Anti-fungal effects of lactic acid bacteria from pickles on the growth and sterigmatocystin production of Aspergillus versicolor.

Sterigmatocystin (STC) is an emerging mycotoxin that poses a significant threat to the food security of cereal crops. To mitigate STC contamination in maize, this study employed selected lactic acid bacteria as biocontrol agents against Aspergillus versicolor, evaluating their biocontrol potential and analyzing the underlying mechanisms. Lactiplantibacillus plantarum HJ10, isolated from pickle, exhibited substantial in vitro antifungal activity and passed safety assessments, including antibiotic resistance and hemolysis tests. In vivo experiments demonstrated that L. plantarum HJ10 significantly reduced the contents of A. versicolor and STC in maize (both >84 %). The impact of heat, enzymes, alkali, and other treatments on the antifungal activity of cell-free supernatant (CFS) was investigated. Integrated ultra-high-performance liquid chromatography (UPLC) and gas chromatography-mass spectrometry (GC-MS) analysis revealed that lactic acid, acetic acid, and formic acid are the key substances responsible for the in vitro antifungal activity of L. plantarum HJ10. These metabolites induced mold apoptosis by disrupting cell wall structure, increasing cell membrane fluidity, reducing enzyme activities, and disrupting energy metabolism. However, in vivo antagonism by L. plantarum HJ10 primarily occurs through organic acid production and competition for growth space and nutrients. This study highlights the potential of L. plantarum HJ10 in reducing A. versicolor and STC contamination in maize.

Enantioselective Construction of Quaternary Stereocenters via A Chiral Spiro Phosphoric Acid-Assisted Formal Gold Carbene gem-Dialkylation Reaction.

Enantioselective construction of all-carbon quaternary stereocenters has attracted much attention over the past few decades. A variety of catalytic asymmetric methods have been disclosed based on the use of presynthesized complex reagents that impart congested steric hindrance to the reaction center, which generally produce the chiral molecules through forming one C-C bond. The use of readily available reagents that could build two C-C bonds on the same carbonic center with the concomitant assembly of quaternary stereocenters remains challenging. Herein, we disclose a catalytic asymmetric alkyne multifunctionalization reaction using a gold complex and a chiral spiro phosphoric acid (SPA) for synergistic catalysis. In this method, the readily accessible internal alkynes served as the key gold carbene precursors, followed by carbene gem-dialkylation through Mannich-type addition of enolate species or stepwise formal cycloaddition with methylenimines that are derived from 1,3,5-triazinanes in the presence of SPA. The reaction provides practical access to poly-functionalized chiral linear and cyclic ketones that bear two adjacent quaternary stereocenters in generally good yields and excellent enantioselectivities, leading to an essential complement to the asymmetric construction of quaternary stereocenters using readily available materials with high bond formation efficiency.

Investigating the Pharmacological Mechanisms of Total Flavonoids from Eucommia ulmoides Oliver Leaves for Ischemic Stroke Protection.

The aim of this study was to explore how the total flavonoids from Eucommia ulmoides leaves (EULs) regulate ischemia-induced nerve damage, as well as the protective effects mediated by oxidative stress. The cell survival rate was significantly improved compared to the ischemic group (p < 0.05) after treatment with the total flavonoids of EULs. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) decreased, while catalase (CAT) and glutathione (GSH) increased, indicating that the total flavonoids of EULs can significantly alleviate neurological damage caused by ischemic stroke by inhibiting oxidative stress (p < 0.01). The mRNA expression level of VEGF increased (p < 0.01), which was consistent with the protein expression results. Meanwhile, the protein expression of ERK and CCND1 increased (p < 0.01), suggesting that the total flavonoids of EULs could protect PC12 cells from ischemic injury via VEGF-related pathways. MCAO rat models indicated that the total flavonoids of EULs could reduce brain ischemia-reperfusion injury. In conclusion, this study demonstrates the potential mechanisms of the total flavonoids of EULs in treating ischemic stroke and their potential therapeutic effects in reducing ischemic injury, which provides useful information for ischemic stroke drug discovery.

Effect of oleic acid-rich rapeseed oil on the physicochemical, rheological, and structural characteristics of wheat dough.

Some wheat-based foods require different doses of oil to moderate quality of dough during processing and the influence mechanisms remain unclear. Therefore, the effect of rapeseed oil addition on physicochemical characteristics and fine structure of dough and underlying mechanism were elucidated by rheometer, scanning microscope and molecular spectroscopic method. Results showed that compared with native dough (without exogenous rapeseed oil), the addition of rapeseed oil changed the fine structure, improved extensibility, but reduced viscoelasticity of the dough. Moreover, high addition especially 20 wt% oil (based on wheat flour) significantly changed gelatinization and retrogradation behaviors of the dough, whilst disrupted gluten network and increased random coil content (32.1%) of dough except that decreased its α-helix (21.2%), ß-sheet (23.1%), disulfide bond (7.9 µmol/g) compared with native dough which were 16.3%, 29.2%, 33.1%, 11.0 µmol/g, respectively. Results in the study could provide a certain understanding for application of vegetable oils in wheat-based products.

Cerebellar gray matter and white matter damage among older adults with prediabetes.

AIMS: To investigate alterations in cerebrum and cerebellum in prediabetes. Cerebellar injury in diabetes is traceable, but it has not been systematically studied, and whether cerebellar injury occurs and the degree of damage in prediabetes are not known. METHODS: The current study investigated cerebral and cerebellar gray matter volume, white matter volume, white matter microstructure and white matter hyperintensity on T1-weighted, T2-weighted fluid-attenuated inversion recovery and diffusion tensor imaging scans in 78 individuals with normal glucose metabolism, 92 with prediabetes, and 108 with type 2 diabetes. RESULTS: Participants with prediabetes showed significant gray matter and white matter atrophy, microstructural damage in the cerebellar and cerebral regions. Additionally, widespread structural alterations were observed in the diabetic stage. The function of the damaged brain area was further decoded in Neurosynth, and the damaged cerebellar area with prediabetic lesions was closely related to motor function, while the area affected by diabetes was related to complex cognitive function in addition to motor function. CONCLUSIONS: Cerebellar injury had already appeared in the prediabetic stage, and cerebellar injury was aggravated in the diabetic stage; therefore, the cerebellum is a key area that is damaged early in the development of diabetes.

Inhibitory effects of chlorophyll pigments on the bioaccessibility of ß-carotene: Influence of chlorophyll structure and oil matrix.

Chlorophylls and ß-carotene are fat-soluble phytochemicals in daily diets, while their bioaccessibility interaction remains unknown. Eight dietary chlorophylls and their derivatives (chlorophyll a, chlorophyll b, pheophytin a, pheophytin b, chlorophyllide a, chlorophyllide b, pheophorbide a, pheophorbide b) were combined with ß-carotene in six different oil matrices (corn oil, coconut oil, medium-chain triglycerides, peanut oil, olive oil and fish oil) and were subjected to in vitro digestion. Generally, chlorophylls significantly decreased ß-carotene bioaccessibility by competitive incorporation into micelles. Dephytylated chlorophylls had a greater inhibitory effect on the micellarization and bioaccessibility of ß-carotene compared to phytylated chlorophylls. In their co-digestion system, olive oil group exhibited the smallest particle size and biggest zeta potential in both digesta and micelles. For chlorophylls, the phytol group and their levels are key factors, which was also buttressed by the mice model where additional supplementation of pheophorbide a significantly hindered the accumulation of ß-carotene and retinoids compounds.

Determination of twelve neonicotinoid pesticides in chili using an improved QuEChERS method with UPLC-Q-TOF/MS.

In this study, a QuEChERS method based on citrate was developed and utilized for the analysis of twelve neonicotinoid pesticides in fresh red chilies, fresh green chilies, and dried chilies, coupled with ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS). In the sample preparation, acetonitrile containing 1% formic acid was used as the extraction solvent. Anhydrous sodium sulfate replaced the traditional anhydrous magnesium sulfate for water removal, effectively eliminating the issues of salt caking. Graphitized carbon black, octadecyl silica, and primary secondary amine were used as cleaning agents. The method showed good sensitivity, with the limits of quantification below 0.03 mg/kg for fresh chilies and below 0.15 mg/kg for dried chilies. Values of matrix effects ranged from -19.5% to 8.4%, and the recovery was 86.9% - 105.2%. The analytical method provided an effective tool for the high throughput detection of neonicotinoid pesticide residues in multiple chili matrices.

Isolation and evaluation of probiotics from traditional Chinese foods for aflatoxin B1 detoxification: Geotrichum candidum XG1 (yeast) and mechanistic insights.

Identifying aflatoxin-detoxifying probiotics remains a significant challenge in mitigating the risks associated with aflatoxin contamination in crops. Biological detoxification is a popular technique that reduces mycotoxin hazards and garners consumer acceptance. Through multiple rounds of screening and validation tests, Geotrichum candidum XG1 demonstrated the ability to degrade aflatoxin B1 (AFB1) by 99-100%, exceeding the capabilities of mere adsorption mechanisms. Notably, the degradation efficiency was demonstrably influenced by the presence of copper and iron ions in the liquid medium, suggesting a potential role for proteases in the degradation process. Subsequent validation experiments with red pepper revealed an 83% reduction in AFB1 levels following fermentation with G. candidum XG1. Furthermore, mass spectrometry analysis confirmed the disruption of the AFB1 furan ring structure, leading to a subsequent reduction in its toxicity. Collectively, these findings establish G. candidum XG1 as a promising candidate for effective aflatoxin degradation, with potential applications within the food industry.

Antifungal mechanisms of binary combinations of volatile organic compounds produced by lactic acid bacteria strains against Aspergillusflavus.

Aspergillus flavus（A. flavus）, a common humic fungus known for its ability to infect agricultural products, served as the subject of investigation in this study. The primary objective was to assess the antifungal efficacy and underlying mechanisms of binary combinations of five volatile organic compounds (VOCs) produced by lactic acid bacteria, specifically in their inhibition of A. flavus. This assessment was conducted through a comprehensive analysis, involving biochemical characterization and transcriptomic scrutiny. The results showed that VOCs induce notable morphological abnormalities in A. flavus conidia and hyphae. Furthermore, they disrupt the integrity of the fungal cell membrane and cell wall, resulting in the leakage of intracellular contents and an increase in extracellular electrical conductivity. In terms of cellular components, VOC exposure led to an elevation in malondialdehyde content while concurrently inhibiting the levels of total lipids, ergosterol, soluble proteins, and reducing sugars. Additionally, the impact of VOCs on A. flavus energy metabolism was evident, with significant inhibition observed in the activities of key enzymes, such as Na+/K+-ATPase, malate dehydrogenase, succinate dehydrogenase, and chitinase. And they were able to inhibit aflatoxin B1 synthesis. The transcriptomic analysis offered further insights, highlighting that differentially expressed genes (DEGs) were predominantly associated with membrane functionality and enriched in pathways about carbohydrate and amino acid metabolism. Notably, DEGs linked to cellular components and energy-related mechanisms exhibited down-regulation, thereby corroborating the findings from the biochemical analyses. In summary, these results elucidate the principal antifungal mechanisms of VOCs, which encompass the disruption of cell membrane integrity and interference with carbohydrate and amino acid metabolism in A. flavus.

p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial.

p75 neurotrophin receptor (p75NTR) signaling pathways substantially overlap with degenerative networks active in Alzheimer disease (AD). Modulation of p75NTR with the first-in-class small molecule LM11A-31 mitigates amyloid-induced and pathological tau-induced synaptic loss in preclinical models. Here we conducted a 26-week randomized, placebo-controlled, double-blinded phase 2a safety and exploratory endpoint trial of LM11A-31 in 242 participants with mild to moderate AD with three arms: placebo, 200 mg LM11A-31 and 400 mg LM11A-31, administered twice daily by oral capsules. This trial met its primary endpoint of safety and tolerability. Within the prespecified secondary and exploratory outcome domains (structural magnetic resonance imaging, fluorodeoxyglucose positron-emission tomography and cerebrospinal fluid biomarkers), significant drug-placebo differences were found, consistent with the hypothesis that LM11A-31 slows progression of pathophysiological features of AD; no significant effect of active treatment was observed on cognitive tests. Together, these results suggest that targeting p75NTR with LM11A-31 warrants further investigation in larger-scale clinical trials of longer duration. EU Clinical Trials registration: 2015-005263-16 ; ClinicalTrials.gov registration: NCT03069014 .

Role of ERK in gender difference of fibromyalgia pain.

This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis of dissected dorsal root ganglions from both genders. Both male and female rats exhibited a similar pain behavior trend, with females demonstrating a lower pain threshold. Protein analysis of the dorsal root ganglion (DRG) showed a significant increase in phosphorylated ERK after the second acid injection in all groups. However, phosphorylation of ERK was observed in the dorsal root ganglion, with higher levels in the male ipsilateral group compared to the female group. Moreover, there was a no difference between the left and right sides in males, whereas the significant difference was observed in females. In conclusions, the administration of acid injections induced painful behavior in rats, and concurrent with this, a significant upregulation of pERK was observed in the dorsal root ganglia, with a greater magnitude of increase in males than females, and in the contralateral side compared to the ipsilateral side. Our findings shed light on the peripheral mechanisms underlying chronic pain disorders and offer potential avenues for therapeutic intervention.

Vascular Risk Factors and Brain Health in Aging: Insights from a Community-Based Cohort Study.

Background: The aging population and high rates of Alzheimer's disease (AD) create significant medical burdens, prompting a need for early prevention. Targeting modifiable risk factors like vascular risk factors (VRFs), closely linked to AD, may provide a promising strategy for intervention. Objective: This study investigates how VRFs influence cognitive performance and brain structures in a community-based cohort. Methods: In this cross-sectional study, 4,667 participants over 50 years old, drawn from the Beijing Ageing Brain Rejuvenation Initiative project, were meticulously examined. Cognitive function and VRFs (diabetes mellitus, hypertension, hyperlipidemia, obesity, and smoking), were comprehensively assessed through one-to-one interviews. Additionally, a subset of participants (n = 719) underwent MRI, encompassing T1-weighted and diffusion-weighted scans, to elucidate gray matter volume and white matter structural network organization. Results: The findings unveil diabetes as a potent detriment to memory, manifesting in atrophy within the right supramarginal gyrus and diminished nodal efficiency and degree centrality in the right inferior parietal lobe. Hypertension solely impaired memory without significant structural changes. Intriguingly, individuals with comorbid diabetes and hypertension exhibited the most pronounced deficits in both brain structure and cognitive performance. Remarkably, hyperlipidemia emerged as a factor associated with enhanced cognition, and preservation of brain structure. Conclusions: This study illuminates the intricate associations between VRFs and the varied patterns of cognitive and brain structural damage. Notably, the synergistic effect of diabetes and hypertension emerges as particularly deleterious. These findings underscore the imperative to tailor interventions for patients with distinct VRF comorbidities, especially when addressing cognitive decline and structural brain changes.

Catalytic (4+2) Annulation via Regio- and Enantioselective Interception of in-situ Generated Alkylgold Intermediate.

A regio- and stereoselective stepwise (4+2) annulation of N-propargylamides and α,ß-unsaturated imines/ketones has been accomplished with synergetic catalysis by a combination of a gold-complex and a chiral quinine-derived squaramide (QN-SQA), leading to highly functionalized chiral tetrahydropyridines/dihydropyrans in good to high yields with generally excellent enantioselectivity. Mechanistic studies and DFT calculations indicate that the in situ formed alkylgold species is the key intermediate in this transformation, and the amide group served as a traceless directing group in this highly selective transformation. This method complements the enantioselective (4+2) annulation of allene reagents, providing the formal internal C-C π-bond cycloaddition products, which is challenging and remains elusive.

Combining Blood-Based Biomarkers and Structural MRI Measurements to Distinguish Persons with and without Significant Amyloid Plaques.

Background: Amyloid-ß (Aß) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing Aß plaques more affordably. We have previously proposed an MRI-based hippocampal morphometry measure to be an indicator of Aß plaques. Objective: To develop and validate an integrated model to predict brain amyloid PET positivity combining MRI feature and plasma Aß42/40 ratio. Methods: We extracted hippocampal multivariate morphometry statistics from MR images and together with plasma Aß42/40 trained a random forest classifier to perform a binary classification of participant brain amyloid PET positivity. We evaluated the model performance using two distinct cohorts, one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score. Results: Results from ADNI (mean age 72.6, Aß+ rate 49.5%) and BAI (mean age 66.2, Aß+ rate 36.9%) datasets revealed the integrated multimodal (IMM) model's superior performance over unimodal models. The IMM model achieved prediction accuracies of 0.86 in ADNI and 0.92 in BAI, surpassing unimodal models based solely on structural MRI (0.81 and 0.87) or plasma Aß42/40 (0.73 and 0.81) predictors. CONCLUSIONS: Our IMM model, combining MRI and BBBM data, offers a highly accurate approach to predict brain amyloid PET positivity. This innovative multiplex biomarker strategy presents an accessible and cost-effective avenue for advancing Alzheimer's disease diagnostics, leveraging diverse pathologic features related to Aß plaques and structural MRI.

Brain Fluid Clearance After Traumatic Brain Injury Measured Using Dynamic Positron Emission Tomography.

Brain fluid clearance by pathways including the recently described paravascular glymphatic system is a critical homeostatic mechanism by which metabolic products, toxins, and other wastes are removed from the brain. Brain fluid clearance may be especially important after traumatic brain injury (TBI), when blood, neuronal debris, inflammatory cells, and other substances can be released and/or deposited. Using a non-invasive dynamic positron emission tomography (PET) method that models the rate at which an intravenously injected radiolabeled molecule (in this case 11C-flumazenil) is cleared from ventricular cerebrospinal fluid (CSF), we estimated the overall efficiency of brain fluid clearance in humans who had experienced complicated-mild or moderate TBI 3-6 months before neuroimaging (n = 7) as compared to healthy controls (n = 9). While there was no significant difference in ventricular clearance between TBI subjects and controls, there was a significant group difference in dependence of ventricular clearance upon tracer delivery/blood flow to the ventricles. Specifically, in controls, ventricular clearance was highly, linearly dependent upon blood flow to the ventricle, but this relation was disrupted in TBI subjects. When accounting for blood flow and group-specific alterations in blood flow, ventricular clearance was slightly (non-significantly) increased in TBI subjects as compared to controls. Current results contrast with past studies showing reduced glymphatic function after TBI and are consistent with possible differential effects of TBI on glymphatic versus non-glymphatic clearance mechanisms. Further study using multi-modal methods capable of assessing and disentangling blood flow and different aspects of fluid clearance is needed to clarify clearance alterations after TBI.

[Discussion on the surgical timing of rupture and hemorrhage of renal angiomyolipoma].

OBJECTIVE: To investigate the effect of different surgical timing on the surgical treatment of renal angiomyolipoma (RAML) with rupture and hemorrhage. METHODS: The demographic data and perioperative data of 31 patients with rupture and hemorrhage of RAML admitted to our medical center from June 2013 to February 2023 were collected. The surgery within 7 days after hemorrhage was defined as a short-term surgery group, the surgery between 7 days and 6 months after hemorrhage was defined as a medium-term surgery group, and the surgery beyond 6 months after hemorrhage was defined as a long-term surgery group. The perioperative related indicators among the three groups were compared. RESULTS: This study collected 31 patients who underwent surgical treatment for RAML rupture and hemorrhage, of whom 13 were males and 18 were females, with an average age of (46.2±11.3) years. The short-term surgery group included 7 patients, the medium-term surgery group included 12 patients and the long-term surgery group included 12 patients. In terms of tumor diameter, the patients in the long-term surgery group were significantly lower than those in the recent surgery group [(6.6±2.4) cm vs. (10.0±3.0) cm, P=0.039]. In terms of operation time, the long-term surgery group was significantly shorter than the mid-term surgery group [(157.5±56.8) min vs. (254.8±80.1) min, P=0.006], and there was no significant difference between other groups. In terms of estimated blood loss during surgery, the long-term surgery group was significantly lower than the mid-term surgery group [35 (10, 100) mL vs. 650 (300, 1 200) mL, P < 0.001], and there was no significant difference between other groups. In terms of intraoperative blood transfusion, the long-term surgery group was significantly lower than the mid-term surgery group [0 (0, 0) mL vs. 200 (0, 700) mL, P=0.014], and there was no significant difference between other groups. In terms of postoperative hospitalization days, the long-term surgery group was significantly lower than the mid-term surgery group [5 (4, 7) d vs. 7 (6, 10) d, P=0.011], and there was no significant difference between other groups. CONCLUSION: We believe that for patients with RAML rupture and hemorrhage, reoperation for more than 6 months is a relatively safe time range, with minimal intraoperative bleeding. Therefore, it is more recommended to undergo surgical treatment after the hematoma is systematized through conservative treatment.

[1-11C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects.

BACKGROUND: Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer's disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid. METHODS: 24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aß+) and 16 Aß- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC. RESULTS: LOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aß+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress. CONCLUSION: The data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.

Early postnatal moderate catch­up growth in rats with nutritional intrauterine growth restriction preserves pulmonary vascular and cognitive function in adulthood.

Intrauterine growth restriction (IUGR) with rapid postnatal catch-up growth is strongly associated with pulmonary vascular dysfunction in adulthood, whereas IUGR with delayed growth in early postnatal life results in long-term brain deficits. In the present study, it was hypothesized that IUGR with early moderate catch-up growth may alleviate pulmonary vascular remodeling in adulthood without affecting memory function. An IUGR model was established by restricting maternal nutrition during pregnancy. Different growth patterns were achieved by adjusting the litter size in each group during lactation. Rats meeting the weight requirement at weaning were selected for subsequent studies at three time points (3, 9 and 13 weeks). Cognitive function was evaluated using a Y-maze. Invasive hemodynamic measurements were conducted to measure the mean pulmonary arterial pressure (mPAP). In addition, primary pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were cultured to investigate their role in the increase in mPAP following rapid catch-up growth. The results showed that memory function deficits in the rats in the delayed growth group were associated with reduced proliferation of neural stem cells in the subgranular zone of the hippocampus. Furthermore, moderate catch-up growth at the three time points improved memory function while maintaining a normal mPAP. In adult IUGR rats experiencing rapid catch-up growth, although memory function improved, elevated mPAP and medial thickening of pulmonary arterioles were observed. Additionally, PASMCs exhibited excessive proliferation, migration and anti-apoptotic activity in the rapid catch-up group, and PVECs also displayed excessive proliferation. These results suggested that moderate catch-up growth after IUGR is a better strategy for optimal cognition and cardiovascular health in adulthood compared with rapid catch-up growth or delayed growth.

In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation.

The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.

Atrophy network mapping of clinical subtypes and main symptoms in frontotemporal dementia.

Frontotemporal Dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different FTD clinical subtypes and determine the specific localization of the network for apathy and disinhibition. Eighty FTD patients [45 behavioral variant FTD (bvFTD) and 35 semantic variant progressive primary aphasia (svPPA)] and 58 healthy controls (HCs) at Xuanwu Hospital were enrolled as Dataset 1; 112 FTD patients including 50 bvFTD, 32 svPPA, and 30 non-fluent variant PPA (nfvPPA) cases, and 110 HCs from Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) dataset were included as Dataset 2. Initially, single-subject atrophy maps were defined by comparing cortical thickness in each FTD patient versus HCs. Next, the network of brain regions functionally connected to each FTD patient's location of atrophy was determined using seed-based functional connectivity in a large (n = 1000) normative connectome. Finally, we used atrophy network mapping to define clinical subtype-specific network (45 bvFTD, 35 svPPA and 58 HCs in Dataset 1; 50 bvFTD, 32 svPPA, 30 nfvPPA and 110 HCs in Dataset 2) and symptom-specific networks [combined dataset 1 and 2, apathy without depression Vs non-apathy without depression (80:26), disinhibition Vs non-disinhibition (88:68)]. We compare the result with matched symptom networks derived from patients with focal brain lesions or conjunction analysis. Through the analysis of two datasets, we identified heterogeneity in atrophy patterns among FTD patients. However, these atrophy patterns are connected to a common brain network. The primary regions affected by atrophy in FTD included the frontal and temporal lobes, particularly the anterior temporal lobe. bvFTD connects to frontal and temporal cortical areas, svPPA mainly impacts the anterior temporal region, and nfvPPA targets the inferior frontal gyrus and precentral cortex regions. The apathy-specific network was localized in the orbital frontal cortex and ventral striatum, while the disinhibition-specific network was localized in the bilateral orbital frontal gyrus and right temporal lobe. Apathy and disinhibition atrophy networks resemble known motivational and criminal lesion networks respectively. A significant correlation was found between the apathy/disinhibition scores and functional connectivity between atrophy maps and the peak of the networks. This study localizes the common network of clinical subtypes and main symptoms in FTD, guiding future FTD neuromodulation interventions.