Liver as a new target organ in Alzheimer's disease: insight from cholesterol metabolism and its role in amyloid-beta clearance.

Alzheimer's disease, the primary cause of dementia, is characterized by neuropathologies, such as amyloid plaques, synaptic and neuronal degeneration, and neurofibrillary tangles. Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs, targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment. Metabolic abnormalities are commonly observed in patients with Alzheimer's disease. The liver is the primary peripheral organ involved in amyloid-beta metabolism, playing a crucial role in the pathophysiology of Alzheimer's disease. Notably, impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease. In this review, we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism. Furthermore, we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Single-cell RNA Sequencing Demonstrates the Heterogeneity of Different Molecular Subtypes in Gastric Cancer.

Gastric cancer is a disease with high molecular and phenotypic heterogeneity. We integrated 119,878 cells from different molecular subtypes of gastric cancer and conducted comprehensive analysis. We found that patients with different molecular subtypes of gastric cancer showed significantly different cell composition heterogeneity, and the proportion of plasma cells was higher in GS tumors. After that, we constructed subtype-specific lncRNA-gene regulatory networks and identified subtype-specific lncRNA-related biological functions and pathways. Our study found that MALAT1-CTNNB1 regulatory pairs existed in CIN subtype, XIST-KLF2 regulatory pairs existed in GS subtype, and KCNQ1OT1-CCND2 regulatory pairs existed in MSI subtype. Next, we identified subtype-specific lncRNAs associated with prognosis. Our study found that NEAT1 could be used as prognostic factors for CIN tumors, and MALAT1 and XIST could be used as prognostic factors for GS tumors. In addition, we characterized the interactions between tumor cells and tumor microenvironment cells in different molecular subtypes of gastric cancer. In conclusion, we revealed the heterogeneity among different TCGA molecular subtypes of gastric cancer at the single-cell level, and identified the subtype-specific lncRNAs associated with prognosis. Our study may contribute to the in-depth understanding of the heterogeneity of gastric cancer and the prediction of patient prognosis.

Research progress on degradation of biodegradable micro-nano plastics and its toxic effect mechanism on soil ecosystem.

Biodegradable plastics (BPs) are known to decompose into micro-nano plastics (BMNPs) more readily than conventional plastics (CPs). Given the environmental risks posed by BMNPs in soil ecosystems, their impact has garnered increasing attention. However, research focusing on the toxic effects of BMNPs on soils remains relatively limited. The degradation process and duration of BMNPs in soil are influenced by numerous factors, which directly impact the toxic effects of BMNPs. This highlights the urgent need for further research. In this context, this review delineates the classification of BPs, investigates the degradation processes of BPs along with their influencing factors, summarizes the toxic effects on soil ecosystems, and explores the potential mechanisms that underlie these toxic effects. Finally, it provides an outlook on related research concerning BMNPs in soil. The results indicate that specific BMNPs release additives at a faster rate during decomposition, degradation, and aging, with certain compounds exhibiting increased bioavailability. Importantly, a substantial body of research has shown that BMNPs generally manifest more pronounced toxic effects in comparison to conventional micro-nano plastics (CMNPs). The toxic effects associated with BMNPs encompass a decline in soil quality and microbial biomass, disruption of nutrient cycling, inhibition of plant root growth, and negative impacts on invertebrate reproduction, survival, and fertilization rates. The rough and complex surfaces of BMNPs contribute to increased mechanical damage to tested organisms, enhance absorption by microorganisms, and disrupt normal physiological functions. Notably, the toxic effects of BMNPs on soil ecosystems are influenced by factors including concentration, type of BMNPs, exposure conditions, degradation products, and the nature of additives used. Therefore, it is crucial to standardize detection technologies and toxicity testing conditions for BMNPs. In conclusion, this review provides scientific evidence that supports effective prevention and management of BMNP pollution, assessment of its ecological risks, and governance of BMNPs-related products.

Co-doped MOF-5 and carbon nanotube nanoparticles enhancing stability and high output performance in core-shell nanofibers for piezoelectric nanogenerators.

The interfacial interaction of carbon nanotubes (CNTs) significantly enhances the output capability of piezoelectric nanogenerators (PENGs). However, overcoming the limitation of low specific surface area in one-dimensional materials remains a significant challenge. This paper introduces a hydrothermal method for composite MOF (C-M) using CNTs and MOF-5, demonstrating localized co-doping between them. Coaxial electrospun piezoelectric fiber membranes (C-MNF) were then prepared using PVDF/PAN as the matrix. Benefiting from C-M's excellent crystallinity and its synergistic interaction with the polymer matrix, the C-MNF-based PENG showed a 125 % increase in output voltage, reaching âˆ¼25 V, compared to coaxial membranes simply mixing MOF-5 and CNTs. As a result, its short-circuit current was âˆ¼1.8 µA, with a piezoelectric coefficient d33 of âˆ¼400 pC N-1. Consequently, this material exhibits superior piezoelectric output capabilities, paving the way for future functional material fabrication.

Interventions to enhance mental health and wellbeing among international college students: A systematic review and meta-analysis protocol.

BACKGROUND: International students contribute significantly to both the economy and the intellectual and cultural landscape of host countries. Their interactions with domestic students foster personal, socioeconomic, and political development, promopting a broader understanding of diverse cultures and values. This highlights how crucial international education is for staying competitive globally. However, international students often face challenges such as poor mental health, linguistic and cultural barriers, acculturative stress, and limited health literacy. Therefore, supporting their academic success and well-being on college campuses is essential. This protocol aims to describe strategies used to evaluate the effect of interventions on international students' mental health and wellbeing and propose directions for future research based on the evidence. METHODS: We will conduct an extensive search in several databases including CINAHL, PubMed, Web of Science, PsyInFO, ERIC, and Google Scholar with no date limits. Two reviewers will independently screen the literature and extract data. We will then conduct meta-analyses of the extracted data. DISCUSSION: To the best of our knowledge, this study is the first systematic review with meta-analysis focusing on interventions to enhance mental health and wellbeing among international college students. This study will provide most updated empirical evidence on the effects of interventions aimed to improve international students' mental health and wellbeing. The findings from this study will summarize the importance of a range of interventions being available to international students who experience psychological distress and the effectiveness of each intervention. This study will also highlight the gap for researchers to focus on for future studies. TRIAL REGISTRATION: PROSPERO registration number: CRD42024528767.

Efficient Strategy to Discover DNA Aptamers Against Low Abundance Cell Surface Proteins in Scarce Samples.

Molecular recognition probes targeting cell surface proteins such as aptamers play crucial roles in precise diagnostics and therapy. However, the selection of aptamers against low-abundance proteins in situ on the cell surface, especially in scarce samples, remains an unmet challenge. In this study, we present a single-round, single-cell aptamer selection method by employing a digital DNA sequencing strategy, termed DiDS selection, to address this dilemma. This approach incorporates a molecular identification card for each DNA template, thereby mitigating biases introduced by multiple PCR amplifications and ensuring the accurate identification of aptamer candidates. Through DiDS selection, we successfully obtained a series of high-quality aptamers against cell lines, clinical specimens, and neurons. Subsequent analyses for target identification revealed that aptamers derived from DiDS selection exhibit recognition capabilities for proteins with varying abundance levels. In contrast, multiple rounds of selection resulted in the enrichment of only one aptamer targeting a high-abundance target. Moreover, the comprehensive profiling of cell surfaces at the single-cell level, utilizing an enriched aptamer pool, revealed unique molecular patterns for each cell line. This streamlined approach holds promise for the rapid generation of specific recognition molecules targeting cell surface proteins across a broad range of expression levels and expands its applications in cell profiling, specific probe identification, biomarker discovery, etc.

Exploring thermophysical properties of CoCrFeNiCu high entropy alloy via molecular dynamics simulations.

High entropy alloys (HEAs) are alloys composed of five or more primary elements in equal or nearly equal proportions of atoms. In the present study, the thermophysical properties of the CoCrFeNiCu high entropy alloy (HEA) were investigated by a molecular dynamics (MD) method at nanoscale. The effects of the content of individual elements on lattice thermal conductivity k p were revealed, and the results suggested that adjusting the atomic content can be a way to control the lattice thermal conductivity of HEAs. The effects of temperature on k p were investigated quantitively, and a power-law relationship of k p with T -0.419 was suggested, which agrees with previous findings. The effects of temperature and the content of individual elements on volumetric specific heat capacity C v were also studied: as the temperature increases, the C v of all HEAs slightly decreases and then increases. The effects of atomic content on C v varied with the comprising elements. To further understand heat transfer mechanisms in the HEAs, the phonon density of states (PDOS) at different temperatures and varying atomic composition was calculated: Co and Ni elements facilitate the high-frequency vibration of phonons and the Cu environment weakens the heat transfer via low-frequency vibration of photons. As the temperature increases, the phonon mean free path (MFP) in the equiatomic CoCrFeNiCu HEA decreases, which may be attributed to the accelerated momentum of atoms and intensified collisions of phonons. The present research provides theoretical foundations for alloy design and have implications for high-performance alloy smelting.

Boosting hydrogen evolution performance of nanofiber membrane-based composite photocatalysts with multifunctional carbon dots.

Recent progress in the co-spinning of nanofibers and semiconductor particles offers a promising strategy for the development of photocatalytic devices, solving aggregation and catalyst recovery challenges. However, composite photocatalysts based on nanofiber membranes often suffer from poor conductivity, low hydrophilicity, and easy recombination of photogenerated electron-hole pairs in the semiconductor components. Here, to tackle the aforementioned issues of ZnIn2S4/polyacrylonitrile (ZIS/PAN) nanofiber-based catalysts, we prepared a composite carbon dots/ZnIn2S4/polyacrylonitrile (CZP) nanofiber membrane by blending carbon dots (CDs) with ZIS/PAN using the electrospinning process. The hydrogen evolution performance of the CZP photocatalyst was significantly improved by CDs, which enhanced the hydrophilicity, increased the light absorption, facilitated the transfer of photogenerated electrons, and reduced the recombination of photogenerated electron-hole pairs. Notably, the optimal CZP photocatalyst achieved a hydrogen evolution rate of 2250 µmol g-1h-1, which is about 23 % higher than that of the nanofiber membrane without CDs and 4.55 times higher than that of ZIS particles. The present work successfully improved the CZP nanofiber membrane of photocatalytic hydrogen evolution performance, and the membrane may benefit further device development by eliminating the need for stirring and simplifying the recovery process.

Simultaneous determination of canonical purine metabolism using a newly developed HILIC-MS/MS in cultured cells.

Purine metabolism acts as the core role in human metabolic network. It offers purine metabolites as raw material for building blocks in cell survival and proliferation. Purine metabolites are the most abundant metabolic substrates in organisms. There are few reports to simultaneously quantify canonical purine metabolism in cells. A novel hydrophilic interaction liquid chromatography coupled with mass spectrometry (HILIC-MS/MS) method was developed to simultaneously determine purines profile in biological samples. Chromatographic separation was achieved using a HILIC (Waters Xbridge™ Amide) column. Different optimizing chromatographic conditions and mass spectrometric parameters were tested in order to provide the best separation and the lowest limit of quantification (LLOQ) values for targeted metabolites. The validation was evaluated according to the Food and Drug Administration guidelines. The limit of determination (LOD) and the LOQ values were in the range of 0.02-8.33 ng mL-1 and 0.1-24.5 ng mL-1, respectively. All calibration curves displayed good linear relationship of with excellent correlation coefficient (r) ranging from 0.9943 to 0.9999. Both intra-day and inter-day variability were below 15 %, respectively. Trueness, expressed as relative error, was always within ±15 %. In addition, no derivatization procedure and ion-pair reagents are in need. The innovated approach demonstrates high sensitivity, strong specificity, and good repeatability, making it suitable for absolute quantitative studies of canonical purine metabolism in cultured cells.

Impacts of industrial agglomeration on the energy consumption structure's low-carbon transition process: A spatial and nonlinear perspective.

Based on panel data collected from 2003 to 2020 across 30 provinces in China, the paper employs the spatial vector angle method and spatial Durbin model to investigate industrial agglomeration's nonlinear and spatial spillover effects on the energy consumption structure's low-carbon transition process (Lct). The results indicate the following: First, the influence of industrial agglomeration on Lct exhibits an inverted U-shaped pattern. As the degree of industrial agglomeration expands, its effect on Lct shifts from positive to negative. Second, industrial agglomeration demonstrates spatial spillover effects. It promotes the improvement of Lct in neighboring provinces through agglomeration effects. However, the continuous expansion of industrial agglomeration inhibits the improvement of Lct in neighboring provinces through congestion effects. Third, the heterogeneity test finds that industrial agglomeration has a significant role in promoting Lct in the samples of eastern region, but this effect is not significant in the samples of western and middle regions.

Zebrafish phd1 enhances mavs-mediated antiviral responses in a hydroxylation-independent manner.

PHD1 is a member of the prolyl hydroxylase domain protein (PHD1-4) family, which plays a prominent role in the post-translational modification of its target proteins by hydroxylating proline residues. The best-characterized targets of PHD1 are hypoxia-inducible factor α (HIF-1α and HIF-2α), two master regulators of the hypoxia signaling pathway. In this study, we show that zebrafish phd1 positively regulates mavs-mediated antiviral innate immunity. Overexpression of phd1 enhances the cellular antiviral response. Consistently, zebrafish lacking phd1 are more susceptible to spring viremia of carp virus infection. Further assays indicate that phd1 interacts with mavs through the C-terminal transmembrane domain of mavs and promotes mavs aggregation. In addition, zebrafish phd1 attenuates K48-linked polyubiquitination of mavs, leading to stabilization of mavs. However, the enzymatic activity of phd1 is not required for phd1 to activate mavs. In conclusion, this study reveals a novel function of phd1 in the regulation of antiviral innate immunity.IMPORTANCEPHD1 is a key regulator of the hypoxia signaling pathway, but its role in antiviral innate immunity is largely unknown. In this study, we found that zebrafish phd1 enhances cellular antiviral responses in a hydroxylation-independent manner. Phd1 interacts with mavs through the C-terminal transmembrane domain of mavs and promotes mavs aggregation. In addition, phd1 attenuates K48-linked polyubiquitination of mavs, leading to stabilization of mavs. Zebrafish lacking phd1 are more susceptible to spring viremia of carp virus infection. These findings reveal a novel role for phd1 in the regulation of mavs-mediated antiviral innate immunity.

Phosphomolybdates for Dual-Mode Photoelectrochemical Sensing toward Trace Chromium(VI) and Tetracycline.

Highly sensitive photoelectrochemical (PEC) sensors for trace carcinogens, such as heavy metal chromium(VI) [Cr(VI)] and antibiotic tetracycline (TC) are crucial. Herein, by integration of photoactive and redox phosphomolybdates with conjugated organic components, types of dual-mode PEC sensors were synthesized for sensing trace Cr(VI) and TC pollutants, with formulas of (H2bimb)2[Co2(bimb)1.5][Co(H2O)4][Co(P4Mo6O31H6)2]·6H2O (1), (H2bib)2[Co(H2O)3][Co2(H2O)5][Co(P4Mo6O31H6)2]·9H2O (2), and (H2bib)6[Co(Hbib)2(H2O)5][Co(P4Mo6O31H7)2]2·15H2O (3), where bimb represents 1,4-bis(1-imidazolyl)benzene and bib is 4,4'-bis(imidazolyl)bibphenyl. Hybrid 1 consisted of a three-dimensional framework structure constructed by Co{P4Mo6}2 clusters and one-dimensional (1D) {Co-bimb} chains, hybrid 2 exhibited 1D Co ion-bridged Co{P4Mo6}2 chains hydrogen-bonding with [H2bib]2+ cations, and hybrid 3 showed a discrete hybrid structure built upon a Co{P4Mo6}2 cluster modified by the {Co-bib} unit. Hybrids 1-3 displayed wide spectral absorption and excellent electrochemical redox properties, enabling dual-mode PEC responses to Cr(VI) reduction and TC oxidation. For Cr(VI) detection, hybrids 1-3 exhibited high sensitivities of 364.40, 225.72, and 124.29 µA·µM-1 as well as "nM" level detection limits (LODs) of 4.9, 10.0, and 11.0 nM, respectively. For TC detection, the sensitivities of hybrids 1-3 were 494.72, 308.78, and 174.03 µA·µM-1 and the LODs were 5.2, 6.1, and 12.9 nM, respectively. This research offers significant insights into designing efficient PEC sensors for the detection of environmental pollutants.

Mitochondrial copper overload promotes renal fibrosis via inhibiting pyruvate dehydrogenase activity.

Copper is a trace element essential for numerous biological activities, whereas the mitochondria serve as both major sites of intracellular copper utilization and copper reservoir. Here, we investigated the impact of mitochondrial copper overload on the tricarboxylic acid cycle, renal senescence and fibrosis. We found that copper ion levels are significantly elevated in the mitochondria in fibrotic kidney tissues, which are accompanied by reduced pyruvate dehydrogenase (PDH) activity, mitochondrial dysfunction, cellular senescence and renal fibrosis. Conversely, lowering mitochondrial copper levels effectively restore PDH enzyme activity, improve mitochondrial function, mitigate cellular senescence and renal fibrosis. Mechanically, we found that mitochondrial copper could bind directly to lipoylated dihydrolipoamide acetyltransferase (DLAT), the E2 component of the PDH complex, thereby changing the interaction between the subunits of lipoylated DLAT, inducing lipoylated DLAT protein dimerization, and ultimately inhibiting PDH enzyme activity. Collectively, our study indicates that mitochondrial copper overload could inhibit PDH activity, subsequently leading to mitochondrial dysfunction, cellular senescence and renal fibrosis. Reducing mitochondrial copper overload might therefore serve as a strategy to rescue renal fibrosis.

Decomposition Analysis of Depressive Symptom Differences Among Older Adults With Hypertension Between Urban and Rural Areas: Cross-Sectional Study.

Background: Hypertension is the most prevalent chronic disease among China's older population, which comprises a growing proportion of the overall demographic. Older individuals with chronic diseases have a higher risk of developing depressive symptoms than their healthy counterparts, as evidenced in China's older population, where patients with hypertension exhibit varying rates of depression depending on residing in urban or rural areas. Objective: This study aimed to investigate factors influencing and contributing to the disparities in depressive symptoms among older urban and rural patients with hypertension in China. Methods: We used a cross-sectional study design and derived data from the 8th Chinese Longitudinal Health Longevity Survey of 2018. The Fairlie model was applied to analyze the factors contributing to disparities in depressive symptoms between urban and rural older populations with hypertension. Results: The sample size for this study was 5210, and 12.8% (n=669) of participants exhibited depressive symptoms. The proportions of depressive symptoms in rural and urban areas were 14.1% (n=468) and 10.7% (n=201), respectively. In rural areas, years of education (1-6 years: odds ratio [OR] 0.68, 95% CI 1.10-1.21; ≥7 years: OR 0.47, 95% CI 0.24-0.94), alcohol consumption (yes: OR 0.52, 95% CI 0.29-0.93), exercise (yes: OR 0.78, 95% CI 0.56-1.08), and sleep duration (6.0-7.9 hours: OR 0.29, 95% CI 0.17-0.52; 8.0-9.9 hours: OR 0.24, 95% CI 0.13-0.43; ≥10.0 hours: OR 0.22, 95% CI 0.11-0.41) were protective factors against depressive symptoms in older adults with hypertension, while gender (female: OR 1.94, 95% CI 1.33-2.81), self-reported income status (poor: OR 3.07, 95% CI 2.16-4.37), and activities of daily living (ADL) dysfunction (mild: OR 1.69, 95% CI 1.11-2.58; severe: OR 3.03, 95% CI 1.46-6.32) were risk factors. In urban areas, age (90-99 years: OR 0.37, 95% CI 0.16-0.81; ≥100 years: OR 0.19, 95% CI 0.06-0.66), exercise (yes: OR 0.33, 95% CI 0.22-0.51), and sleep duration (6.0-7.9 hours: OR 0.27, 95% CI 0.10-0.71; 8.0-9.9 hours: OR 0.16, 95% CI 0.06-0.44; ≥10.0 hours: OR 0.18, 95% CI 0.06-0.57) were protective factors, while years of education (1-6 years: OR 1.91, 95% CI 1.05-3.49), self-reported income status (poor: OR 2.94, 95% CI 1.43-6.08), and ADL dysfunction (mild: OR 2.38, 95% CI 1.39-4.06; severe: OR 3.26, 95% CI 1.21-8.76) were risk factors. The Fairlie model revealed that 91.61% of differences in depressive symptoms could be explained by covariates, including years of education (contribution 63.1%), self-reported income status (contribution 13.2%), exercise (contribution 45.7%), sleep duration (contribution 20.8%), ADL dysfunction (contribution -9.6%), and comorbidities (contribution -22.9%). Conclusions: Older patients with hypertension in rural areas had more depressive symptoms than their counterparts residing in urban areas, which could be explained by years of education, self-reported income status, exercise, sleep duration, ADL dysfunction, and comorbidities. Factors influencing depressive symptoms had similarities regarding exercise, sleep duration, self-reported income status, and ADL dysfunction as well as differences regarding age, gender, years of education, and alcohol consumption.

Assembling the 2D-3D-2D Heterostructure of Quasi-2D Perovskites for High-Performance Solar Cells.

Quasi-two-dimensional (quasi-2D) layered perovskites with mixed dimensions offer a promising avenue for stable and efficient solar cells. However, randomly distributed three-dimensional (3D) perovskites near the film surface limit the device performance of quasi-2D perovskites due to increased nonradiative recombination and ion migration. Herein, we construct a 2D (n = 4 top)-3D-2D (n = 2 bottom) heterostructure of quasi-2D perovskites by using 3-chlorobenzylamine iodine, which can effectively reduce defect density and restrain ion migration. A champion efficiency of 22.22% for quasi-2D perovskite solar cells is achieved due to remarkably reduced nonradiative voltage loss and increased electron extraction. Additionally, the 2D-3D-2D perovskite solar cells also exhibit excellent thermal and humidity stabilities, retaining over 90 and 85% of the initial efficiencies after 2000 h under a heat stress of 65 °C and at air ambient of ∼50% humidity, respectively. Our results provide a general approach to tune perovskite films for suppressing ion migration and achieving high-performance perovskite solar cells.

Molybdenum Disulfide Induced Phase Control Synthesis of Multi-dimensional Co3S4-MoS2 Heteronanostructures via Cation Exchange.

Phase control over cation exchange (CE) reactions has emerged as an important approach for the synthesis of nanomaterials (NMs). Although factors such as crystal structure and morphology have been studied for the phase engineering of CE reactions in NMs, there remains a lack of systematic investigation to reveal the impact factors in heterogeneous materials. Herein, we report a molybdenum disulfide induced phase control method for synthesizing multidimensional Co3S4-MoS2 heteronanostructures (HNs) via cation exchange. MoS2 in parent Cu1.94S-MoS2 HNs are proved to affect the thermodynamics and kinetics of CE reactions, and facilitate the formation of Co3S4-MoS2 HNs with controlled phase. This MoS2 induced phase control method can be extended to other parent HNs with multiple dimensions, which shows its universality. Further, theoretical calculations demonstrate that Co3S4 (111)/MoS2 (001) exhibits a higher adhesion work, providing further evidence that MoS2 enables phase control in the HNs CE reactions, inducing the generation of novel Co3S4-MoS2 HNs. As a proof-of-concept application, the obtained Co3S4-MoS2 heteronanoplates (HNPls) show remarkable performance in hydrogen evolution reactions (HER) under alkaline media. This synthetic methodology provides a unique way to control the crystal structure and fills the gap in the study of heterogeneous materials on CE reaction over phase engineering.

Atmospheric pressure plasma preconditioning reduces oxygen and glucose deprivation induced human neuronal SH-SY5Y cells apoptosis by activating protective autophagy and ROS/AMPK/mTOR pathway.

Reactive oxygen species (ROS)/reactive nitrogen species (RNS) exert a "double edged" effect on the occurrence and development of ischemic stroke. We previously indicate that atmospheric pressure plasma (APP) shows a neuroprotective effect in vitro based on the ROS/RNS generations. However, the mechanism is still unknown. In this work, SH-SY5Y cells were treated with oxygen and glucose deprivation (OGD) injuries for stimulating the ischemic stroke pathological injury process. A helium APP was used for SH-SY5Y cell treatment for evaluating the neuroprotective impacts of APP preconditioning against OGD injuries with the optimized parameters. During the preconditioning, APP significantly raised the extracellular and intracellular ROS/RNS production. As a result, APP preconditioning increased SH-SY5Y cell autophagy by elevating LC3-II/LC3-I ratio and autophagosome formation. Meanwhile, APP preconditioning reduced cell apoptosis caused by OGD with the increased APP treatment time, which was abolished by pretreatment with autophagy inhibitor 3-methyladenine (3-MA). The ROS scavenger N-acetyl-L-cysteine (NAC) alone or combined with NO scavenger carboxy-PTIO abolished the APP preconditioning induced SH-SY5Y autophagy and the cytoprotection, whereas the NO scavenger alone did not. In addition, we observed the elevated phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphorylation of mammalian target of rapamycin (mTOR) in APP treated SH-SY5Y cells. This effect was attenuated by AMPK inhibitor Compound C (CC), the ROS scavenger NAC and autophagy inhibitor 3-MA. Furthermore, the cytoprotective effect of APP was preliminarily confirmed in the rats of middle cerebral artery occlusion (MCAO) model. Results showed that APP inhalation by rats during MCAO process could improve neurological functions, reduce cell apoptosis in brain tissues and decrease cerebral infarct volume. Our data suggested that ROS produced by APP preconditioning played a vital role in the neuroprotective effect of SH-SY5Y cells against OGD injuries by activating autophagy and ROS/AMPK/mTOR pathway.

Advances in biomaterials for oral-maxillofacial bone regeneration: spotlight on periodontal and alveolar bone strategies.

The intricate nature of oral-maxillofacial structure and function, coupled with the dynamic oral bacterial environment, presents formidable obstacles in addressing the repair and regeneration of oral-maxillofacial bone defects. Numerous characteristics should be noticed in oral-maxillofacial bone repair, such as irregular morphology of bone defects, homeostasis between hosts and microorganisms in the oral cavity and complex periodontal structures that facilitate epithelial ingrowth. Therefore, oral-maxillofacial bone repair necessitates restoration materials that adhere to stringent and specific demands. This review starts with exploring these particular requirements by introducing the particular characteristics of oral-maxillofacial bones and then summarizes the classifications of current bone repair materials in respect of composition and structure. Additionally, we discuss the modifications in current bone repair materials including improving mechanical properties, optimizing surface topography and pore structure and adding bioactive components such as elements, compounds, cells and their derivatives. Ultimately, we organize a range of potential optimization strategies and future perspectives for enhancing oral-maxillofacial bone repair materials, including physical environment manipulation, oral microbial homeostasis modulation, osteo-immune regulation, smart stimuli-responsive strategies and multifaceted approach for poly-pathic treatment, in the hope of providing some insights for researchers in this field. In summary, this review analyzes the complex demands of oral-maxillofacial bone repair, especially for periodontal and alveolar bone, concludes multifaceted strategies for corresponding biomaterials and aims to inspire future research in the pursuit of more effective treatment outcomes.