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Rhythm, as a prominent characteristic of auditory experiences such as speech and music, is known to facilitate attention, yet its contribution to working memory (WM) remains unclear. Here, human participants temporarily retained a 12-tone sequence presented rhythmically or arrhythmically in WM and performed a pitch change-detection task. Behaviorally, while having comparable accuracy, rhythmic tone sequences showed a faster response time and lower response boundaries in decision-making. Electroencephalographic recordings revealed that rhythmic sequences elicited enhanced non-phase-locked beta-band (16 Hz-33 Hz) and theta-band (3 Hz-5 Hz) neural oscillations during sensory encoding and WM retention periods, respectively. Importantly, the two-stage neural signatures were correlated with each other and contributed to behavior. As beta-band and theta-band oscillations denote the engagement of motor systems and WM maintenance, respectively, our findings imply that rhythm facilitates auditory WM through intricate oscillation-based interactions between the motor and auditory systems that facilitate predictive attention to auditory sequences.
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In sensory neurons that transmit pain signals, whether acute or chronic, voltage-gated sodium channels (VGSCs) are crucial for regulating excitability. NaV1.1, NaV1.3, NaV1.6, NaV1.7, NaV1.8, and NaV1.9 have been demonstrated and defined their functional roles in pain signaling based on their biophysical properties and distinct patterns of expression in each subtype of sensory neurons. Scorpions and spiders are traditional Chinese medicinal materials, belonging to the arachnid class. Most of the studied species of them have evolved venom peptides that exhibit a wide variety of knottins specifically targeting VGSCs with subtype selectivity and conformational specificity. This review provides an overview on the exquisite knottins from scorpion and spider venoms targeting pain-related NaV channels, describing the sequences and the structural features as well as molecular determinants that influence their selectivity on special subtype and at particular conformation, with an aim for the development of novel research tools on NaV channels and analgesics with minimal adverse effects.
Subject(s)
Pain , Scorpion Venoms , Signal Transduction , Spider Venoms , Voltage-Gated Sodium Channels , Animals , Scorpion Venoms/chemistry , Scorpion Venoms/pharmacology , Scorpion Venoms/metabolism , Spider Venoms/pharmacology , Spider Venoms/chemistry , Spider Venoms/metabolism , Voltage-Gated Sodium Channels/metabolism , Voltage-Gated Sodium Channels/drug effects , Voltage-Gated Sodium Channels/chemistry , Voltage-Gated Sodium Channels/physiology , Pain/drug therapy , Pain/metabolism , Humans , Signal Transduction/drug effects , Signal Transduction/physiology , Scorpions/metabolism , Voltage-Gated Sodium Channel Blockers/pharmacology , Voltage-Gated Sodium Channel Blockers/chemistry , Amino Acid Sequence , Spiders/metabolismABSTRACT
In recent years, PM2.5 and O3 have been the two main pollutants affecting public health in China, but the interaction of the two pollutants on human health remains unclear. A two-stage analytical approach was used to investigate the relationships of PM2.5-O3 co-pollution with nonaccidental, cardiovascular, and respiratory mortality levels across 14 cities in China. We first utilized a generalized additive model (GAM) to determine the city-specific associations of PM2.5 and O3 with daily mortality. The associations were then combined at the national and regional levels using meta-analysis. To investigate the potential interactions between the two pollutants and cause-specific mortality, we performed stratified analyses by co-pollutant exposure levels and the synergy index (SI) (SI > 1 indicates a synergistic interaction). The effect of changes in the two pollutants' concentrations (in 10 µg/m3 increases) on mortality was assessed. The stratification analysis results suggested that each 10 µg/m3 increase in PM2.5 at lag0-1 (lag01) in the low, moderate, and high strata of the O3 concentrations increased nonaccidental mortality by 0.07% (95% confidence interval: -0.03%, 0.17%), 0.33% (0.13%, 0.53%), and 0.68% (0.30%, 1.06%), respectively, with significant between-group differences (p < 0.001). Moreover, each 10 µg/m3 increase in O3 (lag01) in the low, moderate, and high strata of the PM2.5 concentrations increased nonaccidental mortality by 0.15% (-0.06%, 0.36%), 0.53% (0.19%, 0.87%), and 0.75% (0.14%, 1.36%), respectively, with significant between-group differences (p < 0.001). We also found substantial synergistic interactions between the two pollutants and nonaccidental, cardiovascular, and respiratory mortality levels, with SI values of 1.48, 1.51, and 1.33, respectively. Additionally, a subgroup analysis revealed that the interaction of these two pollutants on nonaccidental mortality were greater in South China compared to elsewhere, and during the warm season compared to during the cold season. Our findings suggested that the simultaneous control of PM2.5 and O3 within the context of combined air pollution could significantly decrease the disease risk, especially in southern China and during the warm season.
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Objectives: Research shows a close association between aberrant immune reactions in osteonecrotic tissues and immune cell infiltration. However, due to limitations in sample size and dataset comprehensiveness, the causal relationship between them is not fully established. This study aims to determine whether there is a causal relationship using a larger and more diverse dataset. Methods: We conducted a comprehensive Mendelian Randomization (MR) analysis to investigate the causal relationship between immune cell characteristics and osteonecrosis. Utilizing publicly available genetic data, we explored the causal relationships between 731 immune cell features and 604 cases from the FinnGen Finnish database, as well as 257 cases from the UK Biobank database with osteonecrosis data. The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. In addition, considering data from the two databases used in this study, a meta-analysis was conducted on the significant immune cells associated with osteonecrosis (FDR <0.05). Results: our findings suggested that specific immune cell signatures, such as CD20- % lymphocytes, CD62L-monocytes, and CD33br HLA DR+ CD14-cells were associated with increased odds of osteonecrosis. In contrast, EM CD4+ activated cells and DP (CD4+ CD8+) T cells were associated with decreased odds. Notably, osteonecrosis was associated with a potential decrease in CD45 on immature MDSC cell content. Conclusion: From a genetic perspective, we demonstrated a close association between immune cells and osteonecrosis. These findings significantly enhance our understanding of the interplay between immune cell infiltration and the risk of osteonecrosis, contributing to the potential design of therapeutic strategies from an immunological standpoint.
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Background: Previous studies have explored the role of plasma proteins on osteonecrosis. This Mendelian randomization (MR) study further assessed plasma proteins on osteonecrosis whether a causal relationship exists and provides some evidence of causality. Methods: Summary-level data of 4,907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals by the deCODE Genetics Consortium. The outcome data for osteonecrosis were sourced from the FinnGen study, comprising 1,543 cases and 391,037 controls. MR analysis was conducted to estimate the associations between protein and osteonecrosis risk. Additionally, Phenome-wide MR analysis, and candidate drug prediction were employed to identify potential causal circulating proteins and novel drug targets. Results: We totally assessed the effect of 1,676 plasma proteins on osteonecrosis risk, of which 71 plasma proteins had a suggestive association with outcome risk (P < 0.05). Notably, Heme-binding protein 1 (HEBP1) was significant positively associated with osteonecrosis risk with convening evidence (OR, 1.40, 95% CI, 1.19 to 1.65, P = 3.96 × 10-5, P FDR = 0.044). This association was further confirmed in other MR analysis methods and did not detect heterogeneity and pleiotropy (all P > 0.05). To comprehensively explore the health effect of HEBP1, the phenome-wide MR analysis found it was associated with 136 phenotypes excluding osteonecrosis (P < 0.05). However, no significant association was observed after the false discovery rate adjustment. Conclusion: This comprehensive MR study identifies 71 plasma proteins associated with osteonecrosis, with HEBP1, ITIH1, SMOC1, and CREG1 showing potential as biomarkers of osteonecrosis. Nonetheless, further studies are needed to validate this candidate plasma protein.
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Following the publication of the above article, the authors drew to the attention of the Editorial Office that, after having reviewed all the figures and the data of their drawing software, they discovered that the pictures in the 'Control' and 'DEX' groups of Fig. 4D on p. 904 had been incorrectly imported into Fig. 6 on p. 905 when assembling this figure, effectively replacing the original and correctly placed images in Fig. 6D and E. The original (and correct) version of Fig. 6 is shown on the next page. All the authors agree with the publication of this Corrigendum, and express their gratitude to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 41: 899907, 2018; DOI: 10.3892/ijmm.2017.3297].
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OBJECTIVE: To characterize the retinal microvasculature and structure in subjective cognitive decline (SCD) and identify the potential biomarker for the early stage of the Alzheimer's disease (AD) spectrum. METHODS: In this study, 35 patients with SCD, 36 with cognitive impairment, and 29 with normal cognition (NC) were enrolled. Optical coherence tomography angiography was employed to assess retinal vascular density, fovea avascular zone area, and retinal thickness. The parameters reflecting retinal perfusion and structure were compared among the three groups. In addition, the association between retinal parameters, cerebral blood flow (CBF), and peripheral blood biomarkers in the SCD stage was analyzed. RESULTS: The superficial vascular complex (SVC) vascular density in the macula and retinal nerve fiber layer thickness in the peripapillary were significantly reduced in individuals with SCD compared to NC. Furthermore, there was a positive correlation between macular ganglion cell complex thickness and CBF in SCD. INTERPRETATION: The retinal microvasculature and structure exhibit alterations in individuals with SCD. Macular ganglion cell complex thickness demonstrates correlations with cerebral perfusion. The retina holds potential as a novel biomarker for early detection of AD.
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Vitamin C (VC) serves as a pivotal nutrient for anti-oxidation process, metabolic responses, and stem cell differentiation. However, its precise contribution to placenta development and gestation remains obscure. Here, we demonstrated that physiological levels of VC act to stabilize Hand1, a key bHLH transcription factor vital for the development trajectory of trophoblast giant cell (TGC) lineages, thereby promoting the differentiation of trophoblast stem cells into TGC. Specifically, VC administration inactivated c-Jun N-terminal kinase (JNK) signaling, which directly phosphorylates Hand1 at Ser48, triggering the proteasomal degradation of Hand1. Conversely, a loss-of-function mutation at Ser48 on Hand1 not only significantly diminished both intrinsic and VC-induced stabilization of Hand1 but also underscored the indispensability of this residue. Noteworthy, the insufficiency of VC led to severe defects in the differentiation of diverse TGC subtypes and the formation of labyrinth's vascular network in rodent placentas, resulting in failure of maintenance of pregnancy. Importantly, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm substantially affected the differentiation of primary and secondary TGC in E8.5 mouse placentas. Thus, these findings uncover the significance of JNK inactivation and consequential stabilization of Hand1 as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps maintenance of pregnancy.
Subject(s)
Ascorbic Acid , Basic Helix-Loop-Helix Transcription Factors , Cell Differentiation , JNK Mitogen-Activated Protein Kinases , Placentation , Trophoblasts , Animals , Female , Pregnancy , Ascorbic Acid/pharmacology , Ascorbic Acid/metabolism , Placentation/genetics , Mice , JNK Mitogen-Activated Protein Kinases/metabolism , JNK Mitogen-Activated Protein Kinases/genetics , Cell Differentiation/drug effects , Trophoblasts/metabolism , Trophoblasts/drug effects , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Placenta/metabolism , Phosphorylation , Humans , Mice, Inbred C57BLABSTRACT
Daily experiences often involve the processing of multiple sequences, yet storing them challenges the limited capacity of working memory (WM). To achieve efficient memory storage, relational structures shared by sequences would be leveraged to reorganize and compress information. Here, participants memorized a sequence of items with different colors and spatial locations and later reproduced the full color and location sequences one after another. Crucially, we manipulated the consistency between location and color sequence trajectories. First, sequences with consistent trajectories demonstrate improved memory performance and a trajectory correlation between reproduced color and location sequences. Second, sequences with consistent trajectories show neural reactivation of common trajectories, and display spontaneous replay of color sequences when recalling locations. Finally, neural reactivation correlates with WM behavior. Our findings suggest that a shared common structure is leveraged for the storage of multiple sequences through compressed encoding and neural replay, together facilitating efficient information organization in WM.
When we memorize a grocery list before heading into the store, we make use of our working memory. This type of neural process allows us to temporarily store the knowledge needed for a task, yet its capacity is limited. Having to recall more than one type of information at the same time, in particular, can quickly create challenges. Exactly how the brain maximizes the use of this limited working memory space remains unclear. One possible strategy would be to take advantage of the patterns or connections that exist between seemingly unrelated pieces of information for example, by remembering to buy apples, oranges and bananas under one broader 'fruit' category. To explore if this may be the case, Qiaoli Huang and Huan Luo designed a memory task in which two types of information were either connected through an underlying pattern (aligned trajectory condition) or completely independent (misaligned trajectory condition). Participants watched three colored dots appearing on screen one after the other, in such a way that they seemed to 'travel' around an imaginary circle. The volunteers were then asked to recall, in order, the location and color of each dot. Performance increased when color and location information were structured in the same way that is, when both emerged from the three dots traveling around a circle or a color wheel with the same trajectory. Recording the brain activity of the participants 'live' as they performed the task indicates that, in the aligned trajectory condition, the brain 'compresses' both types of information and extracts their common structure. Even when participants were asked to recall only the location of the dots, their brain also spontaneously replayed the related color information. Taken together, these findings provide new insights into how working memory aids in multitasking, a crucial aspect of our daily lives, and lay the groundwork for further exploration of this capability.
Subject(s)
Memory, Short-Term , Memory, Short-Term/physiology , Humans , Male , Female , Young Adult , AdultABSTRACT
Introduction of nonhexagons and/or heteroatoms allows for finely tuning the physicochemical properties of nanographenes. Heteroatoms doping have dominated the modulation of nanographenes with tunable bandgap, rich electrochemical activities and so on. The pair of nonhexagons, for instance, pentagon-heptagon pairs, have furnished nanographenes with aromatic and/or antiaromatic characteristics, open-shell properties and so on. In order to meet the growing demand for versatile nanographenes in materials science, research on novel nanographenes with heteroatom doped nonhexagonal pairs has been aroused in recent years. In this review, we focus on nanographenes with nitrogen-doped nonhexagonal paris including the synthesis, structure analysis, photophysical properties, and potential applications in organic devices.
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OBJECTIVE: This study was performed to explore the predictive value of the diaphragmatic thickness fraction (DTF) combined with the integrated pulmonary index (IPI) for the extubation outcome in patients with severe acute pancreatitis (SAP). METHODS: This prospective study involved 93 patients diagnosed with SAP and treated with mechanical ventilation in our hospital from October 2020 to September 2023. The patients were divided into a successful extubation group (61 patients) and an extubation failure group (32 patients) based on the extubation outcomes. The predictive value of the DTF, IPI, and their combination for extubation failure was analyzed. RESULTS: The DTF and IPI were independent risk factors for extubation failure in patients with SAP undergoing mechanical ventilation. In addition, the combination of the DTF and IPI showed predictive value for extubation failure in these patients. CONCLUSION: The DTF and IPI hold predictive value for extubation failure in patients with SAP undergoing mechanical ventilation, and their combined use may improve the predictive efficiency.
Subject(s)
Airway Extubation , Diaphragm , Respiration, Artificial , Humans , Male , Female , Middle Aged , Prospective Studies , Respiration, Artificial/methods , Diaphragm/physiopathology , Diaphragm/diagnostic imaging , Adult , Pancreatitis/therapy , Pancreatitis/pathology , Pancreatitis/diagnostic imaging , Predictive Value of Tests , Lung/diagnostic imaging , Lung/physiopathology , Lung/pathology , Ventilator Weaning/methods , Aged , Prognosis , Risk Factors , Severity of Illness IndexABSTRACT
Glucose is widely used in the reconstitution of intravenous medications, which often include antimicrobials. How glucose affects antimicrobial activity has not been comprehensively studied. The present work reports that glucose added to bacteria growing in a rich medium suppresses the bactericidal but not the bacteriostatic activity of several antimicrobial classes, thereby revealing a phenomenon called glucose-mediated antimicrobial tolerance. Glucose, at concentrations corresponding to blood-sugar levels of humans, increased survival of Escherichia coli treated with quinolones, aminoglycosides, and cephalosporins with little effect on minimal inhibitory concentration. Glucose suppressed a ROS surge stimulated by ciprofloxacin. Genes involved in phosphorylated fructose metabolism contributed to glucose-mediated tolerance, since a pfkA deficiency, which blocks the formation of fructose-1,6-bisphosphate, eliminated protection by glucose. Disrupting the pentose phosphate pathway or the TCA cycle failed to alter glucose-mediated tolerance, consistent with an upstream involvement of phosphorylated fructose. Exogenous sodium pyruvate or sodium citrate reversed glucose-mediated antimicrobial tolerance. Both metabolites bypass the effects of fructose-1,6-bisphosphate, a compound known to scavenge hydroxyl radical and chelate iron, activities that suppress ROS accumulation. Treatment with these two compounds constitutes a novel way to mitigate the glucose-mediated antimicrobial tolerance that may exist during intravenous antimicrobial therapy, especially for diabetes patients.
Subject(s)
Anti-Bacterial Agents , Escherichia coli , Glucose , Microbial Sensitivity Tests , Reactive Oxygen Species , Glucose/metabolism , Reactive Oxygen Species/metabolism , Escherichia coli/drug effects , Escherichia coli/genetics , Anti-Bacterial Agents/pharmacology , Humans , Microbial Viability/drug effects , Pentose Phosphate Pathway/drug effects , Fructosediphosphates/pharmacology , Fructosediphosphates/metabolismABSTRACT
The grass family (Poaceae) dominates ~43 % of Earth's land area and contributes 33 % of terrestrial primary productivity that is critical to naturally regulating atmosphere CO2 concentration and global climate change. Currently grasses comprise ~11,780 species and ~50 % of them (~6000 species) utilize C4 photosynthetic pathway. Generally, grass species have smaller leaves under colder and drier environments, but it is unclear whether the primary drivers of leaf size differ between C3 and C4 grasses on a global scale. Here, we analyzed 34 environmental variables, such as latitude, elevation, mean annual temperature, mean annual precipitation, and solar radiation etc., through a comparatively comprehensive database of ~3.0 million occurrence records from 1380 C3 and 978 C4 grass species (2358 species in total). Results from this study confirm that C4 grasses have occupied habitats with lower latitudes and elevations, characterized by warmer, sunnier, drier and less fertile environmental conditions. Grass leaf size correlates positively with mean annual temperature and precipitation as expected. Our results also demonstrate that the mean temperature of the wettest quarter of the year is the primary control for C3 leaf size, whereas C4 leaf size is negatively correlated with the difference between summer and winter temperatures. For C4 grasses, phylogeny exerts a significant effect on leaf size but is less important than environmental factors. Our findings highlight the importance of evolutionarily contrasting variations in leaf size between C3 and C4 grasses for shaping their geographical distribution and habitat suitability at the global scale.
Subject(s)
Ecosystem , Plant Leaves , Poaceae , Poaceae/anatomy & histology , Plant Leaves/anatomy & histology , Photosynthesis , Climate ChangeABSTRACT
Soil salinization is one of the leading threats to global ecosystems, food security, and crop production. Plant growth-promoting rhizobacteria (PGPRs) are potential bioinoculants that offer an alternative eco-friendly agricultural approach to enhance crop productivity from salt-deteriorating lands. The current work presents bacterial strain CNUC13 from maize rhizosphere soil that exerted several PGPR traits and abiotic stress tolerance. The strain tolerated up to 1000 mM NaCl and 30% polyethylene glycol (PEG) 6000 and showed plant growth-promoting (PGP) traits, including the production of indole-3-acetic acid (IAA) and siderophore as well as phosphate solubilization. Phylogenetic analysis revealed that strain CNUC13 was Microbacterium azadirachtae. Maize plants exposed to high salinity exhibited osmotic and oxidative stresses, inhibition of seed germination, plant growth, and reduction in photosynthetic pigments. However, maize seedlings inoculated with strain CNUC13 resulted in significantly improved germination rates and seedling growth under the salt-stressed condition. Specifically, compared with the untreated control group, CNUC13-treated seedlings exhibited increased biomass, including fresh weight and root system proliferation. CNUC13 treatment also enhanced photosynthetic pigments (chlorophyll and carotenoids), reduced the accumulation of osmotic (proline) and oxidative (hydrogen peroxide and malondialdehyde) stress indicators, and positively influenced the activities of antioxidant enzymes (catalase, superoxide dismutase, and peroxidase). As a result, CNUC13 treatment alleviated oxidative stress and promoted salt tolerance in maize. Overall, this study demonstrates that M. azadirachtae CNUC13 significantly enhances the growth of salt-stressed maize seedlings by improving photosynthetic efficiency, osmotic regulators, oxidative stress resilience, and antioxidant enzyme activity. These findings emphasize the potential of utilizing M. azadirachtae CNUC13 as a bioinoculant to enhance salt stress tolerance in maize, providing an environmentally friendly approach to mitigate the negative effects of salinity and promote sustainable agriculture.
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Monolayer transition metal dichalcogenides (TMDs) are considered promising building blocks for next-generation photonic and optoelectronic devices, owing to their fascinating optical properties. However, their inherent weak light absorption and low quantum yield severely hinder their practical applications. Here, we report up to 18000-fold photoluminescence (PL) enhancement in a monolayer WSe2-coupled plasmonic nanocavity. A spectroscopy-assisted nanomanipulation technique enables the assembly of a nanocavity with customizable resonances to simultaneously enhance the excitation and emission processes. In particular, precise control over the magnetic cavity mode facilitates spectral and spatial overlap with the exciton, resulting in plasmon-exciton intermediate coupling that approaches the maximum emission rate in the hybrid system. Meanwhile, the cavity mode exhibits high radiation directivity, which overwhelmingly directs surface-normal PL emission and leads to a 17-fold increase in the collection efficiency. Our approach opens up a new avenue to enhance the PL intensity of monolayer TMDs, facilitating their implementation in highly efficient optoelectronic devices.
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Although deep networks have succeeded in various signal classification tasks, the time sequence samples used to train the deep models are usually required to reach a certain length. Especially, in brain computer interface (BCI) research, around 3.5s-long motor imagery (MI) Electroencephalography (EEG) samples are needed to obtain satisfactory classification performance. This time-span requirement of the training samples makes real-time MI BCI systems impossible to implement based on deep networks, which restricts the related researches within laboratory and makes practical application hard to accomplish. To address this issue, a double-point observation deep network (DoNet) is developed to classify ultra-short samples buried in noise. First, an analytical solution is developed theoretically to perform ultra-short signal classification based on double-point couples. Then, a signal-noise model is constructed to study the interference of noise on classification based on double-point couples. Based on which, an independent identical distribution condition is utilized to improve the classification accuracy in a data-driven manner. Combining the theoretical model and data-driven mechanism, DoNet can construct a steady data-distribution for the double-point couples of the samples with the same label. Therefore, the conditional probability of each double-point couple of a test sample can be obtained. With a voting strategy, the samples can be accurately classified by fusing these conditional probabilities. Meanwhile, the noise interference can be suppressed. DoNet has been evaluated on two public EEG datasets. Compared to most state-of-the-art methods, the 1s-long EEG signal classification accuracy has been improved by more than 3%.
Subject(s)
Brain-Computer Interfaces , Electroencephalography , Signal Processing, Computer-Assisted , Electroencephalography/methods , Electroencephalography/classification , Humans , Algorithms , Deep Learning , Imagination/physiology , Brain/physiologyABSTRACT
The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton's jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-ß/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-ß, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery.
Subject(s)
Fractures, Stress , Humans , Animals , Rabbits , Cartilage , Chondrocytes , Transforming Growth Factor beta , Transforming Growth FactorsABSTRACT
Colonisation by bacterial pathogens typically precedes invasive infection and seeds transmission. Thus, effective decolonisation strategies are urgently needed. The literature reports attempts to use phages for decolonisation. To assess the in-vivo efficacy and safety of phages for bacterial decolonisation, we performed a systematic review by identifying relevant studies to assess the in-vivo efficacy and safety of phages for bacterial decolonisation. We searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and the Cochrane Library to identify relevant articles published between Jan 1, 1990, and May 12, 2023, without language restrictions. We included studies that assessed the efficacy of phage for bacterial decolonisation in humans or vertebrate animal models. This systematic review is registered with PROSPERO, CRD42023457637. We identified 6694 articles, of which 56 (51 animal studies and five clinical reports) met the predetermined selection criteria and were included in the final analysis. The gastrointestinal tract (n=49, 88%) was the most studied bacterial colonisation site, and other sites were central venous catheters, lung, nose, skin, and urinary tract. Of the 56 included studies, the bacterial load at the colonisation site was reported to decrease significantly in 45 (80%) studies, but only five described eradication of the target bacteria. 15 studies reported the safety of phages for decolonisation. No obvious adverse events were reported in both the short-term and long-term observation period. Given the increasing life-threatening risks posed by bacteria that are difficult to treat, phages could be an alternative option for bacterial decolonisation, although further optimisation is required before their application to meet clinical needs.
Subject(s)
Bacterial Infections , Bacteriophages , Humans , Bacterial Infections/therapy , Animals , Bacteria/virology , Phage Therapy/methodsABSTRACT
The incorporation of pentagon-heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a method for the stepwise construction of pentagon-heptagon pairs in helical nanographenes by the dehydrogenation of [6]helicene units was developed. Three helical nanographenes containing pentagon-heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon-heptagon pairs. The embedded pentagon-heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon-heptagon pairs.
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OBJECTIVE: To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism. METHODS: A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed. RESULTS: The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c.1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+PVS1_Supporting+PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved. CONCLUSION: The c.1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.