Targeting CaMKII-δ9 Ameliorates Cardiac Ischemia/Reperfusion Injury by Inhibiting Myocardial Inflammation.

BACKGROUND: CaMKII (Ca2+/calmodulin-dependent kinase II) plays a central role in cardiac ischemia/reperfusion (I/R) injury-an important therapeutic target for ischemic heart disease. In the heart, CaMKII-δ is the predominant isoform and further alternatively spliced into 11 variants. In humans, CaMKII-δ9 and CaMKII-δ3, the major cardiac splice variants, inversely regulate cardiomyocyte viability with the former pro-death and the latter pro-survival. However, it is unknown whether specific inhibition of the detrimental CaMKII-δ9 prevents cardiac I/R injury and, if so, what is the underlying mechanism. Here, we aim to investigate the cardioprotective effect of specific CaMKII-δ9 inhibition against myocardial I/R damage and determine the underlying mechanisms. METHODS: The role and mechanism of CaMKII-δ9 in cardiac I/R injury were investigated in mice in vivo, neonatal rat ventricular myocytes, and human embryonic stem cell-derived cardiomyocytes. RESULTS: We demonstrate that CaMKII-δ9 inhibition with knockdown or knockout of its feature exon, exon 16, protects the heart against I/R-elicited injury and subsequent heart failure. I/R-induced cardiac inflammation was also ameliorated by CaMKII-δ9 inhibition, and compared with the previously well-studied CaMKII-δ2, CaMKII-δ9 overexpression caused more profound cardiac inflammation. Mechanistically, in addition to IKKß (inhibitor of NF-κB [nuclear factor-κB] kinase subunit ß), CaMKII-δ9, but not δ2, directly interacted with IκBα (NF-κB inhibitor α) with its feature exon 13-16-17 combination and increased IκBα phosphorylation and consequently elicited more pronounced activation of NF-κB signaling and inflammatory response. Furthermore, the essential role of CaMKII-δ9 in myocardial inflammation and damage was confirmed in human cardiomyocytes. CONCLUSIONS: We not only identified CaMKII-δ9-IKK/IκB-NF-κB signaling as a new regulator of human cardiomyocyte inflammation but also demonstrated that specifically targeting CaMKII-δ9, the most abundant CaMKII-δ splice variant in human heart, markedly suppresses I/R-induced cardiac NF-κB activation, inflammation, and injury and subsequently ameliorates myocardial remodeling and heart failure, providing a novel therapeutic strategy for various ischemic heart diseases.

First report of southern blight caused by Athelia rolfsii on Spotted laurel (Aucuba japonica) in China.

Aucuba japonica, also known as spotted laurel, is a woody, broadleaf, evergreen shrub with variegated leaves in the Garryaceae family, widely used in urban parks, green spaces and landscaping. In October 2019, an outbreak of a disease with southern blight symptoms was observed on A. japonica planted as a green barrier in Kunshan city, Jiangsu province of China (N31°32'37", E120°00'41"). The disease incidence was estimated up to 30%. The infected plants showed symptoms including brown to black necrotic stems, white mycelium and white to dark reddish brown sclerotia at the base of the stem and decayed tissues. Fifteen samples (10 sclerotia and 5 mycelial fragments) were collected from symptomatic plants for causal agent isolation. The sclerotia were disinfected with 70% ethanol for 2 to 3 s and 5% NaClO for 2 min, rinsed three times with sterile water, then cultivated on potato dextrose agar (PDA) plate at 25°C. Mycelial fragments were transferred to PDA plates by an inoculation needle directly. In total 15 fungal strains were obtained and purified by transferring single hyphal tips to fresh media. All the strains showed consistent phenotype, white mycelia on PDA, with an average growth rate of 13.6 to 16.9 mm/day (n=30), and mycelia with clamp connections were observed under the microscope. Globose sclerotia formed at 4 days post inoculation (dpi), initially whitish, turning to beige and eventually dark reddish brown. The number of sclerotia produced per plate ranged from 280 to 486 (mean = 378; n = 30), and the diameter of mature sclerotia ranged from 0.8- to 1.6-mm (mean = 1.24; n = 150). Three strains YKY2020.02, YKY2020.03, and YKY2020.07 were selected for further molecular identification. Genomic DNA was extracted from these strains using a CTAB method (Mahadevakumar et al. 2018). ITS primer pair ITS1/ITS4 was used to amplify the internal transcribed spacer region (White et al. 1990). PCR products were then sequenced by Sangon Biotech (Shanghai, China), and subsequently, the ITS sequences (686 bp) were deposited in GenBank under accession number OM647806, OP279917 and OP279918, respectively. All sequences showed 99-100% similarity with Athelia rolfsii sequences from GenBank by BLAST analysis in NCBI. The phylogenetic tree of ITS sequences generated by the neighbor-joining analysis in MEGA-X also shows that all selected strains clustered with different strains of A. rolfsii into one big branch, indicating that these strains are the same. Based on morphological and molecular characteristics, these strains were identified as A. rolfsii (Curzi) C.C. Tu & Kimbr. (syn. Sclerotium rolfsii) (Stevens 1931; Paul et al. 2017). Pathogenicity tests were conducted on healthy plants of A. japonica (n = 15). Five-day-old mycelial discs (5 mm) were inoculated at the basal part of the plants with mycelial side inward and secured with wet absorbent cotton, while plants inoculated with sterile water were used as a control (n = 5). All plants were kept in a greenhouse with a temperature of 26 to 33°C and an average relative humidity higher than 65%. At 5 dpi, all inoculated plants showed symptoms similar to those observed in fields. Control plants remained asymptomatic. To fulfill Koch's postulates, identities of all the causal pathogens were confirmed by reisolation in PDA and identification by morphology. To our knowledge, this is the first report of A. rolfsii causing southern blight on A. japonica worldwide. Our findings are important for future disease control strategy development.

Effects of skim milk fermented with Lactobacillus plantarum WW on the constitutions of rats fed a high-fat diet.

This study investigated the effects of Lactobacillus plantarum WW-fermented skim milk (FSM) on the physiques of rats fed a high-fat diet and the mechanism of lipid lowering. Sprague-Dawley rats were randomly divided into a normal diet group (A), a high-fat diet group (B), a skim milk diet group (C), and an L. plantarum WW FSM diet group (D). After 12-wk feeding, we found that treatment with L. plantarum WW FSM could significantly alleviate symptoms in the pathological group. Meanwhile, high-throughput sequencing analysis showed that L. plantarum WW FSM also had a certain regulatory effect on the intestinal microorganisms in rats, which can increase the number of lactic acid bacteria and Bacteroides in the intestine. More importantly, real-time quantitative PCR and Western blot analysis showed that the probiotic was also involved in the expression of genes related to fat metabolism, especially the PPARB and CEBPB genes. Our study supports the hypothesis that the WW strain of L. plantarum could be a potential probiotic to be used in functional foods to alter lipid metabolism and reduce cholesterol levels.

Dynamic changes in insulin and glucagon during disease progression in rhesus monkeys with obesity-related type 2 diabetes mellitus.

AIMS: To investigate the progression of obesity-related type 2 diabetes mellitus (T2DM) in rhesus monkeys, especially dynamic changes in insulin and glucagon. MATERIALS AND METHODS: We followed a cohort of 52 rhesus monkeys for 7 years throughout the progression of obesity-related T2DM. Intravenous glucose tolerance tests were performed every 6 months to evaluate dynamic changes in glucose, insulin and glucagon levels. RESULTS: Obesity in rhesus monkeys increased the overall mortality and T2DM morbidity. During the progression of T2DM, glucagon remained consistently elevated, while insulin initially increased in compensation but then dropped to below normal levels when the monkeys developed overt T2DM. After a glucose challenge, both the first and second phases of insulin secretion increased during the early stage of T2DM; in later stages the first phase was delayed and the second phase was diminished. CONCLUSION: Our findings showed that, beside the decreased insulin level, hyperglucagonaemia also plays an important role in the development of T2DM.

A huge benign fibrous histiocytoma arising from the renal capsule: report of a case.

BACKGROUND: Neoplasms originating in the renal capsule are very rare. Benign fibrous histiocytoma(BFH) most commonly occurs in the dermis and subcutis, few cases of this tumor appear in the renal capsule. In particular, BFH larger than 20 cm are scarce. Here we report a rare huge one measuring 23 × 13 × 7 cm. CASE PRESENTATION: We report a 64-year-old man who presented with a few-months history of dull pain in the right groin. The tumor had its point of origin in the renal capsule which is a rare condition. Histologically, the tumor was composed of intersecting fascicles of fibroblastic cells forming a "storiform" pattern. Immunohistochemical studies were also performed, ultimately leading to the diagnosis of BFH. The patient was treated with radical nephrectomy. No recurrence was detected 4 months after surgery. CONCLUSIONS: BFH arising from the renal capsule was very rare. In particular, the case of more than twenty centimeters is extremely rare. The clinical presentation of renal BFH might be only a mass. However, differential diagnosis from renal cell carcinoma proved to be impossible before surgical intervention. It is difficult to diagnose only by means of histopathology, but the immunohistochemical method can provide a clear and definite diagnosis.

Central role of RIPK1-VDAC1 pathway on cardiac impairment in a non-human primate model of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by destructive polyarthritis and systemic complications. It increases cardiovascular morbidity and mortality. However, the mechanism underlying RA-related cardiac damage remains largely unknown. Here, we found and characterized a non-human primate (NHP) model with spontaneous RA similar to the human conditions. Compared with the control group, the cardiac function in RA monkeys showed progressively deterioration; histologically, we found significantly increased inflammatory cell infiltration, cell death, and fibrosis in RA monkey heart tissue. Mechanistically, the upregulated receptor-interacting protein kinase 1 (RIPK1) in RA monkey heart tissue bound to voltage-dependent anion-selective channel 1 (VDAC1), increased VDAC1 oligomerization, and subsequently induced cardiac cell death and functional impairment. These findings identified that RIPK1-VDAC1 pathway is a promising target to treat cardiac impairment in RA. This unique model of RA will provide a valuable tool for mechanistic and translational studies.

Polyhydroxy steroids isolated from starfish (Asterina pectinifera) and their embryotoxicity.

Many marine organisms possess an essential capacity to produce secondary metabolites that exhibit toxic characteristics. A new polyhydroxy steroid, 24-methyl-5α-cholestane-24(28)-ene-3ß, 4ß, 6α, 7α, 8, 15ß, 16ß, 26-octol-6-O-sodium sulphate (1) was isolated from starfish (Asterina pectinifera), along with five polar steroid compounds (2-6) that were previously identified. NMR (1H and 13C NMR, 1H-1H COSY, HSQC, HMBC, and NOESY) and HR-ESI-MS were employed for structure elucidations. The embryotoxicity and teratogenicity of the isolated compounds were assessed using embryos of marine medaka (Oryzias melastigma). Compound 5 exhibited moderate embryotoxicity (96h-LC50: 65 µM).

Intestinal SURF4 is essential for apolipoprotein transport and lipoprotein secretion.

OBJECTIVE: Lipoprotein assembly and secretion in the small intestine are critical for dietary fat absorption. Surfeit locus protein 4 (SURF4) serves as a cargo receptor, facilitating the cellular transport of multiple proteins and mediating hepatic lipid secretion in vivo. However, its involvement in intestinal lipid secretion is not fully understood. In this study, we investigated the role of SURF4 in intestinal lipid absorption. METHODS: We generated intestine-specific Surf4 knockout mice and characterized the phenotypes. Additionally, we investigated the underlying mechanisms of SURF4 in intestinal lipid secretion using proteomics and cellular models. RESULTS: We unveiled that SURF4 is indispensable for apolipoprotein transport and lipoprotein secretion. Intestine-specific Surf4 knockout mice exhibited ectopic lipid deposition in the small intestine and hypolipidemia. Deletion of SURF4 impeded the transport of apolipoprotein A1 (ApoA1), proline-rich acidic protein 1 (PRAP1), and apolipoprotein B48 (ApoB48) and hindered the assembly and secretion of chylomicrons and high-density lipoproteins. CONCLUSIONS: SURF4 emerges as a pivotal regulator of intestinal lipid absorption via mediating the secretion of ApoA1, PRAP1 and ApoB48.

The Sweetgum Inscriber, Acanthotomicus suncei (Coleoptera: Curculionidae: Scolytinae) Reared on Artificial Diets and American Sweetgum Logs.

The sweetgum inscriber, Acanthotomicus suncei (Coleoptera: Curculionidae: Scolytinae), is a recently discovered pest of American sweetgum planted in China, with a potential for causing a devastating invasion into North America. Research on the beetle has been hampered by a dwindling access to breeding material. We tested the effect of four artificial diets on A. suncei's developmental time, length and weight of adults, egg hatching rate, pupation rate, and eclosion rate. Additionally, we evaluated the same parameters on A. suncei reared on American sweetgum logs. Only one diet supported the full development of A. suncei after 30 d. Beetles reared on this diet, which was made of small quantities of agar and additives (i.e., inositol, potassium sorbate, and methylparaben), supported the shortest developmental time of 45.55 ± 1.24 d. Beetles reared on American sweetgum logs exhibited a longer developmental time of 59.52 ± 4.52 d. Beetles reared on the artificial diet were markedly bigger and heavier than those reared on American sweetgum logs (p < 0.01). The egg hatching rate (58.90% ± 6.80%) and eclosion rate (86.50% ± 4.69%) of A. suncei on the artificial diet were significantly greater than those on sweetgum logs. However, the pupation rate (38.60% ± 8.36%) was much lower on the artificial diet than on the sweetgum logs. Here, we reported the best artificial diet for A. suncei and discuss the advantages and disadvantages over rearing the beetle on American sweetgum logs.

An accurate, efficient, and economical identification technology for black twig borer based on species-specific cytochrome C oxidase subunit I PCR assay.

Xylosandrus compactus (Eichhoff) (Coleoptera: Curculionidae, Scolytinae) is a worldwide invasive species that causes huge economic loss and environmental damage in many countries. Traditional morphological characteristics make it hard to identify scolytines due to their tiny size. Besides, the intercepted insect samples are incomplete, and the limitation of insect (larvae and pupae) morphology makes morphological identification more difficult. The majority of the damage is caused by adults and fungi that serve as nutrition for their larvae. They destroy plant trunks, branches, and twigs, affecting plant transport tissues in both weak and healthy plants. An accurate, efficient, and economical molecular identification technique for X. compactus not restricted by professional taxonomic knowledge is necessary. In the present study, a molecular identification tool based on the mitochondrial DNA gene, cytochrome C oxidase subunit I (COI) was developed. A species-specific COI (SS-COI) PCR assay was designed to identify X. compactus regardless of the developmental stage. Twelve scolytines commonly found in eastern China, namely Xylosandrus compactus, X. crassiusculus, X. discolor, X. germanus, X. borealis, X. amputates, X. eupatorii, X. mancus, Xyleborinus saxesenii, Euwallacea interjectus, E. fornicatus, and Acanthotomicus suncei, were included in the study. Additionally, specimens of X. compactus from 17 different areas in China, as well as a specimen collected from the United Stated, were also analyzed. Results demonstrated the accuracy and high efficiency of the assay, regardless of the developmental stage or the type of specimen. These features provide a good application prospect for fundamental departments and can be used to prevent the harmful consequences of the spread of X. compactus.

Targeting ANGPTL3 by GalNAc-conjugated siRNA ANGsiR10 lowers blood lipids with long-lasting and potent efficacy in mice and monkeys.

Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by in vivo and in vitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15 weeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development.

Blocking IL-6 signaling improves glucose tolerance via SLC39A5-mediated suppression of glucagon secretion.

BACKGROUND AND AIMS: Hyperinsulinemia, hyperglucagonemia, and low-grade inflammation are frequently presented in obesity and type 2 diabetes (T2D). The pathogenic regulation between hyperinsulinemia/insulin resistance (IR) and low-grade inflammation is well documented in the development of diabetes. However, the cross-talk of hyperglucagonemia with low-grade inflammation during diabetes progression is poorly understood. In this study, we investigated the regulatory role of proinflammatory cytokine interleukin-6 (IL-6) on glucagon secretion. METHODS: The correlations between inflammatory cytokines and glucagon or insulin were analyzed in rhesus monkeys and humans. IL-6 signaling was blocked by IL-6 receptor-neutralizing antibody tocilizumab in obese or T2D rhesus monkeys, glucose tolerance was evaluated by intravenous glucose tolerance test (IVGTT). Glucagon and insulin secretion were measured in isolated islets from wild-type mouse, primary pancreatic α-cells and non-α-cells sorted from GluCre-ROSA26EYFP (GYY) mice, in which the enhanced yellow fluorescent protein (EYFP) was expressed under the proglucagon promoter, by fluorescence-activated cell sorting (FACS). Particularly, glucagon secretion in α-TC1 cells treated with IL-6 was measured, and RNA sequencing was used to screen the mediator underlying IL-6-induced glucagon secretion. SLC39A5 was knocking-down or overexpressed in α-TC1 cells to determine its impact in glucagon secretion and cytosolic zinc density. Dual luciferase and chromatin Immunoprecipitation were applied to analyze the signal transducer and activator of transcription 3 (STAT3) in the regulation of SLC39A5 transcription. RESULTS: Plasma IL-6 correlate positively with plasma glucagon levels, but not insulin, in rhesus monkeys and humans. Tocilizumab treatment reduced plasma glucagon, blood glucose and HbA1c in spontaneously obese or T2D rhesus monkeys. Tocilizumab treatment also decreased glucagon levels during IVGTT, and improved glucose tolerance. Moreover, IL-6 significantly increased glucagon secretion in isolated islets, primary pancreatic α-cells and α-TC1 cells. Mechanistically, we found that IL-6-activated STAT3 downregulated the zinc transporter SLC39A5, which in turn reduced cytosolic zinc concentration and ATP-sensitive potassium channel activity and augmented glucagon secretion. CONCLUSIONS: This study demonstrates that IL-6 increases glucagon secretion via the downregulation of zinc transporter SLC39A5. This result revealed the molecular mechanism underlying the pathogenesis of hyperglucagonemia and a previously unidentified function of IL-6 in the pathophysiology of T2D, providing a potential new therapeutic strategy of targeting IL-6/glucagon to preventing or treating T2D.

Alternate-Day High Fat-Normal Chow Diet Ameliorates HFD-Induced Obesity and Restores Intestinal Immunity.

Purpose: To investigate the effect of alternating-day diet regimens on high-fat diet-induced metabolic disorders in mice. Materials and Methods: Eight-week-old C57BL/6J mice were fed with either a continuous normal chow diet (CD, n = 10), a continuous high-fat diet (HFD, n = 10), HFD alternating every 24 h with fasting (H-ADF, n = 20), or HFD alternating every 24 h with chow diet (H-ADC, n = 20) for 12 weeks. Weights were recorded weekly and oral glucose tolerance tests were performed 6 weeks after initiating the regimens. At the end of the study, blood samples were collected and serum insulin and lipids were measured; tissues were collected for histology and RNA-seq analysis. Results: HFD significantly increased body weight and fat percentage, while HFD alternating with fasting or CD did not significantly affect body weight and fat percentage. The glucose intolerance induced by HFD was also significantly ameliorated in these two diet intervention groups. HFD-induced elevation of total cholesterol, low-density lipoprotein and insulin were also reduced in H-ADF and H-ADC groups. Moreover, HFD-disturbed immunity, presented by Lysozyme C-1 (Lyz1) immunostaining and RNA-seq, was restored in both alternating-regimen groups, especially, with H-ADC. At the transcriptional level, some cell proliferation and lipid absorption pathways were down-regulated in both H-ADF and H-ADC groups compared to the continuous HFD group. Conclusion: Alternating an HFD with a normal diet every 24 h effectively controls weight and prevents metabolic disorders and may act by affecting both fat absorption and intestinal immunity.

Effects of Comamonas testosteroni on dissipation of polycyclic aromatic hydrocarbons and the response of endogenous bacteria for soil bioremediation.

Bioremediation is a promising method of treating polycyclic aromatic hydrocarbons (PAHs) in contaminated soil; however, the understanding of the efficiency and the way of microbial inoculants work in complex soil environments is limited. Comamonas testosteroni (Ct) strains could efficiently degrade PAHs, especially naphthalene (Nap) and phenanthrene (Phe). This study aimed to explore the functional role of Ct in soil indigenous microorganisms and analyze the effect of Ct addition on PAHs concentration in PAH-contaminated soil. The results showed that inoculation with Ct degraded naphthalene (Nap), phenanthrene (Phe), and benzo [α] pyrene (BaP) significantly; the degradation rates were 63.38%, 81.18%, and 37.98% on day 25, respectively, suggesting that the low molecular weights of Nap and Phe were more easily degraded by microorganisms than those of BaP. We speculated that BaP and Phe might be converted into Nap for further degradation, which is the main reason for the low degradation rate of Nap detected after 10-25 days. Network analysis showed that inoculation with Ct significantly increased bacteria community abundance closely related to PAHs. Structural equation models confirmed that Steroidobacter, as functional bacteria, could affect the degradation of Nap and BaP. Inoculated Ct effectively enhanced the synergy among indigenous bacteria to degrade PAHs. This finding will help understand the function of inoculated Ct strains in PAH-contaminated soil at the laboratory level.

[Changes of carotid artery elasticity before and after CPAP in patients with obstructive sleep apnea by ultrasonic ultrafast pulse wave velocity technique].

Objective:To examine the changes of carotid artery elasticity in patients with obstructive sleep apnea（OSA） before and after continuous positive airway pressure（CPAP） treatment by ultrafast pulse wave velocity（UFPWV） technique，and to explore the influencing factors of carotid artery elasticity in OSA patients，and to provide guidance for clinical prevention and treatment of cardiovascular complications. Methods：Fifty cases of moderate and severe OSA patients diagnosed with PSG monitoring from January 2020 to December 2020 were collected as the OSA group，at the same time，40 healthy subjects who participated in physical examination and matched with OSA group in age and gender were selected as the control group.The OSA group was treated with CPAP for 12 weeks.Clinical indicators，carotid intima-media thickness（IMT），and pulse wave velocity at the beginning of systole（PWVBS） and pulse wave velocity at the end of systole（PWVES） were recorded in the control group，and the above data were collected in the OSA group before and after treatment.The changes of various indicators between the control group and the OSA group，and between the OSA group before and after treatment were compared.The correlative factors and influencing factors of PWVBS and PWVES are analyzed. Results：The serum lipid indexes，IMT，PWVBS and PWVES in OSA group were higher than those in control group（P<0.05）.Comparison between post-treatment and pre-treatment with CPAP in OSA group：PWVBS，PWVES，apnea hypopnea index（AHI），blood oxygen saturation（SaO2） less than 90% of the time，the percentage of monitoring time when SaO2 was less than 90%（T90），low density lipoprotein cholesterol（LDL-C）and triglyceride（TG） were decreased（P<0.05）.Lowest blood oxygen saturation（LSaO2） and high density lipoprotein cholesterol（HDL-C） increased（P<0.05）.Age，systolic blood pressure，IMT，AHI，T90 and time of oxygen saturation below 90% were positively correlated with PWVBS and PWVES，while HDL-C and LSaO2 were negatively correlated with them（P<0.05）.The risk factors of PWVBS and PWVES included systolic blood pressure，AHI，TC，T90.Conclusion：Moderate and severe OSA can reduce arterial elasticity.CPAP can improve carotid artery elasticity function in patients with OSA.UFPWV technique is more sensitive to quantitatively evaluate the changes of arterial elasticity in patients with OSA than traditional two-dimensional ultrasound.

EasyFlyTracker: A Simple Video Tracking Python Package for Analyzing Adult Drosophila Locomotor and Sleep Activity to Facilitate Revealing the Effect of Psychiatric Drugs.

The mechanism of psychiatric drugs (stimulant and non-stimulant) is still unclear. Precision medication of psychiatric disorders faces challenges in pharmacogenetics and pharmacodynamics research due to difficulties in recruiting human subjects because of possibility of substance abuse and relatively small sample sizes. Drosophila is a powerful animal model for large-scale studies of drug effects based on the precise quantification of behavior. However, a user-friendly system for high-throughput simultaneous tracking and analysis of drug-treated individual adult flies is still lacking. It is critical to quickly setup a working environment including both the hardware and software at a reasonable cost. Thus, we have developed EasyFlyTracker, an open-source Python package that can track single fruit fly in each arena and analyze Drosophila locomotor and sleep activity based on video recording to facilitate revealing the psychiatric drug effects. The current version does not support multiple fruit fly tracking. Compared with existing software, EasyFlyTracker has the advantages of low cost, easy setup and scaling, rich statistics of movement trajectories, and compatibility with different video recording systems. Also, it accepts multiple video formats such as common MP4 and AVI formats. EasyFlyTracker provides a cross-platform and user-friendly interface combining command line and graphic configurations, which allows users to intuitively understand the process of tracking and downstream analyses and automatically generates multiple files, especially plots. Users can install EasyFlyTracker, go through tutorials, and give feedback on http://easyflytracker.cibr.ac.cn. Moreover, we tested EasyFlyTracker in a study of Drosophila melanogaster on the hyperactivity-like behavior effects of two psychiatric drugs, methylphenidate and atomoxetine, which are two commonly used drugs treating attention-deficit/hyperactivity disorder (ADHD) in human. This software has the potential to accelerate basic research on drug effect studies with fruit flies.

Invasion History of Sirex noctilio Based on COI Sequence: The First Six Years in China.

Sirex noctilio F. (Hymenoptera: Siricidae: Siricinae), a new invasive species in China, is a significant international forestry pest which, transported via logs and related wood packing materials, has led to environmental damage and substantial economic loss in many countries around the world. It was first detected in China in 2013, and since then infestations have been found in 18 additional sites. Using a 322 bp fragment of the mitochondrial barcode gene COI, we studied the genetic diversity and structure of S. noctilio populations in both native and invaded ranges, with a specific focus in China. Twelve haplotypes were found across the native and invaded distribution of the pest, of which three were dominant; among these there were only one or two mutational steps between each pair of haplotypes. No obvious genetic structure was found other than in Chinese populations. China has a unique and dominant haplotype not found elsewhere, and compared with the rest of the world, the genetic structure of Chinese populations suggested a multiple invasion scenario.

[Effects of Comamonas testosteroni on PAHs degradation and bacterial community structure in Leymus chinensis rhizosphere soil].

To investigate the degradation of polycyclic aromatic hydrocarbons (PAHs) and the changes of rhizosphere microorganisms in the rhizosphere soil of Leymus chinensis during the remediation of PAHs contaminated soil by Comamonas testosteroni (C.t)-assisted Leymus chinensis, we evaluated the removal of PAHs in the rhizosphere of Leymus chinensis using gas chromatography-mass spectrometry (GC-MS), analyzed the bacterial community and the diversity in Leymus chinensis rhizosphere soil by high-throughput sequencing technology, characterized the correlation among PAHs degradation and bacterial community components performing redundancy analysis (RDA) and network analysis, and predicted PAHs degradation potential via PICRUSt software in this paper. The degradation of PAHs in the rhizosphere of Leymus chinensis was promoted, the abundance and diversity of bacteria and the correlation among bacteria and PAHs were changed, and the degradation potential of PAHs in Leymus chinensis rhizosphere soil was enhanced in the later stage of phytoremediation (60-120 d) due to the incorporation of C.t. The accelerated degradation of three PAHs (Nap, Phe, BaP) was accompanied by the differ abundance and correlation of Proteobacteria (Sphingomonas, MND1, Nordella), Actinomycetes (Rubrobacter, Gaiella), Acidobacteria (RB41) and Bacteroides (Flavobacterium) affected by C.t. The results provide new insight into the microorganism choices for microbial assisted plant remediation of soil PAHs and the mechanisms of enhanced PAHs degradation via the combination of Comamonas testosteroni engineering bacteria and plants.

Characterization of spontaneously-developed non-alcoholic fatty liver disease in aged rhesus monkeys.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a global epidemic afflicting 20-30% in the general population. The animal model of NAFLD available at the present are less clinically relevant. In this study. We aimed to establish a NAFLD model of rhesus monkeys and develop an ultrasonographic steatosis score (USS) system to grade hepatic steatosis in this model. METHODS: We performed hepatic ultrasonography and blood biochemical tests on 86 rhesus monkeys with and without metabolic syndrome (MetS), among which 45 animals were further assessed by histopathological analysis. RESULTS: The liver histological features of rhesus monkeys NAFLD were resemble to those of NAFLD patients. There was a close correlation between the histological steatosis grade and the USS (Spearman's coefficient, 0.705, p < 0.001). The USS sensitivity was 87.5% and the specificity was 94.6% when the cut-off was USS2. In addition, the prevalence of MetS was significantly higher in the USS2-3 group. Multiple risk factors of cardiometabolic disease, including obesity, insulin resistance and dyslipidemia were significantly correlated with the USS. CONCLUSIONS: NAFLD was developed spontaneously among aging in rhesus monkeys (with increased prevalence in the MetS monkeys), which provided an ideal model for NAFLD. The newly developed USS system can be used to evaluate fatty liver in the rhesus monkey. The model as well as the noninvasive assessment methodology will provide a powerful tool for mechanistic studies and preclinical test of novel therapies for NAFLD.

RIPK1 Binds MCU to Mediate Induction of Mitochondrial Ca2+ Uptake and Promotes Colorectal Oncogenesis.

The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation. These findings identify the RIPK1-MCU pathway as a promising target to treat colorectal cancer.Significance: RIPK1-mediated cell proliferation through MCU is a central mechanism underlying colorectal cancer progression and may prove to be an important therapeutic target for colorectal cancer treatment. Cancer Res; 78(11); 2876-85. ©2018 AACR.