The Effects of Simultaneous Aerobic Exercise and Video Game Training on Executive Functions and Brain Connectivity in Older Adults.

OBJECTIVE: The study was designed to examine the effects of simultaneous combination of aerobic exercise and video game training on executive functions (EFs) and brain functional connectivity in older adults. DESIGN: A four-armed, quasi-experimental study. SETTING AND PARTICIPANTS: Community-dwelling adults aged 55 years and older. METHODS: A total of 97 older adults were divided into one of four groups: aerobic exercise (AE), video game (VG), combined intervention (CI), and passive control (PC). Participants in intervention groups received 32 sessions of training over a 4-month period at a frequency of twice a week. EFs was evaluated using a composite score derived from a battery of neuropsychological tests. The Montreal Cognitive Assessment (MoCA) was employed to evaluate overall cognitive function, while the 6-Minute Walking Test (6MWT) was utilized to gauge physical function. Additionally, the functional connectivity (FC) of the frontal-parietal networks (FPN) was examined as a neural indicator of cognitive processing and connectivity changes. RESULTS: In terms of EFs, both VG and CI groups demonstrated improvement following the intervention. This improvement was particularly pronounced in the CI group, with a large effect size (Hedge's g = 0.83), while the VG group showed a medium effect size (Hedge's g = 0.56). A significant increase in MoCA scores was also observed in both the VG and CI groups, whereas a significant increase in 6MWT scores was observed in the AE and CI groups. Although there were no group-level changes observed in FC of the FPN, we found that changes in FC was behaviorally relevant as increased FC was associated with greater improvement in EFs. CONCLUSION: The study offers preliminary evidence that both video game training and combined intervention could enhance EFs in older adults. Simultaneous combined intervention may hold greater potential for facilitating EFs gains. The initial evidence for correlated changes in brain connectivity and EFs provides new insights into understanding the neural basis underlying the training gains.

Electrophysiological evidence for context reinstatement effects on object recognition memory.

Reinstating the context present at encoding during the test phase generally enhances recognition memory compared with changing the context when specific item-context associations are established during encoding. However, it remains unclear whether context reinstatement improves the performance in differentiating between old and similar items in recognition memory tests and what underlying cognitive processes are involved. Using the context reinstatement paradigm together with event-related potentials (ERP), we examined the context-dependent effects of background scenes on recognition discrimination among similar objects. Participants were instructed to associate intentionally specific objects with background scenes during the encoding phase and subsequently complete an object recognition memory task, during which old and similar new objects were presented superimposed over the studied old or similar new background scenes. Electroencephalogram was recorded to measure the electrophysiological manifestations of cognitive processes associated with episodic retrieval. Behavioral results revealed enhanced performance in differentiating old from similar objects in the old context, as opposed to the similar context condition. Importantly, ERP results indicated a more pronounced recollection-related parietal object old/new effect in the old context compared to the similar context condition. This suggests that the ability to distinguish between old and similar objects in recognition memory is primarily driven by recollection rather than familiarity, particularly when the encoding context is reinstated during the test phase. Our findings are in line with the account that the impact of context reinstatement on object recognition memory is attributable to the enhanced recollection of specific item-context associations during retrieval and provides evidence for the specificity of episodic associative representations.

Integrative chemical and multiomics analyses of tetracycline removal mechanisms in Pseudomonas sp. DX-21.

Tetracycline (TC), widely found in various environments, poses significant risks to ecosystems and human health. While efficient biodegradation removes TC, the mechanisms underlying this process have not been elucidated. This study investigated the molecular mechanisms underlying TC biosorption and transfer within the extracellular polymeric substances (EPS) of strain DX-21 and its biodegradation process using fourier transform infrared spectroscopy, molecular docking, and multiomics. Under TC stress, DX-21 increased TC biosorption by secreting more extracellular polysaccharides and proteins, particularly the latter, mitigating toxicity. Moreover, specialized transporter proteins with increased binding capacity facilitated TC movement from the EPS to the cell membrane and within the cell. Transcriptomic and untargeted metabolomic analyses revealed that the presence of TC led to the differential expression of 306 genes and significant alterations in 37 metabolites. Notably, genes related to key enzymes, such as electron transport, peroxidase, and oxidoreductase, exhibited significant differential expression. DX-21 combated and degraded TC by regulating metabolism, altering cell membrane permeability, enhancing oxidative defense, and enhancing energy availability. Furthermore, integrative omics analyses indicated that DX-21 degrades TC via various enzymes, reallocating resources from other biosynthetic pathways. These results advance the understanding of the metabolic responses and regulatory mechanisms of DX-21 in response to TC.

Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients.

BACKGROUND: Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children. AIMS: The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients. METHODS: A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range. RESULTS: For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose. CONCLUSION: It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.

Removal of nitrate nitrogen by Pseudomonas JI-2 under strong alkaline conditions: Performance and mechanism.

The nitrate nitrogen removal characteristics of Pseudomonas JI-2 under strong alkaline conditions and the composition and functional groups of extracellular polymeric substance were analyzed. Furthermore, nontargeted metabonomics and bioinformatics technology were used to investigate the alkaline tolerance mechanism. JI-2 removed 11.05 mg N/(L·h) of nitrate with the initial pH, carbon to nitrogen ratio and temperature were 11.0, 8 and 25 °C respectively. Even when the pH was maintained at 11.0, JI-2 could still effectively remove nitrate. JI-2 contains a large number of Na+/H+ antiporters, such as Mrp, Mnh (mnhACDEFG) and Pha (phaACDEFG), which can stabilize the intracellular acid-base environment, and SlpA can enable quick adaptation to alkaline conditions. Moreover, JI-2 responds to the strong alkaline environment by secreting more polysaccharides, acidic functional groups and compatible solutes and regulating key metabolic processes such as pantothenate and CoA biosynthesis and carbapenem biosynthesis. Therefore, JI-2 can survive in strong alkaline environments and remove nitrate efficiently.

The performance and mechanism of tetracycline and ammonium removal by Pseudomonas sp. DX-21.

To remove ammonium and tetracycline (TC) from wastewater, a new strain, DX-21, was isolated and exhibited simultaneous removal ability. The performance of DX-21 in TC removal, its removal mechanism, and the potential toxicities of the degradation products were investigated with genomics, mass spectrometry, density functional theory calculations, quantitative structure-activity relationship analyses, and Escherichia coli exposure experiments. DX-21 exhibited removal of ammonium (9.64 mg·L-1·h-1) via assimilation, and TC removal (0.85 mg·L-1·h-1) primarily occurred through cell surface bio-adsorption and biodegradation. Among the 12 identified degradation products, the majority exhibited lower toxicities than TC. Moreover, potential degradation pathways were proposed, including hydroxylation and deamination. Furthermore, DX-21 possessed TC resistance genes, various oxygenases and peroxidases that could potentially contribute to TC degradation. DX-21 colonized activated sludge and significantly enhanced the biodegradation of TC. Therefore, DX-21 showed potential for treating wastewater containing both ammonium and TC.

A Combined Intervention of Aerobic Exercise and Video Game in Older Adults: The Efficacy and Neural Basis on Improving Mnemonic Discrimination.

BACKGROUND: Mnemonic discrimination is very vulnerable to aging. Previous studies have reported that aerobic exercise and enriched cognitive stimulation (e.g., video games) could improve mnemonic discrimination in older adults. The animal model suggested that combining the 2 training methods could result in a larger improvement. However, there is limited evidence on the potential superior efficacy of combined intervention with human participants. Moreover, the neural basis of this potential superior is poorly understood. METHODS: We conducted a 16-week intervention trial with 98 community-dwelling older adults assigned to one of the four groups (combined training, aerobic cycling alone, video game alone, or passive control). Mnemonic discrimination was measured as the primary behavioral outcome, hippocampal volume, and functional connectivity of the default mode network (DMN) were measured as neural indicators. RESULTS: Participants receiving the combined intervention demonstrated the largest effect size of mnemonic discrimination improvement. Magnetic resonance image results indicated aerobic exercising increased left hippocampal volume, while video-game training counteracted the decline of DMN functional connectivity with aging. The synergy of hippocampal structural and functional plasticity observed in the combined training group explained why the largest intervention benefits were obtained by this group. CONCLUSION: Despite the nonrandomized design (i.e., likely self-selection bias), our results provide new evidence that combined intervention of exercise and cognitive training is more effective than single intervention for older adults. Parallel to animal studies, aerobic exercise and the video game with enriched cognitive stimulation could induce hippocampal plasticity through separate structural and functional pathways. CLINICAL TRIALS REGISTRATION NUMBER: ChiCTR1900022702.

The presence of copper ions alters tetracycline removal pathway in aerobic granular sludge: Performance and mechanism.

This study investigated the removal characteristics of tetracycline (TC) in the presence of copper ions (Cu2+) in aerobic granular sludge by analyzing the TC removal pathway, composition and functional group changes of extracellular polymeric substances (EPS), and microbial community structure. The TC removal pathway changed from cell biosorption to EPS biosorption, and the microbial degradation rate of TC was reduced by 21.37% in the presence of Cu2+. Cu2+ and TC induced enrichment of denitrifying bacteria and EPS-producing bacteria by regulating the expression of signaling molecules and amino acid synthesis genes to increase the content of EPS and -NH2 groups in EPS. Although Cu2+ reduced the content of acidic hydroxyl functional groups (AHFG) in EPS, an increase in TC concentration stimulated the secretion of more AHFG and -NH2 groups in EPS. The long-term presence of TC presence of the relative abundances of Thauera, Flavobacterium and Rhodobacter and improved the removal efficiency.

A full evaluation of chiral phenylpyrazole pesticide flufiprole and the metabolites to non-target organism in paddy field.

Pesticides applied to paddy fields may pose considerable danger to non-target aquatic organisms and further threaten human health. Flufiprole is a pesticide used in rice fields; considering the widespread existence of rice-fish-farming ecosystems, the acute toxicities of flufiprole enantiomers and its six metabolites (fipronil, flufiprole sulfide, flufiprole sulfone, detrifluoromethylsulfinyl flufiprole, desulfinyl flufiprole, and flufiprole amide) to four common aquatic organisms in rice fields including Misgurnus anguillicaudatus (pond loach), Carassius gibelio (Prussian carp), Pelophylax nigromaculatus (black-spotted frog), and Daphnia magna (water flea) were investigated. Genotoxicity, pathological changes and the effects on the antioxidant system of M. anguillicaudatus were also evaluated after exposure. The LC50 (EC50) values showed that fipronil and desulfinyl flufiprole were the most toxic compounds and were approximately about six times as toxic as flufiprole. No enantioselective toxicity was observed between the two enantiomers. The activity of antioxidant defense enzymes and the content of malondialdehyde (MDA) in the liver and gills of M. anguillicaudatus were significantly increased by the chemicals in most cases. In addition, fipronil and desulfinyl flufiprole were found to induce an increase in the micronucleus rate in M. anguillicaudatus. Histopathological analysis showed that the liver of M. anguillicaudatus was not significantly affected by flufiprole. Our study demonstrated a potential negative effect on flufiprole-treated aquatic organisms. As an alternative to fipronil, the environmental risk of flufiprole and its metabolites to non-target organisms in rice fields cannot be ignored.