Intraventricular administration of glial cell line-derived neurotrophic factor (GDNF) in primate and humans to study Parkinson's disease (PD) has revealed the potential for GDNF to induce weight loss. Our previous data indicate that bilateral continuous hypothalamic GDNF overexpression via recombinant adeno-associated virus (rAAV) results in significant failure to gain weight in young rats and weight loss in aged rats. Based on these previous results, we hypothesized that because the nigrostriatal tract passes through the lateral hypothalamus, motor hyperactivity mediated by nigrostriatal dopamine (DA) may have been responsible for the previously observed effect on body weight. In this study, we compared bilateral injections of rAAV2/5-GDNF in hypothalamus versus substantia nigra (SN) in aged Brown-Norway X Fisher 344 rats. Nigrostriatal GDNF overexpression resulted in significantly greater weight loss than rats treated in hypothalamus. The nigral or hypothalamic GDNF-induced weight loss was unrelated to motor activity levels of the rats, though some of the weight loss could be attributed to a transient reduction in food intake. Forebrain DA levels did not account for the observed effects on body weight, although GDNF-induced increases in nucleus accumbens DA may have partially contributed to this effect in the hypothalamic GDNF-treated group. However, only nigrostriatal GDNF overexpression induced activation of phosphorylated extracellular signal-regulated kinase (p-ERK) in a small population of corticotrophin-releasing factor [corticotrophin-releasing hormone (CRH)] neurons located specifically in the medial parvocellullar division (MPD) of the paraventricular nucleus of the hypothalamus. Activation of these hypothalamic CRH neurons likely accounted for the observed metabolic effects leading to weight loss in obese rats.

BackgroundEndosymbiotic bacteria inhabit a variety of arthropods including ticks and may have multiple effects on the host’s survival, reproduction or pathogen acquisition and transmission. Rhipicephalus haemaphysaloides is one of the most widely distributed tick species in China. The symbiotic bacteria composition and their impacts to R. haemaphysaloides ticks have not been studied. The present study investigated the composition of microbial community in R. haemaphysaloides ticks and then assessed the effects of endosymbionts on the host’s fecundity by antibiotic treatment experiments.MethodsThe microbial population of female and male R. haemaphysaloides ticks was analyzed using Illumina Miseq sequencing of 16S rRNA gene. Thirty engorged female ticks were then randomly divided into five groups and injected with ampicillin, ciprofloxacin, kanamycin, tetracycline, or phosphate-buffered solution (PBS), respectively. Effects of antibiotic treatments on maternal oviposition, egg hatching and density of endosymbionts were evaluated.ResultsIllumina Miseq sequencing showed that Coxiella and Rickettsia were the predominant bacterial genera inhabiting R. haemaphysaloides ticks. Antibiotic treatment experiments found that kanamycin reduced the density of Coxiella-like endosymbiont (Coxiella-LE hereafter) in eggs, ciprofloxacin reduced the density of Rickettsia-like endosymbiont (Rickettsia-LE), and tetracycline had effect on both endosymbionts, while ampicillin affected neither. Meanwhile hatching rates of eggs were observed to decrease greatly in the kanamycin or tetracycline-treated group but maintained in the ampicillin or ciprofloxacin-treated group. Furthermore, the reduced hatching rates were found to be associated with density of Coxiella-LE in eggs.ConclusionsThe findings indicate that Coxiella-LE is essential for the reproduction of R. haemaphysaloides ticks, and that kanamycin can be used to study the role of Coxiella-LE on ticks.

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Background Adequate cytology is limited by insufficient cytologists in a large‐scale cervical cancer screening. We aimed to develop an artificial intelligence (AI)‐assisted cytology system in cervical cancer screening program. Methods We conducted a perspective cohort study within a population‐based cervical cancer screening program for 0.7 million women, using a validated AI‐assisted cytology system. For comparison, cytologists examined all slides classified by AI as abnormal and a randomly selected 10% of normal slides. Each woman with slides classified as abnormal by either AI‐assisted or manual reading was diagnosed by colposcopy and biopsy. The outcomes were histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results Finally, we recruited 703 103 women, of whom 98 549 were independently screened by AI and manual reading. The overall agreement rate between AI and manual reading was 94.7% (95% confidential interval [CI], 94.5%‐94.8%), and kappa was 0.92 (0.91‐0.92). The detection rates of CIN2+ increased with the severity of cytology abnormality performed by both AI and manual reading (Ptrend < 0.001). General estimated equations showed that detection of CIN2+ among women with ASC‐H or HSIL by AI were significantly higher than corresponding groups classified by cytologists (for ASC‐H: odds ratio [OR] = 1.22, 95%CI 1.11‐1.34, P < .001; for HSIL: OR = 1.41, 1.28‐1.55, P < .001). AI‐assisted cytology was 5.8% (3.0%‐8.6%) more sensitive for detection of CIN2+ than manual reading with a slight reduction in specificity. Conclusions AI‐assisted cytology system could exclude most of normal cytology, and improve sensitivity with clinically equivalent specificity for detection of CIN2+ compared with manual cytology reading. Overall, the results support AI‐based cytology system for the primary cervical cancer screening in large‐scale population.