Aerobic fitness as a moderator of acute aerobic exercise effects on executive function.

This study aimed to investigate the moderating role of aerobic fitness on the effect of acute exercise on improving executive function from both behavioral and cerebral aspects. Thirty-four young individuals with motor skills were divided into high- and low-fitness groups based on their maximal oxygen uptake. Both groups completed 30 min of moderate-intensity aerobic exercise on a power bike. Executive function tests (Flanker, N-back, More-odd-shifting) were performed before and after exercise and functional near-infrared spectroscopy was used to monitor prefrontal cerebral blood flow changes during the tasks. The results indicated significant differences between the two groups regarding executive function. Participants with lower aerobic fitness performed better than their higher fitness counterparts in inhibitory control and working memory, but not in cognitive flexibility. This finding suggests that the aerobic fitness may moderate the extent of cognitive benefits gained from acute aerobic exercise. Furthermore, the neuroimaging data indicated negative activation in the frontopolar area and dorsolateral prefrontal cortex in response to three complex tasks. These findings underscore the importance of considering individual aerobic fitness when assessing the cognitive benefits of exercise and could have significant implications for tailoring fitness programs to enhance cognitive performance.

Pepsin-mediated inflammation in laryngopharyngeal reflux via the ROS/NLRP3/IL-1ß signaling pathway.

BACKGROUND: Laryngopharyngeal reflux (LPR) is one of the most common disorders in otorhinolaryngology, affecting up to 10% of outpatients visiting otolaryngology departments. In addition, 50% of hoarseness cases are related to LPR. Pepsin reflux-induced aseptic inflammation is a major trigger of LPR; however, the underlying mechanisms are unclear. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome has become an important bridge between stimulation and sterile inflammation and is activated by intracellular reactive oxygen species (ROS) in response to danger signals, leading to an inflammatory cascade. In this study, we aimed to determine whether pepsin causes LPR-associated inflammatory injury via mediating inflammasome activation and explore the potential mechanism. METHODS: We evaluated NLRP3 inflammasome expression and ROS in the laryngeal mucosa using immunofluorescence and immunohistochemistry. Laryngeal epithelial cells were exposed to pepsin and analyzed using flow cytometry, western blotting, and real-time quantitative PCR to determine ROS, NLRP3, and pro-inflammatorycytokine levels. RESULTS: Pepsin expression was positively correlated with ROS as well as caspase-1 and IL-1ß levels in laryngeal tissues. Intracellular ROS levels were elevated by increased pepsin concentrations, which were attenuated by apocynin (APO)-a ROS inhibitor-in vitro. Furthermore, pepsin significantly induced the mRNA and protein expression of thioredoxin-interacting protein, NLRP3, caspase-1, and IL-1ß in a dose-dependent manner. APO and the NLRP3 inhibitor, MCC950, inhibited NLRP3 inflammasome formation and suppressed laryngeal epithelial cell damage. CONCLUSION: Our findings verified that pepsin could regulate the NLRP3/IL-1ß signaling pathway through ROS activation and further induce inflammatory injury in LPR. Targeting the ROS/NLRP3 inflammasome signaling pathway may help treat patients with LPR disease.

Protective factors for children with autism spectrum disorder during COVID-19-related strict lockdowns: a Shanghai autism early developmental cohort study.

BACKGROUND: COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns. METHODS: Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects. RESULTS: Compared with the lockdown-free group, the ASD children experienced the longer duration of strict lockdown had less clinical improvement (ß = 0.49, 95% confidence interval (CI) [0.19-0.79], p = 0.001) and this difference was greatest for social cognition (2.62 [0.94-4.30], p = 0.002). We found that this association was modulated by parental agreeableness in a protective way (-0.11 [-0.17 to -0.05], p = 0.002). This protective effect was enhanced in the ASD children with larger grey matter volumes in the brain's mentalizing network, including the temporal pole, the medial superior frontal gyrus, and the superior temporal gyrus. CONCLUSIONS: This longitudinal neuroimaging cohort study identified that the parental agreeableness interacting with the ASD children's social brain development reduced the negative impact on clinical symptoms during the strict lockdown.

CD39hi identifies an exhausted tumor-reactive CD8+ T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

Maslinic acid alleviates alcoholic liver injury in mice and regulates intestinal microbiota via the gut-liver axis.

BACKGROUND: Maslinic acid (MA), a pentacyclic triterpene acid, is widely distributed in natural plants and mainly found in the fruit and leaves of olives and hawthorn. MA has been reported as having many health-promoting functions, such as anticancer, anti-inflammation and neuroprotective activities. According to previous study, hawthorn extract has certain hepatoprotective effects. However, the detailed mechanism is still unclear, especially the effect of MA on gut microbiota. RESULTS: Our study reveals that MA effectively counteracts alcohol-induced liver injury and oxidative stress. It mitigates alcohol-induced intestinal barrier damage, reverses increased permeability and reduces translocation of lipopolysaccharide (LPS). This prevents LPS/Toll-like receptor 4 activation, leading to decreased TNF-α and IL-1ß production. Furthermore, MA rebalances gut microbiota by reversing harmful bacterial abundance and enhancing beneficial bacteria post-alcohol consumption. CONCLUSION: MA, through modulation of gut microbiota, alleviates alcohol-induced liver injury via the gut-liver axis. These findings support the potential use of MA as a functional food ingredient for preventing or treating alcoholic liver disease. © 2024 Society of Chemical Industry.

Enantiopure Corral[4]BINOLs as Ultrastrong Receptors for Recognition and Differential Sensing of Steroids.

The precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral[4]BINOLs (C[4]BINOLs), a pair of enantiomeric conjugated deep-cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C[4]BINOLs demonstrated exceptionally high recognition affinities (up to 1012 M-1) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C[4]BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations.

Adaptive and Ultrahigh-Affinity Recognition in Water by Sulfated Conjugated Corral[5]arene.

The pursuit of synthetic receptors with high binding affinities has long been a central focus in supramolecular chemistry, driven by their significant practical relevance in various fields. Despite the numerous synthetic receptors that have been developed, most exhibit binding affinities in the micromolar range or lower. Only a few exceptional receptors achieve binding affinities exceeding 109  M-1 , and their substrate scopes remain rather limited. In this context, we introduce SC[5]A, a conjugated corral-shaped macrocycle functionalized with ten sulfate groups. Owing to its deep one-dimensional confined hydrophobic cavity and multiple sulfate groups, SC[5]A displays an extraordinarily high binding strength of up to 1011  M-1 towards several size-matched, rod-shaped organic dications in water. Besides, its conformation exhibits good adaptability, allowing it to encapsulate a wide range of other guests with diverse molecular sizes, shapes, and functionalities, exhibiting relatively strong affinities (Ka =106 -108  M-1 ). Additionally, we've explored the preliminary application of SC[5]A in alleviating blood coagulation induced by hexadimethrine bromide in vitro and in vivo. Therefore, the combination of ultrahigh binding affinities (towards complementary guests) and adaptive recognition capability (towards a wide range of functional guests) of SC[5]A positions it as exceptionally valuable for numerous practical applications.

Recent advances in research on biocontrol of postharvest fungal decay in apples.

Apple is the largest fruit crop produced in temperate regions and is a popular fruit worldwide. It is, however, susceptible to a variety of postharvest fungal pathogens, including Penicillium expansum, Botrytis cinerea, Botryosphaeria dothidea, Monilia spp., and Alternaria spp. Decays resulting from fungal infections severely reduce apple quality and marketable yield. Biological control utilizing bacterial and fungal antagonists is an eco-friendly and effective method of managing postharvest decay in horticultural crops. In the current review, research on the pathogenesis of major decay fungi and isolation of antagonists used to manage postharvest decay in apple is presented. The mode of action of postharvest biocontrol agents (BCAs), including recent molecular and genomic studies, is also discussed. Recent research on the apple microbiome and its relationship to disease management is highlighted, and the use of additives and physical treatments to enhance biocontrol efficacy of BCAs is reviewed. Biological control is a critical component of an integrated management system for the sustainable approaches to apple production. Additional research will be required to explore the feasibility of developing beneficial microbial consortia and novel antimicrobial compounds derived from BCAs for postharvest disease management, as well as genetic approaches, such as the use of CRISPR/Cas9 technology.

Children with autism spectrum disorder perform comparably to their peers in a parent-child cooperation task.

This study investigates whether and how parent's cooperation affects child's cooperation, and whether that differs between children with/without autism spectrum disorder (ASD). The experiment involved a cooperative key-pressing task completed first by parent-parent dyads and then by parent-child dyads, meanwhile brain activity in the right frontal-parietal cortex of dyad partners was measured synchronously. The results showed the following: ASD children exhibited performance comparable to those of their peers, as was the level of brain synchronization with their parents, which was mainly due to parents with ASD children tending to adjust their own response patterns to match those of their children. These findings suggest that parents can somewhat actively mitigate the lower interpersonal synchronization ability of ASD children, in behavioral or/and neural level.

Sarsasapogenin, a principal active component absorbed into blood of total saponins of Anemarrhena, attenuates proliferation and invasion in rheumatoid arthritis fibroblast-like synoviocytes through downregulating PKM2 inhibited pathological glycolysis.

Increased glycolytic in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) not only contributes to early-stage disease pathogenesis but leads to sustained proliferation of FLS. Given the importance of PKM2 in glycolysis and apoptosis, PKM2 is considered a potential therapeutic and drug discovery target in RA. Total saponins of anemarrhena (TSA), a class of steroid saponins, originated from Anemarrhena asphodeloides Bge. In this study, we verified that 200 mg/kg TSA could significantly alleviate inflammation and the pathological characteristics of RA and inhibit synovial hyperplasia in AA rats. We confirmed that sarsasapogenin (SA) was the principal active ingredient absorbed into the blood of TSA by the UPLC/Q Exactive MS test. Then we used TNF-α-induced MH7A to get the conclusion that 20 µM SA could effectively inhibit the glycolysis by inhibiting the activity of PKM2 tetramer and glucose uptake. Moreover, 20 µM SA could suppress proliferation, migration, invasion, and cytokine release of FLS, interfere with the growth cycle of FLS, and induce FLS apoptosis by depressing the phosphorylation of PKM2. At last, In-1, a potent inhibitor of the PKM2 was used to reverse verify the above results. Taken together, the key mechanisms of SA on RA treatment through downregulating the activity of PKM2 tetramer and phosphorylation of PKM2 inhibited pathological glycolysis and induced apoptosis to exert inhibition on the proliferation and invasion of RA FLS.

GL-YOLO-Lite: A Novel Lightweight Fallen Person Detection Model.

The detection of a fallen person (FPD) is a crucial task in guaranteeing individual safety. Although deep-learning models have shown potential in addressing this challenge, they face several obstacles, such as the inadequate utilization of global contextual information, poor feature extraction, and substantial computational requirements. These limitations have led to low detection accuracy, poor generalization, and slow inference speeds. To overcome these challenges, the present study proposed a new lightweight detection model named Global and Local You-Only-Look-Once Lite (GL-YOLO-Lite), which integrates both global and local contextual information by incorporating transformer and attention modules into the popular object-detection framework YOLOv5. Specifically, a stem module replaced the original inefficient focus module, and rep modules with re-parameterization technology were introduced. Furthermore, a lightweight detection head was developed to reduce the number of redundant channels in the model. Finally, we constructed a large-scale, well-formatted FPD dataset (FPDD). The proposed model employed a binary cross-entropy (BCE) function to calculate the classification and confidence losses. An experimental evaluation of the FPDD and Pascal VOC dataset demonstrated that GL-YOLO-Lite outperformed other state-of-the-art models with significant margins, achieving 2.4-18.9 mean average precision (mAP) on FPDD and 1.8-23.3 on the Pascal VOC dataset. Moreover, GL-YOLO-Lite maintained a real-time processing speed of 56.82 frames per second (FPS) on a Titan Xp and 16.45 FPS on a HiSilicon Kirin 980, demonstrating its effectiveness in real-world scenarios.

Nickel-Catalyzed Asymmetric Synthesis of P-Stereogenic Phosphanyl Hydrazine Building Blocks.

Catalytic asymmetric methods for the synthesis of synthetically versatile P-stereogenic building blocks offer an efficient and practical approach for the diversity-oriented preparation of P-chiral phosphorus compounds. Herein, we report the first nickel-catalyzed synthesis of P-stereogenic secondary aminophosphine-boranes by the asymmetric addition of primary phosphines to azo compounds. We further demonstrate that the P-H and P-N bonds on these phosphanyl hydrazine building blocks can be reacted sequentially and stereospecifically to access various P-stereogenic compounds with structural diversity.

A Chiral Emissive Conjugated Corral for High-Affinity and Highly Enantioselective Recognition in Water.

Accurately distinguishing between enantiomeric molecules is a fundamental challenge in the field of chemistry. However, there is still significant room for improvement in both the enantiomeric selectivity (KR(S) /KS(R) ) and binding strength of most reported macrocyclic chiral receptors to meet the demands of practical application scenarios. Herein, we synthesized a water-soluble conjugated tubular host-namely, corral[4]BINOL-using a chiral 1,1'-bi-2-naphthol (BINOL) derivative as the repeating unit. The conjugated chiral backbone endows corral[4]BINOL with good fluorescent emission (QY=34 % ) and circularly polarized luminescence (|glum | up to 1.4×10-3 ) in water. Notably, corral[4]BINOL exhibits high recognition affinity up to 8.6×1010  M-1 towards achiral guests in water, and manifested excellent enantioselectivity up to 18.7 towards chiral substrates, both of which represent the highest values observed among chiral macrocycles in aqueous solution. The ultrastrong binding strength, outstanding enantioselectivity, and facile accessibility, together with the superior fluorescent and chiroptical properties, endow corral[4]BINOL with great potential for a wide range of applications.

Linolenic Acid-Metronidazole: a Compound Relieving Drug Resistance and Inhibiting Helicobacter pylori.

Metronidazole (Met) is the first choice for treating Helicobacter pylori (Hp). However, Hp is easy to resistant, making Met unable to be widely used. How to overcome Hp's Met resistance is still an issue. In this study, Met was used as the primary raw material with linolenic acid to prepare a novel compound-linolenic acid-metronidazole (Lla-Met). The MIC, minimum bactericidal concentration (MBC), colonization amount of Hp in gastric mucosa, etc., were evaluated, respectively. Lla-Met was successfully prepared by the detection of nuclear magnetic resonance, etc., and its MIC and MBC to Hp were 2~4 µg/mL, 8~16 µg/mL. Moreover, in vivo experiments, Lla-Met significantly reduced the colonization of drug-resistant Hp in gastric mucosa. In the toxicity test, Lla-Met inhibited rate to GES-1 and BGC823 cells were 15% at 128 µg/mL; the mice were administered 10 times treatment Lla-Met treatment (240 mg/kg), have no difference significant injuries were found in their stomach, liver, spleen, kidney, and weight. In addition, Hp G27 continued for 18 days in vitro with sub-Lla-Met concentration, G27 did not show drug resistance to Lla-Met; Lla-Met did not exert an effect on non-Hp species with 128 µg/mL; Compared with a neutral environment, when the acid concentration is 3.0, Lla-Met is not decomposed and has better stability. Conclusion: Lla-Met, a newly prepared compound, has relatively well antibacterial of Met-resistant and sensitive Hp, with a capability of overcoming the metronidazole resistance of Hp.

Distribution, phenotype, functional and clinical relevance of CD8+CD103+ tissue-resident memory T cells in human gastric cancer.

CD8+CD103+ tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8+CD103+ TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8+CD103+ TRMs are CD45RA-CCR7- effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8+CD103+ TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8+CD103+ TRMs, and such anti-PD-1-mediated reinvigoration of CD8+CD103+ TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8+CD103+ TRMs are positively correlated with GC progression and poor patients' survival. Our data suggest that restoring CD8+CD103+ TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC.

Downregulation of HSPA12A underlies myotoxicity of local anesthetic agent bupivacaine through inhibiting PGC1α-mediated mitochondrial integrity.

Local anesthetics (LAs) are widely used for intraoperative anesthesia and postoperative analgesia. However, LAs (e.g. Bupivacaine) can evoke myotoxicity that closely associated to mitochondrial damage. PGC1a is a mast co-factor for mitochondrial quality control. We have recently demonstrated that PGC1a can be activated by HSPA12A in hepatocytes, suggesting a possibility that HSPA12A protects from LAs myotoxicity through activating PGC1α-mediated mitochondrial integrity. Here, we reported that HSPA12A was downregulated during Bupivacaine-induced myotoxicity in skeletal muscles of mice in vivo and C2c12 myoblast cultures in vitro. Intriguingly, overexpression of HSPA12A attenuated the Bupivacaine-induced C2c12 cell death. We also noticed that the Bupivacaine-induced decrease of glucose consumption and ATP production was improved by HSPA12A overexpression. Moreover, overexpression of HSPA12A in C2c12 cells attenuated the Bupivacaine-induced decrease of mitochondrial contents and increase of mitochondrial fragmentation. The Bupivacaine-induced reduction of PGC1α expression and nuclear localization was markedly attenuated by HSPA12A overexpression. Importantly, pretreatment with a selective PGC1α inhibitor (SR-18292) abolished the protection of HSPA12A from Bupivacaine-induced death and mitochondrial loss in C2c12 cells. Altogether, the findings indicate that downregulation of HSPA12A underlies myotoxicity of Local anesthetic agent Bupivacaine through inhibiting PGC1α-mediated Mitochondrial Integrity. Thus, HSPA12A might represent a viable strategy for preventing myotoxicity of LAs.

Eco-friendly management of postharvest fungal decays in kiwifruit.

Kiwifruit is purchased by consumers worldwide and is increasing in demand. Unfortunately, kiwifruit is susceptible to postharvest decay caused by a variety of fungal pathogens, including Botrytis cinerea, Penicillium expansum, Alternaria alternata, Botryosphaeria dothidea, and Diaporthe spp. Among these pathogens, B. cinerea is the most prevalent and devastating. Infections by these fungal pathogens result in a deterioration in fruit quality and a reduction in marketable yield. Eco-friendly methods to control kiwifruit postharvest decay have been explored as alternatives to the use of synthetic fungicides. In this review, we provide an overview and discuss the virulence and pathogenesis of fungi that are causal agents of kiwifruit decay, especially B. cinerea, including recent molecular and genomic studies. Advances in pre- and postharvest measures for postharvest decay management, including biological control, physical applications, the use of natural compounds and plant hormones, and the use of combined methods, are also reviewed. Eco-friendly control measures are a critical component of an integrated management approach for sustainable production of kiwifruit. The need for further research on the use of microbial consortia for the management of postharvest diseases of kiwifruit is also discussed.

Stanniocalcin1 knockdown induces ferroptosis and suppresses glycolysis in prostate cancer via the Nrf2 pathway.

Stanniocalcin1 (STC1) is a secreted glycoprotein, which is highly expressed in prostate cancer cells. However, the biological functions of STC1 in modulating ferroptosis and glycolysis in prostate cancer are still not clear. The viability of PC-3 and DU145 cells was detected by CCK-8 assay. The relative Fe2+ level was detected by an Iron Assay Kit. MDA level was detected by Lipid Peroxidation MDA Assay Kit. Glucose uptake and lactate product were measured by Glycolysis Assay Kit and Lactate Assay Kit. In this study, STC1 was highly expressed in prostate cancer tissue specimens and cells. STC1 knockdown suppressed prostate cancer cell proliferation, and upregulated Fe2+ level, reduced glutathione (GSH) level, downregulated GPX4 and SLC7A11 protein expressions in PC-3 cells and DU145 cells. Besides, STC1 knockdown decreased glucose uptake, lactate product, and ATP level, as well as downregulated glycolysis-related protein HK2 and LDHA protein expressions. In addition, STC1 knockdown repressed the Nrf2/HO-1/NQO1 pathway. Nrf2 pathway activator, Oltipraz, upregulated Nrf2, total NQO1, and HO-1 expressions in PC-3 cells and DU145 cells. Moreover, Nrf2 pathway activator Oltipraz reversed the effect of STC1 knockdown on Fe2+ level and GPX4, SLC7A11, HK2, LDHA protein expressions in PC-3 cells and DU145 cells. Finally, STC1 knockdown restrained the tumor volume, tumor weight, and glycolysis in prostate cancer in vivo. Thus, STC1/Nrf2 pathway is a vital pathway to induce ferroptosis and suppress glycolysis in prostate cancer.

Long-term consumption of alcohol exacerbates neural lesions by destroying the functional integrity of the blood-brain barrier.

Recently, increasing numbers of studies have shown that the consumption of large amounts of alcohol is a major risk factor for dementias, which has led to widespread concern about the harmful effects of alcohol consumption on health. However, the pathological changes in the brain caused by this habit are not clear. This study aimed to investigate the possible causes by determining the permeability of the blood-brain barrier (BBB), pathomorphological changes, the mRNA, and protein expressions of adhesion proteins and the concentrations of ß-amyloid (Aß) and some related functional proteins in the brains of C57BL/6 and APPswe/PS1dE9 mice before and after intragastric administration of alcohol for 2 months. The results showed that long-term consumption of alcohol aggravated cognitive decline, increased the permeability of the BBB, led to pathomorphological changes and downregulated some related structural proteins (zonula occludens-1, VE-cadherin, and occludin) and functional proteins (major facilitator superfamily domain-containing protein-2a (Mfsd2a), low-density lipoprotein receptor-related protein-1 (LRP1), receptor for advanced glycation end products (RAGE), and aquaporin-4 (AQP4)) in the BBB but did not increase the concentration of Aß1-42. These novel findings suggested that long-term consumption of alcohol induces neural lesions, which is related to the destruction of the integrity of the BBB.

Drinking water temperature affects cognitive function and progression of Alzheimer's disease in a mouse model.

Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer's disease (AD). However, whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied. In this study, we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms. Cognitive function of mice was assessed using passive avoidance test, open field test, and Morris water maze. Wild-type Kunming mice receiving intragastric water (IW, 10 mL/kg, 2 times/day) at 0 °C for consecutive 15 days displayed significant cognitive defects accompanied by significant decrease in gain of body weight, gastric emptying rate, pepsin activity, and an increase in the energy charge in the cortex when compared with mice receiving the same amount of IW at 25 °C (a temperature mimicking most common drinking habits in human), suggesting the altered neuroenergetics may cause cognitive decline. Similarly, in the transgenic APPwse/PS1De9 familial AD mice and their age- and gender-matched wild-type C57BL/6 mice, receiving IW at 0 °C, but not at 25 °C, for 35 days caused a significant time-dependent decrease in body weight and cognitive function, accompanied by a decreased expression of PI3K, Akt, the glutamate/GABA ratio, as well as neuropathy with significant amyloid lesion in the cortex and hippocampus. All of these changes were significantly aggravated in the APPwse/PS1De9 mice than in the control C57BL/6 mice. These data demonstrate that daily beverage at 0 °C may alter brain insulin-mediated neuroenergetics, glutamate/GABA ratio, cause cognitive decline and neuropathy, and promote AD progression.