The relationship between the secondary structure and the emulsifying ability of protein-based particles and the Pickering emulsions stabilized by the zein-lysine complex.

Due to the sustainability and widespread use of proteins, protein-based materials are extensively utilized in the preparation of Pickering emulsions. However, the relationship between the secondary structure of proteins and their emulsifying ability has not been further investigated. This study used the addition of three different amino acids to influence the interaction between zein chains, which may induce changes in the secondary structure of the prepared zein complex particles. This study demonstrates that the emulsifying properties of proteins, such as dispersibility, zeta potential, three-phase contact angles, interfacial affinity, adsorption rates, and the volume of the stabilized oil phase, are closely related to the ß-sheet content of the complex particles, providing a theoretical reference for protein-based stabilizers. Additionally, amino acids, as the blocks of proteins, have high compatibility with proteins, and using amino acids as modifiers aligns with the safety requirements for food processing. In this study, the prepared zein-lysine complex particles have good emulsifying ability, capable of stabilizing a 50 (v/v)% emulsion at a lower concentration (10 mg mL-1), and the prepared emulsion exhibits high-temperature stability and ionic resistance. This characteristic makes the emulsion potentially valuable for application in systems with high salt concentrations and those that may undergo heat treatment.

Polyacrylamide Regulated Phytohormone Balance and Starch Degradation to Promote Seed-Potato Sprouting and Emergence.

Potatoes are typically seeded as tubers, and their slow sprouting significantly impacts production. Therefore, the effects of polyacrylamide (20 g·L-1, 30 g·L-1, and 40 g·L-1) as a seed potato dressing on sprouting, seedling growth, and biomass were investigated. The phytohormone content, respiratory intensity, and starch metabolism enzyme activity were analyzed to elucidate the physiological mechanisms involved. The sprouting rate significantly increased after 20 g·L-1 and 30 g·L-1 treatments by 40.63% and 15.63%, respectively. The sprouting energy was the highest (52.0%) at 20 g·L-1, 7.67 times higher than the control. The 20 g·L-1 and 30 g·L-1 treatments also promoted emergence and growth, with the emergence rate increasing by 18.18% and 27.27% and growth increasing by over 8.1% and 11.9%, respectively. These effects were related to changes in phytohormone content and accelerated starch conversion. After treatment, the auxin and cytokinin contents in the apical buds increased significantly at the germination initiation stage, and during the germination and vigorous growth phases, the auxin, cytokinin, and gibberellin contents increased. Polyacrylamide treatment activated α-amylase and promoted starch degradation, increasing soluble sugar content to provide nutrients and energy for sprouting. This study provides a promising approach for promoting potato tuber sprouting and seedling growth.

Toll-like receptor 4 damages the intestinal epithelial cells by activating endoplasmic reticulum stress in septic rats.

Background: The severity of acute gastrointestinal injury (AGI) is a critical determinant of survival in sepsis. However, there is no specifically interventional management for gastrointestinal dysfunction. Toll-like Receptor 4 (TLR4) is an important contributor to sepsis-induced multiple organ dysfunction syndrome. So, we investigated the effect of TLR4 on leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) + cells and goblet cells and its potential mechanism. Methods: A cecal ligation and puncture (CLP) model reflecting the development of clinical sepsis was developed. Tak-242, a TLR4 inhibitor, was administered to septic rats at a dose of 3 mg/kg via intraperitoneal injection. Immunohistochemistry was performed to detect TLR4 and Lgr5+ cells. AB-PAS staining was performed to detect goblet cells. MUC1 and MUC2 secreted by goblet cells, biomarkers of endoplasmic reticulum (ER) stress and inflammatory cytokines in the intestine were detected by western blotting and real-time PCR. Results: We found that the upregulation of the TLR4/NF-κB signaling pathway activated intestinal inflammatory response in sepsis. Meanwhile, the structure of intestinal mucosa was destroyed, Lgr5+ cells and goblet cells count were significantly reduced, and the secretory function of goblet cells also decreased. Further studies have found that TLR4 increased the levels of activating transcription factor-6 (ATF6), XBP1, ER chaperone (Bip) and CHOP, but did not activate the protein kinase RNA (PKR)-like ER kinase (P-PERK). Conclusion: We concluded that the inhibition of TLR4/NF-κB signaling pathway can reduce intestinal inflammatory response, protect intestinal mucosa, protect Lgr5+ cells, goblet cells and relieve ER stress. Our findings suggest that Tak-242 protects Lgr5+ cells and goblet cells after sepsis, partly may be through the suppression of ER stress. Thus, inhibition of TLR4-mediated ER stress may be a promising therapy of septic AGI.

Engineered Cancer Nanovaccines: A New Frontier in Cancer Therapy.

Vaccinations are essential for preventing and treating disease, especially cancer nanovaccines, which have gained considerable interest recently for their strong anti-tumor immune capabilities. Vaccines can prompt the immune system to generate antibodies and activate various immune cells, leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and surgery. To enhance the flexibility and targeting of vaccines, nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level, enabling more controlled and precise drug delivery to enhance immune responses. Cancer nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within nanomaterials. The small size of these nanomaterials allows for precise targeting of T cells, dendritic cells, or cancer cells, thereby eliciting a more potent anti-tumor response. In this paper, we focus on the classification of carriers for cancer nanovaccines, the roles of different target cells, and clinically tested cancer nanovaccines, discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation, while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

Spatial-Dependent Spectral Response of Acousto-Optic Tunable Filters with Inhomogeneous Acoustic Distribution.

The spectral response of an acousto-optic tunable filter (AOTF) is crucial for an AOTF based spectral imaging system. The acousto-optic (AO) interaction within the spatial-distributed area of the acoustic field determines the spectral response of the light incidence. Assuming an ideally uniform acoustic field distribution, phase-matching geometries can be applied to calculate the anisotropic Bragg diffraction in AO interactions, determining the wavelength and direction of the diffracted light. In this ideal scenario, the wavelength of the diffracted light depends solely on the direction of the incident light. However, due to the non-ideal nature of the acoustic field, the wavelength of the diffracted light exhibits slight variations with incident position. In this paper, an analytical model is proposed to calculate the spatial-dependent spectral response of the diffracted light under non-uniform acoustic field distribution. The study computes the variation pattern of the diffracted light amplitude caused by the inhomogeneous acoustic distribution. The theoretical considerations and computational model are confirmed by AOTF frequency scanning experiments. The study demonstrates that the distribution of the acoustic field leads to non-uniform spatial-spectral response in the AOTF, and the spatial AO interaction computational model can provide data support for calibrating AOTF systems in imaging applications.

Hepatic and extrahepatic metabolic modulation in hbv-related decompensated cirrhosis and acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (RatioHep/Port, RatioPeri/Hep, and RatioPort/Peri) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher RatioPeri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher RatioPort/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

Spatiotemporal trends in the burden of colorectal cancer incidence and risk factors at country level from 1990 to 2019.

BACKGROUND AND AIM: Worldwide, the incidence of colorectal cancer (CRC) continues to rise and remains a major public health concern. This study aimed to analyze the temporal and spatial trends in CRC incidence and related risk factors at the country level. METHODS: Data on CRC and related risk factors were obtained from the Global Burden of Disease Study (GBD) 2019 study. Temporal trends were evaluated using estimated annual percentage change while spatial trends were analyzed using spatial autocorrelation and autoregression. Additionally, linear mixed-effects models were employed to identify risk factors linked to CRC incidence. RESULTS: Globally, from 1990 to 2019, the incidence cases of CRC increased by 157.23%. At the national level, the incidence of CRC increased in most countries, with the highest increases of age-standardized incidence rate (ASIR) in Equatorial Guinea, Vietnam, and China. In both 1990 and 2019, global spatial clustering of CRC ASIR highlighted hotspots in Europe, characterized by elevated CRC ASIR levels. A comparative analysis of risk factors between hotspot countries and others indicated that gender and alcohol use exerted greater influence in hotspots than elsewhere. CONCLUSION: Although from 1990 to 2019, the highest growth in ASIR of CRC has been observed in African, Asian, and Latin American countries, the hotspots are still concentrated in Europe. In the identified hotspots, gender and alcohol use exert a more significant impact on CRC incidence compared with other countries. Thus, we should pay attention to countries where the CRC incidence is increasing and these risk factors.

Cancer-associated fibroblasts derived fibronectin extra domain A promotes sorafenib resistance in hepatocellular carcinoma cells by activating SHMT1.

Resistance to sorafenib, an effective first-line treatment for advanced hepatocellular carcinoma (HCC), greatly compromised the prognosis of patients. The extracellular matrix is one of the most abundant components of the tumor microenvironment. Beyond acting as a physical barrier, it remains unclear whether cell interactions and signal transduction mediated by the extracellular matrix contribute to sorafenib resistance. With the analysis of primary HCC organoid RNA-seq data combined with in vivo and in vitro experiments validation, we discovered that fibronectin extra domain A (FN-EDA) derived from cancer-associated fibroblasts played a critical role in sorafenib resistance. Mechanistically, FN-EDA stimulates the up-regulation of the key one-carbon metabolism enzyme SHMT1 in HCC cells via the TLR4/NF-κB signaling pathway, thereby countering the oxidative stress induced by sorafenib. Moreover, we reinforced the clinical significance of our discoveries by conducting in vivo assays with an immunodeficiency subcutaneous xenograft tumor model, which was established using primary cancer-associated fibroblasts derived from clinical HCC tissues, and through the analysis of HCC samples obtained from The Cancer Genome Atlas (TCGA) database. Our findings suggest that targeting the FN-EDA/SHMT1 pathway could be a potential strategy to improve sorafenib responsiveness in HCC patients.

USP7 deubiquitinates epigenetic reader ZMYND8 to promote breast cancer cell migration and invasion.

The ubiquitin-proteasome system (UPS), which involves E3 ligases and deubiquitinates (DUBs), is critical for protein homeostasis. The epigenetic reader ZMYND8 (zinc finger MYND-type containing 8) has emerged as an oncoprotein, and its protein levels are elevated in various types of cancer, including breast cancer. However, the mechanism by which ZMYND8 protein levels are increased in cancer remains elusive. Although ZMYND8 has been reported to be regulated by the E3 ligase FBXW7, it is still unknown whether ZMYND8 could be modulated by DUBs. Here, we identified USP7 (ubiquitin carboxyl-terminal hydrolase 7) as a bona fide DUB for ZMYND8. Mechanically, USP7 directly binds to the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF (tumor necrosis factor receptor-associated factor) domain and UBL (ubiquitin-like) domain and removes F-box and WD repeat domain containing 7 (FBXW7)-catalyzed poly-ubiquitin chains on lysine residue 1034 (K1034) within ZMYND8, thereby stabilizing ZMYND8 and stimulating the transcription of ZMYND8 target genes ZEB1 (zinc finger E-box binding homeobox 1) and VEGFA (Vascular Endothelial Growth Factor A). Consequently, USP7 enhances the capacity of breast cancer cells for migration and invasion through antagonizing FBXW7-mediated ZMYND8 degradation. Importantly, the protein levels of USP7 positively correlates with those of ZMYND8 in breast cancer tissues. These findings delineate an important layer of migration and invasion regulation by the USP7-ZMYND8 axis in breast cancer cells.

Assessing the efficacy of natural soil biotin on soil quality, microbial diversity, and Rhododendron simsii growth for sustainable landscape architecture.

Fertilization significantly influences soil quality and its sustainable use in urban garden maintenance. The widespread application of inorganic fertilizers has raised ecological concerns due to their potential environmental impacts. Organic fertilizers, while beneficial, often have slow effects and are costly. Biofertilizers, with their eco-friendly nature and low carbon footprint, are gaining attention for their multifaceted role in supporting plant growth. Despite the focus on fruit trees, vegetables, and medicinal plants, ornamental plants have been understudied. This study aims to evaluate the efficacy of a novel microbial fertilizer, 'natural soil biotin', on Rhododendron plants, specifically the Azalea hybrid 'Carnation'. The study employed a comparative approach to assess the impact of different fertilization strategies on soil properties, microbial diversity, enzyme activity, plant morphology, and physiological parameters. The application of 'natural soil biotin' was compared with the use of inorganic and organic fertilizers. The combined application of 'natural soil biotin' was found to effectively enhance soil properties and mitigate the impact of other fertilizers on soil pH. It also improved the relative abundance of beneficial microbial groups such as Proteobacteria, Ascomycota, and Basidiomycota. Furthermore, the mixed application significantly increased the activities of urease and sucrase in Rhododendron plants, which promoted their growth, development, and stress resistance. The results indicate that the mixed application of 'natural soil biotin' with inorganic and organic fertilizers not only improved the soil quality but also enhanced the efficiency of fertilizer utilization. This approach led to increased economic and environmental benefits in Rhododendron cultivation. The findings contribute to the foundation for soil improvement and ecological restoration, suggesting that 'natural soil biotin' could be a promising alternative or supplement to traditional fertilization methods in sustainable landscape architecture.

High internal phase Pickering emulsions stabilized by Zein-hyaluronic acid conjugate particles and their application in active substances protection.

In recent years, active substances have been extensively applied in the fields of food, cosmetics, and pharmaceuticals. However, their preservation and transportation have posed challenges due to issues such as oxidation and photodegradation. This study proposes a method for synthesizing Zein-Hyaluronic Acid (Zein-HA) conjugate particles via the Schiff base reaction, utilizing these conjugate particles to encapsulate and protect active substances within a stable emulsion system. Compared to zein, the modified conjugate particles exhibit significantly improved dispersibility, amphiphilicity, interfacial affinity, and emulsifying properties. Consequently, these particles are capable of stabilizing high internal phase Pickering emulsions with an oil phase volume fraction of up to 80 (v/v)%, thereby enabling the carriage of a higher load of active components. Furthermore, the prepared emulsions demonstrate excellent storage stability, resistance to ionic strength (250-2000 mM NaCl), and outstanding antioxidative characteristics. Moreover, after 8 h of UV light exposure, the retention rates of the active substances (curcumin, astaxanthin, and resveratrol) exceed 60 %. Therefore, these emulsions hold substantial potential to be applied as a carrier system in the food, cosmetics, and pharmaceutical industries.

Preparation of functionalized porous chitin carbon to enhance the H2O2 production and Fe3+ reduction properties of Electro-Fenton cathodes for efficient degradation of RhB.

The performance of Electro-Fenton (EF) cathode materials is primarily assessed by H2O2 yield and Fe3+ reduction efficiency. This study explores the impact of pore structure in chitin-based porous carbon on EF cathode effectiveness. We fabricated mesoporous carbon (CPC-700-2) and microporous carbon (ZPC-700-3) using template and activation methods, retaining nitrogen from the precursors. CPC-700-2, with mesopores (3-5 nm), enhanced O2 diffusion and oxygen reduction, producing up to 778 mg/L of H2O2 in 90 min. ZPC-700-3, with a specific surface area of 1059.83 m2/g, facilitated electron transport and ion diffusion, achieving a Fe2+/Fe3+ conversion rate of 79.9%. EF systems employing CPC-700-2 or ZPC-700-3 as the cathode exhibited superior degradation performance, achieving 99% degradation of Rhodamine B, efficient degradation, and noticeable decolorization. This study provides a reference for the preparation of functionalized carbon cathode materials for efficient H2O2 production and effective Fe3+ reduction in EF systems.

A temperature-compensated CO2 detection system based on non-dispersive infrared spectral technology.

The concentration of carbon dioxide (CO2) is an important indicator for coal mine safety. Real-time monitoring of CO2 concentration is of great importance for taking actions in advance to avoid the occurrence of potential accidents. To address the issues of poor portability and high cost associated with existing coal mine CO2 detection equipment, this paper develops a miniaturized CO2 detection system based on non-dispersive infrared (NDIR) technology. This sensor integrates an infrared light source and a dual-channel pyroelectric detector into a reflective gas chamber, thereby achieving an extended optical path and higher system sensitivity within limited space. Meanwhile, the noise interference was greatly mitigated by using hardware and software filtering techniques. Based on principle analysis, the Lambert-Beer law was parametrically corrected, and then, a model relationship between the dual-channel voltage ratio and concentration was established. In addition, temperature compensation for zero and span values was introduced to improve the adaptability of the detection results to temperature changes. Testing results indicate that the developed detection system can realize CO2 measurement in the concentration range of 0 to 50 000 ppm within a temperature range of 0-40 °C, with a maximum detection error of less than 0.12% and a repeatability deviation of less than 1.04%. During a stability test for 12 h, the maximum concentration drift is 0.07%, indicating that the developed system meets the requirements for monitoring CO2 safety in coal mines.

Assessing ChatGPT as a Medical Consultation Assistant for Chronic Hepatitis B: Cross-Language Study of English and Chinese.

BACKGROUND: Chronic hepatitis B (CHB) imposes substantial economic and social burdens globally. The management of CHB involves intricate monitoring and adherence challenges, particularly in regions like China, where a high prevalence of CHB intersects with health care resource limitations. This study explores the potential of ChatGPT-3.5, an emerging artificial intelligence (AI) assistant, to address these complexities. With notable capabilities in medical education and practice, ChatGPT-3.5's role is examined in managing CHB, particularly in regions with distinct health care landscapes. OBJECTIVE: This study aimed to uncover insights into ChatGPT-3.5's potential and limitations in delivering personalized medical consultation assistance for CHB patients across diverse linguistic contexts. METHODS: Questions sourced from published guidelines, online CHB communities, and search engines in English and Chinese were refined, translated, and compiled into 96 inquiries. Subsequently, these questions were presented to both ChatGPT-3.5 and ChatGPT-4.0 in independent dialogues. The responses were then evaluated by senior physicians, focusing on informativeness, emotional management, consistency across repeated inquiries, and cautionary statements regarding medical advice. Additionally, a true-or-false questionnaire was employed to further discern the variance in information accuracy for closed questions between ChatGPT-3.5 and ChatGPT-4.0. RESULTS: Over half of the responses (228/370, 61.6%) from ChatGPT-3.5 were considered comprehensive. In contrast, ChatGPT-4.0 exhibited a higher percentage at 74.5% (172/222; P<.001). Notably, superior performance was evident in English, particularly in terms of informativeness and consistency across repeated queries. However, deficiencies were identified in emotional management guidance, with only 3.2% (6/186) in ChatGPT-3.5 and 8.1% (15/154) in ChatGPT-4.0 (P=.04). ChatGPT-3.5 included a disclaimer in 10.8% (24/222) of responses, while ChatGPT-4.0 included a disclaimer in 13.1% (29/222) of responses (P=.46). When responding to true-or-false questions, ChatGPT-4.0 achieved an accuracy rate of 93.3% (168/180), significantly surpassing ChatGPT-3.5's accuracy rate of 65.0% (117/180) (P<.001). CONCLUSIONS: In this study, ChatGPT demonstrated basic capabilities as a medical consultation assistant for CHB management. The choice of working language for ChatGPT-3.5 was considered a potential factor influencing its performance, particularly in the use of terminology and colloquial language, and this potentially affects its applicability within specific target populations. However, as an updated model, ChatGPT-4.0 exhibits improved information processing capabilities, overcoming the language impact on information accuracy. This suggests that the implications of model advancement on applications need to be considered when selecting large language models as medical consultation assistants. Given that both models performed inadequately in emotional guidance management, this study highlights the importance of providing specific language training and emotional management strategies when deploying ChatGPT for medical purposes. Furthermore, the tendency of these models to use disclaimers in conversations should be further investigated to understand the impact on patients' experiences in practical applications.

Short-term effects of ambient nitrogen dioxide on medical emergency calls for epileptic seizures: A time-series study.

Short-term exposure to air pollution has previously been studied in relation to certain neurological disorders, but there is still a lack of convincing data linking air pollution to epileptic seizures. The study's goal was to investigate how exposure to ambient nitrogen dioxide (NO2) affected the number of patients seeking assistance at the Wuhan Emergency Medical Center due to epileptic seizures. We gathered data on medical emergency calls (MECs), daily ambient air pollution concentrations (SO2, NO2, PM2.5, PM10, CO, and O3), and meteorological variables in Wuhan, China, spanning from January 1, 2017, to November 30, 2019. To investigate the potential influence of ambient nitrogen dioxide on MECs for epileptic seizures, we carried out a time-series investigation using the general additive model (GAM). Additionally, analyses stratified by season, age, and gender were performed. A total of 8989 records of MECs for epileptic seizures were enrolled in our study during the period. Statistical analysis indicates that a rise of 10 µg/m3 in NO2 concentration is linked to a 0.17% increase in daily MECs for epileptic seizures (95% confidence interval [CI]: 0.02%, 0.32%). Furthermore, people aged 14-59 years were more susceptible(2.25%, P < 0.05). The short-term effects of NO2 exposure on daily MECs for epileptic seizures were stronger in warm seasons than in cool seasons (0.55% vs. -0.10%, P < 0.0001). Our findings suggests that short-term exposure to ambient NO2 was positively correlated with daily MECs for epileptic seizures in Wuhan, China. Additionally, we observed that these associations were stronger in patients aged above 14 but under 60 years and the warmer seasons (from April to September).

Trends in the burden of female infertility among adults aged 20-49 years during 1990-2019: an analysis of data from the Global Burden of Disease Study 2019.

OBJECTIVES: The aim of this analysis was to investigate the worldwide distribution and trends in the burden of female infertility (FI). DESIGN AND SETTING: Analysis of cross-sectional data from 1990 to 2019 from the Global Burden of Disease (GBD) Study 2019. PARTICIPANTS: Adults aged 20-49 years in various geographical regions, Sociodemographic Index (SDI) levels and populations across 204 countries worldwide. OUTCOME MEASURES: Disability-adjusted life years (DALYs), age-standardised DALY rates and estimated annual percentage changes (EAPCs) for FI over the research period. RESULTS: The global burden of FI, as measured by DALYs and age-standardised DALY rates among adults aged 20-49 years, exhibited an upward trend from 1990 to 2019. Regions such as Tropical Latin America (EAPC: 3.76, 95% CI 2.76 to 4.77), South Asia (EAPC: 1.74, 95% CI 1.01 to 2.48) and Andean Latin America (EAPC: 8.54, 95% CI 6.79 to 10.32) had higher DALYs. The age-standardised DALY rates notably increased in low-middle-SDI and low-SDI countries, with EAPCs of 1.42 (95% CI 0.76 to 2.10) and 1.25 (95% CI 0.30 to 2.21), respectively. Despite lower overall DALYs in high-SDI countries, they experienced the highest EAPC in DALYs (1.57, 95% CI 1.30 to 1.83) during the period 1990-2019. China and India consistently had the highest DALYs for FI globally in both 1990 and 2019, while Africa and Latin America bore a significantly greater burden of the disease compared with other regions. CONCLUSION: The GBD Study data on FI among adults aged 20-49 years revealed a rising global trend in FI from 1990 to 2019, with notable variations across different regions.

The potential benefits of PGC-1α in treating Alzheimer's disease are dependent on the integrity of the LLKYL L3 motif: Effect of regulating mitochondrial axonal transportation.

Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). The transcriptional coactivator PPARγ coactivator 1 (PGC-1a) has been identified as a key regulator of mitochondrial biogenesis and function. However, the precise structure/function relationship between PGC-1a and mitochondrial quality control remains incompletely understood. In this study, we investigated the impact of PGC-1a on AD pathology and its underlying mechanisms with a specific focus on mitochondrial axonal transport. Additionally, we generated two PGC-1α mutants by substituting leucine residues at positions 148 and 149 within the LKKLL motif or at positions 209 and 210 within the LLKYL motif with alanine. Subsequently, we examined the effects of these mutants on mutAPP-induced abnormalities in anterograde and retrograde axonal transport, disrupted mitochondrial distribution, and impaired mitophagy. Mutagenesis studies revealed that the LLKYL motif at amino acid position 209-210 within PGC-1α plays an essential role in its interaction with estrogen-related receptors (ERRα), which is necessary for restoring normal mitochondrial anterograde axonal transport, maintaining proper mitochondrial distribution, and ultimately preventing neuronal apoptosis. Furthermore, it was found that the Leu-rich motif at amino acids 209-210 within PGC-1α is crucial for rescuing mutAPP-induced impairment in mitophagy and loss of membrane potential by restoring normal mitochondrial retrograde axonal transport. Conversely, mutation of residues 148 and 149 in the LKKLL motif does not compromise the effectiveness of PGC-1α. These findings provide valuable insights into the molecular determinants governing specificity of action for PGC-1α involved in regulating mutAPP-induced deficits in mitochondrial axonal trafficking. Moreover, they suggest a potential therapeutic target for addressing Alzheimer's disease.

Integrative genomic analysis reveals cancer-associated mutations in patients with ophthalmic tumors.

OBJECTIVE: Apart from the role of the retinoblastoma gene, the genomic events associated with poor outcomes in patients with ophthalmic tumors are poorly understood. METHODS: We retrospectively analyzed 48 patients with six types of ophthalmic tumors. We searched for high-frequency mutated genes and susceptibility genes in these patients using combined exome and transcriptome analysis. RESULTS: We identified four clearly causative genes (TP53, PTCH1, SMO, BAP1). Susceptibility gene analysis identified hotspot genes, including RUNX1, APC, IDH2, and BRCA2, and high-frequency gene analysis identified several genes, including TP53, TTN, and MUC16. Transcriptome analysis identified 5868 differentially expressed genes, of which TOP2A and ZWINT were upregulated in all samples, while CFD, ELANE, HBA1, and HBB were downregulated. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the phosphoinositide 3-kinase (PI3K)-Akt and Transcriptional misregulation in cancer signaling pathways may be involved in ophthalmic tumorigenesis. CONCLUSIONS: TP53 is clearly involved in ophthalmic tumorigenesis, especially in basal cell carcinoma, and the PI3K-Akt signaling pathway may be an essential pathway involved in ophthalmic tumorigenesis. RUNX1, SMO, TOP2A, and ZWINT are also highly likely to be involved in ophthalmic tumorigenesis, but further functional experiments are needed to verify the mechanisms of these genes in regulating tumorigenesis.

Correlated Charge Density Wave Insulators in Chirally Twisted Triple Bilayer Graphene.

Electrons residing in a flat-band system can play a vital role in triggering spectacular phenomenology due to relatively large interactions and spontaneous breaking of different degeneracies. In this work, we demonstrate chirally twisted triple bilayer graphene, a new moiré structure formed by three pieces of helically stacked Bernal bilayer graphene, as a highly tunable flat-band system. In addition to the correlated insulators showing at integer moiré fillings, commonly attributed to interaction induced symmetry broken isospin flavors in graphene, we observe abundant insulating states at half-integer moiré fillings, suggesting a longer-range interaction and the formation of charge density wave insulators which spontaneously break the moiré translation symmetry. With weak out-of-plane magnetic field applied, as observed half-integer filling states are enhanced and more quarter-integer filling states appear, pointing toward further quadrupling moiré unit cells. The insulating states at fractional fillings combined with Hartree-Fock calculations demonstrate the observation of a new type of correlated charge density wave insulators in graphene and points to a new accessible twist manner engineering correlated moiré electronics.

GORASP2 promotes phagophore closure and autophagosome maturation into autolysosomes.

As the central hub of the secretory pathway, the Golgi apparatus plays a crucial role in maintaining cellular homeostasis in response to stresses. Recent studies have revealed the involvement of the Golgi tether, GORASP2, in facilitating autophagosome-lysosome fusion by connecting LC3-II and LAMP2 during nutrient starvation. However, the precise mechanism remains elusive. In this study, utilizing super-resolution microscopy, we observed GORASP2 localization on the surface of autophagosomes during glucose starvation. Depletion of GORASP2 hindered phagophore closure by regulating the association between VPS4A and the ESCRT-III component, CHMP2A. Furthermore, we found that GORASP2 controls RAB7A activity by modulating its GEF complex, MON1A-CCZ1, thereby impacting RAB7A's interaction with the HOPS complex. The assembly of both STX17-SNAP29-VAMP8 and YKT6-SNAP29-STX7 SNARE complexes was also attenuated without GORASP2. These findings suggest that GORASP2 helps seal autophagosomes and activate the RAB7A-HOPS-SNAREs membrane fusion machinery for autophagosome maturation, highlighting its membrane tethering function in response to stresses.Abbreviations: BafA1: bafilomycin A1; ESCRT: endosomal sorting complex required for transport; FPP: fluorescence protease protection; GEF: guanine nucleotide exchange factor; GFP: green fluorescent protein; GORASP2: golgi reassembly stacking protein 2; GSB: glucose starvation along with bafilomycin A1; HOPS: homotypic fusion and protein sorting; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; PBS: phosphate-buffered saline; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PK: proteinase K; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SIM: structured illumination microscopy; UVRAG: UV radiation resistance associated.