Evolving brain network dynamics in early childhood: Insights from modular graph metrics.

Modular dynamic graph theory metrics effectively capture the patterns of dynamic information interaction during human brain development. While existing research has employed modular algorithms to examine the overall impact of dynamic changes in community structure throughout development, there is a notable gap in understanding the cross-community dynamic changes within different functional networks during early childhood and their potential contributions to the efficiency of brain information transmission. This study seeks to address this gap by tracing the trajectories of cross-community structural changes within early childhood functional networks and modeling their contributions to information transmission efficiency. We analyzed 194 functional imaging scans from 83 children aged 2 to 8 years, who participated in passive viewing functional magnetic resonance imaging sessions. Utilizing sliding windows and modular algorithms, we evaluated three spatiotemporal metrics-temporal flexibility, spatiotemporal diversity, and within-community spatiotemporal diversity-and four centrality metrics: within-community degree centrality, eigenvector centrality, between-community degree centrality, and between-community eigenvector centrality. Mixed-effects linear models revealed significant age-related increases in the temporal flexibility of the default mode network (DMN), executive control network (ECN), and salience network (SN), indicating frequent adjustments in community structure within these networks during early childhood. Additionally, the spatiotemporal diversity of the SN also displayed significant age-related increases, highlighting its broad pattern of cross-community dynamic interactions. Conversely, within-community spatiotemporal diversity in the language network exhibited significant age-related decreases, reflecting the network's gradual functional specialization. Furthermore, our findings indicated significant age-related increases in between-community degree centrality across the DMN, ECN, SN, language network, and dorsal attention network, while between-community eigenvector centrality also increased significantly for the DMN, ECN, and SN. However, within-community eigenvector centrality remained stable across all functional networks during early childhood. These results suggest that while centrality of cross-community interactions in early childhood functional networks increases, centrality within communities remains stable. Finally, mediation analysis was conducted to explore the relationships between age, brain dynamic graph metrics, and both global and local efficiency based on community structure. The results indicated that the dynamic graph metrics of the SN primarily mediated the relationship between age and the decrease in global efficiency, while those of the DMN, language network, ECN, dorsal attention network, and SN primarily mediated the relationship between age and the increase in local efficiency. This pattern suggests a developmental trajectory in early childhood from global information integration to local information segregation, with the SN playing a pivotal role in this transformation. This study provides novel insights into the mechanisms by which early childhood brain functional development impacts information transmission efficiency through cross-community adjustments in functional networks.

Cell-Based Micro/Nano-Robots for Biomedical Applications: A Review.

Micro/nano-robots are powerful tools for biomedical applications and are applied in disease diagnosis, tumor imaging, drug delivery, and targeted therapy. Among the various types of micro-robots, cell-based micro-robots exhibit unique properties because of their different cell sources. In combination with various actuation methods, particularly externally propelled methods, cell-based microrobots have enormous potential for biomedical applications. This review introduces recent progress and applications of cell-based micro/nano-robots. Different actuation methods for micro/nano-robots are summarized, and cell-based micro-robots with different cell templates are introduced. Furthermore, the review focuses on the combination of cell-based micro/nano-robots with precise control using different external fields. Potential challenges, further prospects, and clinical translations are also discussed.

SE-FSCNet: full-scale connection network for single-shot phase demodulation.

The accuracy of phase demodulation has significant impact on the accuracy of fringe projection 3D measurement. Currently, researches based on deep learning methods for extracting wrapped phase mostly use U-Net as the subject of network. The connection method between its hierarchies has certain shortcomings in global information transmission, which hinders the improvement of wrapped phase prediction accuracy. We propose a single-shot phase demodulation method for fringe projection based on a novel full-scale connection network SE-FSCNet. The encoder and decoder of the SE-FSCNet have the same number of hierarchies but are not completely symmetrical. At the decoder a full-scale connection method and feature fusion module are designed so that SE-FSCNet has better abilities of feature transmission and utilization compared with U-Net. A channel attention module based on squeeze and excitation is also introduced to assign appropriate weights to features with different scales, which has been proved by the ablation study. The experiments conducted on the test set have demonstrated that the SE-FSCNet can achieve higher precision than the traditional Fourier transform method and the U-Net in phase demodulation.

A Coupled Calibration Method for Dual Cameras-Projector System with Sub-Pixel Accuracy Feature Extraction.

Binocular structured light systems are widely used in 3D measurements. In the condition of complex and local highly reflective scenes, to obtain more 3D information, binocular systems are usually divided into two pairs of devices, each having a Single Camera and a Projector (SCP). In this case, the binocular system can be seen as Dual Cameras-Projector (DCP) system. In the DCP calibration, the Left-SCP and Right-SCP need to be calibrated separately, which leads to inconsistent parameters for the same projector, thus reducing the measurement accuracy. To solve this problem and improve manoeuvrability, a coupled calibration method using an orthogonal phase target is proposed. The 3D coordinates on a phase target are uniquely determined by the binocular camera in DCP, rather than being calculated separately in each SCP. This ensures the consistency of the projector parameters. The coordinates of the projector image plane are calculated through the unwrapped phase, while the parameters are calibrated by the plane calibration method. In order to extract sub-pixel accuracy feature points, a method based on polynomial fitting using an orthogonal phase target is exploited. The experimental results show that the reprojection error of our method is less than 0.033 pixels, which improves the calibration accuracy.

Crystal structures of N-terminally truncated telomerase reverse transcriptase from fungi‡.

Telomerase plays critical roles in cellular aging, in the emergence and/or development of cancer, and in the capacity for stem-cell renewal, consists of a catalytic telomerase reverse transcriptase (TERT) and a template-encoding RNA (TER). TERs from diverse organisms contain two conserved structural elements: the template-pseudoknot (T-PK) and a helical three-way junction (TWJ). Species-specific features of the structure and function of telomerase make obtaining a more in-depth understanding of the molecular mechanism of telomerase particularly important. Here, we report the first structural studies of N-terminally truncated TERTs from Candida albicans and Candida tropicalis in apo form and complexed with their respective TWJs in several conformations. We found that Candida TERT proteins perform only one round of telomere addition in the presence or absence of PK/TWJ and display standard reverse transcriptase activity. The C-terminal domain adopts at least two extreme conformations and undergoes conformational interconversion, which regulates the catalytic activity. Most importantly, we identified a conserved tertiary structural motif, called the U-motif, which interacts with the reverse transcriptase domain and is crucial for catalytic activity. Together these results shed new light on the structure and mechanics of fungal TERTs, which show common TERT characteristics, but also display species-specific features.

Quercitrin Is a Novel Inhibitor of Salmonella enterica Serovar Typhimurium Type III Secretion System.

The purpose was to screen type III secretory system (T3SS) inhibitors of Salmonella enterica serovar Typhimurium (S. Typhimurium) from natural compounds. The pharmacological activities and action mechanisms of candidate compounds in vivo and in vitro were systematically studied and analyzed. Using a SipA-ß-lactamase fusion reporting system, we found that quercitrin significantly blocked the translocation of SipA into eukaryotic host cells without affecting the growth of bacteria. Adhesion and invasion assay showed that quercitrin inhibited S. Typhimurium invasion into host cells and reduced S. Typhimurium mediated host cell damage. ß-galactosidase activity detection and Western blot analysis showed that quercitrin significantly inhibited the expression of SPI-1 genes (hilA and sopA) and effectors (SipA and SipC). The results of animal experiments showed that quercitrin significantly reduced colony colonization and alleviated the cecum pathological injury of the infected mice. Small molecule inhibitor quercitrin directly inhibited the function of T3SS and provided a potential antibiotic alternative against S. Typhimurium infection. Importance: T3SS plays a crucial role in the bacterial invasion and pathogenesis of S. Typhimurium. Compared with conventional antibiotics, small molecules could inhibit the virulence factors represented by S. Typhimurium T3SS. They have less pressure on bacterial vitality and a lower probability of producing drug resistance. Our results provide strong evidence for the development of novel inhibitors against S. Typhimurium infection.

NCs-Delivered Pesticides: A Promising Candidate in Smart Agriculture.

Pesticides have been used extensively in the field of plant protection to maximize crop yields. However, the long-term, unmanaged application of pesticides has posed severe challenges such as pesticide resistance, environmental contamination, risk in human health, soil degradation, and other important global issues. Recently, the combination of nanotechnology with plant protection strategies has offered new perspectives to mitigate these global issues, which has promoted a rapid development of NCs-based pesticides. Unlike certain conventional pesticides that have been applied inefficiently and lacked targeted control, pesticides delivered by nanocarriers (NCs) have optimized formulations, controlled release rate, and minimized or site-specific application. They are receiving increasing attention and are considered as an important part in sustainable and smart agriculture. This review discussed the limitation of traditional pesticides or conventional application mode, focused on the sustainable features of NCs-based pesticides such as improved formulation, enhanced stability under harsh condition, and controlled release/degradation. The perspectives of NCs-based pesticides and their risk assessment were also suggested in this view for a better use of NCs-based pesticides to facilitate sustainable, smart agriculture in the future.

Hepatitis E virus infection during pregnancy: Advances in animal models.

Hepatitis E virus (HEV) is one of the major pathogens causing acute viral hepatitis worldwide, which usually causes acute self-limited diseases in general individuals. However, it can lead to high mortality and adverse pregnancy outcomes in pregnant women. Due to the lack of effective and stable cell culture models for HEV, the establishment of suitable animal models for HEV infection during pregnancy is necessary. An electronic search of the relevant database was conducted to identify eligible articles. Main animal models for the study of HEV infection during pregnancy include rabbits, swine, nonhuman primates and Mongolian gerbils. These animal models have been used to study the prevention, treatment and possible mechanisms of HEV infection during pregnancy. Studies using these animal models have investigated the potential pathogenesis of HEV infection during pregnancy. It has been found that immune mechanism (changes in the CD4/CD8 ratio and cytokines), hormonal changes (increase in pregnancy-related hormones) and viral factors (different genotypes and genome structures) can lead to HEV-related adverse pregnancy outcomes in animal models. In this review, we aimed to comprehensively present the characteristics of different animal models and the pathogenesis of HEV-related adverse pregnancy outcomes.

Exploring the mechanism of interaction between TBG and halogenated thiophenols: Insights from fluorescence analysis and molecular simulation.

Thyroxine-binding globulin (TBG) plays a vital role in regulating metabolism, growth, organ differentiation, and energy homeostasis, exerting significant effects in various key metabolic pathways. Halogenated thiophenols (HTPs) exhibit high toxicity and harmfulness to organisms, and numerous studies have demonstrated their thyroid-disrupting effects. To understand the mechanism of action of HTPs on TBG, a combination of competitive binding experiments, multiple fluorescence spectroscopy techniques, molecular docking, and molecular simulations was employed to investigate the binding mechanism and identify the binding site. The competition binding assay between HTPs and ANS confirmed the competition of HTPs with thyroid hormone T4 for the active site of TBG, resulting in changes in the TBG microenvironment upon the binding of HTPs to the active site. Key amino acid residues involved in the binding process of HTPs and TBG were further investigated through residue energy decomposition. The distribution of high-energy contributing residues was determined. Analysis of root-mean-square deviation (RMSD) demonstrated the stability of the HTPs-TBG complex. These findings confirm the toxic mechanism of HTPs in thyroid disruption, providing a fundamental reference for accurately assessing the ecological risk of pollutants and human health. Providing mechanistic insights into how HTPS causes thyroid diseases.

Analysis of Binding Modes between Three Perfluorosulfonates and GPER Based on Computational Simulation and Multiple Spectral Methods.

Perfluorinated compounds (PFCs) belong to a significant category of global environmental pollutants. Investigating the toxicological effects of PFCs within biological systems is of critical significance in various disciplines such as life sciences, environmental science, chemistry, and ecotoxicology. In this study, under simulated human physiological conditions (pH = 7.4), a combination of multiple spectroscopic techniques and computational simulations was employed to investigate the impact of perfluorinated compounds (PFCs) on the G protein-coupled estrogen receptor (GPER). Additionally, the research focused on exploring the binding modes and toxicological mechanisms between PFCs and GPER at the molecular level. All three perfluorinated sulfonic acids (PFSAs) can induce quenching of GPER fluorescence through static quenching and non-radiative energy transfer. Steady-state fluorescence calculations at different temperatures revealed apparent binding constants in the order of 106, confirming a strong binding affinity between the three PFSAs and GPER. Molecular docking studies indicated that the binding sites of PFSAs are located within the largest hydrophobic cavity in the head region of GPER, where they can engage in hydrogen bonding and hydrophobic interactions with amino acid residues within the cavity. Fourier transform infrared spectroscopy, three-dimensional fluorescence, and molecular dynamics simulations collectively indicate that proteins become more stable upon binding with small molecules. There is an overall increase in hydrophobicity, and alterations in the secondary structure of the protein are observed. This study deepens the comprehension of the effects of PFCs on the endocrine system, aiding in evaluating their potential impact on human health. It provides a basis for policy-making and environmental management while also offering insights for developing new pollution monitoring methods and drug therapies.

Developmental dynamics of brain network modularity and temporal co-occurrence diversity in childhood.

OBJECTIVE: Brain development during childhood involves significant structural, functional, and connectivity changes, reflecting the interplay between modularity, information interaction, and functional segregation. This study aims to understand the dynamic properties of brain connectivity and their impact on cognitive development, focusing on temporal co-occurrence diversity patterns. METHODS: We recruited 481 children aged 6 to 12 years from the Healthy Brain Network database. Functional MRI data were used to construct dynamic functional connectivity matrices with a sliding window approach. Modular structures were identified using multilayer network community detection, and the Dagum Gini coefficient decomposition technique, which uniquely allows for multi-faceted exploration of modular temporal co-occurrence diversities, quantified these diversities. Mediation analysis assessed the impact on small-world properties. RESULTS: Temporal co-occurrence diversity in brain networks increased with age, especially in the default mode, frontoparietal, and salience networks. These changes were driven by disparities within and between communities. The small-world coefficient increased with age, indicating improved information processing efficiency. To validate the impact of changes in spatiotemporal interaction disparities during childhood on information transmission within brain networks, we used mediation analysis to verify its effect on alterations in small-world properties. CONCLUSION: This study highlights the critical developmental changes in brain modularity and spatiotemporal interaction patterns during childhood, emphasizing their role in cognitive maturation. These insights into neural mechanisms can inform the diagnosis and intervention of developmental disorders.

Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis.

OBJECTIVES: Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms. METHODS: In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins. RESULTS: PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system. CONCLUSION: PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.

Effect of Soy Protein Isolate on the Quality Characteristics of Silver Carp Surimi Gel during Cold Storage.

This study mainly investigated the effect of soy protein isolate (SPI) on the gel quality of silver carp surimi under different storage conditions (storage temperatures of 4 °C, -20 °C, and -40 °C, and storage times of 0, 15, and 30 d). The results found that 10% SPI could inhibit the growth of ice crystals, improve the water distribution, enhance the water holding capacity of the gels, and strengthen the interaction between surimi and proteins. Compared to the control group, the composite silver carp surimi gel exhibited superior quality in texture, chemical interactions, and rheological properties during cold storage. Fourier transform infrared spectroscopy revealed an increasing trend in α-helix and ß-turn content and a decreasing trend of ß-sheet and random coil content. As storage time increased, the gel deterioration during cold storage inhibitory effect of the treatment group was superior to the control group, with the best results observed at -40 °C storage conditions. Overall, SPI was a good choice for maintaining the quality of silver carp surimi gel during cold storage, which could significantly reduce the changes in the textural properties during cold storage with improved water holding capacity.

Potential analgesic effect of a novel cannabidiol nanocrystals powder for the treatment of neuropathic pain.

BACKGROUND: The current analgesics often prevent patients from getting effective treatment due to their adverse effects. Cannabidiol (CBD) is well tolerated, has few side effects and has been extensively investigated in analgesia. However, its oral bioavailability is extremely low. In order to solve this problem, we developed the cannabidiol nanocrystals (CBD-NC) in the earlier stage. METHODS: In this study, we evaluated the nociceptive behaviours associated with neuropathic pain (NP) induced by the spared nerve injury (SNI) model. Assessment of pain threshold was evaluated by paw withdraw threshold (PWT) and paw withdrawal latency (PWL). The improving effect on the motor dysfunction was determined by rota-rod testing. To assess the neuroprotective effect, nerve demyelination and expression of peripheral myelin protein PMP22 were measured with myelin sheath staining and western blotting. Protein expressions in microglia of spinal cord were tested by western blot to explore the underlying mechanism. RESULTS: Compared with the CBD oil solution, CBD-NC significantly reduced mechanical allodynia and thermal hyperalgesia in rats. CBD-NC could improve motor dysfunction induced by SNI in rats, significantly reverse the demyelination and increase the expression of the marker protein of peripheral myelin. Underlying spinal analgesic mechanism of microglia and related factors were preliminarily confirmed. CONCLUSIONS: CBD-NC administration is an effective treatment for NP associated with SNI, and the analgesic effect of CBD-NC was significantly better than that of CBD oil sol. By contrast, CBD-NC has a fast-acting and long-term effect in the treatment of NP. Our study further supports the potential therapeutic effect of CBD-NC on NP. SIGNIFICANCE: The absolute bioavailability of the CBD-NC intramuscular injection formulation can reach 203.31%, which can solve the problem of low oral bioavailability. This research evaluated the therapeutic effect of CBD-NC on NP associated with the SNI model for the first time. All available date showed that whatever the analgesic or neuroprotective effect of CBD-NC, it was significantly better than that of CBD oil sol., which was consistent with the results of the pharmacokinetic. This research supports the initiation of more trials testing the efficacy of CBD-NC for treating NP.

The molecular mechanisms of TRß receptor interaction with polychlorinated biphenyls: A multispectral and computational exploration.

The thyroid hormone (TH) system is susceptible to the toxic effects of polychlorinated biphenyls (PCBs). Pollutants may disrupt the TH system by binding to serum TH transport proteins or interacting with thyroid hormone receptors (TRs) in target cells. However, the molecular mechanism of interaction with the Thyroid Hormone Receptor Beta (TRß) is not fully understood. This study employed fluorescence, UV-visible absorption, three-dimensional fluorescence, and Fourier-transform infrared spectroscopy, along with molecular docking and molecular dynamics simulations, to investigate the interaction between TRß and PCBs. Moreover, molecular docking and fluorescence resonance energy transfer (FRET) findings suggest that TRß and PCBs underwent resonance energy transfer consistent with Förster's theory. The root mean square deviation (RMSD) and docking outcomes indicate that the TRß-PCB29 complex exhibited optimal structural stability. Thus, the study concludes that integrating spectroscopic data with molecular docking is essential for a comprehensive analysis. Further analysis of intermolecular interactions using quantum chemistry and reduced density gradient analysis (RDG) analysis revealed that van der Waals forces are the primary drivers of PCBs to TRß.

Abnormal white matter changes in Alzheimer's disease based on diffusion tensor imaging: A systematic review.

Alzheimer's disease (AD) is a degenerative neurological disease in elderly individuals. Subjective cognitive decline (SCD), mild cognitive impairment (MCI) and further development to dementia (d-AD) are considered to be major stages of the progressive pathological development of AD. Diffusion tensor imaging (DTI), one of the most important modalities of MRI, can describe the microstructure of white matter through its tensor model. It is widely used in understanding the central nervous system mechanism and finding appropriate potential biomarkers for the early stages of AD. Based on the multilevel analysis methods of DTI (voxelwise, fiberwise and networkwise), we summarized that AD patients mainly showed extensive microstructural damage, structural disconnection and topological abnormalities in the corpus callosum, fornix, and medial temporal lobe, including the hippocampus and cingulum. The diffusion features and structural connectomics of specific regions can provide information for the early assisted recognition of AD. The classification accuracy of SCD and normal controls can reach 92.68% at present. And due to the further changes of brain structure and function, the classification accuracy of MCI, d-AD and normal controls can reach more than 97%. Finally, we summarized the limitations of current DTI-based AD research and propose possible future research directions.

Investigation of functional connectivity in Bell's palsy using functional magnetic resonance imaging: prospective cross-sectional study.

Background: The most common cause of lower motor neuron facial palsy is Bell's palsy (BP). BP results in partial or complete inability to automatically move the facial muscles on the affected side and, in some cases, to close the eyelids, which can cause permanent eye damage. This study investigated changes in brain function and connectivity abnormalities in patients with BP. Methods: This study included 46 patients with unilateral BP and 34 healthy controls (HCs). Resting-state brain functional magnetic resonance imaging (fMRI) images were acquired, and Toronto Facial Grading System (TFGS) scores were obtained for all participants. The fractional amplitude of low-frequency fluctuation (fALFF) was estimated, and the relationship between the TFGS and fALFF was determined using correlation analysis for brain regions with changes in fALFF in those with BP versus HCs. Brain regions associated with TFGS were used as seeds for further functional connectivity (FC) analysis; relationships between FC values of abnormal areas and TFGS scores were also analyzed. Results: Activation of the right precuneus, right angular gyrus, left supramarginal gyrus, and left middle occipital gyrus was significantly decreased in the BP group. fALFF was significantly higher in the right thalamus, vermis, and cerebellum of the BP group compared with that in the HC group (P<0.05). The FC between the left middle occipital gyrus and right angular gyrus, left precuneus, and right middle frontal gyrus increased sharply, but decreased in the left angular gyrus, left posterior cingulate gyrus, left middle frontal gyrus, inferior cerebellum, and left middle temporal gyrus. Furthermore, the fALFF in the left middle occipital gyrus was negatively correlated with TFGS score (R=0.144; P=0.008). Conclusions: The pathogenesis of BP is closely related to functional reorganization of the cerebral cortex. Patients with BP have altered fALFF activity in cortical regions associated with facial motion feedback monitoring.

Clusterin regulates TRPM2 to protect against myocardial injury induced by acute myocardial infarction injury.

BACKGROUND: Clusterin and transient receptor potential melastatin 2 (TRPM2) play significant roles in acute myocardial infarction (AMI), but their interactions in AMI are unclear. METHODS: Myocardial infarction was induced by ligation of the left anterior descending coronary artery in wild-type C57BL/6J male mice. Infarct size and myocardium pathology were evaluated after 6, 12, and 24 h of ischemia. The expression levels of clusterin and TRPM2 were measured in the myocardium. Furthermore, myocardial infarction was induced in TRPM2 knockout (TRPM2-/-) C57BL/6J male mice to evaluate the expression of clusterin. H9C2 cells with various levels of TRPM2 expression were used to analyze the effects of clusterin under hypoxic conditions. RESULTS: Following AMI, myocardial hypertrophy and TRPM2 expression increased in a time-dependent manner. In contrast, the expression of clusterin decreased in an infarct time-dependent manner. Knockout of TRPM2 protected against myocardial injury and resulted in upregulation of clusterin. In the H9C2 cells, cultured under hypoxic conditions treatment with clusterin or silencing of TRPM2 significantly increased cell viability and decreased TRPM2 expression. Treatment with clusterin protected against TRPM2 overexpression-induced damage in hypoxia-treated H9C2 cells. CONCLUSION: This study characterized the effects of clusterin on TRPM2 in AMI, which may guide development of new treatment strategies for AMI.

Piceatannol-3'-O-ß-d-glucopyranoside alleviates nephropathy via regulation of High mobility group B-1 (HMGB1)/Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) signalling pathway.

OBJECTIVES: Nephrotic syndrome (NS) remains a therapeutic challenge for nephrologists. Piceatannol-3'-O-ß-d-glucopyranoside (PG) is a major active ingredient in Quzha. The purpose of the study was to assess the renoprotection of PG. METHODS: In vitro, the podocyte protection of PG was assessed in MPC-5. SD rats were injected with adriamycin to induce nephropathy in vivo. The determination of biochemical changes and inflammatory cytokines was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyse expression levels of proteins. KEY FINDINGS: The results showed that PG improved adriamycin-induced podocyte injury, attenuated nephropathy, improved hypoalbuminemia and hyperlipidaemia, and lowered cytokine levels. The podocyte protection of PG was further verified by reduction of desmin and increasing synaptopodin expression. Furthermore, treatment with PG down-regulated the expression of HMGB1, TLR4 and NF-κB along with its upstream regulator, IKKß and yet up-regulated IκBα expression by western blot analysis. CONCLUSIONS: Overall, our data showed that PG has a favourable renoprotection in experimental nephrosis, apparently by amelioration of podocyte injury. PG might mediate these effects via modulation of the HMGB1/TLR4/NF-κB signalling pathway. The study first provides a promising leading compound for the treatment of NS.

Relationship among number of close friends, subclinical geriatric depression, and subjective cognitive decline based on regional homogeneity of functional magnetic resonance imaging data.

The relationship between geriatric depression and dementia has been widely debated, and the neurological mechanisms underlying subjective cognitive decline (SCD) associated with social relationships remain elusive. Subclinical geriatric depression (SGD) is common in patients with SCD, and close friends (CFs) have a great influence on a person's social life. Studies have proven that communication or leisure activities with CFs can improve the cognitive performance of elderly. However, it remains unclear whether the engagement of specific brain regions mediates having CFs, SGD, and SCD. In this study, we aimed to assess the association between social relationships (that is, CFs), SGD, and SCD from the perspective of brain function. We examined the data of 66 patients with SCD and 63 normal controls (NC). Compared with NC, SGD was significantly inversely correlated with the number of CFs in the SCD group. We calculated regional homogeneity (ReHo) of functional magnetic resonance imaging (MRI) data of each subject. At a corrected threshold, the right occipital gyrus (SOG.R) and right fusiform gyrus (FFG.R) exhibited positive correlation with SGD in patients with SCD. Mediation analyses to query the inter-relationships between the neural markers and clinical variables exhibited a best fit of the model with CFs → FFG.R → SGD → SOG.R → SCD. These findings suggested a pathway whereby social relationships alter the function of specific brain regions, and SGD may be an early symptom of SCD. We observed that the FFG.R mediate social relationships and SGD, and the abnormality of the SOG.R may be a key factor in the SCD caused by depression. Moreover, a greater number of CFs may reduce the risk of developing SGD.