A longitudinal study of the brain structure network changes in HIV patients with ANI: combined VBM with SCN.

Background: Despite the widespread adoption of combination antiretroviral therapy (cART) in managing HIV, the virus's impact on the brain structure of patients remains significant. This study aims to longitudinally explore the persistent effects of HIV on brain structure, focusing on changes in gray matter volume (GMV) and structural covariance network (SCN) among patients at the Asymptomatic Neurocognitive Impairment (ANI) stage. Methods: This research involved 45 HIV patients diagnosed with ANI and 45 demographically matched healthy controls (HCs). The participants were observed over a 1.5-year period. Differences in GMV between groups were analyzed using voxel-based morphometry (VBM), while the graph theory model facilitated the establishment of topological metrics for assessing network indices. These differences were evaluated using two-sample t-tests and paired-sample t-tests, applying the network-based statistics method. Additionally, the study examined correlations between GMV and cognitive performance, as well as clinical variables. Results: Compared with HCs, HIV patients demonstrated reduced GMV in the right middle temporal gyrus and left middle frontal gyrus (FWE, p < 0.05), along with decreased betweenness centrality (BC) in the left anterior cingulate and paracingulate cortex. Conversely, an increase in the clustering coefficient (Cp) was observed (FDR, p < 0.05). During the follow-up period, a decline in GMV in the right fusiform gyrus (FWE, p < 0.05) and a reduction in node efficiency (Ne) in the triangular part of the inferior frontal gyrus were noted compared with baseline measurements (FDR, p < 0.05). The SCN of HIV patients exhibited small-world properties across most sparsity levels (Sigma >1), and area under the curve (AUC) analysis revealed no significant statistical differences between groups. Conclusion: The findings suggest that despite the administration of combination antiretroviral therapy (cART), HIV continues to exert slow and sustained damage on brain structures. However, when compared to HCs, the small-world properties of the patients' SCNs did not significantly differ, and the clustering coefficient, indicative of the overall information-processing capacity of the brain network, was slightly elevated in HIV patients. This elevation may relate to compensatory effects of brain area functions, the impact of cART, functional reorganization, or inflammatory responses.

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.

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.

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.

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.

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.

The Characterization of the Key Aroma Compounds in Non-Smoked Bacon by Instrumental and Sensory Methods.

The aroma profiles in non-smoked bacon were investigated via GC-O-MS, GC × GC-TOFMS, and GC-IMS. GC-O-MS is advantageous for detecting aldehydes. GC × GC-TOFMS is more sensitive to hydrocarbons and alcohols, while GC-IMS detects a balanced range of categories. Only 9 of the 239 detected volatiles were identifiable by all three methods. Therefore, the combination of all three methods proved to be the most effective way to comprehensively analyze the aroma profiles of bacon. Recombination and omission tests were performed using aroma compounds with a flavor dilution (FD) factor greater than 27; five volatiles were identified as key aroma compounds in non-smoked bacon, including hexanal, (E,E)-2,4-decadienal, 1-octen-3-ol, dihydro-5-pentyl-2(3H)-furanone, and 3-methyl-butanoic acid. Among these, hexanal and 1-octen-3-ol exhibited relatively high FD factors and odor activity values (OAVs), so they were confirmed as the primary contributors. Meanwhile, seven volatiles contributed to the unique aroma of non-smoked bacon in different regions. The difference in the aroma of bacon in different regions is mainly due to the content of various volatiles rather than the type. A comprehensive analysis of the aroma in non-smoked bacon can reveal theoretical information for improving the process and quality control of the product.

Effect of cellulase on dough structure and quality characteristics of tough biscuits enriched with potato whole flour.

Potato whole flour is a promising way to improve the nutrition of tough biscuits, while its gluten-free characteristic was difficult to form acceptable texture properties. In this study, cellulase was used to degrade the cellulose in dough enriched with potato whole flour, so as to mitigate the interference of cellulose with the gluten network, resulting in forming the potato whole flour biscuit with great characteristics. Results indicated that cellulase within 0.2% led to the gradually reduced G' and G'' values of dough from 5.50×104 to 4.00×104 and 2.66×104 to 1.35×104, respectively. Cellulase at 0.2% resulted in the significantly increased tensile properties of the dough compared to the control. The incorporation of cellulase within 0.2% also led to the tightly ordered and intact network structure base on the results of SEM, disulfide bonds determination and FTIR. Those results indicated that cellulase was beneficial to improve the baking quality of dough, which was conductive to form tough biscuit with great characteristics. The hardness, crunchiness, crispness and specific volume analysis results confirmed that 0.2% cellulase resulted in the significantly decreased hardness by 45.25% and the significantly increased specific volume, crunchiness and crispness by 24.74%, 121.20% and 156.47%, respectively. Overall, cellulase ultimately improved the quality of the biscuits by improving the properties and structure of the dough. It was of great significance for the utilization of potato whole flour resources and the industrial production of its tough biscuits. PRACTICAL APPLICATION: The results showed that inclusion of cellulase led to the reduced hardness and increased crunchiness, crispness, and specific volume of potato whole flour tough biscuits. Cellulase could be used as a potential improver of tough biscuits. This study will provide guidance for practical uses of cellulase in improving potato whole flour dough and tough biscuit quality.

ML241 Antagonizes ERK 1/2 Activation and Inhibits Rotavirus Proliferation.

Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs.

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.

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.

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.

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.

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.

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.

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.

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.

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.