Molecular Basis of the Granular Characteristics of Small-Granule Starch: A Comparative Study.

Small-granule starches (SGSs) have technological advantages over starches of conventional sizes for many applications. The study compared the granular characteristics of three SGSs (from amaranth, quinoa, and taro) with those of maize and potato starches and revealed their molecular basis. The results indicated that the supramolecular architecture of starch granules was not necessarily correlated with granule size. Acid hydrolysis of amaranth and quinoa starches was fast due to not only their small granule sizes but also the defects in the supramolecular structure, to which short external and internal chain lengths of amaranth and quinoa amylopectins contributed. By comparison, the granular architecture of taro starch granules was more stable partly due to the longer external chain length of taro amylopectin. Comparison of the molecular composition of branched subunits (released by using α-amylase of Bacillus amyloliquefaciens) in amylopectins and that in lintnerized starches suggested a significant heterogeneous degradation of amaranth and quinoa starches at supramolecular levels.

Astrocyte-derived CHI3L1 signaling impairs neurogenesis and cognition in the demyelinated hippocampus.

Cognitive dysfunction is a feature in multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. A notable aspect of MS brains is hippocampal demyelination, which is closely associated with cognitive decline. However, the mechanisms underlying this phenomenon remain unclear. Chitinase-3-like (CHI3L1), secreted by activated astrocytes, has been identified as a biomarker for MS progression. Our study investigates CHI3L1's function within the demyelinating hippocampus and demonstrates a correlation between CHI3L1 expression and cognitive impairment in patients with MS. Activated astrocytes release CHI3L1 in reaction to induced demyelination, which adversely affects the proliferation and differentiation of neural stem cells and impairs dendritic growth, complexity, and spine formation in neurons. Our findings indicate that the astrocytic deletion of CHI3L1 can mitigate neurogenic deficits and cognitive dysfunction. We showed that CHI3L1 interacts with CRTH2/receptor for advanced glycation end (RAGE) by attenuating ß-catenin signaling. The reactivation of ß-catenin signaling can revitalize neurogenesis, which holds promise for therapy of inflammatory demyelination.

Encapsulation of chrysin and rutin using self-assembled nanoparticles of debranched quinoa, maize, and waxy maize starches.

Chrysin and rutin are natural polyphenols with multifaceted biological activities but their applications face challenges in bioavailability. Encapsulation using starch nanoparticles (SNPs) presents a promising approach to overcome the limitations. In this study, chrysin and rutin were encapsulated into self-assembled SNPs derived from quinoa (Q), maize (M), and waxy maize (WM) starches using enzyme-hydrolysis. Encapsulation efficiencies ranged from 74.3 % to 79.1 %, with QSNPs showing superior performance. Simulated in vitro digestion revealed sustained release and higher antioxidant activity in QSNPs compared to MSNPs and WMSNPs. Variations in encapsulation properties among SNPs from different sources were attributed to the differences in the structural properties of the starches. The encapsulated SNPs exhibited excellent stability, retaining over 90 % of chrysin and 85 % of rutin after 15 days of storage. These findings underscore the potential of SNP encapsulation to enhance the functionalities of chrysin and rutin, facilitating the development of fortified functional foods with enhanced bioavailability and health benefits.

SPG21, a potential oncogene targeted by miR-128-3p, amplifies HBx-induced carcinogenesis and chemoresistance via activation of TRPM7-mediated JNK pathway in hepatocellular carcinoma.

PURPOSE: Chronic hepatitis B virus (HBV) infection is the primary risk factor for the malignant progression of hepatocellular carcinoma (HCC). It has been reported that HBV X protein (HBx) possesses oncogenic properties, promoting hepatocarcinogenesis and chemoresistance. However, the detailed molecular mechanisms are not fully understood. Here, we aim to investigate the effects of miR-128-3p/SPG21 axis on HBx-induced hepatocarcinogenesis and chemoresistance. METHODS: The expression of SPG21 in HCC was determined using bioinformatics analysis, quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC). The roles of SPG21 in HCC were elucidated through a series of in vitro and in vivo experiments, including real-time cellular analysis (RTCA), matrigel invasion assay, and xenograft mouse model. Pharmacologic treatment and flow cytometry were performed to demonstrate the potential mechanism of SPG21 in HCC. RESULTS: SPG21 expression was elevated in HCC tissues compared to adjacent non-tumor tissues (NTs). Moreover, higher SPG21 expression correlated with poor overall survival. Functional assays revealed that SPG21 fostered HCC tumorigenesis and invasion. MiR-128-3p, which targeted SPG21, was downregulated in HCC tissues. Subsequent analyses showed that HBx amplified TRPM7-mediated calcium influx via miR-128-3p/SPG21, thereby activating the c-Jun N-terminal kinase (JNK) pathway. Furthermore, HBx inhibited doxorubicin-induced apoptosis by engaging the JNK pathway through miR-128-3p/SPG21. CONCLUSION: The study suggested that SPG21, targeted by miR-128-3p, might be involved in enhancing HBx-induced carcinogenesis and doxorubicin resistance in HCC via the TRPM7/Ca2+/JNK signaling pathway. This insight suggested that SPG21 could be recognized as a potential oncogene, offering a novel perspective on its role as a prognostic factor and a therapeutic target in the context of HCC.

Whey protein hydrolysates and infant formulas: Effects on physicochemical and biological properties.

Whey protein hydrolysates are recognized for their substantial functional and biological properties. Their high digestibility and amino acid composition make them a valuable ingredient to hydrolyzed whey infant formulas, enhancing both product functionality and nutritional values for infant growth. It is important to understand the functional and biological properties of whey protein hydrolysates for their applications in infant formula systems. This review explored preparation methods of whey protein hydrolysates for infant formula-based applications. The effects of whey protein hydrolysate on the physicochemical and biological properties of hydrolyzed whey infant formulas were summarized. The influences of whey protein hydrolysates on the functional and nutritional properties of formulas from manufacturing to infant consumption were discussed. Whey protein hydrolysates are crucial components in the preparation of infant formula, tailored to meet the functional and nutritional demands of the product. The selection of enzyme types and hydrolysis parameters is decisive for obtaining "optimal" whey protein hydrolysates that match the intended characteristics. "Optimal" whey protein hydrolysates offer diverse functionalities, including solubility, emulsification and production stability to hydrolyzed whey infant formulas during manufacturing processes and formulations. They simultaneously promote protein digestibility, infant growth and other potential health benefits, including reduced allergenic potential, as supported by in vitro, in vivo and clinical trials. Overall, the precise selection of enzymes and hydrolysis parameters in the production of whey protein hydrolysates is crucial in achieving the desired characteristics and functional benefits for hydrolyzed whey infant formulas, making them critical in the development of infant nutrition products.

Predictive impact of sarcopenia in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: A retrospective study.

Background: Sarcopenia, characterised by an ongoing loss of skeletal muscle mass and reduced strength and function, is frequently observed in patients with non-small cell lung cancer (NSCLC). However, the relationship between sarcopenia and the prognosis of NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. This aimed to assess whether sarcopenia is an independent prognostic factor for survival in patients with advanced NSCLC receiving ICIs. Methods: For this retrospective cohort study, we analysed the medical records of patients attending our hospital aged 18-75 years who were newly diagnosed with stage IIIB to stage IV NSCLC, and who had received ICIs as first- or second-line therapy between May 2019 and April 2022. The skeletal muscle index (SMI) was calculated from computed tomography (CT) images and relevant clinical characteristics within 4 weeks of initiating treatment and used to diagnose sarcopenia status. The Kaplan-Meier method and log-rank test were used to calculate and compare patients' progression-free survival (PFS). Cox proportional hazard regression was used to examine the associations between sarcopenia and survival outcomes. The chi-square test was used to compare treatment response outcomes, such as the objective response rate (ORR), disease control rate (DCR), and immunotherapy-related adverse events (irAEs), between individuals with and without sarcopenia. Additionally, the Student's t-test was utilised to compare SMI values between patients by their objective response (OR) and disease control (DC). Finally, the Mann-Whitney U test was used to compare nutritional and inflammatory indicators between the sarcopenia groups. Results: The study enrolled 70 patients, of whom 34 (48.6%) were diagnosed with sarcopenia. The median PFS of patients with and without sarcopenia was 7.5 vs. 13.4 months, respectively (p = 0.006). The proportional hazards regression analysis showed sarcopenia to be an independent prognostic factor for shorter PFS (hazard ratio (HR): 0.504, 95% CI: 0.265-0.962, p = 0.038). Using chi square tests, we found significant differences in the ORR (20.59% vs. 58.33%, p = 0.001) and occurrence of any irAEs (44.1% vs. 22.2%, p = 0.028) between the sarcopenia and the non-sarcopenia groups, respectively. The Student's t-test showed a significant difference in SMI between the ORR group and the non-ORR group (49.99 ± 7.00 vs. 42.98 ± 2.18 cm2/m2, p = 0.0015). While the sarcopenia group were with significantly a lower CD4+/CD8+ ratios and a higher C-reactive protein (CRP) level (p = 0.026, p = 0.011, respectively). Conclusions: This study found that sarcopenia is a significant predictor of a poor prognosis for patients with advanced NSCLC receiving ICIs. Multiple inflammatory and immune functions related to prognosis also differ by sarcopenia status.

Study on the structure-activity relationship of rice immunopeptides based on molecular docking.

Research on food-derived immunoregulatory peptides has attracted increasing attention of scientists worldwide. However, the structure-activity relationship of rice immunopeptides was not clearly. Herein, 114 rice immunopeptides were obtained by simulating the enzymatic hydrolysis of rice proteins and were further analyzed by NetMHCIipan-4.0. Subsequently, the molecular docking was used to simulate the binding of immunoreactive peptides to major histocompatibility complex class II (MHC-II) molecules. Results show that S, R, D, E, and T amino acid could easily form hydrogen bonds with MHC-II molecules, thus enhancing innate and adaptive immunity. Finally, glucose-modified rice immunopeptides were to investigate the binding of the peptides with MHC-II molecules after glycosylation modification; this provided a theoretical basis for the targeted modification of the generated immunopeptides. All in all, the present study provides a theoretical foundation to further utilize rice processing byproducts and other food products to enhance immunity.

Modifications of whey proteins for emulsion based applications: Current status, issues and prospectives.

Whey proteins are a major group of dairy proteins with high potential for various food based applications. Whey protein isolate has a limited range of functionalities. This functional range can be expanded using diverse modification methods to suit specific applications. This review summarizes the recent advances in the modifications of whey proteins using chemical, physical, and enzymatic methods and their combinations as well as the modification effects on the physicochemical properties. The uses of these modified whey proteins in emulsion based food and beverage systems are described. The limitations in the studies summarized are critically discussed, while future research directions are suggested on how to better utilize whey proteins for emulsion based uses through modifications.

An updated review of functional ingredients of Manuka honey and their value-added innovations.

Manuka honey (MH) is a highly prized natural product from the nectar of Leptospermum scoparium flowers. Increased competition on the global market drives MH product innovations. This review updates comparative and non-comparative studies to highlight nutritional, therapeutic, bioengineering, and cosmetic values of MH. MH is a good source of phenolics and unique chemical compounds, such as methylglyoxal, dihydroxyacetone, leptosperin glyoxal, methylsyringate and leptosin. Based on the evidence from in vitro, in vivo and clinical studies, multifunctional bioactive compounds of MH have exhibited anti-oxidative, anti-inflammatory, immunomodulatory, anti-microbial, and anti-cancer activities. There are controversial topics related to MH, such as MH grading, safety/efficacy, implied benefits, and maximum levels of contaminants concerned. Artificial intelligence can optimize MH studies related to chemical analysis, toxicity prediction, multi-functional mechanism exploration and product innovation.

Epigenetic addition of m5C to HBV transcripts promotes viral replication and evasion of innate antiviral responses.

Eukaryotic five-methylcytosine (m5C) is an important regulator of viral RNA splicing, stability, and translation. However, its role in HBV replication remains largely unknown. In this study, functional m5C sites are identified in hepatitis B virus (HBV) mRNA. The m5C modification at nt 1291 is not only indispensable for Aly/REF export factor (ALYREF) recognition to promote viral mRNA export and HBx translation but also for the inhibition of RIG-I binding to suppress interferon-ß (IFN-ß) production. Moreover, NOP2/Sun RNA methyltransferase 2 (NSUN2) catalyzes the addition of m5C to HBV mRNA and is transcriptionally downregulated by the viral protein HBx, which suppresses the binding of EGR1 to the NSUN2 promoter. Additionally, NSUN2 expression correlates with m5C modification of type I IFN mRNA in host cells, thus, positively regulating IFN expression. Hence, the delicate regulation of NSUN2 expression induces m5C modification of HBV mRNA while decreasing the levels of m5C in host IFN mRNA, making it a vital component of the HBV life cycle. These findings provide new molecular insights into the mechanism of HBV-mediated IFN inhibition and may inform the development of new IFN-α based therapies.

A hybrid photocatalytic system enables direct glucose utilization for methanogenesis.

Integration of methanogenic archaea with photocatalysts presents a sustainable solution for solar-driven methanogenesis. However, maximizing CH4 conversion efficiency remains challenging due to the intrinsic energy conservation and strictly restricted substrates of methanogenic archaea. Here, we report a solar-driven biotic-abiotic hybrid (biohybrid) system by incorporating cadmium sulfide (CdS) nanoparticles with a rationally designed methanogenic archaeon Methanosarcina acetivorans C2A, in which the glucose synergist protein and glucose kinase, an energy-efficient route for glucose transport and phosphorylation from Zymomonas mobilis, were implemented to facilitate nonnative substrate glucose for methanogenesis. We demonstrate that the photo-excited electrons facilitate membrane-bound electron transport chain, thereby augmenting the Na+ and H+ ion gradients across membrane to enhance adenosine triphosphate (ATP) synthesis. Additionally, this biohybrid system promotes the metabolism of pyruvate to acetyl coenzyme A (AcCoA) and inhibits the flow of AcCoA to the tricarboxylic acid (TCA) cycle, resulting in a 1.26-fold augmentation in CH4 production from glucose-derived carbon. Our results provide a unique strategy for enhancing methanogenesis through rational biohybrid design and reprogramming, which gives a promising avenue for sustainably manufacturing value-added chemicals.

Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia.

Human endogenous retroviruses (HERVs) are remnants of retroviral infections in human germline cells from millions of years ago. Among these, ERVW-1 (also known as HERV-W-ENV, ERVWE1, or ENVW) encodes the envelope protein of the HERV-W family, which contributes to the pathophysiology of schizophrenia. Additionally, neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia. Here, our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset (GSE53987) were mainly related to ferroptosis and its associated pathways. Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes, particularly Glutathione peroxidase 4 (GPX4) and solute carrier family 3 member 2 (SLC3A2), in schizophrenia patients compared to normal controls. Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia. Studies indicated that ERVW-1 increased iron levels, malondialdehyde (MDA), and transferrin receptor protein 1 (TFR1) expression while decreasing glutathione (GSH) levels and triggering the loss of mitochondrial membrane potential, suggesting that ERVW-1 can induce ferroptosis. Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities. Moreover, Ferrostatin-1 (Fer-1), the ferroptosis inhibitor, reversed the iron accumulation and mitochondrial membrane potential loss, as well as restored the expressions of ferroptosis markers GSH, MDA, and TFR1 induced by ERVW-1. In conclusion, ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2, revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

Prognostic value of neutrophil-to-lymphocyte ratio on proteinuria remission in patients with idiopathic membranous nephropathy.

BACKGROUND: As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. However, NLR in idiopathic membranous nephropathy (IMN) has been rarely studied. We sought to assess the role of NLR in predicting proteinuria remission in IMN. METHODS: This retrospective study involved 561 patients with IMN from January 2018 to December 2022 in Department of Nephrology of Wuhan Central Hospital. All baseline data were collected before the immunosuppressive regiment was administered. The Cox proportional hazards model and Kaplan-Meier curve were applied to assess the prognostic value of NLR for proteinuria remission. RESULTS: The area under the receiver operating characteristic curve revealed that the optimal cut-off NLR value for predicting proteinuria non-remission was 2.63, with a sensitivity and specificity of 58.2% and 72.7%, respectively. Kaplan-Meier curves showed a lower rate of proteinuria remission in patients with high NLR compared with low NLR (Log-rank = 5.04, p = 0.025). Multivariate Cox regression analysis showed that high NLR was an independent risk factor for proteinuria non-remission after adjustment (HR = 1.579, 95% CI 1.052-2.683, p = 0.023). Subgroup analysis indicated that high NLR was a risk factor for proteinuria non-remission especially in IMN patients with 24 h proteinuria ≥ 1 g (HR = 1.818, 95% CI 1.031-2.573, p = 0.012) and chronic kidney disease (CKD) stage 3-4 (HR = 1.935, 95% CI 1.084-2.495, p = 0.015). CONCLUSION: The current study shows that NLR is an independent risk factor for proteinuria non-remission in IMN. More attention should be paid to IMN patients with high NLR, especially for those patients with 24 h proteinuria ≥ 1 g and CKD stage 3-4.

FSS-inspired transmitarray for dynamic beamforming and gain control.

In this paper, we propose a concept of combining the methodology of phase coding modulation with frequency selective surface (FSS) inspired transmitarray (TA) to achieve the ability of dynamical beamforming and gain control in microwave regime. The TA element composed of five-layer stacked bandpass FSS units separated by small air gaps. Each FSS unit comprises a metallic octagon slot with a pair of varactor diodes loaded along the polarization direction. The elaborately designed feeding network makes it possible to modulate the transmission phase of each element. Different phase coding sequences are performed through changing the bias voltage configurations, then the radiation far field of the proposed TA can be tailored in real time. Dynamic beamforming and gain control under different encoding arrangements are exhibited to demonstrate the physical mechanism of electromagnetic (EM) manipulation with this method. The proposed strategy is verified by numerical simulations and experiment. This work adds new function for TA and can reshape its application prospect, such as reconfigurable beam emitter for multilink data transmission, long range point-to-point (PTP) wireless links and radio frequency energy harvesting.

Three-dimensional atomic structure and local chemical order of medium- and high-entropy nanoalloys.

Medium- and high-entropy alloys (M/HEAs) mix several principal elements with near-equiatomic composition and represent a model-shift strategy for designing previously unknown materials in metallurgy1-8, catalysis9-14 and other fields15-18. One of the core hypotheses of M/HEAs is lattice distortion5,19,20, which has been investigated by different numerical and experimental techniques21-26. However, determining the three-dimensional (3D) lattice distortion in M/HEAs remains a challenge. Moreover, the presumed random elemental mixing in M/HEAs has been questioned by X-ray and neutron studies27, atomistic simulations28-30, energy dispersive spectroscopy31,32 and electron diffraction33,34, which suggest the existence of local chemical order in M/HEAs. However, direct experimental observation of the 3D local chemical order has been difficult because energy dispersive spectroscopy integrates the composition of atomic columns along the zone axes7,32,34 and diffuse electron reflections may originate from planar defects instead of local chemical order35. Here we determine the 3D atomic positions of M/HEA nanoparticles using atomic electron tomography36 and quantitatively characterize the local lattice distortion, strain tensor, twin boundaries, dislocation cores and chemical short-range order (CSRO). We find that the high-entropy alloys have larger local lattice distortion and more heterogeneous strain than the medium-entropy alloys and that strain is correlated to CSRO. We also observe CSRO-mediated twinning in the medium-entropy alloys, that is, twinning occurs in energetically unfavoured CSRO regions but not in energetically favoured CSRO ones, which represents, to our knowledge, the first experimental observation of correlating local chemical order with structural defects in any material. We expect that this work will not only expand our fundamental understanding of this important class of materials but also provide the foundation for tailoring M/HEA properties through engineering lattice distortion and local chemical order.

Enrichment of resistant starch in starch-protein hydrolysate binary matrix by modulating pH during thermal processing.

Controlling the digestion features of starch-based food matrices following thermal processing plays vital roles in reducing risks of metabolic diseases such as obesity and type II diabetes. To date, it remains largely unclear how regulating the pH during thermal processing alters the microstructure and digestion features of starch-based matrix including protein hydrolysates. Considering this, corn starch (CS) and soybean protein isolate (SPI) (or its hydrolysates (SPIH)) were used to prepare thermally-processed CS-SPI and CS-SPIH binary matrices under different pH values (3 to 9), followed by inspection of changes in the structures and digestibility using combined methods. It was found that including SPI (especially SPIH) caused structural changes of those binary systems, such as reduced network sizes, increased V-crystals and reduced nanoscale structures, which could allow more resistant starch (RS). This phenomenon was especially true when including SPIH with regulated pH value. For instance, SPIH inclusion at pH 5 caused the highest RS content (about 20.30%), presumably linked to the reduced molecule size of SPIH with strengthened aggregation at pH 5. In contrast, the acidic (pH 3) and alkaline (pH 9) conditions allowed reduced short-range orders and tailored porous networks and thus less RS (ca. 17.46% at pH 3 and 16.74% at pH 9).

Granular architecture of lotus seed starch and its impact on physicochemical properties.

Lotus seed starch has high apparent amylose content (AAM). A representative definition of its granular architecture (e.g., lamellar structure) remained absent. This study defined the granular shape, crystalline and lamellar structures, and digestibility of twenty-two samples of lotus seed starch (LS) by comparing with those of potato and maize starches. LS granules had more elongated shape and longer repeat distance of lamellae than potato and maize starch granules. The enzymatic susceptibility of LS granules was more affected by AAM than granular architecture. Using these LSs as a model system, the relationships between lamellar structure of starch granules and properties of their gelatinized counterparts were investigated. In LSs, thinner amorphous lamella and thicker crystalline lamella were associated with higher swelling power and yield stress. The relationships were found to be connected via certain structural characteristics of amylopectin.

Effect of preoperative arterial diameter on hospitalization and mortality in patients undergoing hemodialysis with forearm arteriovenous fistula access.

BACKGROUND: As pointed out by the recent Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Vascular Access, the current quality of evidence supporting preoperative vascular anatomy and patient outcomes is suboptimal and insufficient to make recommendations. This study assessed arteriovenous fistulas (AVFs) created with different preoperative arterial diameters on hospitalization and mortality rates in patients undergoing hemodialysis at the authors' center. METHODS: Data from 261 patients who underwent HD between 2017 and 2019 were retrospectively examined. Differences in mortality and hospitalization rates between patients with different preoperative arterial diameters were compared, and risk factors for mortality and hospitalization were analyzed. RESULTS: Smaller preoperative artery diameter (<2 mm) was associated with all-cause mortality (risk ratio [RR] 1.61 [95% confidence interval (CI) 1.45-1.90]; p < 0.01), and access-related (RR 1.68 [95% CI 1.24-2.44]; p < 0.01), and congestive heart failure (CHF)-related (RR 0.67 [95% CI 0.38-1.01]; p = 0.04) hospitalization. Longer catheter-dependent duration (⩾60 days) was associated with access-related hospitalization (RR 1.48 [95% CI 1.07-2.11]; p = 0.03), and higher postoperative brachial artery blood flow (⩾1500 mL/min) was associated with CHF-related hospitalization (RR 1.58 [95% CI 1.02-2.29]; p < 0.01). Higher postoperative brachial artery blood flow (⩾1500 mL/min) was associated with all-cause mortality (hazard ratio [HR] 1.20 [95% CI 1.09-2.32]; p = 0.04), whereas preoperative artery diameter (HR 0.98 [95% CI 0.93-1.86]; p = 0.08) and catheter-dependent duration (HR 1.06 [95% CI 0.47-2.13]; p = 0.82) were not associated with all-cause mortality. CONCLUSION: In this cohort, smaller preoperative artery diameter was associated with all-cause and access-related hospitalizations, while a larger preoperative artery and higher postoperative brachial blood flow were associated with CHF-related hospitalization. However, only higher postoperative brachial blood flow was associated with all-cause mortality.

Captive ERVWE1 triggers impairment of 5-HT neuronal plasticity in the first-episode schizophrenia by post-transcriptional activation of HTR1B in ALKBH5-m6A dependent epigenetic mechanisms.

BACKGROUND: Abnormalities in the 5-HT system and synaptic plasticity are hallmark features of schizophrenia. Previous studies suggest that the human endogenous retrovirus W family envelope (ERVWE1) is an influential risk factor for schizophrenia and inversely correlates with 5-HT4 receptor in schizophrenia. To our knowledge, no data describes the effect of ERVWE1 on 5-HT neuronal plasticity. N6-methyladenosine (m6A) regulates gene expression and impacts synaptic plasticity. Our research aims to systematically investigate the effects of ERVWE1 on 5-HT neuronal plasticity through m6A modification in schizophrenia. RESULTS: HTR1B, ALKBH5, and Arc exhibited higher levels in individuals with first-episode schizophrenia compared to the controls and showed a strong positive correlation with ERVWE1. Interestingly, HTR1B was also correlated with ALKBH5 and Arc. Further analyses confirmed that ALKBH5 may be an independent risk factor for schizophrenia. In vitro studies, we discovered that ERVWE1 enhanced HTR1B expression, thereby activating the ERK-ELK1-Arc pathway and reducing the complexity and spine density of 5-HT neurons. Furthermore, ERVWE1 reduced m6A levels through ALKBH5 demethylation. ERVWE1 induced HTR1B upregulation by improving its mRNA stability in ALKBH5-m6A-dependent epigenetic mechanisms. Importantly, ALKBH5 mediated the observed alterations in 5-HT neuronal plasticity induced by ERVWE1. CONCLUSIONS: Overall, HTR1B, Arc, and ALKBH5 levels were increased in schizophrenia and positively associated with ERVWE1. Moreover, ALKBH5 was a novel risk gene for schizophrenia. ERVWE1 impaired 5-HT neuronal plasticity in ALKBH5-m6A dependent mechanism by the HTR1B-ERK-ELK1-Arc pathway, which may be an important contributor to aberrant synaptic plasticity in schizophrenia.