Lifestyle factors associated with episodic memory in middle-aged and older adults: evidence from a 9-year longitudinal study.

BACKGROUND: Episodic memory naturally deteriorates with age, and its deficits are widely recognized as the most significant feature and the most sensitive indicator of cognitive decline. It has been suggested that adopting a healthy lifestyle can play a protective role in preserving episodic memory. This study aimed to systematically examine the relationship between lifestyle factors (social activities, leisure activities, physical activities, internet use, smoking, alcohol drinking, and sleep quality) and episodic memory in middle-aged and older adults. METHODS: The current study included 10,392 participants from the Chinese Health and Retirement Longitudinal Survey. A linear mixed model was used to explore the associations between lifestyle factors and episodic memory performance and the age- and sex-specific effects of the association. RESULTS: Low-frequency alcohol drinking, higher engagement in social, leisure, and physical activities, increased internet use, and improved sleep quality were associated with better episodic memory performance in middle-aged and older adults. Stratified analyses demonstrated that internet use significantly correlated with episodic memory performance in middle-aged adults but not in older adults. On the other hand, sleep quality showed a significant association with episodic memory performance in women but not in men. CONCLUSIONS: This study highlights the association between various lifestyle factors and episodic memory performance, with variations observed based on age and sex. Adopting healthy lifestyle factors can have positive effects on episodic memory in middle-aged adults, emphasizing the importance of adhering to healthy lifestyles from middle age onwards to counteract episodic memory decline.

Chinese Herbal Compound Xiaoliu Pingyi Recipe Inhibits the Growth of Lung Adenocarcinoma by Regulating the Tumor Vascular Microenvironment.

BACKGROUND: The traditional Chinese medicine (TCM) Xiaoliu Pingyi recipe (XLPYR) has been clinically used for several decades, demonstrating favorable therapeutic effects. However, the underlying regulatory mechanisms remain unclear. The aim of this study was to explore the anti-tumor effects of XLPYR and its regulatory role in the vascular microenvironment through in vivo and in vitro experiment. MATERIALS AND METHODS: In the in vivo study, a C57BL/6J mouse model of lung adenocarcinoma (LUAD) allografts was established, and various interventions were administered for 14 days (Model group: administered normal saline via oral gavage; Pemetrexed (PEM) group: intraperitoneally injected with a solution of pemetrexed, once every 3d; XLPYR group: administered XLPYR via oral gavage; Combination (COMBI) group: received XLPYR via oral gavage simultaneously with intraperitoneal injection of pemetrexed solution). Tumor volume and weight were then compared among the groups. The impact of XLPYR on the tumor vascular microenvironment was assessed using immunohistochemistry staining. In the in vitro study, XLPYR-containing serum was prepared by oral administration to SD rats. The CCK-8 assay evaluated the effect of the serum on the proliferation of normal lung epithelial BEAS-2B cells and LUAD A549 cells, determining the optimal intervention concentrations. The cell migration and invasion abilities were evaluated using the wound-healing assay and Transwell assay, respectively. Finally, ELISA assay measured VEGF secretion levels in the LUAD cell supernatant, and RT-qPCR and Western Blot were employed to detect differences in HIF-1α, VEGFA, Ang-2, and PI3K/Akt mRNA and protein expression levels in both in vivo and in vitro experiments. RESULTS: In the in vivo study, XLPYR significantly inhibited the growth of mice LUAD allografts, with enhanced anti-tumor effects observed with prolonged drug intervention. Immunohistochemistry staining revealed reduced MVD and increased pericyte coverage in all intervention groups. Regarding vascular function, FITC-Dextran extravasation in the tumor tissues of the Model group was significantly higher than in the intervention groups, particularly with lower extravasation in the COMBI group compared to the PEM group. In the in vitro study, XLPYR demonstrated a time- and concentration-dependent inhibitory effect on LUAD cells, and with greater sensitivity in inhibiting LUAD cells compared to BEAS-2B cells. The wound-healing assay and Transwell assay confirmed that XLPYR significantly suppressed the migration and invasion abilities of LUAD cells. ELISA experiments further revealed a significant decrease in VEGF expression in the supernatant of each intervention group. RT-qPCR and Western Blot results showed consistent findings between the in vivo and in vitro experiments. HIF-1α, VEGFA, and Ang-2 mRNA and protein expression levels were significantly downregulated in the PEM group, XLPYR group, and COMBI group. There were no significant differences in the expression of PI3K and Akt mRNA and total protein, but the expression levels of phosphorylated p-PI3K and p-Akt were notably downregulated. CONCLUSION: XLPYR significantly inhibited C57BL/6J mouse LUAD allograft growth and improved the vascular microenvironment, thereby intervening in tumor angiogenesis and inducing vascular normalization. It suppressed LUAD cell proliferation, migration, and invasion, while reducing VEGF concentration in the cell supernatant. The regulatory mechanism may involve inhibiting PI3K/Akt protein phosphorylation and downregulating angiogenesis-related factors, such as HIF-1α, VEGF, and Ang-2.

Brain imaging of a gamified cognitive flexibility task in young and older adults.

The study aimed to develop and validate a gamified cognitive flexibility task through brain imaging, and to investigate behavioral and brain activation differences between young and older adults during task performance. Thirty-one young adults (aged 18-35) and 31 older adults (aged 60-80) were included in the present study. All participants underwent fMRI scans while completing the gamified cognitive flexibility task. Results showed that young adults outperformed older adults on the task. The left inferior frontal junction (IFJ), a key region of cognitive flexibility, was significantly activated during the task in both older and young adults. Comparatively, the percent signal change in the left IFJ was stronger in older adults than in young adults. Moreover, older adults demonstrated more precise representations during the task in the left IFJ. Additionally, the left inferior parietal lobule (IPL) and superior parietal lobule in older adults and the left middle frontal gyrus (MFG) and inferior frontal gyrus in young adults were also activated during the task. Psychophysiological interaction analyses showed significant functional connectivity between the left IFJ and the left IPL, as well as the right precuneus in older adults. In young adults, significant functional connectivity was found between the left IFJ and the left MFG, as well as the right angular. The current study provides preliminary evidence for the validity of the gamified cognitive flexibility task through brain imaging. The findings suggest that this task could serve as a reliable tool for assessing cognitive flexibility and for exploring age-related differences of cognitive flexibility in both brain and behavior.

Two Undescribed Germacrane-Type Sesquiterpenoids from Salvia cavaleriei var. simplicifolia Stib. and Their Anti-Alzheimer's Disease Activity.

Two undescribed germacrane-type sesquiterpenoids, salcasins A (1) and B (2), together with three known compounds (3-5) were isolated and identified from the whole plant of Salvia cavaleriei var. simplicifolia Stib. The structures of the undescribed compounds were elucidated on the basis of spectroscopic methods, such as HR-ESI-MS, 1D and 2D NMR data. The relative configurations of 1 and 2 were established by analyzing their NOESY spectra as well as by 13C NMR calculations with DP4+ probability analyses. The absolute configurations of 1 and 2 were determined by comparing experimental and calculated ECD spectra. Furthermore, the in vivo anti-Alzheimer's disease activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. Among all isolated compounds, salcasin A (1) significantly delayed AD-like symptoms of worm paralysis, which may be a potential anti-AD candidate agent.

Acceptability Assessment of an Executive Function Training Game FISHERMAN for Older Adults.

Objective: In recent years, an increasing number of gamification tools have been developed for older adults; however, few studies have explored the acceptability of these tools after initial use and sustained use in older adults. In the current study, we focus on "FISHERMAN," an executive function training game containing a cognitive game and an exergame, with the aim of investigating and comparing the acceptability of both versions of "FISHERMAN" after initial use and 3 months of sustained use in older adults. Materials and Methods: Seventy-six older adults were randomly assigned to the cognitive game training group or the exergame training group. Participants completed two 1-hour sessions per week for 12 weeks. Acceptability was evaluated through a validated, 7-point, self-rating, Interactive Technology Art Installation Technology Acceptance Model Questionnaire after the first and last training sessions, with higher ratings representing higher acceptability. The questionnaire included 22 items and 9 acceptability dimensions: usage behavior, intention to use, perceived usefulness, perceived ease of use, perceived playfulness, subjective norm, image, output quality, and result demonstrability. Descriptive statistics were conducted to evaluate acceptability after initial and sustained use. Two-way (time: initial use and sustained use; group: cognitive game group and exergame group) repeated ANOVAs were conducted to investigate the differences in acceptability. Post hoc, within-group, paired-sample t test analyses were performed to evaluate changes in game acceptability for each group over time. Results: After initial use and 3 months of sustained use, the average scores for overall acceptability and individual dimensions exceeded 5.5 of 7 points in both groups. The two groups presented different changes from initial use to sustained use. The overall acceptability, usage behavior, perceived usefulness, and perceived ease of use were significantly improved after training within the cognitive game group, while perceived playfulness was significantly reduced within the exergame group. Conclusions: The current study provided preliminary evidence that older adults had high acceptability for both the cognitive game and exergame versions of "FISHERMAN." After sustained use, acceptability of the cognitive game increased and acceptability of the exergame decreased, highlighting the importance of assessing game acceptability after initial and sustained use.

Effects of lifestyle and its interaction with anemia on cognitive function in older adults: A longitudinal study.

A better understanding of the impact of lifestyle factors on cognitive function in older adults is critical for developing intervention strategies to achieve successful aging. Moreover, older adults who fulfill the World Health Organization criteria for anemia have a significantly higher risk of developing dementia. In the current study, we aimed to assess the buffering effects of lifestyle on cognitive function in older Chinese adults through a nationally representative survey. The sample consisted of 1201 participants (mean age: 82.39 ± 12.08 years, 52.1% female) from the 2011/2012 and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey. Multiple linear regression analyses were used to explore the relationship between changes in lifestyle factors and the rate of cognitive function changes, as well as the effects of the interaction between lifestyle factors and anemia on cognitive function changes. Increased levels of participation in leisure activities, social activities, and dietary diversity delayed cognitive decline. Persistent anemia accelerated cognitive decline, while frequent participation in leisure activities delayed cognitive decline due to anemia. The increased levels of participation in leisure activities, social activities, and dietary diversity can alleviate the cognitive decline caused by aging itself, and more frequently participation in leisure activities can also alleviate the adverse effects of anemia on cognitive function in older adults.

Transposon-based identification of genes involved in the rimocidin biosynthesis in Streptomyces rimosus M527.

The transposon mutagenesis strategy has been employed to generate random insertion mutants and analyze the correlation between genes and secondary metabolites in the genus Streptomyces. In this study, our primary objective was to identify an unknown gene involved in rimocidin biosynthesis and elucidate its role in rimocidin production in Streptomyces rimosus M527. To achieve this, we established a random mutant library of S. rimosus M527 using a Tn5 transposon-mediated random mutagenesis strategy. Among the 137 isolated mutants, M527-G10 and M527-W5 exhibited the most significant variations in antagonistic activity against the plant pathogenic fungus Fusarium oxysporum f. sp. cucumerinum. Specifically, M527-G10 displayed a 72.93% reduction, while M527-W5 showed a 49.8% increase in rimocidin production compared to the wild-type (WT) strain S. rimosus M527. Subsequently, we employed a plasmid rescue strategy to identify the insertion loci of the transposon in the genomes of mutants M527-G10 and M527-W5, revealing a response regulator transcription factor (rrt) and a hypothetical protein (hyp), respectively. The roles of rrt and hyp in rimocidin biosynthesis were determined through gene deletion, overexpression in the WT strain, and complemented expression in the transposon mutants. Notably, the gene-deletion mutants M527-ΔRRT and M527-ΔHYP exhibited similar behavior in rimocidin production compared to the corresponding transposon mutants M527-G10 and M527-W5, suggesting that transposon insertions in genes rrt and hyp led to alterations in rimocidin production. Furthermore, both gene deletion and overexpression of rrt and hyp had no discernible effects on cell growth. These results reveal that genes rrt and hyp have positive and negative impacts on rimocidin production in S. rimosus M527, respectively.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

Ethyl caffeate attefnuates Aß-induced toxicity in Caenorhabditis elegans AD models via the insulin/insulin-like growth factor-1 signaling pathway.

The pathogenesis of Alzheimer's disease (AD), a multifactorial progressive neurodegenerative disease associated with aging, is unclear. Ethyl caffeate is a plant polyphenol that has been reported to have neuroprotective effects, but the mechanisms by which it acts are unclear. In this study, for the first time, we investigated the molecular mechanism of its anti-AD properties using the Caernorhabditis elegans model. The results of our experiments showed that ethyl caffeate delayed the paralysis symptoms of CL4176 to a different extent and reduced the exogenous 5-hydroxytryptophan-induced paralysis phenotype. Further studies revealed that ethyl caffeate lowered Aß plaques and depressed the expression of Aß monomers and oligomers, but did not influence the mRNA levels of Aß. Moreover, it was able to bring paraquat-induced ROS levels down to near-standard conditions. Real-time quantitative PCR experiment showed a significant upregulation of the transcript abundance of daf-16, skn-1 and hsf-1, key factors associated with the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway (IIS), and their downstream genes sod-3, gst-4 and hsp-16.2. It was further shown that ethyl caffeate activated the translocation of DAF-16 and SKN-1 from the cytoplasm to the nucleus and enhanced the expression of sod-3::GFP, gst-4::GFP and hsp-16.2::GFP in transgenic nematodes. This meant that the protection against Aß toxicity by ethyl caffeate may be partly through the IIS signaling pathway. In addition, ethyl caffeate suppressed the aggregation of polyglutamine proteins in AM141, which indicated a potential protective effect against neurodegenerative diseases based on abnormal folding and aggregation of amyloid proteins. Taken together, ethyl caffeate is expected to develop as a potential drug for the management of AD.

Effects of exergame and bicycle exercise intervention on blood pressure and executive function in older adults with hypertension: A three-group randomized controlled study.

Management of hypertension and prevention of cognitive decline are challenging public health problems. However, the effects of exergame intervention on blood pressure (BP) remain to be explored, and whether exergame intervention is an effective alternative to traditional physical exercise intervention for older adults with hypertension remains to be demonstrated. This study aimed to explore the effectiveness of moderate-intensity exergame intervention and bicycle exercise training on BP and executive function in older hypertensive patients. A total of 128 participants were randomly assigned to the exergame intervention group (n = 41), bicycle exercise intervention group (n = 44), and control group (n = 43). The intervention groups exercised for 60 min, 3 times per week, for 16 weeks, while the control group maintained their normal lifestyle. The results revealed that there were no significant differences between two intervention groups and control group in systolic BP and diastolic BP changes (ps > 0.05). Both intervention groups demonstrated significant improvements in working memory when compared with control group (exergame intervention group: -461.9 ms, p = 0.025; bicycle exercise intervention group: -470.1 ms, p = 0.021). There were no significant differences in systolic BP, diastolic BP, or working memory between the two intervention groups after 16 weeks of training (ps > 0.05). No difference in inhibition or cognitive flexibility was observed between the intervention and control groups (ps > 0.05). The current results showed that moderate-intensity exergame intervention did not produce significant benefits in reducing BP, but yielded similar beneficial effects in working memory to that of bicycle exercise intervention. More studies are needed on whether exergame intervention has the potential to be a promising supplemental therapeutic tool for older adults with hypertension.

FISHERMAN: A Serious Game for Executive Function Assessment of Older Adults.

Executive functions (EFs) are essential for daily living activities but decline with age. Convenient assessment and timely intervention have particular significance for older adults. However, the traditional laboratory tasks of EFs are typically monotonous and inconvenient. The current study aimed to develop an interesting and convenient supplementary tool to assess EFs for older adults. According to the theory of EFs, we developed a serious game, FISHERMAN, to assess EFs. The game includes three subgames, Cautious Fisherman, Agile Fisherman, and Wise Fisherman, targeting core components of inhibition, shifting, and working memory, respectively. The current study aims to verify the reliability and validity of the game. One hundred and eight healthy older adults participated in this study and were tested through the FISHERMAN game and a battery of cognitive tests. The results show that the FISHERMAN game has high internal consistency reliability and good construct validity as well as criterion-related validity, suggesting that the game design is valid and can be used in EFs assessment for older adults. Future studies are warranted to establish the norm of the FISHERMAN game in older adults and investigate whether the FISHERMAN game can be generalized to other populations.

Identifying the Antitumor Effects of Curcumin on Lung Adenocarcinoma Using Comprehensive Bioinformatics Analysis.

Background: As the main component of turmeric (Curcuma longa L.), curcumin is widely used in the treatment of various diseases. Previous studies have demonstrated that curcumin has great potential as a therapeutic agent, but the lack of understanding of the functional mechanism of the drug has hindered the widespread use of the natural product. In the present study, we used comprehensive bioinformatics analysis and in vitro experiments to explore the anti-tumor mechanism of curcumin. Materials and Methods: LUAD mRNA expression data were obtained from TCGA database and differentially expressed genes (DEGs) were identified using R software. Functional enrichment analysis was conducted to further clarify its biological properties and hub genes were identified by a protein-protein interaction (PPI) network analysis. Survival analysis and molecular docking were used to analyze the effectiveness of the hub genes. By an in vitro study, we evaluated whether curcumin could influence the proliferation, migration, and invasion activities of LUAD cells. Results: In this study, 1783 DEGs from LUAD tissue samples compared to normal samples were evaluated. Functional enrichment analysis and the PPI network revealed the characteristics of the DEGs. We performed a topological analysis and identified 10 hub genes. Of these, six genes (INS, GCG, SST, F2, AHSG, and NPY) were identified as potentially effective biomarkers of LUAD. The molecular docking results indicated that curcumin targets in regulating lung cancer may be INS and GCG. We found that curcumin significantly inhibited the proliferation, migration, and invasion of LUAD cells and significantly decreased the expression of the INS and GCG genes. Conclusion: The results of this study suggest that the therapeutic effects of curcumin on LUAD may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for LUAD prevention and treatment.

The Effect of Exergame Training on Physical Functioning of Healthy Older Adults: A Meta-Analysis.

Exergames have attracted increasing attention from both the public and researchers. Although previous systematic reviews provided evidence that exergame training is beneficial for improving balance or mobility in older adults, multidimensional physical function measurements, including balance, upper body strength, lower body strength, aerobic endurance, and gait, might help us achieve more robust and reliable results. This meta-analysis aims to quantify the effects of exergame training on overall and specific physical function in healthy older adults. We systematically searched exergame training studies published between January 1985 and June 2021. Forty-eight studies were included in the present meta-analysis, with a total of 1099 participants included in the training group and 1098 participants in the control group. Random-effects meta-analyses found that older adults obtained a small benefit in overall physical function performance (g = 0.43, 95% confidence interval [CI] = 0.33 to 0.53), moderate benefits in balance (g = 0.59, 95% CI = 0.46 to 0.71), upper body strength (g = 0.65, 95% CI = 0.20 to 1.10), lower body strength (g = 0.51, 95% CI = 0.37 to 0.65), and aerobic endurance (g = 0.65, 95% CI = 0.44 to 0.86), a small benefit in gait (g = 0.33, 95% CI = 0.08 to 0.59), and negligible effects on upper body flexibility (g = 0.13, 95% CI = -0.06 to 0.32) and lower body flexibility (g = 0.10, 95% CI = -0.45 to 0.67) from exergame training. The mini-mental state examination score was positively associated with the overall training efficacy (ß = 0.08, P = 0.01), while body mass index and the sample size in the training group were negatively associated with the overall training efficacy (ß = -0.01, P < 0.01; ß = -0.004, P < 0.01). The current meta-analytic findings revealed that exergame training produced general benefits for overall physical function and different effects on specific physical function domains in older adults.

Effects of exergame and video game training on cognitive and physical function in older adults: A randomized controlled trial.

Few studies have simultaneously explored the training effects of exergame and video game. The purpose of this study was to investigate the effects of exergame and video game training on cognitive and physical function in healthy older adults. Eighty-four healthy older adults were randomly assigned to exergame training group, video game training group, and control group. Cognitive and physical function was measured before and after the training. Both training groups improved in verbal memory and aerobic endurance, but the training effects were greater in the exergame training group. The exergame training group also showed significant improvement in lower limb strength and balance. The current study provides evidence that exergame training, incorporating both cognitive engagement and physical activity, exerts greater benefits than cognitively engaging video game training alone. The findings shed lights into the future use of exergame in preventing cognitive and physical function decline in older adults.

Risk Factors for Intraoperative Periprosthetic Femoral Fractures in Patients with Hip Dysplasia Undergoing Total Hip Arthroplasty with Uncemented Prostheses.

OBJECTIVES: To determine the potential risk factors for intraoperative periprosthetic femoral fractures in patients with developmental dysplasia of the hip (DDH) undergoing total hip arthroplasty (THA). METHODS: This was a retrospective study. Patients who were diagnosed with DDH and undergoing THA (by artificial joint replacement) at our hospital from January 1999 to December 2019 were included in this study. Clinical and radiological factors were obtained from their medical records, such as age, sex, Crowe classification, morphological features of proximal femur, and features of surgical procedure. The outcome of interest was the occurrence of intraoperative periprosthetic femoral fracture, which was recorded and classified according to the Vancouver classification system. According to the fracture status, the patients were divided into two groups: the fracture group and the non-fracture group. Multivariate logistic regression model was built to identify the risk factors for these fractures. RESULTS: A total of 1252 hips were finally included. Intraoperative periprosthetic femoral fractures were identified in 62 hips. The incidence of intraoperative periprosthetic femoral fractures in patients with DDH undergoing THA was 4.95%. There were 22 patients (proportion = 35.48%, incidence = 1.76%) with Type A fractures, 38 (proportion = 61.29%, incidence = 3.04%) with Type B fractures, and two (proportion = 3.23%, incidence = 0.16%) with Type C fractures. Six independent risk factors for intraoperative periprosthetic femoral fractures were identified: osteoporosis (OR = 3.434; 95% CI, 1.963-6.007), previous surgical history (OR = 4.797; 95% CI, 2.446-9.410), Dorr Type A canal (OR = 3.025; 95% CI, 1.594-5.738), retained femoral neck length (OR = 1.121; 95% CI, 1.043-1.204), implanted metaphyseal-diaphyseal fixation stems (OR = 3.208; 95% CI, 1.562-6.591), and implanted stem with anteversion design (OR = 2.916; 95% CI, 1.473-5.770). CONCLUSIONS: The overall incidence of intraoperative periprosthetic femoral fractures in patients with DDH undergoing THA was 4.95%, which was at a moderate level compared to patients with other diseases undergoing THA. Six independent risk factors were identified: osteoporosis, previous surgical history, Dorr Type A canal, insufficient neck osteotomy level, implantation of metaphyseal-diaphyseal fixation stem, and implantation of a stem with an anteversion design. Comprehending these risk factors might help surgeons prevent the occurrence of these intraoperative periprosthetic femoral fractures in patients with DDH.

Prognostic Significance of Serum PD-L1 Level in Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma Treated with Combination Cytotoxic Chemotherapy.

BACKGROUND: There are no useful biomarkers for the clinical outcome of advanced esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the prognostic value of soluble PD-L1 (sPD-L1) in serum of patients with locally advanced or metastatic ESCC who received cytotoxic chemotherapy as first-line treatment. MATERIALS AND METHODS: This study evaluated the expression pattern of PD-L1 by immunohistochemistry and sPD-L1 concentration, and correlation with clinicopathological factors and overall survival (OS) in 190 patients with ESCC. RESULTS: sPD-L1 concentration was highly expressed in ESCC, especially in female patients. Patients with a high sPD-L1 level (≥0.63 ng/mL) had a shorter OS than those with a low sPD-L1 level (<0.63 ng/mL). In a multivariate analysis, high sPD-L1 concentration remained an independent prognostic factor of OS after adjustment for possible confounders. However, tissue PD-L1 expression level was non-prognostic in this study. CONCLUSION: There was no significant correlation between serum sPD-L1 concentration and tissue PD-L1 expression level. sPD-L1 concentration before treatment could be an effective and convenient biomarker of prognosis in patients with locally advanced or metastatic ESCC treated with combination cytotoxic chemotherapy.

Nano-realgar suppresses lung cancer stem cell growth by repressing metabolic reprogramming.

BACKGROUND: Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. METHODS: The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. RESULTS: Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. CONCLUSIONS: These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.

Age-related impairment of navigation and strategy in virtual star maze.

BACKGROUND: Although it is well known that aging impairs navigation performance, the underlying mechanisms remain largely unknown. Egocentric strategy requires navigators to remember a series of body-turns without relying on the relationship between environmental cues. Previous study suggested that the egocentric strategy, compared with non-egocentric strategy, was relatively unimpaired during aging. In this study, we aimed to examine strategy use during virtual navigation task and the underlying cognitive supporting mechanisms in older adults. METHODS: Thirty young adults and thirty-one older adults were recruited from the local community. This study adapted star maze paradigm using non-immersive virtual environment. Participants moved freely in a star maze with adequate landmarks, and were requested to find a fixed destination. After 9 learning trials, participants were probed in the same virtual star maze but with no salient landmarks. Participants were classified as egocentric or non-egocentric strategy group according to their response in the probe trial. RESULTS: The results revealed that older adults adopting egocentric strategy completed the navigation task as accurate as young adults, whereas older adults using non-egocentric strategy completed the navigation task with more detours and lower accuracy. The relatively well-maintained egocentric strategy in older adults was related to better visuo-spatial ability. CONCLUSIONS: Visuo-spatial ability might play an important role in navigation accuracy and navigation strategy of older adults. This study demonstrated the potential value of the virtual star maze in evaluating navigation strategy and visuo-spatial ability in older adults.

Prognostic Value of Long Noncoding RNA SPRY4-IT1 on Survival Outcomes in Human Carcinomas: A Systematic Review and Meta-Analysis with TCGA Database.

BACKGROUND: Emerging evidences have shown that long noncoding RNA SPRY4-IT1 can be aberrantly expressed in human cancers, and it could be an unfavorable prognostic factor in cancer patients. However, the prognostic mechanism of SPRY4-IT1 is still unclear. This study is aimed at evaluating its potential predictive value for cancer prognosis. METHODS: We thoroughly searched PubMed, Embase, Web of Science, and MEDLINE databases so as to explore the relationship between SPRY4-IT1 expression and cancer prognosis value. Then, TCGA datasets were used to validate the results of our meta-analysis. RESULTS: In all, seventeen studies involving 1650 patients were included in this meta-analysis. Pooled results showed that high expression of SPRY4-IT1 was significantly correlated with poor OS (HR = 1.96, 95% confidence interval (CI) = 1.47-2.62, P < 0.001) in cancer patients. Furthermore, exploration of TCGA dataset further validated that SPRY4-IT1 was aberrantly expressed in various cancers, which partially confirmed our results in this meta-analysis. CONCLUSIONS: The present systematic review and meta-analysis implicated that the aberrant expressions of lncRNA SPRY4-IT1 were strongly associated with clinical survival outcomes in various cancers and therefore might serve as a promising biomarker for predicting prognosis of human cancers.