The insula is involved in the pathophysiology of chronic pain. However, the possible role of the insula in people with anterior shoulder pain (ASP) remains unclear. To assess insula-related structural and functional abnormalities in people with ASP compared to healthy controls (HCs). Cross-sectional study. Structural and functional magnetic resonance imaging data were acquired from 27 people with ASP and 20 HCs. Voxel-based morphometry method was used to detect changed gray matter volume (GMV) in the insula between the two groups. The changed insular regions were selected as seeds to further evaluate the structural and functional abnormalities in the two groups using sample entropy, structural covariance and functional connectivity (FC) methods. Receiver operating characteristic (ROC) curves were used to evaluate potential biomarkers for ASP. Correlations between neuroimaging findings and clinical characteristics were then assessed in people with ASP. Compared to HCs, people with ASP showed increased GMV in the bilateral anterior insula (AI). The AI-based sample entropy analysis showed significant differences between the two groups. Altered AI-based patterns of structural covariance and FC between the two groups were connected to certain regions within the salience network, default mode network and sensorimotor network. ROC analysis exhibited better classification accuracies in FC of the right AI with the left posterior insula and right superior temporal gyrus. The current findings suggest that aberrant insula-related structure and function may be associated with abnormal sensory information processing, dysfunction of relevant brain networks and disturbed motor control in people with ASP.
Endometriosis (EMs) is a common cause of ovarian dysfunction and infertility, closely linked to iron overload-induced oxidative stress and ferroptosis. While electroacupuncture (EA) has shown promise in treating reproductive disorders, its role in regulating ovarian ferroptosis in EMs remains unclear. This study aimed to investigate the protective effects and underlying mechanisms of EA on ovarian function in a mouse model of EMs, which simulated the chronic pelvic hemorrhage observed in patients. Comprehensive evaluations were performed using hematoxylin-eosin staining, qRT-PCR, Western blot, immunohistochemistry, immunofluorescence, and biochemical assays to assess ovarian function, iron metabolism, oxidative stress, and ferroptosis-related markers. The results demonstrated that EA treatment significantly restored estrous cyclicity, increased ovarian weight and index, improved serum hormone levels, promoted multi-stage follicular development, and reduced follicular atresia. EA also alleviated ovarian iron overload and oxidative stress. Mechanistically, EA activated the Nrf2 pathway and its downstream targets, upregulated the anti-ferroptotic protein GPX4, suppressed the pro-ferroptotic factor ACSL4, and consequently reduced lipid peroxidation. In conclusion, this study reveals that EA mitigates granulosa cell ferroptosis and ameliorates EMs-induced ovarian injury by activating Nrf2 to enhance GPX4 activity and inhibit ACSL4-mediated lipid peroxidation. These findings provide experimental evidence supporting EA as a potential complementary therapy for EMs-related infertility.
The rapid transition toward electric vehicles and large-scale energy storage systems has intensified the demand for lithium-ion batteries (LIBs) capable of reliable operation under harsh temperature conditions. However, conventional liquid electrolytes suffer from severe degradation at elevated temperatures. Herein, we report a multifunctional gel polymer electrolyte (GPE) employing a siloxy-functionalized cross-linker, siloxy-pentaerythritol triacrylate (SiO-PETA), to enhance the high-temperature cycling stability and safety of LIBs. The trimethylsilane groups in SiO-PETA effectively scavenge corrosive HF, thereby mitigating cell degradation associated with transition metal dissolution. In addition, the chemically cross-linked polymer matrix encapsulates the liquid components in the GPE, suppressing parasitic side reactions and reducing electrolyte vaporization at elevated temperatures. A graphite/LiNi0.6Co0.2Mn0.2O2 pouch-type cell employing the GPE exhibits superior capacity retention at 70 °C, markedly outperforming a conventional liquid-electrolyte cell. Furthermore, the GPE provides enhanced safety, as evidenced by stable open-circuit voltage at 150 °C and reduced flammability. These results demonstrate that the SiO-PETA-based GPE effectively suppresses electrolyte and electrode degradation, enabling stable LIB operation at high temperatures.
A stepwise sequence for the hydrodefluorination of a fluorobenzene equivalent has been described. By utilization of a P(III)/Pd(II)-P(V)/Pd(0) redox couple, pyramidalized P-CF3-functionalized benzazaphosphole 1 accepts Ph-F from Pd(II) complexes B/C, resulting in the formation of trigonal bipyramidal (TBP) 2 featuring new P-Ph and P-F bonds. The desired release of Ph-H and regeneration of trivalent 1 from pentavalent 2 was silane-dependent. Using smaller silanes, fluoride abstraction forms phosphonium cation 3 with a hydridosilicate counterion, which delivers hydride to the cationic P-center, affording TBP analogues of Type 4. These observable P-H derivatives like 4x selectively expel H-CF3 and P-Ph-functionalized 5 via a highly asynchronous transition state, resembling a heterolytic P-CF3 bond cleavage/deprotonation event. If larger silanes like Ph3Si-H are employed, the targeted Ph-H/1 product pair is generated directly from 2, closing the stoichiometric hydrodefluorination process. The P(III)/Pd(II)-P(V)/Pd(0) mechanism, silane-dependent product formation, and loss of H-CF3 from 4x redox reaction were evaluated by DFT calculations.
GIM/FP/GP:[Formula: see text] Neurology:[Formula: see text].
Emergency Med:[Formula: see text] GIM/FP/GP:[Formula: see text] Neurology:[Formula: see text].
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The Index of ADL was developed to study results of treatment and prognosis in the elderly and chronically ill. Grades of the Index summarize over-all performance in bathing, dressing, going to toilet, transferring, continence, and feeding. More than 2,000 evaluations of 1,001 individuals demonstrated use of the Index as a survey instrument, as an objective guide to the course of chronic illness, as a tool for studying the aging process, and as an aid in rehabilitation teaching. Of theoretical interest is the observation that the order of recovery of Index functions in disabled patients is remarkably similar to the order of development of primary functions in children. This parallelism, and similarity to the behavior of primitive peoples, suggests that the Index is based on primary biological and psychosocial function, reflecting the adequacy of organized neurological and locomotor response.
Water pollution remains a serious global challenge, and biochar has become a sustainable and economically efficient adsorbent for removing various aquatic pollutants. Recent engineering advances, including physical/chemical activation, hetero-atom doping, template-assisted synthesis and O-functionalization, have substantially upgraded its textural and chemical attributes. State-of-the-art activations typically deliver surface areas of 1500-2600 m2 g-1 and Cd(II) uptake capacities in the 200-450 mg g-1 range, whereas La or Mg-modified biochars frequently achieve over 80 % phosphate removal. Despite these advances, the current focus of biochar modification is still on the pore structure and functional groups, and the perspective of decontamination still only focuses on the single adsorption function of biochar. This review proposes a multi-pathway synergistic strategy integrating adsorption, oxidation, precipitation, and complexation, along with non-radical oxidation and metal-biochar collaborative systems for removing heavy metal ions, non-metallic ions, dyes, antibiotics, and pesticides. It systematically analyzes mechanistic coupling in multi-pollutant matrices and environmental influences, establishing a ternary design framework (pore-surface-electronic properties) and a mechanistic hierarchy from passive adsorption to active redox degradation, offering molecular-level guidance for next-generation biochar reactors.
The eukaryotic chaperonin containing T-complex polypeptide-1 (CCT/TRiC) complex, composed of eight distinct subunits (CCT1-CCT8), is essential for cytosolic protein folding; however, its function in plants remains largely unexplored. Moreover, a direct link between CCT and coat protein complex II (COPII) vesicle trafficking-a key step in the early secretory pathway-has not been established in any eukaryotic system. Here, leveraging plant genetics, we investigated the functional relationship between CCT8 and COPII-mediated trafficking in the Arabidopsis root apex. The point mutant cct8-1 exhibited a short-root phenotype resulting from impaired cell division in the root meristem, which was accompanied by disrupted auxin homeostasis. This defect stemmed from a marked reduction in the abundance of multiple PIN-FORMED (PIN) auxin efflux carriers at the plasma membrane, without affecting their polar localization. Mechanistically, CCT8 directly interacted with SEC31B, a core component of the COPII coat. Accordingly, the sec31b-3 mutant phenocopied cct8-1 in root growth, auxin response, and PIN accumulation defects. The CCT8 mutation reduced SEC31B abundance at both the transcriptional and protein levels and compromised ER-to-Golgi transport, thereby diminishing PIN delivery to the plasma membrane. Importantly, overexpression of SEC31B partially rescued the root growth defects and restored PIN2 levels in cct8-1. Together, our findings uncover a previously unrecognized chaperonin-trafficking module in which CCT8 regulates SEC31B to modulate COPII-mediated delivery of PIN proteins, thus linking chaperonin function to auxin-dependent root development.
A cross-sectional study. This study aimed to investigate cognitive impairment in degenerative cervical myelopathy (DCM) and examine its relationship with radiographic spinal cord compression. Degenerative cervical myelopathy is a leading cause of chronic non-traumatic spinal cord injury. While its motor and sensory manifestations are well established, the potential impact on cognitive function remains underexplored. A total of 965 participants were enrolled: 383 DCM patients (Group A), 122 cervical spondylotic radiculopathy (CSR) patients (Group B), and 460 healthy controls (Group C). Cognitive performance was evaluated with the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and the Basic Cognitive Aptitude Test (BCAT). Propensity-score matching (A:B:C=2:1:2) was used to balance age, sex, and education; additional stratified analyses by age (≤50, 51-60, 61-70, and >70 years) and education (≤6, 7-12, and ≥13 years of education) were performed. Compression ratio (CR) and maximum spinal cord compression (MSCC) were measured on cervical MRI. Correlation analyses were used to explore the association between radiographic spinal cord compression and cognitive function. After matching, DCM patients exhibited significantly lower MoCA (20.61 ± 3.76) and MMSE (26.23 ± 2.84) scores than both CSR and control group (all P < 0.001); this disadvantage persisted across every age and educational stratum. MSCC correlated negatively with MoCA (r = -0.118, P = 0.022) and MMSE (r = -0.124, P = 0.017), with stronger associations in single-level DCM (MoCA r = -0.218, P = 0.008; MMSE r = -0.237, P = 0.004). The number of compressed segments did not influence global cognition. Cognitive impairment is significantly associated with DCM, which is influenced by age, education, and the degree of spinal cord compression.
Protein-protein interactions determine cellular functions driven by electrostatic and other noncovalent forces. As an example of negatively charged macromolecule, heparan sulfate interaction with the alarmin high mobility group box 1 (HMGB1) is critical for receptor for advanced glycation end products (RAGE)-mediated signaling. Here we investigated the hypothesis that dendritic polyglycerol (dPG) dendrimers could replace heparan sulfate (i) in functional interactions with HMGB1 and (ii) in regulating interleukin-33 (IL-33) interactions with its receptors to modulate immune responses. To determine potential effects on immune cells in the brain, we investigated the charge-dependent effects of negatively charged sulfated dPG (dPGS), positively charged aminated dPG (dPGA) and hybrid dPG (sulfated and aminated dPGSA) dendrimers on IL-33 and HMGB1 in microglia. We used structural modeling to predict the protein interfaces mediating electrostatic interactions resulting in ligand-receptor complex formation. In addition, proximity ligation assays were performed to verify the binding of HMGB1 and IL-33 to ST2, RAGE and Toll-like receptor 4. Our results show that IL-33, an alarmin of the interleukin-1 family, cross-talks with ST2 and RAGE in lipopolysaccharide-activated human microglia. Notably, dPGS inhibited IL-33 interactions with ST2 but not RAGE, whereas dPGSA inhibited both IL-33 and HMGB1 interactions with their receptors. Thus, this study provides insights in the mechanisms of alarmin-mediated molecular cross-talks in human microglia that are driven by electrostatic interactions and the modulation by differentially charged dendrimers in microglia activated by the pro-inflammagen lipopolysaccharide.
Kidney transplantation outcomes have improved in the short term, but long-term graft survival gains have plateaued. Aging donors and recipients with increasing comorbidities may alter contemporary allograft outcomes. We retrospectively analyzed 2076 consecutive kidney transplants performed at a single Canadian center from 1969 to 2024, representing up to 50 y of complete follow-up. All-cause graft survival (ACGS) and death-censored graft survival were compared across 5 transplant eras using era-stratified Cox regression. The median recipient age increased significantly across the eras from 35 to 54 y (P < 0.01) and the donor age from 28 to 45 y (P < 0.01), paralleled by 3-5-fold increases in pretransplant diabetes and obesity. Death-censored graft survival improved through the early 2000s but has since plateaued, whereas ACGS declined in the modern era (2018-2024) compared with the 1998-2009 peak (P = 0.007). Death with function accounted for >60% of graft losses in recent years, with infectious deaths rising from 21% to 45% (P < 0.01). Increasing donor and recipient age, comorbidities, and delayed graft function independently predicted inferior survival. These findings reveal a reversal in ACGS gains in the contemporary era, highlighting the need for precision immunosuppression strategies tailored to the aging, comorbid transplant population.
Traumatic brain injury (TBI) is a leading cause of mortality and long-term neurological disability, while effective pharmacological therapies for its neurobehavioral consequences remain limited. This systematic review evaluates the therapeutic potential of Ginkgo biloba (GB), particularly the standardized extract EGb 761, in TBI management. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to February 2026. Sixty-five studies met the inclusion criteria, including 42 in vivo experimental studies and 23 clinical trials examining neuroprotective, cognitive, behavioral, or functional outcomes following GB administration. Preclinical evidence consistently demonstrates that Ginkgo biloba (GB) exerts neuroprotective effects through attenuation of oxidative stress, as evidenced by increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, alongside reduced malondialdehyde (MDA) levels. These effects are accompanied by modulation of the Slc7a11-Eif4ebp1 signaling axis, suppression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and regulation of key molecular pathways. Specifically, GB inhibits JAK/STAT and TXNIP/NLRP3 signaling while activating PI3K/AKT-associated pathways and autophagy. Clinical studies indicate potential improvements in cognitive and functional outcomes. However, adverse events, particularly bleeding, have been reported, especially when GB is co-administered with anticoagulants or nonsteroidal anti-inflammatory drugs. This underscores the importance of careful patient monitoring. The current evidence supports the promising neuroprotective potential of GB in traumatic brain injury. Nevertheless, clinical data remain insufficient to justify routine therapeutic use. Large-scale, well-designed, randomized controlled trials are necessary to confirm efficacy, optimize dosing regimens, and establish long-term safety profiles.
Spinal cord injury (SCI) is characterized by primary mechanical trauma and subsequent secondary pathogenic cascades, with chronic neuroinflammation impeding neurological functional recovery. Microglial activation, mitochondrial dysfunction, and mitophagy are key pathological players, while the role of triggering receptor expressed on myeloid cells 1 (TREM1) in SCI remains incompletely elucidated. This study explored TREM1 targeting and the regulation of microglial mitophagy in SCI using 8-week-old female C57BL/6 J mice and BV2 microglial cells. Mice were administered the TREM1 inhibitor LP17 or physiological saline. Assessments included behavioral evaluations, Nissl staining, immunofluorescence staining, Western blot analysis, and transmission electron microscopy. We found that TREM1 expression peaked at 3 days post-SCI and was specifically localized to microglia. LP17 inhibited TREM1 expression, improved 4-week post-injury Basso Mouse Scale scores and footprint parameters, reduced Nissl body loss, and downregulated proinflammatory mediators in the spinal cord and lipopolysaccharide (LPS)-stimulated BV2 cells. LP17 enhanced LPS-induced mitophagy in BV2 cells and activated the AMPKα-PINK1-Parkin signaling pathway. Small interfering RNA-mediated AMPKα knockdown (si-AMPKα) blocked LP17-induced mitophagy and its anti-inflammatory effects. In conclusion, LP17 inhibits TREM1 to alleviate secondary SCI via the AMPKα-PINK1-Parkin-dependent microglial mitophagy pathway, making TREM1 a potential therapeutic target for SCI.
Efficient access to γ-sulfenylated 3-hydroxy-γ-lactams remains limited, because the existing multicomponent methods do not enable γ-heterofunctionalization. We report a mild DBU-promoted cyclization/thiolation cascade that converts β-enamino diketones and thiols into 5-sulfenylated γ-lactams in up to 98% yield with a broad N-aryl/N-alkyl scope and diverse sulfur nucleophiles. Control and in situ NMR experiments supported a nucleophile-initiated mechanism, providing a streamlined route to functionally rich γ-lactam scaffolds for heterocycles and medicinal chemistry.
This study investigated the roles of CREB and NMNATs in sevoflurane-induced cognitive deficits and synaptic alterations in developing hippocampal neurons. 160 postnatal day-7 male SD rats were randomized into four groups: Control; Sevo (3% sevoflurane for 6 h); Sevo+D-cycloserine (DCS, an NMDA receptor agonist); and AP-5 (an NMDA receptor antagonist). Cognitive function was assessed at 8 weeks using the Morris water maze. Dendritic spine density/morphology in hippocampal CA1 was analyzed via Golgi-Cox Staining. Protein levels of NMNAT1, NMNAT2, CREB, and p-CREB were measured by western blot and immunofluorescence. Compared to controls, sevo-exposed rats exhibited significant spatial memory impairment, demonstrated by increased escape latency, longer path length, and fewer platform crossings. This group also showed reduced dendritic spine density and altered morphology in CA1, alongside decreased p-CREB and NMNAT1/2 expression. In contrast, DCS pretreatment before sevo exposure reversed these deficits, restoring cognitive performance, spine density/morphology, and p-CREB/NMNAT1/2 levels. Sevoflurane induces learning/memory deficits and dendritic spine pathology in neonatal rats, likely via NMDA receptor-mediated downregulation of p-CREB and NMNAT1/2. DCS pretreatment effectively mitigates these effects, highlighting that enhancing NMDA receptor activity can counteract sevoflurane-induced neurotoxicity. NMDA receptor modulation represents a promising therapeutic strategy for postoperative cognitive dysfunction.
Healthy aging has emerged as a global priority. However, older adults' participation in health promotion programs remains low, and traditional health promotion models have achieved limited success in fostering sustained engagement among this population. Mobile health (mHealth)-based gamification interventions offer a promising way to address these challenges. However, no published reviews support or oppose the use of mHealth-based gamification interventions as health promotion strategies in older adults. The study aimed to identify mHealth interventions using gamification to promote health among older adults. Our scoping review was conducted following the Joanna Briggs Institute recommendations for scoping reviews and Arksey and O'Malley's framework. The process followed PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Literature Search Extension) checklist. A comprehensive literature search was conducted across 8 databases: PubMed, Scopus, Web of Science, Embase, Cochrane Library, CINAHL, PsycARTICLES, and IEEE Xplore Digital Library, from their inception to December 10, 2025. Two reviewers independently screened titles, abstracts, and full texts via Rayyan, with disagreements resolved by a third reviewer. This scoping review identified 11 studies. Only 1 article was published before 2022. The interventions were found to improve enjoyment and motivation (n=5), cognitive function (n=3), physical activity (n=2), and digital literacy (n=2). Individual studies also reported improvements in mental health (n=1) and adherence (n=1), a reduction in suicidal ideation (n=1), improvements in physical function (n=1), the promotion of social engagement (n=1), and the identification of mild cognitive impairment (n=1). Game elements used were ranked by frequency as progress, challenges, goals, levels, reward, sensation, storytelling or narration, leaderboard, surprise, and avatar. No research was found to use the game element of "social sharing." mHealth types included augmented and virtual reality-based training systems, wearable devices, mobile phones, tablets, and Windows platforms and devices. Notably, only 4 studies applied theoretical frameworks, and 3 omitted the concrete approach to gamification. As the first scoping review to identify and map mHealth-based gamification interventions for older adults, this study highlights their potential as an innovative approach to health promotion. By systematically synthesizing evidence regarding intervention designs, gamification strategies, and preliminary health outcomes, it establishes a foundation for future inquiry. However, this review is limited by the small number of included studies, precluding broad generalizations. Future research should assess long-term impacts, integrate theoretical frameworks, establish reporting guidelines, design personalized social-interactive interventions, and expand to broader health domains. Ultimately, these insights provide targeted guidance for developing age-appropriate digital health solutions, contributing to the realization of active aging.
Polyenes serve as a rigorous test for theoretical models and electronic structure methods, playing a key role in advancing computational and theoretical chemistry. Here, we present a high-level theoretical investigation of linear, all-trans polyenes using energy gradients and nonadiabatic coupling vectors based on an MR-CISD wave function to describe electronic transitions involving the ground state (11Ag-) and three low-lying excited states (21Ag-, 11Bu+, and 21Bu-) of hexatriene, octatetraene, and decapentaene. This approach enables accurate evaluation of both adiabatic and vertical excitation and emission energies, yielding results in excellent agreement with experiment, as well as locating minima on the crossing seam between adiabatic states. Our results show that vertical excitation energies to the 11Bu+ state are blue-shifted by 0.2-0.3 eV relative to the experimental absorption maximum, whereas the vertical emission energy from the 21Ag- state is red-shifted by ∼0.2 eV relative to the experimental emission maximum. Upon relaxation from the Franck-Condon geometry, the 21Ag- state stabilizes by around 1 eV, compared to 0.2-0.3 eV for the 11Bu+ state. An analysis of the S1/S0 crossing seam in hexatriene shows that its minimum involves asymmetric backbone deformations and provides an efficient channel for ultrafast internal conversion to the ground state, consistent with the absence of detectable fluorescence in this molecule. These results demonstrate the power of analytic gradients and nonadiabatic coupling vectors based on an MR-CISD wave function for accurately characterizing the electronic structure and photophysics of polyenes.