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Introduction: Lung adenocarcinoma (LUAD) is one of the major histopathological types of non‐small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. Methods: A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole‐exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA‐LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. Results: The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA‐LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)‐ERK and p‐AKT (Ser473), and the reduced protein level of p‐ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. Conclusion: Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD. [ABSTRACT FROM AUTHOR]

Objective To investigate the cognitive function of the elderly with different exercise frequencies, and to analyze the effect of exercise frequency on the cognitive function of the elderly. Methods By using the method of stratified propor¬tional sampling, 4 414 people aged 60 and above were selected from the streets of Yinzhou district of Ningbo. Mini-mental state examination (MMSE) was used to screen the cognitive function of the elderly in the community, and the generalized linear model was used to analyze the influence of exercise frequency and other factors on the cognitive function of the elder¬ly. Results The average MMSE score of 4 414 elderly people was 27.05±3.25. The MMSE scores of the elderly who never ex¬ercised, rarely exercised, and exercised regularly were 26.03±3.82, 27.04±3.19, and 27.53±2.88, respectively, and the differ¬ence was statistically significant (F=72.596, P < 0.001). There were significant differences in cognitive function among the elderly with different exercise frequencies in the fields of orientation, memory, attention and calculation, recall, and language ability (F=13.120, F=13.309, F=33.508, F=32.575, and F=65.312, P<0.01). The results of generalized linear model analysis showed that after controlling other factors, compared with never exercise, the MMSE scores of rare exercise and regular exer¬cise were 2.291 times (95%CI: 1.808-2.904) and 2.470 times (95%CI: 1.973-3.094), respectively. Conclusion Exercise fre-quency is closely related to the cognitive function of the elderly aged 60 and above in the community. Exercise can alleviate the cognitive dysfunction of the elderly in the community and actively mobilize the whole body to prevent Alzheimer' s dis¬ease. The elderly should be encouraged to participate in more exercises suitable for them. [ABSTRACT FROM AUTHOR]

Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2-amino-nonyl-6-methoxyl-tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism-related genes, including glycolysis-related genes ( PFK1, CDC19 and HXK2), fermentation-related genes ( PDC11, ALD5 and ADH1) and respiratory electron transport chain-related genes ( CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone-cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections. 10b treatment decreased the expression of energy metabolism-related genes, increased generation of endogenous reactive oxygen species (ROS), decreased mitochondrial membrane potential (AM·m), ubiquinone-cytochrome C reductase (complex III) activity and intracellular ATP level in Candida albicans SC5314 strain. Also, addition of antioxidant ascorbic acid (AA) reduced the antifungal activity of 10b significantly. [ABSTRACT FROM AUTHOR]

Summary: This paper presents a complete model of collector system layout optimization for offshore wind farms, which consists of both internal and external designs. The internal design uses the algorithm of self‐tracking minimum spanning tree (ST‐MST) combined with added functions of automatic cable selecting (ACS) and cable crossing avoiding (CCA) to form a radial topology. In addition, the features above are also integrated with the use of direct current transmission in the external design, which applies a self‐designed searching method to find the optimal locations for VSC converters. The internal and external designs constitute the whole model of the offshore wind farm. More specifically, the internal connection begins with the Fuzzy C‐means clustering method to divide the farm into clusters, where each center of the cluster locates a substation connecting to the turbines belonging to it. The external connection of the wind farm considers the use of high voltage direct current, which saves a great amount of reactive power in long distance transmission. Both the internal and external designs apply ST‐MST with ACS and CCA, while the external connection is also given a higher priority as it uses the cables with larger cross sections compared with internal connection. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to investigate the relationship between N-methylN'-nitro-N-nitrosoguanidine (MNNG)-induced lung adenocarcinoma mouse of different stages and the level of exosomes in serum. Methods: Fifty KM mice (4 weeks old, weighing 18-22 g, female) were selected for experiment. MNNG was applied to induce lung adenocarcinoma in mice for model establishment. HE staining method was used to observe pathological changes of lung tissues. Exosomes in serum were extracted, and observed under a Transmission Electron Microscopy (TEM). Western blot was employed to examine the protein levels of exosome markers TSG101 and CD63. Results: HE staining results suggested MNNG-induced lung adenocarcinoma model mice were successfully constructed. The morphology of exosomes in serum of mouse model was observed under an Electron Microscopy, showing clear membrane structures presenting as saucer or concave hemisphere. In addition, the protein level of exosome marker CD63 in advanced mouse model was significantly up-regulated relative to that in the control group. Meanwhile, the expression of exosome marker protein TSG101 was found to be markedly increased in mouse models by comparison with that in control cases. Conclusion: In lung adenocarcinoma model mice, the occurrence and development of lung adenocarcinoma are greatly correlated with the expression level of exosomes in serum, which provides theoretical basis for the diagnosis of pathological staging of lung adenocarcinoma by exosomes.

This study aimed to examine the effects of N-acetyl-L-cysteine (NAC) on protecting neurons function and improving learning and memory deficits in mice. Mice were intracerebroventricularly (icv) injected with the aggregated amyloid beta-peptide (Abeta) to produce Alzheimer's disease (AD). Learning and memory functions in mice were examined by the step through test and the water maze performance. The results showed that the mice pretreated with NAC had significantly greater retention in the step through test and shorter latencies in the water maze performance. Biochemical studies showed the potential role of free radical toxicity and the damage of cholinergic neurons in the Abeta-treated mice. There was an increased lipid peroxidation as indicated by elevated malondehyde (MDA) and decrease of glutathione (GSH) levels. There was also an increase in acetylcholinesterase (AChE) activity and a reduction in the choline acetyltransferase (ChAT) activity and acetylcholine (ACh) levels. NAC pretreatment significantly reversed the elevated MDA, AChE and the reduced GSH, ChAT and ACh in the Abeta-model mice. The results of the present study suggest the potential usage of the neuroprotective action of NAC on AD.