Platelets promote primary hepatocellular carcinoma metastasis through TGF-ß1-mediated cancer cell autophagy.

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.

Chromolaena odorata affects soil nitrogen transformations and competition in tropical coral islands by altering soil ammonia oxidizing microbes.

Invasive plants can change the community structure of soil ammonia-oxidizing microbes, affect the process of soil nitrogen (N) transformation, and gain a competitive advantage. However, the current researches on competition mechanism of Chromolaena odorata have not involved soil nitrogen transformation. In this study, we compared the microbially mediated soil transformations of invasive C. odorata and natives (Pisonia grandis and Scaevola taccada) of tropical coral islands. We assessed how differences in plant biomass and tissue N contents, soil nutrients, N transformation rates, microbial biomass and activity, and diversity and abundance of ammonia oxidizing microbes associated with these species impact their competitiveness. The results showed that C. odorata outcompeted both native species by allocating more proportionally biomass to aboveground parts in response to interspecific competition (12.92 % and 22.72 % more than P. grandis and S. taccada, respectively). Additionally, when C. odorata was planted with native plants, the available N and net mineralization rates in C. odorata rhizosphere soil were higher than in native plants rhizosphere soils. Higher abundance of ammonia-oxidizing bacteria in C. odorata rhizosphere soil confirmed this, being positively correlated with soil N mineralization rates and available N. Our findings help to understand the soil N acquisition and competition strategies of C. odorata, and contribute to improving evaluations and predictions of invasive plant dynamics and their ecological effects in tropical coral islands.

Fulminant fatal pneumonia and bacteremia due to Aeromonas dhakensis in an immunocompetent man: a case report and literature review.

Background: Aeromonas dhakensis is associated with soft tissue infection, bacteremia and gastroenteritis. Involvement of respiratory system in adults is extremely rare. We report a case of fulminant pneumonia and bacteremia due to A. dhakensis in a patient without underlying diseases. Case presentation: A 26-year-old man became ill suddenly with pneumonia after swimming in a river. Despite intensive support measures in the intensive care unit, he died 13 hours after admission and 4 days after his first symptoms. Autopsy showed abundant Gram-negative bacteria, massive inflammatory cell infiltration, edema, necrosis and hemorrhage in lung tissue. A. dhakensis was isolated from blood culture taken at admission and bronchoalveolar lavage fluid (BALF) after intubation. Moreover, A. dhakensis was also detected in lung tissue by metagenomic next-generation sequencing (mNGS) assay. The infection may have come from river water. Conclusion: In patients who develop a fulminant pneumonia after contacting an aquatic environment, A. dhakensis should be alerted and mNGS may aid in the detection of aquatic pathogens by being more sensitive and specific versus traditional bacterial culture.

A Reverse Thinking Based on Partially Methylated Aldononitrile Acetates to Analyze Glycoside Linkages of Polysaccharides Using Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry.

Glycoside linkage analyses of medicine and food homologous plant polysaccharides have always been a key point and a difficulty of structural characterization. The gas chromatography-mass spectrometry (GC-MS) method is one of the commonly used traditional techniques to determine glycoside linkages via partially methylated alditol acetates and aldononitrile acetates (PMAAs and PMANs). Due to the simplicity of derivatization and the highly structural asymmetry of PMANs, reverse thinking is proposed using liquid chromatography-electrospray ionization-multiple reaction monitoring mass spectrometry (LC-ESI-MRM-MS) for the first time to directly determine the neutral and acidic glycosyl linkages of polysaccharides. The complete characterization of glycoside linkages deduced from PMANs was achieved using a combination of tR values, characteristic MRM ion pairs, diagnostic ESI+-MS/MS fragmentation ions (DFIs), and optimal collision energy (OCE). The DFI and OCE parameters were confirmed to be effective for the auxiliary discrimination of some isomers of the PMANs. The practicality of LC-ESI+-MRM-MS was further verified by analyzing the glycoside linkages of polysaccharides in five medicine and food homologous plants. This method can serve as an alternative to GC-MS for the simultaneous determination of neutral and acidic glycosyl linkages in polysaccharides.

Treatment outcomes in tinnitus patients are associated with brain functional network: Evidence from connectome gradient and gene expression analysis.

The neuroimaging mechanisms underlying differences in the outcomes of sound therapy for tinnitus patients remain unclear. We hypothesize that abnormal hierarchical architecture is the neuro-biomarker for treatment outcome explanation. We conducted functional connectome gradient analyses on resting-state functional MRI images that acquired before intervention to investigate differences among the patients with effective treatment (ET, n = 27), ineffective treatment (IT, n = 41), and healthy controls (HC, n = 59). General linear models were used to analyze the associations between intergroup differential regions and clinical characteristics. Partial least squares regression was employed to reveal correlations with gene expression. Compared to HC, both ET and IT groups displayed significant differences in the default mode network. Moreover, the ET group exhibited wider gradient range and greater gradient variance. Also, the gradient scores of the differential regions between the ET and HC groups were significantly correlated with Self-rating Anxiety Scale and Self-rating Depression Scale scores, and exhibited positive correlations with the transcriptional profiles of genes related to depression and anxiety. Our results indicated that the abnormalities of ET group, may be more relevant to psychiatric disorders, bringing a higher possible therapeutic potential due to the plasticity of the nervous system. Connectome gradient dysfunction with genetic evidence may serve as an indicator for identifying diverse treatment outcomes of the sound therapy for tinnitus patients before treatment.

A catalyst family of high-entropy alloy atomic layers with square atomic arrangements comprising iron- and platinum-group metals.

We report a catalyst family of high-entropy alloy (HEA) atomic layers having three elements from iron-group metals (IGMs) and two elements from platinum-group metals (PGMs). Ten distinct quinary compositions of IGM-PGM-HEA with precisely controlled square atomic arrangements are used to explore their impact on hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR). The PtRuFeCoNi atomic layers perform enhanced catalytic activity and durability toward HER and HOR when benchmarked against the other IGM-PGM-HEA and commercial Pt/C catalysts. Operando synchrotron x-ray absorption spectroscopy and density functional theory simulations confirm the cocktail effect arising from the multielement composition. This effect optimizes hydrogen-adsorption free energy and contributes to the remarkable catalytic activity observed in PtRuFeCoNi. In situ electron microscopy captures the phase transformation of metastable PtRuFeCoNi during the annealing process. They transform from random atomic mixing (25°C), to ordered L10 (300°C) and L12 (400°C) intermetallic, and finally phase-separated states (500°C).

High-performance epoxy resin with flame-retardant, transparent, and ultraviolet shielding properties based on a vanillin-based multifunctional macromolecule.

Flame-retardant epoxy resins with tough, transparent, ultraviolet shielding, and low dielectric properties have fascinating prospects in electronic and electrical applications, but it is still challenging at present. In this work, a bio-based macromolecule was synthesized from vanillin (a lignin derivative), phenyl dichlorophosphate, 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO), and poly(propylene glycol) bis(2-aminopropyl ether). The bio-based macromolecule, namely, MFR, was designed and added to the epoxy resin (EP). The cured EP containing 15 wt% MFR (i.e., EP/MFR15) exhibits excellent flame retardancy with an Underwriter Laboratory 94 (UL-94) V-0 rating and a limiting oxygen index (LOI) of 29.2 %. Furthermore, the peak heat release rate (PHRR) and total heat release rate (THR) are drastically reduced by 59.5 % and 40.7 %, respectively. Meanwhile, EP/MFR15 shows 20.3 % and 43.8 % improvements in tensile strength and toughness, respectively. Moreover, MFR simultaneously endows EP with accessional ultraviolet shielding performance and low dielectric constant without sacrificing transparency. This work provides a promising strategy for fabricating a bio-based macromolecular flame retardant and preparing a high-performance EP composite with versatile properties.

The regulatory mechanism of cyclic GMP-AMP synthase on inflammatory senescence of nucleus pulposus cell.

BACKGROUND: Cellular senescence features irreversible growth arrest and secretion of multiple proinflammatory cytokines. Cyclic GMP-AMP synthase (cGAS) detects DNA damage and activates the DNA-sensing pathway, resulting in the upregulation of inflammatory genes and induction of cellular senescence. This study aimed to investigate the effect of cGAS in regulating senescence of nucleus pulposus (NP) cells under inflammatory microenvironment. METHODS: The expression of cGAS was evaluated by immunohistochemical staining in rat intervertebral disc (IVD) degeneration model induced by annulus stabbing. NP cells were harvested from rat lumbar IVD and cultured with 10ng/ml IL-1ß for 48 h to induce premature senescence. cGAS was silenced by cGAS specific siRNA in NP cells and cultured with IL-1ß. Cellular senescence was evaluated by senescence-associated beta-galactosidase (SA-ß-gal) staining and flow cytometry. The expression of senescence-associated secretory phenotype including IL-6, IL-8, and TNF-a was evaluated by ELISA and western blotting. RESULTS: cGAS was detected in rat NP cells in cytoplasm and the expression was significantly increased in degenerated IVD. Culturing in 10ng/ml IL-1ß for 48 h induced cellular senescence in NP cells with attenuation of G1-S phase transition. In senescent NP cells the expression of cGAS, p53, p16, NF-kB, IL-6, IL-8, TNF-α was significantly increased while aggrecan and collagen type II was reduced than in normal NP cells. In NP cells with silenced cGAS, the expression of p53, p16, NF-kB, IL-6, IL-8, and TNF-α was reduced in inflammatory culturing with IL-1ß. CONCLUSION: cGAS was increased by NP cells in degenerated IVD promoting cellular senescence and senescent inflammatory phenotypes. Targeting cGAS may alleviate IVD degeneration by reducing NP cell senescence.

Fragment-based discovery of small molecule inhibitors of the HDGFRP2 PWWP domain.

The PWWP domain of hepatoma-derived growth factor-related protein 2 (HDGFRP2) recognizes methylated histones to initiate the recruitment of homologous recombination repair proteins to damaged silent genes. The combined depletion of HDGFRP2 and its paralog PSIP1 effectively impedes the onset and progression of diffuse intrinsic pontine glioma (DIPG). Here, we discovered varenicline and 4-(4-bromo-1H-pyrazol-3-yl) pyridine (BPP) as inhibitors of the HDGFRP2 PWWP domain through a fragment-based screening method. The complex crystal structures reveal that both Varenicline and BPP engage with the aromatic cage of the HDGFRP2 PWWP domain, albeit via unique binding mechanisms. Notably, BPP represents the first single-digit micromolar inhibitor of the HDGFRP2 PWWP domain with a high ligand efficiency. As a dual inhibitor targeting both HDGFRP2 and PSIP1 PWWP domains, BPP offers an exceptional foundation for further optimization into a chemical tool to dissect the synergetic function of HDGFRP2 and PSIP1 in DIPG pathogenesis.

Heritability of functional gradients in the human subcortico-cortical connectivity.

The human subcortex plays a pivotal role in cognition and is widely implicated in the pathophysiology of many psychiatric disorders. However, the heritability of functional gradients based on subcortico-cortical functional connectivity remains elusive. Here, leveraging twin functional MRI (fMRI) data from both the Human Connectome Project (n = 1023) and the Adolescent Brain Cognitive Development study (n = 936) datasets, we construct large-scale subcortical functional gradients and delineate an increased principal functional gradient pattern from unimodal sensory/motor networks to transmodal association networks. We observed that this principal functional gradient is heritable, and the strength of heritability exhibits a heterogeneous pattern along a hierarchical unimodal-transmodal axis in subcortex for both young adults and children. Furthermore, employing a machine learning framework, we show that this heterogeneous pattern of the principal functional gradient in subcortex can accurately discern the relationship between monozygotic twin pairs and dizygotic twin pairs with an accuracy of 76.2% (P < 0.001). The heritability of functional gradients is associated with the anatomical myelin proxied by MRI-derived T1-weighted/T2-weighted (T1w/T2w) ratio mapping in subcortex. This study provides new insights into the biological basis of subcortical functional hierarchy by revealing the structural and genetic properties of the subcortical functional gradients.

Higher emotional synchronization is modulated by relationship quality in romantic relationships and not in close friendships.

Emotions are fundamental to social interaction and deeply intertwined with interpersonal dynamics, especially in romantic relationships. Although the neural basis of interaction processes in romance has been widely explored, the underlying emotions and the connection between relationship quality and neural synchronization remain less understood. Our study employed EEG hyperscanning during a non-interactive video-watching paradigm to compare the emotional coordination between romantic couples and close friends. Couples showed significantly greater behavioral and prefrontal alpha synchronization than friends. Notably, couples with low relationship quality required heightened neural synchronization to maintain robust behavioral synchronization. Further support vector machine analysis underscores the crucial role of prefrontal activity in differentiating couples from friends. In summary, our research addresses gaps concerning how intrinsic emotions linked to relationship quality influence neural and behavioral synchronization by investigating a natural non-interactive context, thereby advancing our understanding of the neural mechanisms underlying emotional coordination in romantic relationships.

Influence of blood loss on cerebral oxygen saturation in paediatric patients undergoing surgery for scoliosis correction: A retrospective observational study.

AIM: Surgery for congenital scoliosis correction in children is often associated with considerable blood loss. Decrease in regional oxygen saturation (rScO2) can reflect insufficient cerebral perfusion and predict neurological complications. This retrospective observational study explored the relationship between blood loss during this surgery and a decrease in rScO2 in children. METHODS: The following clinical data of children aged 3-14 years who underwent elective posterior scoliosis correction between March 2019 and July 2021 were collected: age, sex, height, weight, baseline rScO2, basal mean invasive arterial pressure (MAP), preoperative Cobb angle, number of surgical segments, preoperative and postoperative haemoglobin level, percentage of lowest rScO2 below the baseline value that lasted 3 min or more during the operation (decline of rScO2 from baseline, D-rScO2%), intraoperative average invasive MAP, end-tidal carbon dioxide pressure, fluid infusion rate of crystalloids and colloids, operation time, and percentage of total blood loss/patient's blood volume (TBL/PBV). RESULTS: A total of 105 children were included in the study. Massive haemorrhage (TBL/PBV ≥50%) was reported in 53.3% of patients, who had significantly higher D-rScO2 (%) (t = -5.264, P < 0.001) than those who had non-massive haemorrhage (TBL/PBV <50%). Multiple regression analysis revealed that TBL/PBV (ß = 0.04, 95% CI: 0.018-0.062, P < 0.05) was significantly associated with D-rScO2%. CONCLUSIONS: Intraoperative massive blood loss in children significantly increased D-rScO2%. Monitoring should be improved, and timely blood supplementation should be performed to ensure maintenance of the blood and oxygen supply to vital organs, improve the safety of anaesthesia, and avoid neurological complications.

Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Bioactive Metal Ion-Coordinated Dynamic Hydrogel with Antibacterial, Immunomodulatory, and Angiogenic Activities for Infected Wound Repair.

The repair of infected wounds is a complex physiopathologic process. Current studies on infected wound treatment have predominantly focused on infection treatment, while the factors related to delayed healing caused by vascular damage and immune imbalance are commonly overlooked. In this study, an extracellular matrix (ECM)-like dynamic and multifunctional hyaluronic acid (HA) hydrogel with antimicrobial, immunomodulatory, and angiogenic capabilities was designed as wound dressing for the treatment of infected skin wounds. The dynamic network in the hydrogel dressing was based on reversible metal-ligand coordination formed between sulfhydryl groups and bioactive metal ions. In our design, antibacterial silver and immunomodulatory zinc ions were employed to coordinate with sulfhydrylated HA and a vasculogenic peptide. In addition to the desired bioactivities for infected wounds, the hydrogel could also exhibit self-healing and injectable abilities. Animal experiments with infected skin wound models indicated that the hydrogel dressings enabled minimally invasive injection and seamless skin wound covering and then facilitated wound healing by efficient bacterial killing, continuous inflammation inhibition, and improved blood vessel formation. In conclusion, the metal ion-coordinated hydrogels with wound-infection-desired bioactivities and ECM-like dynamic structures represent a class of tissue bionic wound dressings for the treatment of infected and chronic inflammation wounds.

Hydroxygenkwanin exerts a neuroprotective effect by activating the Nrf2/ARE signaling pathway.

High levels of reactive oxygen species (ROS) have been associated with the progression of neurodegenerative diseases such as Alzheimer's disease. The activation of the NFE2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway may restore the neuron's redox balance and provide a therapeutic impact. Hydroxygenkwanin (HGK), a dominant flavone from Genkwa Flos, has received expanding attention due to its medicinal activities. Our investigation results demonstrated the ability of HGK to protect the PC12 cells from oxidative damage caused by an excessive hydrogen peroxide load. HGK also showed the ability to upregulate a panel of endogenous antioxidant proteins. Further investigations have demonstrated that the neuroprotection mechanism of HGK is dependent on the activation of the Nrf2/ARE signaling pathway. Activating the Nrf2/ARE pathway by HGK reveals a novel mechanism for understanding the pharmacological functions of HGK. These findings suggest that HGK could be considered for further development as an oxidative stress-related neurological pathologies potential therapeutic drug.

Hollow multi-shelled MOF derivative adsorbent for efficient magnetic solid-phase extraction of several typical endocrine disrupting compounds from water.

Bisphenols and benzophenones are two typical kinds of endocrine-disrupting compounds (EDCs) that have been extensively detected in water environments, posing unanticipated risks to aquatic organisms and humans. It is urgent to develop efficient sample pretreatment methods for precise measurement of such EDCs. In this study, a magnetic and multi-shelled metal-organic framework derivative material has been prepared to extract and enrich trace bisphenols and benzophenones from water. Via a solvothermal reaction induced by sodium citrate followed by a carbonization treatment, a ZIF-67@ZIF-8 derived CoZn-magnetic hierarchical carbon (CoZn-MHC) material has been synthesized as a high-performance magnetic solid-phase extraction (MSPE) adsorbent. This adsorbent exhibited a good specific surface area (213.80 m2⋅g-1) and a saturation magnetization of 63.2 emu·g-1. After the optimization of several parameters (including adsorbent dosage, extraction time, pH, ionic strength, desorption solvent, and solvent volume), an efficient MSPE method for several EDCs (comprising bisphenols and benzophenones) was developed with a good linear range (R2 ≥ 0.990), a high sensitivity range (LODs: 0.793-5.37 ng⋅L-1), and good reusability (RSD ≤4.67 % in five consecutive tests). Furthermore, the material exhibited commendable resistance to matrix interference in natural water samples with the recovery rates of target compounds ranging from 74.8 % to 107 %. We envision that the preparation strategy of this functional metal-organic framework (MOF)-based adsorbent for EDCs may provide insights for relevant research in the future.

Synthesis of All-Benzene Multi-Macrocyclic Nanocarbons by Post-Functionalization of meta-Cycloparaphenylenes.

Expanding the diversity of multi-macrocyclic nanocarbons, particularly those with all-benzene scaffolds, represents intriguing yet challenging synthetic tasks. Complementary to the existing synthetic approaches, here we report an efficient and modular post-functionalization strategy that employs iridium-catalyzed C-H borylation of the highly strained meta-cycloparaphenylenes (mCPPs) and an mCPP-derived catenane. Based on the functionalized macrocyclic synthons, a number of novel all-benzene topological structures including linear and cyclic chains, polycatenane, and pretzelane have been successfully prepared and characterized, thereby showcasing the synthetic utility and potential of the post-functionalization strategy.

Ultrasound-guided erector spinae plane block versus thoracic epidural block for postoperative analgesia in pediatric Nuss surgery: a randomized noninferiority trial.

PURPOSE: Thoracic epidural anesthesia (TEA) is often used for analgesia after thoracic surgery. Erector spinae plane block (ESPB) has been proposed to provide adequate analgesia. We hypothesized that ESPB would be noninferior to TEA as a part of multimodal analgesia in pediatric patients undergoing the Nuss procedure. METHODS: Patients aged 7-18 years and scheduled for the Nuss procedure were randomly allocated to receive bilateral single-shot ESPB or TEA and a multimodal analgesic regimen including parent-controlled intravenous analgesia (PCIA). At 6 h, 12 h, 18 h, and 24 h postoperatively, pain was evaluated using the numeric rating scale (NRS) and opioid consumption was assessed by counting the number of PCIA boluses. The joint primary outcomes were the average pain score and opioid consumption at 24 h after surgery. The secondary outcomes were the NRS scores and the number of opioid boluses administered at different postoperative time points, adverse events, and recovery quality. RESULTS: Three hundred patients underwent randomization, and 286 received ESPB (147 patients) or TEA (139 patients). At 24 h postoperatively, ESPB was noninferior to TEA in terms of the average NRS score (mean difference, - 0.1, 95% confidence interval [CI], - 0.3-0.1, margin = 1, P for noninferiority < 0.001) and the number of opioid boluses administered (mean difference, - 1.1, 95% CI, - 2.8-0.6, margin = 7, P for noninferiority < 0.001). Adverse events and patient recovery were comparable between groups. CONCLUSIONS: The results demonstrate that combined with a multimodal analgesia, ESPB provides noninferior analgesia compared to TEA with respect to pain score and opioid consumption among pediatric patients undergoing the Nuss procedure.

The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents.

BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.

Comparative Analysis of Short-Term and Long-Term Clinical Efficacy of Mesenchymal Stem Cells from Different Sources in Knee Osteoarthritis: A Network Meta-Analysis.

Background: Joint articular injection of mesenchymal stem cells (MSCs) has emerged as a novel treatment approach for osteoarthritis (OA). However, the effectiveness of MSCs derived from different sources in treating OA patients remains unclear. Therefore, this study aimed to explore the differences between the effectiveness and safety of different sources of MSCs. Materials and Methods: For inclusion consideration, we searched trial registries and published databases, including PubMed, Cochrane Library, Embase, and Web of Science databases. Revman (V5.3), STATA (V16.0), and R (V4.0) were utilized for conducting data analysis, while the Cochrane Risk of Bias Tool was employed for assessing the quality of the studies. We derived outcome measures at 6 and 12 months based on the duration of study follow-up, including visual analog scale (VAS) score, WOMAC score, WOMAC pain, WOMAC Functional Limitation, and WOMAC stiffness. The evaluation time for short-term effectiveness is set at 6 months, while 12 months is utilized as the longest follow-up time for most studies to assess long-term effectiveness. Results: The evaluation of literature quality showed that the included studies had excellent methodological quality. A meta-analysis revealed that different sources of MSCs improved knee function and pain more effectively among patients suffering from knee OA (KOA) than controls. The results of the network meta-analysis showed the following: short-term functional improvement (the indexes were evaluated after 6 months of follow-up) (WOMAC total score: bone marrow-derived MSC (BMMSC) vs. adipose-derived MSC (ADMSC) (mean difference (MD) = -20.12, 95% confidence interval (CI) -125.24 to 42.88), umbilical cord-derived MSC (UCMSC) (MD = -7.81, 95% CI -158.13 to 74.99); WOMAC stiffness: BMMSC vs. ADMSC (MD = -0.51, 95% CI -7.27 to 4.29), UCMSC (MD = -0.75, 95% CI -9.74 to 6.63); WOMAC functional limitation: BMMSC vs. ADMSC (MD = -12.22, 95% CI -35.05 to 18.86), UCMSC (MD = -9.31, 95% CI -44.26 to 35.27)). Long-term functional improvement (the indexes were evaluated after 12 months of follow-up) (WOMAC total: BMMSC vs. ADMSC (MD = -176.77, 95% CI -757.1 to 378.25), UCMSC (MD = -181.55, 95% CI -937.83 to 541.13); WOMAC stiffness: BMMSC vs. ADMSC (MD = -0.5, 95% CI -26.05 to 18.61), UCMSC (MD = -1.03, 95% CI -30.44 to 21.69); WOMAC functional limitation: BMMSC vs. ADMSC (MD = -5.18, 95% CI -316.72 to 177.1), UCMSC (MD = -8.33, 95% CI -358.78 to 218.76)). Short-term pain relief (the indexes were evaluated after 6 months of follow-up) (VAS score: UCMSC vs. BMMSC (MD = -10.92, 95% CI -31.79 to 12.03), ADMSC (MD = -14.02, 95% CI -36.01 to 9.81), PLMSC (MD = -17.09, 95% CI -46.31 to 13.17); WOMAC pain relief: BMMSC vs. ADMSC (MD = -11.42, 95% CI -39.52 to 11.77), UCMSC (MD = -6.73, 95% CI -47.36 to 29.15)). Long-term pain relief (the indexes were evaluated after 12 months of follow-up) (VAS score: BMMSC vs. UCMSC (MD = -4.33, 95% CI -36.81 to 27.08), ADMSC (MD = -11.43, 95% CI -37.5 to 13.42); WOMAC pain relief: UCMSC vs. ADMSC (MD = 0.23, 95% CI -37.87 to 38.11), BMMSC (MD = 5.89, 95% CI -25.39 to 51.41)). According to the GRADE scoring system, WOMAC, VAS, and AE scores were of low quality. Conclusion: Meta-analysis suggests MSCs can effectively treat KOA by improving pain and knee function compared to control groups. In terms of functional improvement in KOA patients, both short-term (6-month follow-up) and long-term (12-month follow-up) results indicated that while the differences between most treatments were not statistically significant, bone marrow-derived MSCs may have some advantages over other sources of MSCs. Additionally, BM-MSCs and UC-MSCs may offer certain benefits over ADMSCs in terms of pain relief for KOA patients, although the variances between most studies were not statistically significant. Therefore, this study suggests that BM-MSCs may present clinical advantages over other sources of MSCs.