Masting promotes transformation from predation to mutualism in an oak-weevil-rodent system.

The significance of ecological non-monotonicity (a function whose first derivative changes signs) in shaping the structure and functions of the ecosystem has recently been recognized, but such studies involving high-order interactions are rare. Here, we have proposed a three-trophic conceptual diagram on interactions among trees, rodents, and insects in mast and non-mast years and tested the hypothesis that oak (Quercus wutaishanica) masting could result in increased mutualism and less predation in an oak-weevil-rodent system in a warm temperate forest of China. Our 14-year dataset revealed that mast years coincided with a relatively low rodent abundance but a high weevil abundance. Masting not only benefited seedling recruitment of oaks through increased dispersal by rodents but also a decrease in predation by rodents and weevils, as well as an increase in the overwintering survival of rodents. Masting appeared to have increased weevil survival by reducing predation of infested acorns by rodents. These results suggest that masting benefits all participants in the plant-insect-rodent system by increasing mutualism and reducing predation behavior (i.e., a non-monotonic function). Our study highlights the significance of masting in maintaining the diversity and function of the forest ecosystem by facilitating the transformation from predation to mutualism among trophic species.

Quantitative proteomic analysis to identify potential biomarkers linked to quality traits of beef tripe from different sources.

In this work, the 4D data-independent acquisition (DIA) quantitative strategy was used for differential proteomic analysis of four beef tripe samples from different sources to explore the associations between differentially expressed proteins (DEPs) and meat quality traits. A total of 68 shared DEPs were identified in all comparison groups, which were mainly involved in phosphorylation signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and glucuronic acid pathway. In the correlation analysis between DEPs and quality traits of beef tripe, it was found that 21 proteins were significantly associated with the quality traits in beef tripe, which could be considered as the potential biomarkers of beef tripe quality. This study has successfully uncovered the protein composition of beef tripe for the very first time, which helps to understand the key proteins and biological processes associated with the quality traits of beef tripe from different sources and improve the quality control of beef tripe.

Potato miR394 targets StA/N-INVE and StLCR to negatively regulate late blight resistance.

MicroRNAs (miRNAs) are small noncoding RNAs in eukaryotes. Plant endogenous miRNAs play pivotal roles in regulating plant development and defense responses. MicroRNA394 (miR394) has been reported to regulate plant development, abiotic stresses and defense responses. Previous reports showed that miR394 responded to P. infestans inoculation in potato, indicating that miR394 may be involved in defense responses. In this study, we further investigated its role in potato defense against P. infestans. Stable expression of miR394 in tobacco and potato enhances the susceptibility to P. infestans, which is accompanied with the reduced accumulation of ROS and down-regulation of the PTI (pattern-triggered immunity) marker genes. Besides well-known target StLCR, miR394 also targets StA/N-INVE, which encodes a chloroplast Alkaline/Neutral Invertases (A/N-INVE). Both StLCR and StA/N-INVE positively regulate late blight resistance, while miR394 degrades them. Interestingly, StA/N-INVE is located in the chloroplast, indicating that miR394 may manipulate chloroplast immunity. Degradation of StA/N-INVE may affect the chloroplast function and hence lead to the compromised ROS (reactive oxygen species) burst and reduced retrograde signaling from the chloroplast to the nucleus and cytoplasm. In summary, this study provides new information that miR394 targets and degrades StA/N-INVE and StLCR, which are positive regulators, to enhance potato susceptibility to P. infestans.

Contrasting benthic bacterial and fungal communities in two temperate coastal areas affected by different levels of anthropogenic pressure.

Benthic microbial communities play a crucial role in maintaining the stability and function of estuarine ecosystems. However, their organization and response to multiple stresses in severely disturbed coastal areas remains to be elucidated. In this study, we revealed the presence of contrasting benthic bacterial and fungal communities in the Liaohe (LH) and Yalujiang (YLJ) estuaries, which are located at similar latitudes and are characterized by similar climates but are subjected to different levels of anthropogenic pressure. The results showed that Firmicutes and Chloroflexi were more abundant in LH, which reflected the influence of anthropogenic pressure in this area. Functional analyses indicated that the functional genes involved in the generation of precursor metabolites and energy pathways were more enriched in the LH community, while genes regulating degradation/utilization/assimilation processes were more enriched in the YLJ community. Distance-dependent similarity analysis showed that the bacterial community in LH was more affected by environmental changes, while that in YLJ was more influenced by geographic dispersion. In contrast, no significant distance-dependent similarity was found for the fungal communities in the two areas. In addition, the network analysis showed that the bacterial-fungal network in YLJ was more complex and stable than that in the LH. Our results highlight the important roles of environmental heterogeneity in controlling microbial community composition, biogeographic patterns, and co-occurrence networks. These findings fill knowledge gaps in the understanding of the different response patterns of benthic communities under varying anthropogenic pressures.

The relationship between cardiac oxidative stress, inflammatory cytokine response, cardiac pump function, and prognosis post-myocardial infarction.

This study delves into the potential connections between cardiac oxidative stress, inflammatory cytokine response, cardiac pump function, and prognosis in individuals following myocardial infarction. A total of 276 patients were categorized into two groups: the control group (n = 130) and the observation group (n = 146), based on the drug intervention strategies. The control group received standard drug treatment, while the observation group received early drug intervention targeting antioxidant and anti-inflammatory treatment in addition to standard treatment. Serum levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-9 (IL-6), were assessed using enzyme-linked immuno sorbent assay (ELISA) kits. The Forkhead Box Protein A2 (FOX2) reagent was used to determine the overall oxidation level. Left Ventricular End-Diastolic Diameter (LVEDD), Left Ventricular Ejection Fraction (LVEF), and End-Systolic Diameter (ESD) were measured using Doppler ultrasound. The observation group exhibited significantly reduced serum levels of TNF-α, IL-1ß, and IL-6 compared to the control group (P < 0.05). Moreover, the observation group exerted lower total oxidation levels, OSI, EDD, and ESD compared to the control group (P < 0.05), while the LVEF and TAS levels in the observation group were higher than those in the control group (P < 0.05). Remarkably, the observation group experienced a significant reduction in the incidences of reinfarction, heart failure, arrhythmia, and abnormal valve function compared to the control group (P < 0.05). Decreased cardiac pump function and a more unfavorable prognosis were associated with elevated levels of cardiac oxidative stress and inflammatory factors (P < 0.05). Timely intervention with appropriate medications have a crucial effect in decreasing inflammatory marker levels, mitigating oxidative pressure, and enhancing cardiac pumping capacity and overall prognosis.

Fluorinated Lipid Nanoparticles for Enhancing mRNA Delivery Efficiency.

Lipid nanoparticles (LNPs), a nonviral nucleic acid delivery system, have shown vast potential for vaccine development and disease treatment. LNPs assist mRNA to cross physiological barriers such as cell membranes and endosomes/lysosomes, promoting the intracellular presentation of mRNA. However, the endosome escape efficiency and biosafety of currently commercialized LNPs are still unsatisfactory, resulting in underutilization of mRNA. Herein, we report that fluorinated modification of the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-2000 (PEG-DSPE), termed as FPD, in the LNPs can improve the delivery efficiency of mRNA. FPD accounts for only 1.5% of lipids in LNPs but could mediate a 5-fold and nearly 2-fold enhancement of mRNA expression efficiency in B16F10 tumor cells and primary dendritic cells, respectively. Mechanism studies reveal that FPD promotes the cellular internalization of LNPs as well as endosome escape. In vivo studies substantiate that FPD can augment overall mRNA expression at least 3-fold, either by intravenous or intraperitoneal injection, compared to LNPs prepared with nonfluorinated PEG-lipids at a relatively low mRNA dose. Besides, with the introduction of FPD, mRNA expression in the spleen augmented compared to that of the DMG-PEG commercial formulations. Benefiting from a prudent dosage of fluorine, the fluorinated LNPs display favorable biosafety profiles at cellular and zoological levels.

Cryo-shocked tumor cells deliver CRISPR-Cas9 for lung cancer regression by synthetic lethality.

Although CRISPR-mediated genome editing holds promise for cancer therapy, inadequate tumor targeting and potential off-target side effects hamper its outcomes. In this study, we present a strategy using cryo-shocked lung tumor cells as a CRISPR-Cas9 delivery system for cyclin-dependent kinase 4 (CDK4) gene editing, which initiates synthetic lethal in KRAS-mutant non-small cell lung cancer (NSCLC). By rapidly liquid nitrogen shocking, we effectively eliminate the pathogenicity of tumor cells while preserving their structure and surface receptor activity. This delivery system enables the loaded CRISPR-Cas9 to efficiently target to lung through the capture in pulmonary capillaries and interactions with endothelial cells. In a NSCLC-bearing mouse model, the drug accumulation is increased nearly fourfold in lung, and intratumoral CDK4 expression is substantially down-regulated compared to CRISPR-Cas9 lipofectamine nanoparticles administration. Furthermore, CRISPR-Cas9 editing-mediated CDK4 ablation triggers synthetic lethal in KRAS-mutant NSCLC and prolongs the survival of mice.

Functionalized chitosan hydrogel promotes osseointegration at the interface of3D printed titanium alloy scaffolds.

Autogenous bone transplantation is a prevalent clinical method for addressing bone defects. However, the limited availability of donor bone and the morbidity associated with bone harvesting have propelled the search for suitable bone substitutes. Bio-inspired scaffolds, particularly those fabricated using electron beam melting (EBM) deposition technology, have emerged as a significant advancement in this field. These 3D-printed titanium alloy scaffolds are celebrated for their outstanding biocompatibility and favorable elastic modulus. Thermosensitive chitosan hydrogel, which transitions from liquid to solid at body temperature, serves as a popular carrier in bone tissue engineering. Icariin (ICA), known for its efficacy in promoting osteoblast differentiation from bone marrow mesenchymal stem cells (BMSCs), plays a crucial role in this context. We developed a system combining a 3D-printed titanium alloy with a thermosensitive chitosan hydrogel, capable of local bone regeneration and integration through ICA delivery. Our in vitro findings reveal that this system can gradually release ICA, demonstrating excellent biocompatibility while fostering BMSC proliferation and osteogenic differentiation. Immunohistochemistry and Micro-CT analyses further confirm the effectiveness of the system in accelerating in vivo bone regeneration and enhancing osseointegration. This composite system lays a significant theoretical foundation for advancing local bone regeneration and integration.

Spatiotemporal dynamics of bacterioplankton communities in the estuaries of two differently contaminated coastal areas: Composition, driving factors and ecological process.

Seasonal variations of environmental parameters usually lead to considerable changes in microbial communities. Nevertheless, the specific response patterns of these communities in coastal areas subjected to different levels of contamination remain unclear. Our results revealed notable fluctuations in the bacterioplankton community both seasonally and spatially, with seasonal variations being particularly significant. The diversity and composition of bacterioplankton communities in the estuaries varied significantly across seasons and between seas. Some bacterial phyla that were highly abundant in the dry season (e.g., Patescibacteria and Epsilonbacteraeota) were almost absent in the wet season. Furthermore, the network analysis revealed that the bacterioplankton networks were more complex during the wet season than in the dry season. In the wet season, the estuarine bacterioplankton network in the Yellow Sea region was more complex and stable, while the opposite was true in the dry season. According to the neutral community model, stochastic processes played a more significant role in the formation of bacterioplankton communities during the wet season than during the dry season. Estuarine bacterioplankton communities in the Yellow Sea region were more affected by stochastic processes compared to those in the Bohai Sea. In summary, in the estuaries of two differently contaminated coastal areas, the seasonal increase in nutrient levels enhanced the deterministic processes and network complexity of the bacterioplankton communities.

Exploring potential lipid precursors for aroma formation in non-smoked bacon during hot air drying via untargeted lipidomics and oxidation model.

The effect of drying on the lipid profiles of the lean (LN) and fat (FT) portions of non-smoked bacon was investigated based on a lipidomic approach. The study identified 989 lipids belonging to 26 subclasses in bacon, with triglyceride and phosphatidylethanolamine being the most abundant. Triglycerides, phosphatidylcholines, and phosphatidylethanolamines were significantly decreased, whereas diglycerides, free fatty acids, and lysophospholipids were increased after drying. TG (16:1/18:1/18:2) and TG (16:0/18:1/18:1) were the primary lipids responsible for the binding of volatiles. Based on VIP > 1 and P < 0.05, 355 and 444 differential lipids were observed in the FT and LN portions, respectively. In total, 26 lipids were screened as key precursors for the production of key aroma compounds of bacon in the FT portion, while 127 were screened in the LN portion. PE (18:0/18:2) is believed to be the primary lipid molecule precursors responsible for the development of aroma in both lean and fat portions. This research has enhanced the comprehension of the generation of key aroma compounds derived from lipid oxidation.

Effect of heme proteins on the lipid molecule profile and aroma formation during hot air drying of non-smoked bacon.

Heme proteins and their derivatives play important roles in inducing lipid oxidation to produce volatile compounds during bacon drying. This study investigated the effects of heme proteins and their derivatives (hemoglobin, myoglobin, nitrosylmyoglobin, hemin, Fe2+, and Fe3+) on lipid and volatiles profiles in the washed pig muscle (WPM) model. The results of the study indicated that the inducers primarily caused the oxidation of glycerophospholipids. Furthermore, hemoglobin and myoglobin had the most significant impact, and their potential substrates may include PE (O-18:2/20:4), PE (O-18:1/20:4), PC (16:0/18:1), and PE (O-18:2/18:2). Nitrosomyoglobin has limited ability to promote lipid oxidation and may protect ether phospholipids from oxidation. The analysis of the volatiles in the model revealed that heme proteins and their derivatives have the ability to induce the production of key aroma compounds. The descending order of effectiveness in inducing the production of aroma compounds is as follows: hemoglobin, myoglobin, hemin, and nitrosylmyoglobin. The effectiveness of Fe2+ and Fe3+ is similar to that of nitrosylmyoglobin.

Lyophilized lymph nodes for improved delivery of chimeric antigen receptor T cells.

Lymph nodes are crucial organs of the adaptive immune system, orchestrating T cell priming, activation and tolerance. T cell activity and function are highly regulated by lymph nodes, which have a unique structure harbouring distinct cells that work together to detect and respond to pathogen-derived antigens. Here we show that implanted patient-derived freeze-dried lymph nodes loaded with chimeric antigen receptor T cells improve delivery to solid tumours and inhibit tumour recurrence after surgery. Chimeric antigen receptor T cells can be effectively loaded into lyophilized lymph nodes, whose unaltered meshwork and cytokine and chemokine contents promote chimeric antigen receptor T cell viability and activation. In mouse models of cell-line-derived human cervical cancer and patient-derived pancreatic cancer, delivery of chimeric antigen receptor T cells targeting mesothelin via the freeze-dried lymph nodes is more effective in preventing tumour recurrence when compared to hydrogels containing T-cell-supporting cytokines. This tissue-mediated cell delivery strategy holds promise for controlled release of various cells and therapeutics with long-term activity and augmented function.

Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor.

The limited infiltration and persistence of chimeric antigen receptor (CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading, delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

The Effect of Enzymatic Hydrolysis and Maillard Reaction on the Flavor of Chicken Osteopontin.

To reveal the changes in the flavor quality of chicken osteopontin (CO) before and after enzymatic hydrolysis and a thermal reaction, the present study was carried out to evaluate the volatile compounds and non-volatile compounds in CO. The results show that the chicken boneset enzymatic solution (CBES) presented a notably richer aroma after the enzymatic hydrolysis treatment. At the same time, the concentrations of the total free amino acids (FAAs) and 5'-nucleotides in the CBES increased dramatically. The ERP (enzymatic reaction paste) scores and the ORC (osteopontin reactive cream) scores were exceptionally high in terms of the umami and salty flavor profiles. As precursors, FAAs and 5'-nucleotides also boosted the Maillard reaction, leading to the generation of wide volatile compounds. Compared to CO, CBES, and ORC, the sensory evaluation showed that ERP scored the highest. In summary, the enzymatic hydrolysis treatment coupled with the Maillard reaction significantly enhanced the flavor profile of CO. These findings offer valuable insights into the high-value utilization of bone by-products, making a significant advancement in the field.

Extrusion modification of prolamins from distiller's grains to facilitate the construction of biopolymer films.

BACKGROUND: Distiller's grains (DGs), which are rich in natural ingredients such as prolamins, are often used as low-value feed or discarded directly, resulting in great environmental pollution and resource waste. Prolamins from DGs (PDGs) were found to be a potential material for the construction of biopolymer films due to their good film-forming properties. In this study, extrusion processing was conducted to modify the physicochemical and structural properties of PDGs to facilitate the construction of biopolymer films with superior characteristics. RESULTS: Results indicated that extrusion led to improved solubility (17.91% to 39.95%) and increased disulfide bonds (1.46 to 6.13 µmol g-1 ) in PDGs. The total and sulfur amino acid contents of extruded PDGs were increased by 13.26% and 38.83%, respectively. New aggregation patterns were formed after extrusion according to the results of scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction. Extrusion resulted in reduced surface hydrophobicity of PDGs (10 972 to 3632), sufficient evidence for which could be also found from structure analyses of PDGs. Finally, PDGs extruded at 110 °C were found to facilitate the forming of biopolymer films with superior mechanical properties, water resistance and thermal stability. CONCLUSIONS: Physicochemical and structural properties of PDGs were effectively modified by extrusion processing, and extrusion modification of PDGs could be a great way to facilitate the construction of biopolymer films with superior characteristics. It could provide more possibilities to extend the applications of DGs to alleviate the problems of environmental pollution and resource waste. © 2024 Society of Chemical Industry.

Leveraging Brain Modularity Prior for Interpretable Representation Learning of fMRI.

Resting-state functional magnetic resonance imaging (rs-fMRI) can reflect spontaneous neural activities in the brain and is widely used for brain disorder analysis. Previous studies focus on extracting fMRI representations using machine/deep learning methods, but these features typically lack biological interpretability. The human brain exhibits a remarkable modular structure in spontaneous brain functional networks, with each module comprised of functionally interconnected brain regions-of-interest (ROIs). However, existing learning-based methods cannot adequately utilize such brain modularity prior. In this paper, we propose a brain modularity-constrained dynamic representation learning framework for interpretable fMRI analysis, consisting of dynamic graph construction, dynamic graph learning via a novel modularity-constrained graph neural network (MGNN), and prediction and biomarker detection. The designed MGNN is constrained by three core neurocognitive modules (i.e., salience network, central executive network, and default mode network), encouraging ROIs within the same module to share similar representations. To further enhance discriminative ability of learned features, we encourage the MGNN to preserve network topology of input graphs via a graph topology reconstruction constraint. Experimental results on 534 subjects with rs-fMRI scans from two datasets validate the effectiveness of the proposed method. The identified discriminative brain ROIs and functional connectivities can be regarded as potential fMRI biomarkers to aid in clinical diagnosis.

A Systematic Review and Meta-Analysis of MRI Radiomics for Predicting Microvascular Invasion in Patients with Hepatocellular Carcinoma.

BACKGROUND: The prediction power of MRI radiomics for microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) remains uncertain. OBJECTIVE: To investigate the prediction performance of MRI radiomics for MVI in HCC. METHODS: Original studies focusing on preoperative prediction performance of MRI radiomics for MVI in HCC, were systematically searched from databases of PubMed, Embase, Web of Science and Cochrane Library. Radiomics quality score (RQS) and risk of bias of involved studies were evaluated. Meta-analysis was carried out to demonstrate the value of MRI radiomics for MVI prediction in HCC. Influencing factors of the prediction performance of MRI radiomics were identified by subgroup analyses. RESULTS: 13 studies classified as type 2a or above according to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis statement were eligible for this systematic review and meta-analysis. The studies achieved an average RQS of 14 (ranging from 11 to 17), accounting for 38.9% of the total points. MRI radiomics achieved a pooled sensitivity of 0.82 (95%CI: 0.78 - 0.86), specificity of 0.79 (95%CI: 0.76 - 0.83) and area under the summary receiver operator characteristic curve (AUC) of 0.88 (95%CI: 0.84 - 0.91) to predict MVI in HCC. Radiomics models combined with clinical features achieved superior performances compared to models without the combination (AUC: 0.90 vs 0.85, P < 0.05). CONCLUSION: MRI radiomics has the potential for preoperative prediction of MVI in HCC. Further studies with high methodological quality should be designed to improve the reliability and reproducibility of the radiomics models for clinical application. The systematic review and meta-analysis was registered prospectively in the International Prospective Register of Systematic Reviews (No. CRD42022333822).

Effect of staphylococci fermentation and their synergistic Lactobacillus on the physicochemical characteristics and nonvolatile metabolites of Chinese bacon.

The impacts of Staphylococcus cohnii, S. saprophyticus and their synergistic Lactobacillus plantarum on the quality and flavor of Chinese bacon were investigated by monitoring the physicochemical characteristics and characterizing metabolites with non-targeted metabolomics. Results showed that S. cohnii could increase the tenderness and decrease the oxidation of muscle, while S. saprophyticus stabilized the springiness and increased the proteolysis. The metabolites produced by the co-fermentation of S. cohnii and S. saprophyticus showed a higher hierarchy, then exhibited the highest hierarchy in synergy with L. plantarum. The promising flavor may be related to the arginine biosynthesis, nicotinic acid and nicotinamide metabolism, and pyrimidine metabolism pathways. Staphylococcus contributed to flavor by promoting the accumulation of di- and tripeptides and activating the amino acid metabolic pathway through arginine metabolism. These findings provide thoughts for understanding the fermentation mechanism of Staphylococcus and the targeted modulation of the flavor of Chinese bacon.

Distance-specific functional connectivity strength alterations in human immunodeficiency virus asymptomatic neurocognitive impairment patients: a cross-sectional study.

Background: Asymptomatic neurocognitive impairment (ANI) is the mildest form of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs), and functional connectivity strength (FCS) alternations have been observed in the ANI stage. However, it is not clear whether the FCS alterations are influenced by the anatomical distance. This study sought to investigate distance-specific FCS changes in HIV ANI patients. Methods: In total, 29 patients with HAND and 32 healthy controls (HCs) were enrolled in the study. Between-group differences were detected for short, middle and long range anatomical distance FCS. A correlation analysis was performed to examine the relationship between distance-specific FCS and immunological parameters and neuropsychological tests. A receiver operating characteristic (ROC) analysis was conducted to examine the discriminative performance for HIV ANI patients. Results: In comparison to the HCs, the HAND patients showed increased short-range FCS in the left inferior parietal lobule (IPL), middle-range FCS in the superior temporal gyrus (STG), long-range FCS in the left precuneus (PCC), and decreased FCS in the right postcentral gyrus (PCG) (cluster P<0.05, voxel significance P<0.001). Further, the long-range FCS in the right PCG was negatively correlated with the CD4/CD8 ratio (r=-0.479, 95% confidence interval (CI): -0.735 to -0.104, P=0.015), and the distance-specific FCS also showed good classification performance between the HAND patients and HCs. The left IPL, left STG, right PCG, and left PCC had areas under the curve (AUCs) of 0.875 [95% confidence interval (CI): 0.758-0.949, P<0.0001], 0.806 (95% CI: 0.677-0.900, P<0.0001), 0.855 (95% CI: 0.734-0.935, P<0.0001), and 0.852 (95% CI: 0.754-0.950, P<0.0001), respectively. There was no significant relationship between the distance-specific FCS and the neuropsychological tests. Conclusions: Distance-specific FCS could be used to examine subtle alternations in HIV-infected patients in the ANI stage and help to explain the possible neurophysiological mechanism of HAND.