search was conducted for studies reporting the RPD, LPD, and OPD. Network meta-analysis of postoperative anastomotic fistula (Pancreatic fistula, biliary leakage, gastrointestinal fistula) was performed. RESULTS: Sixty-five studies including 10,026 patients were included in the network meta-analysis. The rank of risk probability of pancreatic fistula for RPD (0.00) was better than LPD (0.37) and OPD (0.62). Thus, the analysis suggests the rank of risk of the postoperative pancreatic fistula for RPD, LPD, and OPD. The rank of risk probability for biliary leakage was similar for RPD (0.15) and LPD (0.15), and both were better than OPD (0.68). CONCLUSIONS: This network meta-analysis provided ranking for three different types of pancreaticoduodenectomy. The RPD and LPD can effectively improve the quality of surgery and are safe as well as feasible for OPD.

Low abundance of insulin-induced gene 1 contributes to SREBP-1c processing and hepatic steatosis in dairy cows with severe fatty liver.

Fatty liver is a major metabolic disorder of high-producing dairy cows during the transition period. In nonruminants, it is well established that insulin-induced gene 1 (INSIG1) plays a crucial role in regulating hepatic lipogenesis by controlling the anchoring of sterol regulatory element-binding protein 1 (SREBP-1) on the endoplasmic reticulum along with SREBP cleavage-activating protein (SCAP). Whether the INSIG1-SCAP-SREBP-1c transport axis is affected in cows experiencing fatty liver is unknown. Thus, the aim of this study was to investigate the potential role of INSIG1-SCAP-SREBP-1c axis in the progression of fatty liver in dairy cows. For in vivo experiments, 24 dairy cows at the start of their fourth lactation (median; range 3-5) and 8 d in milk (median; range 4-12 d) were selected into a healthy group [n = 12; triglyceride (TG) content <1%] and a severe fatty liver group (n = 12; TG content >10%) according to their hepatic TG content. Blood samples were collected for detecting serum concentrations of free fatty acids, ß-hydroxybutyrate, and glucose. Compared with healthy cows, cows with severe fatty liver had higher serum concentrations of ß-hydroxybutyrate and free fatty acids and lower concentration of glucose. Liver biopsies were used to detect the status of INSIG1-SCAP-SREBP-1c axis, and the mRNA expression of SREBP-1c-target lipogenic genes acetyl-CoA carboxylase α (ACACA), fatty acid synthase (FASN), and diacylglycerol acyltransferase 1 (DGAT1). Cows with severe fatty liver had lower protein expression of INSIG1 in the hepatocyte endoplasmic reticulum fraction, greater protein expression of SCAP and precursor SREBP-1c in the hepatocyte Golgi fraction, and greater protein expression of mature SREBP-1c in the hepatocyte nuclear fraction. In addition, the mRNA expression of SREBP-1c-target lipogenic genes ACACA, FASN, and DGAT1 was greater in the liver of dairy cows with severe fatty liver. In vitro experiments were conducted on hepatocytes isolated from 5 healthy 1-d-old female Holstein calves, and hepatocytes from each calf were run independently. First, hepatocytes were treated with 0, 200, or 400 µM palmitic acid (PA) for 12 h. Exogenous PA treatment decreased INSIG1 protein abundance, enhanced the endoplasmic reticulum to Golgi export of SCAP-precursor SREBP-1c complex and the nuclear translocation of mature SREBP-1c, all of which was associated with increased transcriptional activation of lipogenic genes and TG synthesis. Second, hepatocytes were transfected with INSIG1-overexpressing adenovirus for 48 h and treated with 400 µM PA 12 h before the end of transfection. Overexpressing INSIG1 inhibited PA-induced SREBP-1c processing, upregulation of lipogenic genes, and TG synthesis in hepatocytes. Overall, the present in vivo and in vitro results indicated that the low abundance of INSIG1 contributed to SREBP-1c processing and hepatic steatosis in dairy cows. Thus, the INSIG1-SCAP-SREBP-1c axis may be a novel target for treatment of fatty liver in dairy cows.

Procapra Przewalskii Tracking Autonomous Unmanned Aerial Vehicle Based on Improved Long and Short-Term Memory Kalman Filters.

This paper presents an autonomous unmanned-aerial-vehicle (UAV) tracking system based on an improved long and short-term memory (LSTM) Kalman filter (KF) model. The system can estimate the three-dimensional (3D) attitude and precisely track the target object without manual intervention. Specifically, the YOLOX algorithm is employed to track and recognize the target object, which is then combined with the improved KF model for precise tracking and recognition. In the LSTM-KF model, three different LSTM networks (f, Q, and R) are adopted to model a nonlinear transfer function to enable the model to learn rich and dynamic Kalman components from the data. The experimental results disclose that the improved LSTM-KF model exhibits higher recognition accuracy than the standard LSTM and the independent KF model. It verifies the robustness, effectiveness, and reliability of the autonomous UAV tracking system based on the improved LSTM-KF model in object recognition and tracking and 3D attitude estimation.

Single-cell analyses reveal the differentiation shifts of Schwann cells in neonatal rat sciatic nerves.

Schwann cells provide essential physical and chemical support for neurons and play critical roles in the peripheral nervous system. To acquire an enhanced understanding of the genetic characteristics of Schwann cells, we analyzed single-cell transcriptional profiling of Schwann cells in neonatal rat sciatic nerves, ordered the pseudotemporal states of Schwann cells, and determined the magnitude of RNA velocity vectors as well as cell cycle stages of Schwann cell subtypes. We discovered the cellular heterogeneity of Schwann cells in neonatal rat sciatic nerves, revealed the dynamic changes of Schwann cell subtypes, and pointed out the differentiation trajectory from Timp3- and Col5a3-expressing Schwann cell subtype 3 to other Schwann cell subtypes. The functional interpretation further indicated that subtype 3 Schwann cells display genetic signatures of DNA replication and the acquisition of mesenchymal traits. Our study presents a transcriptional summarization of the differentiation states of Schwann cell subtypes in neonatal rat sciatic nerves at single-cell resolution and may serve as a foundation for a deeper comprehension of the involvement of Schwann cells in the development and regeneration of peripheral nerves.

Propionate alleviates fatty acid-induced mitochondrial dysfunction, oxidative stress, and apoptosis by upregulating PPARG coactivator 1 alpha in hepatocytes.

Reduced feed intake during the transition period renders cows unable to meet their energy needs for maintenance and lactation, leading to a state of negative energy balance. Severe negative energy balance initiates fat mobilization and increases circulating levels of free fatty acids (FFA), which could induce hepatic mitochondrial dysfunction, oxidative stress, and apoptosis. Enhancing the hepatic supply of propionate (major gluconeogenic substrate) is a feasible preventive and therapeutic strategy to alleviate hepatic metabolic disorders during the transition period. Whether propionate supply affects pathways beyond gluconeogenesis during high FFA loads is not well known. Thus, the objective of this study was to investigate whether propionate supply could protect calf hepatocytes from FFA-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Hepatocytes were isolated from 5 healthy calves (1 d old, female, 30-40 kg, fasting) and treated with various concentrations of propionate (0, 1, 2, and 4 mM propionate for 12 h) or for different times (2 mM propionate for 0, 3, 6, 12 and 24 h). Furthermore, hepatocytes were treated with propionate (2 mM), fatty acids (1.2 mM), or both for 12 h with or without 50 nM PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator-1 alpha) small interfering RNA. Compared with the control group, protein abundance of PGC-1α was greater with 2 and 4 mM propionate treatment groups. Furthermore, protein abundance of TFAM (mitochondrial function marker mitochondrial transcription factor A) and VDAC1 (voltage-dependent anion channel 1) was greater with 1, 2, and 4 mM propionate, and COX4 (cyclooxygenase 4) was greater with 2 and 4 mM propionate groups. In addition, propionate supply led to an increase in protein abundance of PGC-1α, TFAM, VDAC1, and COX4 over time. Flow cytometry revealed that propionate treatment increased the number of mitochondria in hepatocytes compared with control group, but inhibition of PGC-1α abolished these beneficial effects. The lower protein abundance of PGC-1α, TFAM, COX4, and VDAC1 and activities of superoxide dismutase and glutathione peroxidase, along with greater production of reactive oxygen species, malondialdehyde, and apoptosis rate in response to treatment with high concentrations of FFA suggested an impairment of mitochondrial function and induction of oxidative stress and apoptosis. In contrast, propionate treatment hastened these negative effects. Knockdown of PGC-1α by small interfering RNA impeded the beneficial role of propionate on FFA-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Overall, results demonstrated that propionate supply alleviates mitochondrial dysfunction, oxidative stress, and apoptosis in FFA-treated calf hepatocytes by upregulating PGC-1α. Together, the data suggest that PGC-1α may be a promising target for preventing or improving hepatic function during periods such as the transition into lactation where the FFA load on the liver increases.

MOF-Derived Bifunctional Co0.85Se Nanoparticles Embedded in N-Doped Carbon Nanosheet Arrays as Efficient Sulfur Hosts for Lithium-Sulfur Batteries.

Lithium-sulfur batteries possess the merits of low cost and high theoretical energy density but suffer from the shuttle effect of lithium polysulfides and slow redox kinetics of sulfur. Herein, novel Co0.85Se nanoparticles embedded in nitrogen-doped carbon nanosheet arrays (Co0.85Se/NC) were constructed on carbon cloth as the self-supported host for a sulfur cathode using a facile fabrication strategy. The interconnected porous carbon-based structure of the Co0.85Se/NC could facilitate the rapid electron and ion transfer kinetics. The embedded Co0.85Se nanoparticles can effectively capture and catalyze lithium polysulfides, thus accelerating the redox kinetics and stabilizing sulfur cathodes. Therefore, the Co0.85Se/NC-S cathode could maintain a stable cycle performance for 400 cycles at 1C and deliver a high discharge specific capacity of 1361, 1001, and 810 mAh g-1 at current densities of 0.1, 1, and 3C, respectively. This work provides an efficient design strategy for high-performance lithium-sulfur batteries with high energy densities.

Phosphorus equivalency of phytase with various evaluation indicators of duck in starter.

This study was conducted to evaluate phosphorus (P) equivalency of phytase with various evaluation indicators of ducks in starter (0-14 days). Three hundred and twenty 1-day-old Cherry Valley ducks were randomly assigned to eight groups. The dietary treatments were four levels of available phosphorus (aP) with 0.25%, 0.32%, 0.39%, and 0.46% (treatments I-IV) and four levels of phytase added to low-aP basal diet (treatment I) with 300, 600, 900, and 1200 units (U) per kg (treatments V-VIII). The results were that compared to treatment I, increasing aP and supplementary phytase significantly (p < 0.05) improved body weight (BW), BW gain (BWG), feed intake (FI), live BW, carcass weight, semieviscerated weight, eviscerated weight, leg muscle weight, and decreased feed conversion ratio (FCR). Treatments V and VI did not significantly increase tibia ash, tibia calcium, and tibia P of 14-day-old ducks (p > 0.05). Following the increase of aP level (treatments I-IV), apparent utilization of Ca and P of ducks increased with varying degrees. With the increase of dietary phytase level (treatments V-VIII), the apparent utilization of Ca and P showed no significant difference (p > 0.05) but an increasing trend. Serum P reached the highest level when adding 600 U/kg phytase (treatment VI). Serum Ca and serum alkaline phosphatase activity showed no significant difference among treatments V-VIII (p > 0.05). Based on corn-soybean-rapeseed meal diet, with the evaluation indexes of FI, BWG, tibia ash, tibia Ca, tibia P, and apparent utilization of Ca and P, the addition of 500 U/kg phytase could release aP of 0.03%, 0.04%, 0.02%, 0.01%, 0.02%, 0.08%, and 0.07%, respectively. On the same way, the addition of 1000 U/kg phytase could release aP of 0.07%, 0.09%, 0.06%, 0.02%, 0.07%, 0.09%, and 0.09%, respectively.

Cell populations in neonatal rat peripheral nerves identified by single-cell transcriptomics.

Peripheral nerves connect central nerves with target tissues and organs and execute vital signal transduction functions. Although sub-types of neurons have been defined, the heterogeneity of cell populations in peripheral nerves, especially Schwann cells, has not been well demonstrated. Here, we collected sciatic nerves (SN) and dorsal root ganglia (DRG) from neonatal (1-day old) rats and classified cell populations by high-coverage single-cell sequencing. A total of 10 types of cells, including endothelial cells, erythrocytes, fibroblasts, monocytic cells, neurons, neutrophils, pericytes, satellite cells, Schwann cells, and vascular smooth muscle cells, were identified by transcriptome-based cell typing. The comparisons of cells in neonatal rat SN and DRG revealed distinct atlas in different tissue localizations. Investigations of ligand-receptor interactions showed that there existed direct cell-cell communications between endothelial cells and fibroblasts in SN and among endothelial cells, fibroblasts, and vascular smooth muscle cells in DRG. Schwann cells in neonatal rats were further sub-grouped to four sub-types, including LOC100134871 and Hbb expressing Schwann cell sub-type 1, Cldn19 and Emid1 expressing Schwann cell sub-type 2, Timp3 and Col5a3 expressing Schwann cell sub-type 3, and Cenpf and Mki67 expressing Schwann cell sub-type 4. These Schwann cell sub-types exhibited distinct genetic features and functional enrichments. Collectively, our results illustrated the diversity and cellular complexity of peripheral nerves at the neonatal stage and revealed the heterogeneity of Schwann cells in the peripheral nervous system.

Tau modulates Schwann cell proliferation, migration and differentiation following peripheral nerve injury.

Tau protein (encoded by the gene microtubule-associated protein tau, Mapt) is essential for the assembly and stability of microtubule and the functional maintenance of the nervous system. Tau is highly abundant in neurons and is detectable in astrocytes and oligodendrocytes. However, whether tau is present in Schwann cells, the unique glial cells in the peripheral nervous system, is unclear. Here, we investigated the presence of tau and its coding mRNA, Mapt, in cultured Schwann cells and find that tau is present in these cells. Gene silencing of Mapt promoted Schwann cell proliferation and inhibited Schwann cell migration and differentiation. In vivo application of Mapt siRNA suppressed the migration of Schwann cells after sciatic nerve injury. Consistent with this, Mapt-knockout mice showed elevated proliferation and reduced migration of Schwann cells. Rats injected with Mapt siRNA and Mapt-knockout mice also exhibited impaired myelin and lipid debris clearance. The expression and distribution of the cytoskeleton proteins α-tubulin and F-actin were also disrupted in these animals. These findings demonstrate the existence and biological effects of tau in Schwann cells, and expand our understanding of the function of tau in the nervous system.

Hepatic autophagy and mitophagy status in dairy cows with subclinical and clinical ketosis.

Severe negative energy balance around parturition is an important contributor to ketosis, a metabolic disorder that occurs most frequently in the peripartal period. Autophagy and mitophagy are important processes responsible for breaking down useless or toxic cellular material, and in particular damaged mitochondria. However, the role of autophagy and mitophagy during the occurrence and development of ketosis is unclear. The objective of this study was to investigate autophagy and mitophagy in the livers of cows with subclinical ketosis (SCK) and clinical ketosis (CK). We assessed autophagy by measuring the protein abundance of microtubule-associated protein 1 light chain 3-II (LC3-II; encoded by MAP1LC3) and sequestosome-1 (p62, encoded by SQSTM1), as well as the mRNA abundance of autophagy-related genes 5 (ATG5), 7 (ATG7), and 12 (ATG12), beclin1 (BECN1), and phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3). Mitophagy was evaluated by measuring the protein abundance of the mitophagy upstream regulators PTEN-induced putative kinase 1 (PINK1) and Parkin. Liver and blood samples were collected from healthy cows [n = 15; blood ß-hydroxybutyrate (BHB) concentration <1.2 mM], cows with SCK (n = 15; blood BHB concentration 1.2 to 3.0 mM) and cows with CK (n = 15; blood BHB concentration >3.0 mM with clinical signs) with similar lactation numbers (median = 3, range = 2 to 4) and days in milk (median = 6, range = 3 to 9). The serum activity of aspartate aminotransferase and alanine aminotransferase was greater in cows with CK than in healthy cows. Levels of oxidative stress biomarkers malondialdehyde and hydrogen peroxide were also higher in liver tissue from ketotic cows (SCK and CK) than from healthy cows. Compared with cows with CK and healthy cows, the hepatic mRNA abundance of MAP1LC3, SQSTM1, ATG5, ATG7, ATG12, and PIK3C3 was upregulated in cows with SCK. Compared with healthy cows, cows with SCK had a lower abundance of p62 and a greater abundance of LC3-II, but levels of both were higher in cows with CK. The mRNA abundance of ATG12 was lower in cows with CK than in healthy cows. Furthermore, the hepatic protein abundance of PINK1 and Parkin was greater in cows with SCK and slightly lower in cows with CK than in healthy cows. These data demonstrated differences in the hepatic activities of autophagy and mitophagy in cows with SCK compared with cows with CK. Although the precise mechanisms for these differences could not be discerned, autophagy and mitophagy seem to be involved in ketosis.

The microRNAs let-7 and miR-9 down-regulate the axon-guidance genes Ntn1 and Dcc during peripheral nerve regeneration.

Axon guidance helps growing neural axons to follow precise paths to reach their target locations. It is a critical step for both the formation and regeneration of neuronal circuitry. Netrin-1 (Ntn1) and its receptor, deleted in colorectal carcinoma (Dcc) are essential factors for axon guidance, but their regulation in this process is incompletely understood. In this study, using quantitative real-time RT-PCR (qRT-PCR) and biochemical and reporter gene assays, we found that the Ntn1 and Dcc genes are both robustly up-regulated in the sciatic nerve stump after peripheral nerve injury. Moreover, we found that the microRNA (miR) let-7 directly targets the Ntn1 transcript by binding to its 3'-untranslated region (3'-UTR), represses Ntn1 expression, and reduces the secretion of Ntn1 protein in Schwann cells. We also identified miR-9 as the regulatory miRNA that directly targets Dcc and found that miR-9 down-regulates Dcc expression and suppresses the migration ability of Schwann cells by regulating Dcc abundance. Functional examination in dorsal root ganglion neurons disclosed that let-7 and miR-9 decrease the protein levels of Ntn1 and Dcc in these neurons, respectively, and reduce axon outgrowth. Moreover, we identified a potential regulatory network comprising let-7, miR-9, Ntn1, Dcc, and related molecules, including the RNA-binding protein Lin-28 homolog A (Lin28), SRC proto-oncogene nonreceptor tyrosine kinase (Src), and the transcription factor NF-κB. In summary, our findings reveal that the miRs let-7 and miR-9 are involved in regulating neuron pathfinding and extend our understanding of the regulatory pathways active during peripheral nerve regeneration.

Short communication: Enhanced autophagy activity in liver tissue of dairy cows with mild fatty liver.

During the transition period, dairy cows are challenged by increased energy demands and decreased dry matter intake, which can induce a variety of metabolic disorders, especially fatty liver. Dairy cows suffering from mild or moderate fatty liver in this period show no distinct clinical symptoms, indicating the occurrence of adaptive processes. The process of autophagy (an adaptive response) leads to degradation of intracellular components to generate energy and maintains cellular homeostasis during negative nutrient status. Whether autophagy is involved in metabolic adaptations of the pathological course of mild fatty liver is unclear. Thus, the aim of this study was to determine hepatic autophagy status in dairy cows with mild fatty liver. Liver samples were collected from healthy cows (n = 15), defined as having hepatic triglyceride (TG) content <1% on a wet weight basis, and cows with mild fatty liver (n = 15), defined as having hepatic TG content between 1 and 5%. The abundance of the ubiquitinated proteins, microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3-II) and sequestosome-1 (SQSTM1, also called p62) was lower, whereas the mRNA abundance of MAP1LC3 and SQSTM1 was greater in cows with mild fatty liver. The hepatic mRNA abundance of autophagy-related (ATG) genes ATG5 and ATG7 was greater in response to fatty liver. However, the protein abundance of ATG5 and ATG7 did not differ between healthy and mild fatty liver cows. Together, these data indicate that the formation and degradation of autophagosomes is enhanced in the liver of cows with mild fatty liver. Besides, these results are conducive to define the adaptation mechanisms of dairy cows during the transition period.

Precise Loran-C Signal Acquisition Based on Envelope Delay Correlation Method.

The Loran-C system is an internationally standardized positioning, navigation, and timing service system. It is the most important backup and supplement for the global navigation satellite system (GNSS). However, the existing Loran-C signal acquisition methods are easily affected by noise and cross-rate interference (CRI). Therefore, this article proposes an envelope delay correlation acquisition method that, when combined with linear digital averaging (LDA) technology, can effectively suppress noise and CRI. The selection of key parameters and the performance of the acquisition method are analyzed through a simulation. When the signal-to-noise ratio (SNR) is -16 dB, the acquisition probability is more than 90% and the acquisition error is less than 1 µs. When the signal-to-interference ratio (SIR) of the CRI is -5 dB, the CRI can also be suppressed and the acquisition error is less than 5 µs. These results show that our acquisition method is accurate. The performance of the method is also verified by actual signals emitted by a Loran-C system. These test results show that our method can reliably detect Loran-C pulse group signals over distances up to 1500 km, even at low SNR. This will enable the modern Loran-C system to be a more reliable backup for the GNSS system.

Hepatic nuclear factor kappa B signaling pathway and NLR family pyrin domain containing 3 inflammasome is over-activated in ketotic dairy cows.

Ketosis is an important metabolic disease that can negatively affect the production efficiency of dairy cows. Earlier studies have revealed metabolic and inflammatory alterations in the blood associated with ketosis; however, a link between ketosis and hepatic inflammation has not been well documented. The objective of this study was to investigate whether the nuclear factor kappa B (NF-κB) signaling pathway and NLR family pyrin domain containing 3 (NLRP3) inflammasome were activated in the liver of ketotic cows. Liver and blood samples were collected from healthy (n = 15, control group) and ketotic (n = 15, ketosis group) cows that had a similar number of lactations (median = 3, range = 2 to 4) and days in milk (median = 6 d, range = 3 to 9 d). Results showed that serum levels of fatty acids, ß-hydroxybutyrate (BHB), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were higher and glucose was lower in ketotic cows. Concentrations of serum proinflammatory cytokines IL18, tumor necrosis factor (TNF)-α, and IL1B were greater and the anti-inflammatory cytokine IL10 was lower in the ketosis group. Cows with ketosis had triacylglycerol accumulation in the liver. Upregulation of phosphorylated (p)-NF-κB and p-inhibitor of κB (IκB)α protein abundance in cows with ketosis indicated that the hepatic NF-κB signaling pathway was overactivated. The mRNA abundance of TNFA, inducible nitric oxide synthase (NOS2), IL18, and IL1B were greater and IL10 was lower in ketotic cows. More importantly, the mRNA and protein abundance of NLRP3 and caspase-1 (CASP1) along with CASP1 activity were greater in the liver of cows with ketosis. Overall, the data indicate that the onset of ketosis is accompanied by activation of the NF-κB signaling pathway and NLRP3 inflammasome, resulting in a state of inflammation.

miR-3075 Inhibited the Migration of Schwann Cells by Targeting Cntn2.

Peripheral nerve injury is a complex biological process that involves the expression changes of various coding and non-coding RNAs. Previously, a number of novel miRNAs that were dysregulated in rat sciatic nerve stumps after peripheral nerve injury were identified and functionally annotated by Solexa sequencing. In the current study, we studied one of these identified novel miRNAs, miR-3075, in depth. Results of transwell-based cell migration assay showed that increased expression of miR-3075 suppressed the migration rate of Schwann cells while decreased expression of miR-3075 elevated the migration rate of Schwann cells, demonstrating that miR-3075 inhibited Schwann cell migration. Results of BrdU cell proliferation assay showed that neither miR-3075 mimic nor miR-3075 inhibitor would affect Schwann cell proliferation. We further studied candidate target genes of miR-3075 by using bioinformatic tools and analyzing gene expression patterns and found that miR-3075 might target contactin 2 (Cntn2). Previous study showed that Cntn2 regulated cell migration and myelination. Our current observation suggested that the biological effects of miR-3075 on Schwann cell phenotype might by through the negative regulation of Cntn2. Overall, our study revealed the function of a novel miRNA, miR-3075, and expanded our current understanding of the molecular mechanisms underlying peripheral nerve injury and regeneration.

Novel miR-sc4 regulates the proliferation and migration of Schwann cells by targeting Cdk5r1.

The proliferation and migration of Schwann cells are critical for the repair and regeneration of injured peripheral nerves. Noncoding RNAs, especially microRNAs (miRNAs), have been demonstrated to participate in regulating the biological behaviors of Schwann cells. Numerous differentially expressed novel miRNAs have been identified in the injured sciatic nerve stumps previously by Solexa sequencing. In the current research, we studied the biological function of a novel miRNA, miR-sc4, in detail. Outcomes from proliferation and migration assays suggested that miR-sc4 played an inhibitory role on the proliferation and migration of Schwann cells. Results from bioinformatic analysis, luciferase reporter assay, and rescue experiments suggested that miR-sc4 executed its effect through directly targeting cyclin-dependent kinase 5 activator 1 (Cdk5r1). Collectively, our current study revealed the biological functions of a novel miRNA, showed the effect of miR-sc4 in Schwann cell phenotypic changes, and thus indicated the involvement of miRNAs in peripheral nerve repair and regeneration.

Synthesis and growth mechanism of carbon nanotubes growing on carbon fiber surfaces with improved tensile strength.

An effective approach has been developed for the catalytic decomposition of acetylene (C2H2) by chemical vapor deposition (CVD), to achieve homogeneous growth of carbon nanotubes (CNTs) on the surfaces of carbon fibers. The morphology of CNTs grown on carbon fiber surfaces was observed by a scanning electron microscope and high-resolution transmission electron microscope, which revealed the uniform coverage of CNTs on the carbon fiber surfaces. The single fiber tensile test demonstrated that the tensile strength of carbon fibers could be increased by more than 12% with the catalytic growth of CNTs on their surface. The reparation of the damage caused during the formation of catalyst nanoparticles, and the cross-link of neighboring graphite crystallites induced by CNTs all occurred during the CVD process, which were considered to be the main reasons for improvement. The growth mechanism model of CNTs formation was established based on the thermodynamics principle and the interface microstructure of CNT-grown carbon fiber, illuminating the detailed mechanism for the growth of CNTs and the change of the shape of catalyst particles.

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment.

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.

Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function.

The ability of liver to respond to changes in nutrient availability is essential for the maintenance of metabolic homeostasis. Autophagy encompasses mechanisms of cell survival, including capturing, degrading, and recycling of intracellular proteins and organelles in lysosomes. During negative nutrient status, autophagy provides substrates to sustain cellular metabolism and hence, tissue function. Severe negative energy balance in dairy cows is associated with fatty liver. The aim of this study was to investigate the hepatic autophagy status in dairy cows with severe fatty liver and to determine associations with biomarkers of liver function and inflammation. Liver and blood samples were collected from multiparous cows diagnosed as clinically healthy (n = 15) or with severe fatty liver (n = 15) at 3 to 9 d in milk. Liver tissue was biopsied by needle puncture, and serum samples were collected on 3 consecutive days via jugular venipuncture. Concentrations of free fatty acids and ß-hydroxybutyrate were greater in cows with severe fatty liver. Milk production, dry matter intake, and concentration of glucose were all lower in cows with severe fatty liver. Activities of serum aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, and γ-glutamyl transferase were all greater in cows with severe fatty liver. Serum concentrations of haptoglobin and serum amyloid A were also markedly greater in cows with severe fatty liver. The mRNA expression of autophagosome formation-related gene ULK1 was lower in the liver of dairy cows with severe fatty liver. However, the expression of other autophagosome formation-related genes, beclin 1 (BECN1), phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), autophagy-related gene (ATG) 3, ATG5, and ATG12, did not differ. More important, ubiquitinated proteins, protein expression of sequestosome-1 (SQSTM1, also called p62), and microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3)-II was greater in cows with severe fatty liver. Transmission electron microscopy revealed an increased number of autophagosomes in the liver of dairy cows with severe fatty liver. Taken together, these results indicate that excessive lipid infiltration of the liver impairs autophagic activity that may lead to cellular damage and inflammation.