Association of Combined Healthy Lifestyle Factors With Incident Dementia in Participants With and Without Multimorbidity: A Large Population-Based Prospective Cohort Study.

BACKGROUND: The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. METHODS: We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. RESULTS: Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5-6, patients with multimorbidity and a lifestyle score of 0-1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5-6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5-6 to 0-1. And we observed more pronounced association between them among people younger than 60 years old. CONCLUSIONS: Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity.

PIK3CD induces cell growth and invasion by activating AKT/GSK-3ß/ß-catenin signaling in colorectal cancer.

The catalytic subunit p110δ of phosphoinositide 3-kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small-interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of ß-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3ß (GSK-3ß) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD-mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of ß-catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with ß-catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK-3ß/ß-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.

Serum and cerebrospinal fluid tau protein level as biomarkers for evaluating acute spinal cord injury severity and motor function outcome.

Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm (mild), 25 mm (moderate) and 50 mm (severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups (both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days (serum: r = -0.94; cerebrospinal fluid: r = -0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.

New Nodule Type Found in the Lungs of Pomacea canaliculata, an Intermediate Host of Angiostrongylus cantonensis.

BACKGROUND: Pomacea canaliculata (P.canaliculata) lung nodules, were commonly caused by Angiostrongylus cantonensis infection. Here, we found a new nodule type without any parasites. METHODS: Overall, 447 P. canaliculata snails were collected in Ning Bo, Zhe Jiang, China in 2018. In order to exhibit the similarities and differences between two nodules types (2018, Huzhou Zhejiang, China), both types were collected in formalin for tissue pathological sectioning. Besides, to obtain the microbial community of the new nodule, the 18S ribosomal RNA (rRNA) gene of it was amplified and analyzed using the Illumina second-generation sequencing platform. RESULTS: Although two nodules were found in the lungs of P. canaliculata, they were different in shape and pathology. Illumina sequencing indicated Poterioochromonas sp., a species of golden algae, might be the causing agent of the new nodule. CONCLUSION: We firstly found a new pathological nodule type in the lungs of P. canaliculata, and this nodule might be induced by golden algae infection, however, the direct link between the golden algae and the new nodules, as well as the nodules' impact on the snails' physiology and A. cantonensis infection require further study.

Hydrogen sulfide exposure increases desiccation tolerance in Drosophila melanogaster.

Hydrogen sulfide (H(2)S) has been shown to effect physiological alterations in several animals, frequently leading to an improvement in survival in otherwise lethal conditions. In the present paper, a volatility bioassay system was developed to evaluate the survivorship of Drosophila melanogaster adults exposed to H(2)S gas that emanated from a K(2)S donor. Using this bioassay system, we found that H(2)S exposure significantly increased the survival of flies under arid and food-free conditions, but not under humid and food-free conditions. This suggests that H(2)S plays a role in desiccation tolerance but not in nutritional stress alleviation. To further confirm the suggestion, the mRNA levels of two desiccation tolerance-related genes Frost and Desat2, and a starvation-related gene Smp-30, from the control and treated flies were measured by quantitative real-time PCR. These genes were up-regulated within 2h when the flies transferred to the arid and food-free bioassay system. Addition of H(2)S further increased Frost and Desat2 mRNA levels, in contrast to Smp-30. Thus, our molecular results were consistent with our bioassay findings. Because of the molecular and genetic tools available for Drosophila, the fly will be a useful system for determining how H(2)S regulates various physiological alterations.

Effects of dietary sodium on performance, flight and compensation strategies in the cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae).

BACKGROUND: Sodium is critical for many physiological functions in insects. Herbivorous insects should expend considerable energy to compensate for sodium deficiency due to low sodium concentration in most inland plants upon which they feed. However, sodium compensation behaviors such as mud-puddling have been observed in some species but not in others. We expect that there may be other sodium compensation strategies in insects. Here, we select a rarely mud-puddling insect species, the cotton boll worm, Helicoverpa armigera, and determine the effects of dietary sodium on performance and flight, and examine their means of sodium compensation. RESULTS: When freshly hatched H. armigera neonates were cultured on one of three diets differing in sodium contents (diet A, B and C with a high, middle and low sodium concentrations, respectively), the larvae on diet C grew larger, had a higher mortality rate and a shorter development period than those on diet A and B. The larvae previously fed from 1st to 3rd instar on diet C consumed more subsequent diet when they were transferred to diet A or C at 4th instar, comparing to those previously fed on diet A. Moreover, any 4th-instar larvae on diet C consumed a greater amount of food than those on diet A, no matter which diet the larvae had previously ingested from 1st to 3rd instar. Moths from diet A and B flew more rapidly than those from diet C, with similar sugar and lipid utilization rates among the three test groups. When a 5th-instar cannibal from diet A, B or C and a 5th-instar victim from diet A were housed together, many more cannibals from diet C ate their victims. When a victim from diet A, B or C was provided, a cannibal from diet C was more likely to eat the victim from diet A. When newly emerged moths had been exposed to 3% sodium chloride solution for all scotophase period, the average weight increase (proxy for sodium solution intake) for moths from diet A was lower than those from diet B or C. CONCLUSION: Sodium-deficient diet resulted in rapid growth and development of H. armigera larvae, decreased larvae survival, and reduced flight speed of H. armigera adults. To compensate for sodium deficiency, H. armigera ingested a large quantity of larval food, increased larval cannibalism incidence and harvested sodium during the adult stage.