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1.
Adv Sci (Weinh) ; : e2404266, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38986026

ABSTRACT

Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α-Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α-ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long-standing catalysis challenge. Herein, an unprecedented TBD-switched Pd-catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late-stage modify pharmaceuticals, scalability to large-scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd-catalyzed double isocyanide insertion process, thereby selectively providing the desired α-ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α-ketoimine amide are successfully isolated and determined by X-ray analysis, confirming that they are probable intermediates in the catalytic pathway.

2.
mSystems ; : e0052224, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980058

ABSTRACT

The gut microbiota is essential for providing colonization resistance against pathogens. Dietary sugars markedly shift the composition of the intestinal microbiota and alter host susceptibility to enteric infections. Here, we demonstrate the effect of L-arabinose on bacterial infection by using a mouse infection model with Salmonella enterica serovar Typhimurium (S. Tm). In the presence of microbiota, L-arabinose induces a dramatic expansion of Enterobacteriaceae, thereby decreasing the microbiota diversity and causing more severe systemic infection. However, L-arabinose supplementation does not alter the disease progression of Salmonella infection in a microbiota-depleted mouse model. More importantly, short-term supplementation of L-arabinose fails to exert anti-diabetic effects in Salmonella-infected hyperglycemia mice and still promotes infection. Overall, our work reveals that a high intake of dietary L-arabinose supports a bloom of Enterobacteriaceae in Salmonella-infected gut, further accelerating the process of systemic infection.IMPORTANCEL-arabinose is a promising natural sweetener and food additive for the regulation of hyperglycemia. Since diabetic subjects are more susceptible to infections, the safety of dietary L-arabinose in diabetic patients experiencing infection remains a concern. Our findings reveal that L-arabinose exacerbates Salmonella infection outcome by inducing gut microbiota dysbiosis in mice. High dietary intake of L-arabinose may be deleterious for diabetic individuals undergoing infection.

3.
Adv Sci (Weinh) ; : e2401593, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976573

ABSTRACT

The "Mlx" and "Myc" transcription factor networks cross-communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max-like factor Mlx associate with the Myc-like factors MondoA or ChREBP. The current work demonstrates that body-wide Mlx inactivation, like that of Myc, accelerates numerous aging-related phenotypes pertaining to body habitus and metabolism. The deregulation of numerous aging-related Myc target gene sets is also accelerated. Among other functions, these gene sets often regulate ribosomal and mitochondrial structure and function, genomic stability, and aging. Whereas "MycKO" mice have an extended lifespan because of a lower cancer incidence, "MlxKO" mice have normal lifespans and a higher cancer incidence. Like Myc, the expression of Mlx, MondoA, and ChREBP and their control over their target genes deteriorate with age in both mice and humans. Collectively, these findings underscore the importance of lifelong and balanced cross-talk between the two networks to maintain proper function and regulation of the many factors that can affect normal aging.

4.
J Exp Bot ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970454

ABSTRACT

Plant phenotypic plasticity plays an important role in nitrogen (N) acquisition and use under nitrogen-limited conditions. However, this role has never been quantified as a function of N availability, leaving it unclear whether plastic responses should be considered as potential targets for selection. A combined modelling and experimentation approach was adopted to quantify the role of plasticity on N uptake and plant yield. Based on a greenhouse experiment we considered plasticity in two maize traits: root-to-leaf biomass allocation ratio and emergence rate of axial roots. In a simulation experiment we individually enabled or disabled both plastic responses for maize stands grown across six N levels. Both plastic responses contributed to maintaining a higher N uptake and plant productivity as N-availability declined, compared to stands in which plastic responses were disabled. We conclude that plastic responses quantified in this study may be a potential target trait in breeding programs for greater N uptake across N levels while it may only be important for the internal use of N under N-limited conditions in maize. Given the complexity of breeding for plastic responses, an a priori model analysis is useful to identify which plastic traits to target for enhanced plant performance.

5.
Front Neurol ; 15: 1347682, 2024.
Article in English | MEDLINE | ID: mdl-38895693

ABSTRACT

Background: Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients. Methods: This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment. Results: The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients. Conclusion: Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.

6.
Nat Hum Behav ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886532

ABSTRACT

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.

7.
CNS Neurosci Ther ; 30(6): e14810, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38887969

ABSTRACT

AIMS: To study the changes in cortical thickness and subcortical gray matter structures in children with complete spinal cord injury (CSCI), reveal the possible causes of dysfunction beyond sensory motor dysfunction after CSCI, and provide a possible neural basis for corresponding functional intervention training. METHODS: Thirty-seven pediatric CSCI patients and 34 age-, gender-matched healthy children as healthy controls (HCs) were recruited. The 3D high-resolution T1-weighted structural images of all subjects were obtained using a 3.0 Tesla MRI system. Statistical differences between pediatric CSCI patients and HCs in cortical thickness and volumes of subcortical gray matter structures were evaluated. Then, correlation analyses were performed to analyze the correlation between the imaging indicators and clinical characteristics. RESULTS: Compared with HCs, pediatric CSCI patients showed decreased cortical thickness in the right precentral gyrus, superior temporal gyrus, and posterior segment of the lateral sulcus, while increased cortical thickness in the right lingual gyrus and inferior occipital gyrus. The volume of the right thalamus in pediatric CSCI patients was significantly smaller than that in HCs. No significant correlation was found between the imaging indicators and the injury duration, sensory scores, and motor scores of pediatric CSCI patients. CONCLUSIONS: These findings demonstrated that the brain structural reorganizations of pediatric CSCI occurred not only in sensory motor areas but also in cognitive and visual related brain regions, which may suggest that the visual processing, cognitive abnormalities, and related early intervention therapy also deserve greater attention beyond sensory motor rehabilitation training in pediatric CSCI patients.


Subject(s)
Cerebral Cortex , Magnetic Resonance Imaging , Spinal Cord Injuries , Humans , Spinal Cord Injuries/pathology , Spinal Cord Injuries/diagnostic imaging , Female , Male , Child , Adolescent , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Gray Matter/pathology , Gray Matter/diagnostic imaging , Organ Size
8.
Polymers (Basel) ; 16(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891436

ABSTRACT

To develop a cost-effective, high-viscosity asphalt for porous asphalt pavement, we utilized SBS, tackifier, and solubilizer as the main raw materials, identified the optimal composition through an orthogonal experiment of three factors and three levels, and prepared a low-cost high-viscosity asphalt. We compared its conventional and rheological properties against those of rubber asphalt, SBS modified asphalt, and matrix asphalt, employing fluorescence microscopy and Fourier transform infrared spectroscopy for microstructural analysis. The results indicate that the optimal formula composition for high-viscosity asphalt was 4-5% styrene-butadiene-styrene (SBS) + 1-2% tackifier +0-3% solubilizer +0.15% stabilizer. The components evenly dispersed and the performances were enhanced with chemical and physical modification. Compared with SBS modified asphalt, rubber asphalt, and matrix asphalt, the softening point, 5 °C ductility, and 60 °C dynamic viscosity of high-viscosity asphalt were significantly improved, while the 175 °C Brookfield viscosity was equivalent to SBS modified asphalt. In particular, the 60 °C dynamic viscosity reaches 383,180 Pa·s. Rheological tests indicate that the high- and low-temperature grade of high-viscosity asphalt reaches 88-18 °C, and that high-viscosity asphalt has the best high-temperature resistance to permanent deformation and low-temperature resistance to cracking. It can save about 30% cost compared to commercially available high-viscosity asphalt, which is conducive to the promotion and application of porous asphalt pavement.

9.
CNS Neurosci Ther ; 30(6): e14779, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828650

ABSTRACT

AIMS: Previous neuroimaging studies of vascular cognitive impairment, no dementia (VCIND), have reported functional alterations, but far less is known about the effects of cognitive training on functional connectivity (FC) of intrinsic connectivity networks (ICNs) and how they relate to intervention-related cognitive improvement. This study provides comprehensive research on the changes in intra- and inter-brain functional networks in patients with VCIND who received computerized cognitive training, with a focus on the underlying mechanisms and potential therapeutic strategies. METHODS: We prospectively collected 60 patients with VCIND who were randomly divided into the training group (N = 30) receiving computerized cognitive training and the control group (N = 30) receiving fixed cognitive training. Functional MRI scans and cognitive assessments were performed at baseline, at the 7-week training, and at the 6-month follow-up. Utilizing templates for ICNs, the study employed a linear mixed model to compare intra- and inter-network FC changes between the two groups. Pearson correlation was applied to calculate the relationship between FC and cognitive function. RESULTS: We found significantly decreased intra-network FC within the default mode network (DMN) following computerized cognitive training at Month 6 (p = 0.034), suggesting a potential loss of functional specialization. Computerized training led to increased functional coupling between the DMN and sensorimotor network (SMN) (p = 0.01) and between the language network (LN) and executive control network (ECN) at Month 6 (p < 0.001), indicating compensatory network adaptations in patients with VCIND. Notably, the intra-LN exhibited enhanced functional specialization after computerized cognitive training (p = 0.049), with significant FC increases among LN regions, which correlated with improvements in neuropsychological measures (p < 0.05), emphasizing the targeted impact of computerized cognitive training on language abilities. CONCLUSIONS: This study provides insights into neuroplasticity and adaptive changes resulting from cognitive training in patients with VCIND, with implications for potential therapeutic strategies.


Subject(s)
Brain , Cognitive Dysfunction , Magnetic Resonance Imaging , Nerve Net , Humans , Male , Female , Aged , Cognitive Dysfunction/therapy , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/rehabilitation , Middle Aged , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Brain/diagnostic imaging , Brain/physiopathology , Therapy, Computer-Assisted/methods , Prospective Studies , Cognitive Training
10.
Front Neurosci ; 18: 1357633, 2024.
Article in English | MEDLINE | ID: mdl-38835837

ABSTRACT

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune inflammatory disease of the central nervous system, (CNS) different from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). While numerous studies have delved into the involvement of thyroid antibodies (ATAbs) and thyroid function in NMOSD and MS. The objective of this study is to explore the clinical significance of thyroid dysfunction and ATAbs abnormalities in adult patients with MOGAD. Methods: 36 adult inpatients diagnosed with MOGAD and 47 sex- and age-matched healthy controls were enrolled. Patients were divided into two groups based on the presence or absence of low T3 syndrome. Demographics, clinical characteristics, and results of auxiliary examinations were compared across the subgroups. Moreover, an analysis was conducted to explore the correlations between thyroid hormone levels and Expanded Disability Status Scale (EDSS) scores. Results: Thyroid dysfunction was notably more frequent in MOGAD patients than healthy controls (p < 0.0001), particularly low T3 syndrome (p=0.03). Furthermore, subgroup analyses revealed that the low T3 syndrome group exhibited higher EDSS scores and a higher proportion of individuals with EDSS scores > 3, in comparison to the non-low T3 syndrome group (p = 0.014, p = 0.046). However, no significant differences were observed in demographic characteristics, annual relapse rates, clinical phenotypes, laboratory and MRI results, and EEG abnormalities between the two groups. Additional Spearman's analysis showed significantly negative correlations between the TT3 and FT3 levels with EDSS scores (r = -0.367, p = 0.028; r = -0.377, p = 0.024). Typical brain lesions and paralateral ventricle lesions were significantly rare in patients with positive ATAbs compared to those with negative ATAbs (p = 0.0001, p = 0.03), although the incidence of ATAbs abnormalities did not differ significantly between MOGAD patients and healthy controls. Conclusions: Overall, this study confirmed thyroid dysfunction, especially low T3 syndrome, is frequent in adult MOGAD patients. Patients with low T3 syndrome exhibited elevated EDSS scores and a significantly higher incidence of unfavorable condition. additionally, the correlation analysis model manifests that FT3 and TT3 levels were negatively correlated with EDSS scores. These evidences indicate that low T3 syndrome is associated with the severity of MOGAD exacerbation.

11.
Int J Biol Macromol ; 272(Pt 1): 132816, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38825273

ABSTRACT

Modulating the interactions between biopolymer matrix and nanofillers highly determined the mechanical performances of composite packaging materials. Herein, we innovatively proposed a sort of eco-friendly and mechanically robust carboxymethyl cellulose/graphene oxide/tannic acid/polyetherimide (CMC/GO/TA/PEI, CGTP) composite by employing PEI as cross-linker and TA as proton donor. The amidation reaction between -NH2 and -COOH chemically connected the CMC/GO, CMC/CMC and GO/GO and the physical interaction (e.g. hydrogen bonds and molecular entanglements) was beneficial to form dense structures. The chemical/physical bonds among polymers and nanofillers contributed to dissipate the external energy. The toughness was effectively reinforced from 1.68 MJ/m3 for CGTP0 to 4.63 MJ/m3 for CGTP1.0. Furthermore, the CGTP1.0 composite film also delivered improved gas (moisture and oxygen) barriers, UV protection and antimicrobial features. Originating from these merits, the shelf life of fresh fruits (e.g. strawberries, blueberries and cherry tomatoes) was prolonged at least 5 days under ambient conditions when the packaging box was covered by the fabricated CGTP1.0 film. Our findings not only provided a facial strategy to reinforce the interactions between biopolymer matrix and nanofillers, but also boosted the development of eco-friendly packaging materials with robust structures in the area of food packaging.


Subject(s)
Carboxymethylcellulose Sodium , Food Packaging , Fruit , Graphite , Polymers , Graphite/chemistry , Food Packaging/methods , Carboxymethylcellulose Sodium/chemistry , Polymers/chemistry , Fruit/chemistry , Food Preservation/methods , Nanocomposites/chemistry
12.
Eur J Sport Sci ; 24(6): 637-652, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38874993

ABSTRACT

To assess the evidence for the effect of strength and conditioning on physical qualities and aesthetic competence in dance populations, three electronic databases (PubMed, Scopus, SPORTDiscus) were searched (until September 2022) for studies that met the following criteria: (i) dancers aged >16 years; (ii) structured strength and conditioning intervention; and (iii) with physical qualities and aesthetic competence as outcome measures. Methodological quality and risk of bias of the included studies were assessed through the systematic review tool "QualSyst". Meta-analyses of effect sizes (Hedges' g) with forest plots explored the effects of the strength and conditioning interventions. Thirty-six studies met the inclusion criteria and were included in this review. Meta-analysis indicated strength and conditioning significantly (p < 0.05) improved lower body power (g = 0.90, 95% CI: 0.53-1.27), upper body strength (g = 0.98, 95% CI: 0.39-1.57), lower body strength (g = 1.59, 95% CI: 0.97-2.22), and flexibility (g = 0.86, 95% CI: 0.05-1.66). Strength and conditioning interventions were found to be effective at improving physical qualities in dancers, recommending their participation in additional sessions to enhance overall fitness and ultimately dance performance. It is recommended that future strength and conditioning intervention research should include sample size calculations, with participants recruited from a specific dance genre and skill level in order to evaluate how strength and conditioning influences dance performance.


Subject(s)
Dancing , Muscle Strength , Resistance Training , Humans , Dancing/physiology , Muscle Strength/physiology , Esthetics
13.
IEEE Trans Med Imaging ; PP2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38875085

ABSTRACT

Quantitative infarct estimation is crucial for diagnosis, treatment and prognosis in acute ischemic stroke (AIS) patients. As the early changes of ischemic tissue are subtle and easily confounded by normal brain tissue, it remains a very challenging task. However, existing methods often ignore or confuse the contribution of different types of anatomical asymmetry caused by intrinsic and pathological changes to segmentation. Further, inefficient domain knowledge utilization leads to mis-segmentation for AIS infarcts. Inspired by this idea, we propose a pathological asymmetry-guided progressive learning (PAPL) method for AIS infarct segmentation. PAPL mimics the step-by-step learning patterns observed in humans, including three progressive stages: knowledge preparation stage, formal learning stage, and examination improvement stage. First, knowledge preparation stage accumulates the preparatory domain knowledge of the infarct segmentation task, helping to learn domain-specific knowledge representations to enhance the discriminative ability for pathological asymmetries by constructed contrastive learning task. Then, formal learning stage efficiently performs end-to-end training guided by learned knowledge representations, in which the designed feature compensation module (FCM) can leverage the anatomy similarity between adjacent slices from the volumetric medical image to help aggregate rich anatomical context information. Finally, examination improvement stage encourages improving the infarct prediction from the previous stage, where the proposed perception refinement strategy (RPRS) further exploits the bilateral difference comparison to correct the mis-segmentation infarct regions by adaptively regional shrink and expansion. Extensive experiments on public and in-house NCCT datasets demonstrated the superiority of the proposed PAPL, which is promising to help better stroke evaluation and treatment.

14.
Diagnostics (Basel) ; 14(12)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38928642

ABSTRACT

BACKGROUND: Diffusion tensor imaging (DTI) has been increasingly recognized for its capability to study microstructural changes in the neuropathology of brain diseases. However, the optimal DTI metric and its diagnostic utility for a variety of spinal cord diseases are still under investigation. PURPOSE: To evaluate the diagnostic efficacy of DTI metrics for differentiating between cervical spondylosis, myelitis, and spinal tumors. METHODS: This retrospective study analyzed DTI scans from 68 patients (22 with cervical spondylosis, 23 with myelitis, and 23 with spinal tumors). DTI indicators, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), were calculated. The Kruskal-Wallis test was used to compare these indicators, followed by Receiver Operating Characteristic (ROC) curve analysis, to evaluate the diagnostic efficacy of each indicator across disease pairs. Additionally, we explored the correlations of DTI indicators with specific clinical measurements. RESULTS: FA values were significantly lower in tumor patients compared to those with cervical spondylosis (p < 0.0001) and myelitis (p < 0.05). Additionally, tumor patients exhibited significantly elevated MD and RD values relative to the spondylosis and myelitis groups. ROC curve analysis underscored FA's superior discriminative performance, with an area under the curve (AUC) of 0.902 for differentiating tumors from cervical spondylosis, and an AUC of 0.748 for distinguishing cervical myelitis from spondylosis. Furthermore, a significant negative correlation was observed between FA values and Expanded Disability Status Scores (EDSSs) in myelitis patients (r = -0.62, p = 0.002), as well as between FA values and Ki-67 scores in tumor patients (r = -0.71, p = 0.0002). CONCLUSION: DTI indicators, especially FA, have the potential in distinguishing spondylosis, myelitis, and spinal cord tumors. The significant correlation between FA values and clinical indicators highlights the value of FA in the clinical assessment and prognosis of spinal diseases and may be applied in diagnostic protocols in the future.

15.
Biomacromolecules ; 25(7): 4394-4405, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38859583

ABSTRACT

Combination immunotherapy is being increasingly explored for cancer treatment, leading to various vector materials for the codelivery of immune agents and drugs. However, current tumor vaccines exhibit poor immunogenicity, severely compromising their therapeutic efficacy. Herein, an injectable hydrogel was developed based on dopamine (DA) and Panax notoginseng polysaccharide (PNPS) loaded with hair microparticles (HMPs) to enhance the immunogenicity of tumor vaccines. Photothermal effects of incorporated HMPs can trigger immunogenic cancer cell death and the release of abundant autologous tumor antigens, which are captured by catechol groups. Concomitant breakdown of PNPS recruits and activates dendritic cells (DCs). The macroporous structure of cryogels allows immune cell infiltration and interaction with antigens adsorbed on PNPS and DA cryogels (PD cryogels), thereby provoking potent cytotoxic T-cell responses. Hence, PD cryogels enabling cell infiltration and accelerated DC maturation may serve as a therapeutic vaccination platform against cancer.


Subject(s)
Cancer Vaccines , Cryogels , Dendritic Cells , Panax notoginseng , Polysaccharides , Cancer Vaccines/chemistry , Cancer Vaccines/immunology , Cryogels/chemistry , Cryogels/pharmacology , Panax notoginseng/chemistry , Animals , Mice , Polysaccharides/chemistry , Polysaccharides/pharmacology , Dendritic Cells/immunology , Humans , Female , Mice, Inbred C57BL , Cell Line, Tumor
16.
Spinal Cord ; 62(7): 414-420, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38824252

ABSTRACT

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To study the relationship between the structural changes in the cervical spinal cord (C2/3 level) and the sensorimotor function of children with traumatic thoracolumbar spinal cord injury (TLSCI) and to discover objective imaging biomarkers to evaluate its functional status. SETTING: Xuanwu Hospital, Capital Medical University, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, China. METHODS: 30 children (age range 5-13 years) with TLSCI and 11 typically developing (TD) children (age range 6-12 years) were recruited in this study. Based on whether there is preserved motor function below the neurological level of injury (NLI), the children with TLSCI are divided into the AIS A/B group (motor complete) and the AIS C/D group (motor incomplete). A Siemens Verio 3.0 T MR scanner was used to acquire 3D high-resolution anatomic scans covering the head and upper cervical spinal cord. Morphologic parameters of the spinal cord at the C2/3 level, including cross-sectional area (CSA), anterior-posterior width (APW), and left-right width (LRW) were obtained using the spinal cord toolbox (SCT; https://www.nitrc.org/projects/sct ). Correlation analyses were performed to compare the morphologic spinal cord parameters and clinical scores determined by the International Standard for Neurological Classification of Spinal Cord Injuries (ISNCSCI) examination. RESULTS: CSA and LRW in the AIS A/B group were significantly lower than those in the TD group and the AIS C/D group. LRW was the most sensitive imaging biomarker to differentiate the AIS A/B group from the AIS C/D group. Both CSA and APW were positively correlated with ISNCSCI sensory scores. CONCLUSIONS: Quantitative measurement of the morphologic spinal cord parameters of the cervical spinal cord can be used as an objective imaging biomarker to evaluate the neurological function of children with TLSCI. Cervical spinal cord atrophy in children after TLSCI was correlated with clinical grading; CSA and APW can reflect sensory function. Meanwhile, LRW has the potential to be an objective imaging biomarker for evaluating motor function preservation.


Subject(s)
Cervical Cord , Magnetic Resonance Imaging , Spinal Cord Injuries , Thoracic Vertebrae , Humans , Spinal Cord Injuries/diagnostic imaging , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/pathology , Child , Male , Female , Cross-Sectional Studies , Adolescent , Cervical Cord/diagnostic imaging , Cervical Cord/injuries , Cervical Cord/pathology , Child, Preschool , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/injuries , Lumbar Vertebrae/diagnostic imaging
17.
Heliyon ; 10(11): e31889, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38912500

ABSTRACT

Background: Myocardial segmental motion is associated with cardiovascular pathology, often assessed through myocardial strain features. The stability of the motion can be influenced by myocardial fibrosis. This research aimed to explore the complexity metrics (CM) of myocardial segmental motion curves, observe their correlation with late gadolinium enhancement (LGE) transmural extension (TE), and assess diagnostic efficacy combined with segmental strains in different TE segments. Methods: We included 42 myocardial infarction patients, dividing images into 672 myocardial segments (208 remote, 384 viable, and 80 unviable segments based on TE). Radial and circumferential segmental strain, along with CM for motion curves, were extracted. Correlation between CM and LGE, as well as the potential distinguishing role of CM, was evaluated using Pearson correlation, univariate linear regression (F-test), multivariate regression analysis (T-test), area under curve (AUC), machine learning models, and DeLong test. Results: All CMs showed significant linear correlation with TE (P < 0.001). Six CMs were correlated with TE (r > 0.3), with radial frequency drift (FD) displayed the strongest correlation (r = 0.496, P < 0.001). Radial and circumferential FD significantly differed in higher TE myocardium than in remote segments (P < 0.05). Radial FD had practical diagnostic efficacy (remote vs. unviable AUC = 0.89, viable vs. unviable AUC = 0.77, remote vs. viable AUC = 0.65). Combining CM with segmental strain features boosted diagnostic efficacy than models using only segmental strain features (DeLong test, P < 0.05). Conclusions: The CM of myocardial motion curves has been associated with LGE infarction, and combining CM with strain features improves the diagnosis of different myocardial LGE infarction degrees.

18.
Front Biosci (Landmark Ed) ; 29(6): 210, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38940037

ABSTRACT

Traumatic spinal cord injury (SCI) is a serious disease of the central nervous system. Aside from the limited intrinsic regenerative capacity of neurons, complex microenvironmental disturbances can also lead to further cellular damage and growth inhibition. Programmed cell death regulated by pyroptosis has an important role in the pathogenesis of SCI. While there has been a wealth of new knowledge regarding cellular pyroptosis, a detailed understanding of its role in SCI and possible therapeutic strategies is still lacking. This review summarizes current advances in the regulatory role of pyroptosis-regulated cell death and inflammasome components in the inhibitory microenvironment following SCI, as well as recent therapeutic advances.


Subject(s)
Inflammasomes , Pyroptosis , Spinal Cord Injuries , Spinal Cord Injuries/therapy , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/physiopathology , Humans , Inflammasomes/metabolism , Animals , Neurons/metabolism
19.
Front Microbiol ; 15: 1424489, 2024.
Article in English | MEDLINE | ID: mdl-38939190

ABSTRACT

The expansion of betel palm cultivation is driven by rising demand for betel nut, yet this growth is accompanied by challenges such as decreased agricultural biodiversity and the spread of infectious pathogens. Among these, Yellow Leaf Disease (YLD) emerges as a prominent threat to betel palm plantation. Areca Palm Velarivirus 1 (APV1) has been identified as a primary causative agent of YLD, precipitating leaf yellowing, stunted growth, and diminished yield. However, the precise mechanisms underlying APV1-induced damage remain elusive. Our study elucidates that APV1 infiltrates chloroplasts, instigating severe damage and consequential reductions in chlorophyll a/b and carotene levels, alongside notable declines in photosynthetic efficiency. Moreover, APV1 infection exerts broad regulatory effects on gene expression, particularly suppressing key genes implicated in chloroplast function and photosynthesis. These disruptions correlate with growth retardation, yield diminishment, and compromised nut quality. Intriguingly, the paradoxical destruction of the host's photosynthetic machinery by APV1 prompts inquiry into its evolutionary rationale, given the virus's dependence on host resources for replication and proliferation. Our findings reveal that APV1-induced leaf yellowing acts as a beacon for transmission vectors, hinting at a nuanced "host-pathogen-vector co-evolutionary" dynamic.

20.
Neurosci Bull ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824231

ABSTRACT

The current study aimed to evaluate the susceptibility to regional brain atrophy and its biological mechanism in Alzheimer's disease (AD). We conducted data-driven meta-analyses to combine 3,118 structural magnetic resonance images from three datasets to obtain robust atrophy patterns. Then we introduced a set of radiogenomic analyses to investigate the biological basis of the atrophy patterns in AD. Our results showed that the hippocampus and amygdala exhibit the most severe atrophy, followed by the temporal, frontal, and occipital lobes in mild cognitive impairment (MCI) and AD. The extent of atrophy in MCI was less severe than that in AD. A series of biological processes related to the glutamate signaling pathway, cellular stress response, and synapse structure and function were investigated through gene set enrichment analysis. Our study contributes to understanding the manifestations of atrophy and a deeper understanding of the pathophysiological processes that contribute to atrophy, providing new insight for further clinical research on AD.

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