Multidimensional climatic niche conservatism and invasion risk of Phenacoccus solenopsis.

The cotton mealybug Phenacoccus solenopsis, a globally invasive insect, is listed as a national quarantine pest in agriculture and forestry, which seriously threatens biological safety of China. Niche conservatism is a key assumption of species distribution model. An evaluation of the applicability of using ecological niche models to assess the invasion risk of cotton mealybug, and further optimizing model complexity, are of both theoretical and practical significance. Based on 706 occurrence records and key bioclimatic variables, we used n-dimensional hypervolume niche analysis method to quantify the climatic niche hypervolumes of this pest in both native and invasive sites, and further tested the niche conservatism hypothesis. MaxEnt model parameters were optimized to predict the invasion risk of the mealybug under current and future climate scenarios in China. The results showed that four climatic variables (annual mean temperature, mean temperature of wettest quarter, mean temperature of warmest quarter, and precipitation of driest quarter) were the key climate factors affecting the distribution of cotton mealybug. Compared with native climatic niche (hypervolume volume, HV=40.43), the niche hypervolume of cotton mealybug in the invasive areas was significantly reduced (HV=6.04). Niche contraction (the net differences between the amount of space enclosed by each hypervolume was 0.84) explained 98.8% of niche differentiation, whereas niche shift (the replacement of space between hypervolumes was 0.01) contributed less than 2%. The direction of climatic niche contraction of the pest in different invasive areas was not exactly consistent. The default parameters of MaxEnt model were unreliable (ΔAICc=14.27), and the optimal parameter combination was obtained as follows: feature combination was linear-quadratic-hinge-product and regularization multiplier was 0.5. The most suitable habitats of cotton mealybug were concentrated in the south of Huaihe River-Qinling Mountains line, and the north-central provinces contained a large area of low suitable habitat. The increase of suitable habitat was not significant at the end of 21 century (SSP1-2.6: 1.7%, SSP5-8.5: 0.7%). The multidimensional climatic niche of P. solenopsis was highly conservative. The species distribution model was suitable for analyzing its invasion risk. The northward spread was obvious, and climate change had less impact on the pest.

Fast Charge-Transport Interface on Primary Particles Boosts High-Rate Performance of Li-Rich Mn-Based Cathode Materials.

A Li-rich Mn-based layered oxide cathode (LLO) is one of the most promising cathode materials for achieving high-energy lithium-ion batteries. Nevertheless, the intrinsic problems including sluggish kinetics, oxygen evolution, and structural degradation lead to unsatisfactory performance in rate capability, initial Coulombic efficiency, and stability of LLO. Herein, different from the current typical surface modification, an interfacial optimization of primary particles is proposed to improve the simultaneous transport of ions and electrons. The modified interfaces containing AlPO4 and carbon can effectively increase the Li+ diffusion coefficient and decrease the interfacial charge-transfer resistance, thereby achieving fast charge-transport kinetics. Moreover, the in situ high-temperature X-ray diffraction confirms that the modified interface can improve the thermal stability of LLO by inhibiting the lattice oxygen release on the surface of the delithiated cathode material. In addition, the chemical and visual analysis of the cathode-electrolyte interface (CEI) composition clarifies that a highly stable and conductive CEI film generated on the modified electrode can facilitate interfacial kinetic transmission during cycling. As a result, the optimized LLO cathode exhibits a high initial Coulombic efficiency of 87.3% at a 0.2C rate and maintains superior high-rate stability with a capacity retention of 88.2% after 300 cycles at a 5C high rate.

Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD / 生理学报

The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1β (IL-1β), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1β, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.

Catechin interferes with SCD1 expression and prevents liver fibrosis in mice / 中国药理学通报

Aim To investigate whether catechin can play against CCl

Small molecules facilitate single factor-mediated sweat gland cell reprogramming.

BACKGROUND: Large skin defects severely disrupt the overall skin structure and can irreversibly damage sweat glands (SG), thus impairing the skin's physiological function. This study aims to develop a stepwise reprogramming strategy to convert fibroblasts into SG lineages, which may provide a promising method to obtain desirable cell types for the functional repair and regeneration of damaged skin. METHODS: The expression of the SG markers cytokeratin 5 (CK5), cytokeratin 10 (CK10), cytokeratin 18 (CK18), carcino-embryonic antigen (CEA), aquaporin 5 (AQP5) and α-smooth muscle actin (α-SMA) was assessed with quantitative PCR (qPCR), immunofluorescence and flow cytometry. Calcium activity analysis was conducted to test the function of induced SG-like cells (iSGCs). Mouse xenograft models were also used to evaluate the in vivo regeneration of iSGCs. BALB/c nude mice were randomly divided into a normal group, SGM treatment group and iSGC transplantation group. Immunocytochemical analyses and starch-iodine sweat tests were used to confirm the in vivo regeneration of iSGCs. RESULTS: EDA overexpression drove HDF conversion into iSGCs in SG culture medium (SGM). qPCR indicated significantly increased mRNA levels of the SG markers CK5, CK18 and CEA in iSGCs, and flow cytometry data demonstrated (4.18 ± 0.04)% of iSGCs were CK5 positive and (4.36 ± 0.25)% of iSGCs were CK18 positive. The addition of chemical cocktails greatly accelerated the SG fate program. qPCR results revealed significantly increased mRNA expression of CK5, CK18 and CEA in iSGCs, as well as activation of the duct marker CK10 and luminal functional marker AQP5. Flow cytometry indicated, after the treatment of chemical cocktails, (23.05 ± 2.49)% of iSGCs expressed CK5+ and (55.79 ± 3.18)% of iSGCs expressed CK18+, respectively. Calcium activity analysis indicated that the reactivity of iSGCs to acetylcholine was close to that of primary SG cells [(60.79 ± 7.71)% vs. (70.59 ± 0.34)%, ns]. In vivo transplantation experiments showed approximately (5.2 ± 1.1)% of the mice were sweat test positive, and the histological analysis results indicated that regenerated SG structures were present in iSGCs-treated mice. CONCLUSION: We developed a SG reprogramming strategy to generate functional iSGCs from HDFs by using the single factor EDA in combination with SGM and small molecules. The generation of iSGCs has important implications for future in situ skin regeneration with SG restoration.

Astragalus Polysaccharides Reduce High-glucose-induced Rat Aortic Endothelial Cell Senescence and Inflammasome Activation by Modulating the Mitochondrial Na+/Ca2+ Exchanger.

Vascular endothelial cells play a vital role in atherosclerotic changes and the progression of cardiovascular disease in older adults. Previous studies have indicated that Astragalus polysaccharides (APS), a main active component of the traditional Chinese medicine Astragalus, protect mitochondria and exert an antiaging effect in the mouse liver and brain. However, the effect of APS on rat aortic endothelial cell (RAEC) senescence and its underlying mechanism have not been investigated. In this study, we extracted RAECs from 2-month-old male Wistar rats by the tissue explant method and found that APS ameliorated the high-glucose-induced increase in the frequency of SA-ß-Gal positivity and the levels of the senescence-related proteins p16, p21, and p53. APS increased the tube formation capacity of RAECs under high-glucose conditions. Moreover, APS enhanced the expression of the mitochondrial Na+/Ca2+ exchanger NCLX, and knockdown of NCLX by small interfering RNA (siRNA) transfection suppressed the antiaging effect of APS under high-glucose conditions. Additionally, APS ameliorated RAEC mitochondrial dysfunction, including increasing ATP production, cytochrome C oxidase activity and the oxygen consumption rate (OCR), and inhibited high-glucose-induced NLRP3 inflammasome activation and IL-1ß release, which were reversed by siNCLX. These results indicate that APS reduces high-glucose-induced inflammasome activation and ameliorates mitochondrial dysfunction and senescence in RAECs by modulating NCLX. Additionally, APS enhanced the levels of autophagy-related proteins (LC3B-II/I, Atg7) and increased the quantity of autophagic vacuoles under high-glucose conditions. Therefore, these data demonstrate that APS may reduce vascular endothelial cell inflammation and senescence through NCLX.

Ginsenoside Rb1 alleviates diabetic kidney podocyte injury by inhibiting aldose reductase activity.

Panax notoginseng, a traditional Chinese medicine, exerts beneficial effect on diabetic kidney disease (DKD), but its mechanism is not well clarified. In this study we investigated the effects of ginsenoside Rb1 (Rb1), the main active ingredients of Panax notoginseng, in alleviating podocyte injury in diabetic nephropathy and the underlying mechanisms. In cultured mouse podocyte cells, Rb1 (10 µM) significantly inhibited high glucose-induced cell apoptosis and mitochondrial injury. Furthermore, Rb1 treatment reversed high glucose-induced increases in Cyto c, Caspase 9 and mitochondrial regulatory protein NOX4, but did not affect the upregulated expression of aldose reductase (AR). Molecular docking analysis revealed that Rb1 could combine with AR and inhibited its activity. We compared the effects of Rb1 with eparestat, a known aldose reductase inhibitor, in high glucose-treated podocytes, and found that both alleviated high glucose-induced cell apoptosis and mitochondrial damage, and Rb1 was more effective in inhibiting apoptosis. In AR-overexpressing podocytes, Rb1 (10 µM) inhibited AR-mediated ROS overproduction and protected against high glucose-induced mitochondrial injury. In streptozotocin-induced DKD mice, administration of Rb1 (40 mg·kg-1·d-1, ig, for 7 weeks) significantly mitigated diabetic-induced glomerular injuries, such as glomerular hypertrophy and mesangial matrix expansion, and reduced the expression of apoptotic proteins. Collectively, Rb1 combines with AR to alleviate high glucose-induced podocyte apoptosis and mitochondrial damage, and effectively mitigates the progression of diabetic kidney disease.

Early acute fat embolism syndrome caused by femoral fracture: A case report.

BACKGROUND: Fat embolism syndrome (FES) is a rare complication caused by the presence of fat particles in the microcirculation, which usually occurs within 12-72 h after trauma. At present, there have been few cases of fat embolism presenting within 3 h after trauma. Here, we report a case of femoral fracture complicated with an acute fat embolism caused by a car accident. CASE SUMMARY: A 29-year-old woman with pain, swelling and limited movement of her left lower limb after a car accident was taken by ambulance to our hospital. X-ray examination showed fracture of the middle and lower part of the left femur and fracture of the base of the left fifth metatarsal bone. She was hospitalized and admitted to the orthopedic ward. After the attending doctor performed tibial tubercle bone traction, the patient became confused, followed by respiratory distress. Finally, she was transferred to the intensive care unit. After nearly a month of treatment in the intensive care unit, the patient's cognitive function gradually recovered over 6 mo. CONCLUSION: For patients with early traumatic fractures, young emergency physicians and orthopedics should be aware of the possibility of FES.

The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling.

Non-small cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. Bupivacaine serves as a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of bupivacaine in the NSCLC development remains elusive. Here, we tried to investigate the impact of bupivacaine on the NSCLC progression. Significantly, we revealed that bupivacaine was able to reduce the proliferation and induce the apoptosis of NSCLC cells. Bupivacaine could attenuate the invasion and migration in the cells. Mechanically, the treatment of bupivacaine increased the expression ratio of light chain 3B-II (LC3B-II)/LC3B-I and the expression of Beclin-1 in the NSCLC cells. Meanwhile, the expression of the autophagic adaptor protein p62 was decreased by bupivacaine treatment in the cells. The treatment of bupivacaine attenuated the phosphorylation of AKT and mTOR in the NSCLC cells. The AKT activator SC79 and autophagy inhibitor 3-methyladenine (3-MA) reversed the bupivacaine-inhibited phosphorylation of AKT and mTOR and bupivacaine-induced autophagy, as well as the bupivacaine-attenuated NSCLC progression in the cells. Bupivacaine could inhibit the tumor growth in vivo. In conclusion, we discovered that the local anesthetic bupivacaine inhibited the progression of NSCLC by inducing autophagy through Akt/mTOR signaling. Our finding provides new insights into the mechanism by which bupivacaine attenuates the development of NSCLC. Bupivacaine may serve as a potential anti-tumor candidate for the therapeutic strategy of NSCLC.

From Dendrites to Hemispheres: Changing Lithium Deposition by Highly Ordered Charge Transfer Channels.

Metallic lithium as an anode is an ultimate ideal for rechargeable lithium batteries with high energy density such as lithium-oxygen batteries and lithium-sulfur batteries. However, the excess reactivity and asymmetrical dissolution-deposition of the metallic lithium anode make it impossible to support a stable long charge-discharge cycling. To protect the metallic lithium anode, apparently it needs to adjust the dissolution and deposition of lithium ions, but more essentially, it should reasonably change the distribution and transport of electrons on the surface and interface of the metallic lithium. In this work, anodic aluminum oxide (AAO) membranes are used to build highly ordered channels on the lithium anode surface in which lithium ions can transfer in the channels and electrons can be transported by the lithiation reaction of alumina with an oxygen vacancy-involved process. As a result, the cyclic reaction actually is partially transferred to the AAO surface, and lithium deposition occurs there as a hemispherical appearance but not as dendrites. Meanwhile, the highly ordered characteristics provide a physical effect to make the deposited lithium hemispheres a uniform distribution on the AAO surface. The AAO-regulated lithium anodes could be widely used to improve the cycling performance for metal lithium batteries.

Understanding the Structure-Performance Relationship of Lithium-Rich Cathode Materials from an Oxygen-Vacancy Perspective.

Li-rich layered oxide cathode materials are regarded as an attractive candidate of next-generation Li-ion batteries (LIBs) to realize an energy density of >300 Wh kg-1. However, challenges such as capacity fade, cycle life, oxygen release, and structural transformation still restrain its practical application. Micro/nanotechnology is one of the effective strategies to enhance its structural stability and electrochemical performance. An in-depth understanding of the relationship between micro/nanostructures and the electrochemical performance of Li-rich layered oxides is undoubtedly important for developing high-performance cathode materials. Herein, Li1.2Ni0.13Co0.13Mn0.54O2 with different micro/nanostructures including irregular particles, microspheres, microrods, and orthogonal particles are synthesized. Starting from the amount of surface oxygen vacancies in the different structures, the influence of oxygen vacancies on every step during the charge-discharge processes is analyzed by experimental characterizations and theoretical calculations. It is indicated that intrinsic oxygen vacancies can enhance the electrical conductivity and decrease the energy barrier for ion migration, which exerts a significant influence on promoting the kinetics and capacity. Among the different micro/nanostructures, microrods with abundant oxygen vacancies can not only promote lithium ion transport but also stabilize a cathode electrolyte interface (CEI) film by adjusting the distribution of surface elements with lower nickel content. The microrods deliver an initial discharge capacity of up to 306.1 mAh g-1 at 0.1C rate and a superior cycle performance with a capacity retention of 91.0% after 200 cycles at 0.2C rate.

Improvement in cognitive dysfunction following blast induced traumatic brain injury by thymosin α1 in rats: Involvement of inhibition of tau phosphorylation at the Thr205 epitope.

Cognitive impairment is a significant sequela of traumatic brain injury (TBI) especially blast induced traumatic brain injury (bTBI), which is characterized by rapid impairments of learning and memory ability. Although several neuroprotective agents have been postulated as promising drugs for bTBI in animal studies, very few ideal therapeutic options exist to improve cognitive impairment following bTBI. Thymosin α1(Tα1), a 28-amino-acid protein that possesses immunomodulatory functions, has exhibited beneficial effects in the treatment of infectious diseases, immunodeficiency diseases and cancers. However, it remains unclear whether Tα1 has a therapeutic role in bTBI. Thus, we hypothesized that Tα1 administration could reverse the outcomes of bTBI. The blast induced TBI (bTBI) rat model was established with the compressed gas driven blast injury model system. A consecutive Tα1 therapy (in 1 ml saline, twice a day) at a dose of 200 µg/kg or normal saline (NS) (1 ml, twice a day) for 3 days or 2 weeks was performed. Utilizing our newly designed bTBI model, we investigated the beneficial effects of Tα1 therapy on rats exposed to bTBI including: cognitive functions, general histology, regulatory T (Treg) cells, edema, inflammation reactions and the expression and phosphorylation level of tau via Morris Water Maze test (MWM test), HE staining, flow cytometry, brain water content (BWC) calculation, IL-6 assay and Western blotting, respectively. Tα1 treatment seemed to reduce the 24-hour mortality, albeit with no statistical significance. Moreover, Tα1 treatment markedly improved cognitive dysfunction by decreasing the escape latency in the acquisition phase, and increasing the crossing numbers in the probe phase of MWM test. More interestingly, Tα1 significantly inhibited tau phosphorylation at the Thr205 epitope, but not at the Ser404 and Ser262 epitopes. Tα1 increased the percentage of Treg cells and inhibited plasma IL-6 production on 3d post bTBI. Moreover, Tα1 suppressed brain edema as demonstrated by decrease of BWC. However, there was a lack of obvious change in histopathology in the brain upon Tα1 treatment. This is the first study showing that Tα1 improves neurological deficits after bTBI in rats, which is potentially related to the inhibition of tau phosphorylation at the Thr205 epitope, increased Treg cells and decreased inflammatory reactions and brain edema.

A novel model of blast induced traumatic brain injury caused by compressed gas produced sustained cognitive deficits in rats: involvement of phosphorylation of tau at the Thr205 epitope.

Improvised explosive devices (IEDs) represent the leading causes for casualties among civilians and soldiers in the present war (including counter-terrorism). Traumatic brain injury (TBI) caused by IEDs results in different degrees of impairment of cognition and behavior, but the exact brain pathophysiological mechanism following exposure to blast has not been clearly investigated. Here, we sought to establish a rat model of closed-head blast injury using compressed gas to deliver a single blast only to the brain without systemic injuries. The cognitive functions of these bTBI models were assessed by Morris Water Maze test (MWM test). The HE staining, flow cytometry, ELISA and Western Blotting were used to measure the effects of shock wave on general histology, regulatory T (Treg) cells percentage, inflammatory reactions, the expression and phosphorylation level of tau, respectively. In addition, the brain water content and 24 -h mortality were also assessed. As the distance from the blast source increased, the input pressure did not change, the overpressure decreased, and the mortality decreased. Receiver operating characteristic (ROC) curves for predicting 24 -h mortality using peak overpressure fits with the following areas under ROC curves: 0.833. In 2 weeks after blast injury, cognitive tests revealed significantly decreased performance at 20 cm distance from the blast (about 136.44 kPa) as demonstrated by increased escape latency in the acquisition phase, and decreased crossing numbers in the probe phase of MWM test. Interestingly, a single blast exposure (at 20 cm) lead to significantly increased tau phosphorylation at the Thr205 epitope but not at the Ser404 and Ser262 epitopes at 12 h, 24 h, 3d, and 7d after blast injury. Blast decreased the percentage of CD4+T cells, CD8+T cells, Treg cells and lymphocytes at different time points after blast injury, and blast increased the percentage of neutrophils at 12 h after blast injury and significantly increased IL-6 production at 12 h, 24 h and 3d after blast injury. In addition, blast lead to an increase of brain edema at 24 h and 3d after blast injury. However, no obvious alterations in brain gross pathology were found acutely in the blast-exposed rats. In conclusion, we established a rat model of simple craniocerebral blast injury characterized by impairment of cognitive function, Thr205 phosphorylation of tau, decreased Treg cells and increased inflammatory reactions and brain edema. We expect this model may help clarify the underlying mechanism after blast injury and possibly serve as a useful animal model in the development of novel therapeutic and diagnostic approaches.

Neurosurgery medical robot Remebot for the treatment of 17 patients with hypertensive intracerebral hemorrhage.

OBJECTIVE: To verify the minimally invasive surgical approach and therapeutic effects of using the medical neurosurgery robot Remebot to treat hypertensive intracerebral hemorrhage (HICH). METHODS: Clinical data for 17 HICH patients were analyzed retrospectively. Hematoma evacuation and tube drainage using Remebot frameless stereotaxic techniques were performed for all patients, and urokinase was injected into the hematomas after the operations. RESULTS: Robot-assisted stereotactic techniques can accurately guide hematoma punctures, and no deaths occurred among these patients. The average positioning error was 1.28 ± 0.49 mm. The average drainage duration was 3.4 days. The 3-month postoperative follow-up revealed improved neurological functions and quality of life for all patients. CONCLUSIONS: The medical neurosurgery robot Remebot is minimally invasive, has high positional accuracy, and facilitates surgical planning according to the shape of the hematoma. Therefore, robot-assisted surgery using Remebot represents a safe and effective treatment method for hematoma evacuation and tube drainage in HICH patients.

Modulation of Macrophage Polarization by Human Glomerular Mesangial Cells in Response to the Stimuli in Renal Microenvironment.

Mesangial cell (MC) activation and macrophage infiltration are 2 major events closely related with each other in mesangial proliferative glomerulonephritis. In the anti-Thy 1 nephritis model, macrophages mediate the damage and also the expansion of mesangium through secreting various inflammatory factors; however, in glomerular microenvironment how MCs affect macrophage activity in the presence of various stimuli have not yet been understood. In the present study, we found that resting human MCs (HMCs) constitutively expressed chemokine [C-C motif] ligand 2 (CCL-2) and interleukin (IL)-6 and induced M2 polarization of macrophages in the coculture system. HMC proliferation and migration and expression of IL-6, CCL-2, and macrophage colony-stimulating factor in HMCs were enhanced after platelet-derived growth factor (PDGF)-BB stimulation, among which CCL-2 was responsible for inducing the M2 polarization of macrophages. Furthermore, PDGF-BB-stimulated HMCs alleviated the classical activation of macrophages and drove more intensified M2 polarization of macrophages than resting HMCs did. However, lipopolysaccharide and interferon-γ (IFN-γ) stimulated HMCs maintained the M1 phenotype of cocultured macrophages. In conclusion, MCs actively participated in glomerular inflammation through influencing macrophage polarization. The interplay between MCs and infiltrated macrophages is finely modulated by secretory factors such as PDGF-BB and IFN-γ in response to the renal inflammatory microenvironment.

[Using Machine Learning to Investigate Factors Influencing the Efficacy of "Shoulder Tri-needles Therapy" in Treatment of Shoulder-hand Syndrome in 586 Stroke Patients].

OBJECTIVE: To analyze the factors influencing the therapeutic effect of "Shoulder Tri-needles therapy" in the treatment of shoulder-hand syndrome of stroke patients by using machine learning approach, so as to provide a feasibility for improving clinical efficacy. METHODS: A total of 586 stroke patients with shoulder-hand syndrome eligible for this study were involved in our machine learning experiments for classification of the influential factors. Their data including the age, gender, pulse condition, complexion, tongue quality, tongue coating, disease stage, body mass index (BMI), blood pressure, blood glucose, blood triglyceride, blood total cholesterol, smoking history, drinking history, and final outcomes were extracted from the medical record system (from Oct. of 2014 to Jan. of 2017 in the First Affiliated Hospital and Shenzhen Futian Hospital of Guangzhou University of Chinese Medicine). The single rule algorithm (1 R) was adopted to learn, followed by optimization with Repeated Incremental Pruning to Produce Error Reduction (RIPPER) algorithm, and C 5.0 decision tree algorithm. RESULTS: The accurate classification rates of 1 R, RIPPER and decision tree model were 87.37%(512/586), 95.90% (562/586), and 97.10% (569/586), respectively. The final outcomes of machine learning of this study showed that the disease stage (acute or recovery stage), complexion difference, tongue coating difference, blood pressure level, consumption of alcohol, BMI, and smoking habit were the most important factors influencing the therapeutic effect of "Shoulder Tri-needles" in the treatment of shoulder-hand syndrome of stroke patients. CONCLUSION: The disease stage, complexion and tongue identification, blood pressure level, alcohol drinking and smoking habits, and BMI are the principal factors affecting the therapeutic effect of "Shoulder Tri-needles therapy" in the treatment of shoulder-hand syndrome of stroke patients.

New Mutation of Coenzyme Q10 Monooxygenase 6 Causing Podocyte Injury in a Focal Segmental Glomerulosclerosis Patient.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism. METHODS: Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q10 monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX. RESULTS: Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group. CONCLUSIONS: This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.

Establishment of a novel rat model of blast-related diffuse axonal injury.

Although studies concerning blast-related traumatic brain injury (bTBI) have demonstrated the significance of diffuse axonal injury (DAI), no standard models for this type of injury have been widely accepted. The present study investigated a mechanism of inducing DAI through real blast injury, which was achieved by performing instantaneous high-speed swinging of the rat head, thus establishing a stable animal model of blast DAI. Adult Sprague-Dawley rats weighing 150±10 g were randomly divided into experimental (n=16), control (n=10) and sham control (n=6) groups. The frontal, parietal and occipital cortex of the rats in the experimental group were exposed, whereas those of the control group were unexposed; the sham control group rats were anesthetized and attached to the craniocerebral blast device without experiencing a blast. The rats were subjected to craniocerebral blast injury through a blast equivalent to 400 mg of trinitrotoluene using an electric detonator. Biomechanical parameters, and physical and behavioural changes of the sagittal head swing were measured using a high-speed camera. Magnetic resonance imaging (MRI) scans were conducted at 2, 12, 24 and 48 h after craniocerebral injury, only the experimental group indicated brain stem injury. The rats were sacrificed immediately following the MRI at 48 h for pathological examination of the brain stem using haematoxylin and eosin staining. The results indicated that 14 rats (87.5%) in the experimental group exhibited blast DAI, while no DAI was observed in the control and sham control groups, and the difference between the groups was significant (P<0.05). The present results indicated that this experimental design may serve to provide a stable model of blast DAI in rats.

Long-term acupuncture treatment has a multi-targeting regulation on multiple brain regions in rats with Alzheimer's disease: a positron emission tomography study.

The acute effect of acupuncture on Alzheimer's disease, i.e., on brain activation during treatment, has been reported. However, the effect of long-term acupuncture on brain activation in Alzheimer's disease is unclear. Therefore, in this study, we performed long-term needling at Zusanli (ST36) or a sham point (1.5 mm lateral to ST36) in a rat Alzheimer's disease model, for 30 minutes, once per day, for 30 days. The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning. Positron emission tomography images were processed with SPM2. The brain areas activated after needling at ST36 included the left hippocampus, the left orbital cortex, the left infralimbic cortex, the left olfactory cortex, the left cerebellum and the left pons. In the sham-point group, the activated regions were similar to those in the ST36 group. However, the ST36 group showed greater activation in the cerebellum and pons than the sham-point group. These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer's disease.

Alpha-Lipoic Acid Suppresses Extracellular Histone-Induced Release of the Infammatory Mediator Tumor Necrosis Factor-α by Macrophages.

BACKGROUND/AIMS: This study investigated signaling pathways via which extracellular histones induce the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) release from the macrophage cell line RAW 264.7 and the anti-inflammatory efficacy of the antioxidant alpha-lipoic acid (ALA). METHODS: ELISA and western blotting analyses were conducted to detect the release of TNF-α from histone-stimulated RAW 264.7 macrophages and the associated phospho-activation of MAPKs (ERK and p38) and NF-κB p65. The effects of ALA on the release of TNF-α and phospho-activation of the MAPKs and NF-κB p65 were studied. P < 0.05 was considered statistically significant. RESULTS: Extracellular histones dose-dependently induced TNF-α release from RAW 264.7 cells and increased the phosphorylation of p38, ERK, and NF-κB p65. TNF-α release was markedly suppressed by p38, ERK, and NF-kB inhibitors. ALA reduced histone-induced TNF-α release, ERK/p38 MAPK activation, and NF-kB activation without affecting macrophage viability. CONCLUSION: Histones induce TNF-α release from macrophages by activating the MAPK and NF-kB signaling pathways, while ALA suppresses this response by inhibiting ERK, p38 and NF-kB. These findings identify potentially critical inflammatory signaling pathways in sepsis and molecular targets for sepsis treatment.