Establishment and validation of a gene mutation-based risk model for predicting prognosis and therapy response in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a malignant clonal proliferative disease of hematopoietic system. Despite tremendous progress in uncovering the AML genome, only a small number of mutations have been incorporated into risk stratification and used as therapeutic targets. In this research, we performed to construct a predictive prognosis risk model for AML patients according to gene mutations. Methods: Next-generation sequencing (NGS) technology was utilized to detect gene mutation from 118 patients. mRNA expression profiles and related clinical information were mined from TCGA and GEO databases. Consensus cluster analysis was applied to obtain molecular subtypes, and differences in clinicopathological features, prognosis, and immune microenvironment of different clusters were systematically compared. According to the differentially expressed genes (DEGs) between clusters, univariate and LASSO regression analysis were applied to identify gene signatures to build a prognostic risk model. Patients were classified into high-risk (HR) and low-risk (LR) groups according to the median risk score (RS). Differences in prognosis, immune profile, and therapeutic sensitivity between two groups were analyzed. The independent predictive value of RS was assessed and a nomogram was developed. Results: NGS detected 24 mutated genes, with higher mutation frequencies in CBL (63 %) and SETBP1 (49 %). Two clusters exhibited different immune microenvironments and survival probability (p = 0.0056) were identified. A total of 444 DEGs were screened in two clusters, and a mutation-associated risk model was constructed, including MPO, HGF, SH2B3, SETBP1, HLA-DRB1, LGALS1, and KDM5B. Patients in LR had a superior survival time compared to HR. Predictive performance of this model was confirmed and the developed nomogram further improved the applicability of the risk model with the AUCs for predicting 1-, 3-, 5-year survival rate were 0.829, 0.81 and 0.811, respectively. HR cases were more sensitive to erlotinib, CI-1040, and AZD6244. Conclusion: These findings supplemented the understanding of gene mutations in AML, and constructed models had good application prospect to provide effective information for predicting prognosis and treatment response of AML.

How incubation temperature affects hatchling performance in reptiles: an integrative insight based on plasticity in metabolic enzyme.

Evaluating the effects of temperature variations on animals plays an important role in understanding the threat of climate warming. The effects of developmental temperature on offspring performance are critical in evaluating the effects of warming temperatures on the fitness of oviparous species, but the physiological and biochemical basis of this developmental plasticity is largely unknown. In this study, we incubated eggs of the turtle Pelodiscus sinensis at low (24 °C), medium (28 °C), and high (32 °C) temperatures, and evaluated the effects of developmental temperature on offspring fitness, and metabolic enzymes in the neck and limb muscles of hatchlings. The hatchlings from eggs incubated at the medium temperature showed better fitness-related performance (righting response and swimming capacity) and higher activities of metabolic enzymes (hexokinase, HK; lactate dehydrogenase, LDH) than hatchlings from the eggs incubated at high or low temperatures. In addition, the swimming speed and righting response were significantly correlated with the HK activities in limb (swimming speed) and neck (righting response) muscles, suggesting that the developmental plasticity of energy metabolic pathway might play a role in determining the way incubation temperature affects offspring phenotypes. Integrating the fitness-related performance and the activities of metabolic enzymes, we predict that the P. sinensis from high latitude would not face the detrimental effects of climate warming until the average nest temperatures reach 32 °C.

Phylogenetic placement and comparative analysis of the mitochondrial genomes of Idiostoloidea (Hemiptera: Heteroptera).

The classification system and the higher level phylogenetic relationships of Pentatomomorpha, the second largest infraorder of Heteroptera (Insecta: Hemiptera), have been debated and remain controversial over decades. In particular, the placement and phylogenetic relationship of Idiostoloidea are not well resolved, which hampers a better understanding of the evolutionary history of Pentatomomorpha. In this study, for the first time, we reported the complete mitochondrial genome for two narrowly distributed families of Idiostoloidea (including Idiostolidae and Henicocoridae), respectively. The length of the mitochondrial genome of Monteithocoris hirsutus and Henicocoris sp. is 16,632 and 16,013 bp, respectively. The content of AT is ranging from 75.15% to 80.48%. The mitogenomic structure of Idiostoloidea is highly conservative and there are no gene arrangements. By using the Bayesian inference, maximum likelihood, and Bayesian site-heterogeneous mixture model, we inferred the phylogenetic relationships within Pentatomomorpha and estimated their divergence times based on concatenated mitogenomes and nuclear ribosomal genes. Our results support the classification system of six superfamilies within Pentatomomorpha and confirm the monophyletic groups of each superfamily, with the following phylogenetic relationships: (Aradoidea + (Pentatomoidea + (Idiostoloidea + (Coreoidea + (Pyrrhocoroidea + Lygaeoidea))))). Furthermore, estimated divergence times revealed that most pentatomomorphan superfamilies and families diverged during the Late Jurassic to Early Cretaceous, which coincides with the explosive radiation of angiosperms.

Effect of propofol and ciprofol on the euphoric reaction in patients with painless gastroscopy: A prospective randomized controlled trial.

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P < 0.05), and hemodynamics and SpO2 were more stable during sedation (P < 0.05). Conclusion: There was no significant difference between propofol and ciprofol in terms of euphoria experienced by patients after sedation in patients undergoing gastroscopy. Ciprofol has demonstrated addictive potential similar to that of propofol, warranting careful attention to its addictive potential during clinical application.

Development of a piezo stack - laser Doppler vibrometer sensing approach for characterizing shear wave dispersion and local viscoelastic property distributions.

Laser Doppler vibrometry and wavefield analysis have recently shown great potential for nondestructive evaluation, structural health monitoring, and studying wave physics. However, there are limited studies on these approaches for viscoelastic soft materials, especially, very few studies on the laser Doppler vibrometer (LDV)-based acquisition of time-space wavefields of dispersive shear waves in viscoelastic materials and the analysis of these wavefields for characterizing shear wave dispersion and evaluating local viscoelastic property distributions. Therefore, this research focuses on developing a piezo stack-LDV system and shear wave time-space wavefield analysis methods for enabling the functions of characterizing the shear wave dispersion and the distributions of local viscoelastic material properties. Our system leverages a piezo stack to generate shear waves in viscoelastic materials and an LDV to acquire time-space wavefields. We introduced space-frequency-wavenumber analysis and least square regression-based dispersion comparison to analyze shear wave time-space wavefields and offer functions including extracting shear wave dispersion relations from wavefields and characterizing the spatial distributions of local wavenumbers and viscoelastic properties (e.g., shear elasticity and viscosity). Proof-of-concept experiments were performed using a synthetic gelatin phantom. The results show that our system can successfully generate shear waves and acquire time-space wavefields. They also prove that our wavefield analysis methods can reveal the shear wave dispersion relation and show the spatial distributions of local wavenumbers and viscoelastic properties. We expect this research to benefit engineering and biomedical research communities and inspire researchers interested in developing shear wave-based technologies for characterizing viscoelastic materials.

A blueprint for tumor-infiltrating B cells across human cancers.

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.

Residue changes, degradation, processing factors and their relation between physicochemical properties of pesticides in peanuts during multiproduct processing.

This study systematically investigates the residue changes, processing factors (PFs), and relation between the physicochemical properties of pesticides during peanut processing. Results revealed that peeling, washing, and boiling treatments removed partial or substantial pesticide residues from peanuts with PFs of 0.29-1.10 (most <1). By contrast, pesticides appeared to be partially concentrated during roasting, stir-frying, and deep-frying peanuts with PFs of 0.16-1.25. During oil pressing, 13 of the 28 pesticides were concentrated in the peanut oil (PF range: 1.06-2.01) and 25 of the pesticides were concentrated in the peanut meal (1.07-1.46). Physicochemical parameters such as octanol-water partition coefficient, degradation point, molecular weight, and melting point showed significant correlations with PFs during processing. Notably, log Kow exhibited strong positive correlations with the PFs of boiling, roasting, and oil pressing. Overall, this study describes the fate of pesticides during multiproduct processing, providing guidance to promote the healthy consumption of peanuts for human health.

Capillary-based, multifunctional manipulation of particles and fluids via focused surface acoustic waves.

Surface acoustic wave (SAW)-enabled acoustofluidic technologies have recently atttracted increasing attention for applications in biology, chemistry, biophysics, and medicine. Most SAW acoustofluidic devices generate acoustic energy which is then transmitted into custom microfabricated polymer-based channels. There are limited studies on delivering this acoustic energy into convenient commercially-available glass tubes for manipulating particles and fluids. Herein, we have constructed a capillary-based SAW acoustofluidic device for multifunctional fluidic and particle manipulation. This device integrates a converging interdigitated transducer to generate focused SAWs on a piezoelectric chip, as well as a glass capillary that transports particles and fluids. To understand the actuation mechanisms underlying this device, we performed finite element simulations by considering piezoelectric, solid mechanic, and pressure acoustic physics. This experimental study shows that the capillary-based SAW acoustofluidic device can perform multiple functions including enriching particles, patterning particles, transporting particles and fluids, as well as generating droplets with controlled sizes. Given the usefulness of these functions, we expect that this acoustofluidic device can be useful in applications such as pharmaceutical manufacturing, biofabrication, and bioanalysis.

Robot-assisted chirality-tunable acoustic vortex tweezers for contactless, multifunctional, 4-DOF object manipulation.

Robotic manipulation of small objects has shown great potential for engineering, biology, and chemistry research. However, existing robotic platforms have difficulty in achieving contactless, high-resolution, 4-degrees-of-freedom (4-DOF) manipulation of small objects, and noninvasive maneuvering of objects in regions shielded by tissue and bone barriers. Here, we present chirality-tunable acoustic vortex tweezers that can tune acoustic vortex chirality, transmit through biological barriers, trap single micro- to millimeter-sized objects, and control object rotation. Assisted by programmable robots, our acoustic systems further enable contactless, high-resolution translation of single objects. Our systems were demonstrated by tuning acoustic vortex chirality, controlling object rotation, and translating objects along arbitrary-shaped paths. Moreover, we used our systems to trap single objects in regions with tissue and skull barriers and translate an object inside a Y-shaped channel of a thick biomimetic phantom. In addition, we showed the function of ultrasound imaging-assisted acoustic manipulation by monitoring acoustic object manipulation via live ultrasound imaging.

Exploring the impact of nonylphenol exposure on Litopenaeus vannamei at the histological and molecular levels.

Nonylphenol (NP) is one of the common pollutants in the environment that have toxic effects on aquatic animals. Nevertheless, little is known about the possible toxicity mechanism of NP on the hepatopancreas of Litopenaeus vannamei. In the present study, the detrimental effects of NP on the hepatopancreas of the L. vannamei were explored at the histological and transcriptomic levels. The findings indicated that after NP exposed for 3, 12, and 48 h, the hepatopancreas histology was changed significantly. Transcriptomic analysis showed that a total of 4302, 3651, and 4830 differentially expressed genes (DEGs) were identified at 3, 12, and 48 h following NP exposure. All these DEGs were classified into 12 clusters according to the expression patterns at different time points. GO and KEGG enrichment analyses of DEGs were also performed, immunological, metabolic, and inflammatory related pathways, including arachidonic acid metabolism (ko00590), the PPAR signaling pathway (ko03320), and the regulation of TRP channels by inflammatory mediators (ko04750) were significantly enriched. Six DEGs were selected for validation by quantitative real-time PCR (qRT-PCR) and the results confirmed the reliability of transcriptome data. All results indicated that NP is toxic to L. vannamei by damaging the histopathological structure and disrupting the biological function. The findings would provide a theoretical framework for lowering or limiting the detrimental impacts of NP on aquaculture and help us to further study the molecular toxicity of NP in crustaceans.

A systematic review and meta-analysis of randomized controlled trials comparing low-dose versus standard-dose computed tomography-guided lung biopsy.

BACKGROUND: Despite the existence of several Randomized Controlled Trials (RCTs) investigating Low-Dose Computed Tomography (LDCT) as a guide in lung biopsies, conclusive findings remain elusive. To address this contention, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LDCT-guided lung biopsies. METHODS: A comprehensive search across major databases identified RCTs comparing the effectiveness of LDCT-guided with Standard-Dose Computed Tomography (SDCT)-guided lung biopsies. Subsequently, we utilized a random-effects model meta-analysis to assess diagnostic accuracy, radiation dose, operation duration, and clinical complications associated with these procedures. RESULTS: Out of 292 scrutinized studies, six RCTs representing 922 patients were included in the final analysis. Results indicated the differences between the LDCT and SDCT groups were not different with statistical significance in terms of diagnostic accuracy rates (Intent-to-Treat (ITT) populations: Relative Risk (RR) 1.01, 95% Confidence interval [CI] 0.97-1.06, p = 0.61; Per-Protocol (PP) populations: RR 1.01, 95% CI 0.98-1.04, p = 0.46), incidence of pneumothorax (RR 1.00, 95% CI 0.75-1.35, p = 0.98), incidence of hemoptysis (RR 0.95, 95% CI 0.63-1.43, p = 0.80), and operation duration (minutes) (Mean Differences [MD] -0.34, 95% CI -1.67-0.99, p = 0.61). Notably, LDCT group demonstrated a lower radiation dose (mGy·cm) with statistical significance (MD -188.62, 95% CI -273.90 to -103.34, p < 0.0001). CONCLUSIONS: The use of LDCT in lung biopsy procedures demonstrated equivalent efficacy and safety to standard methods while notably reducing patient radiation exposure.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis through promoting polarization of M2 macrophage.

BACKGROUND: Previous study implied that local M2 polarization of macrophage promoted mucosal edema and exacerbates Th2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We thought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: RT-qPCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 knockout mice were used to establish nasal polyp model with Th2 inflammation and investigate the effects of SIRT5 in macrophages on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophages markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 deficiency mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages through promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting the alternative polarization of macrophage and thus provides a potential target for CRSwNP interventions.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism; GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development. AIM: To investigate the associations of serum D-dimer (D-D) and glycosylated hemoglobin (HbA1c) levels with third-trimester fetal growth restriction (FGR) in GDM patients. METHODS: The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively. Among these women, 63 whose fetuses had FGR were included in the FGR group, and 101 women whose fetuses had normal body weights were included in the normal body weight group (normal group). Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis. The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis, and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression. RESULTS: Serum fasting blood glucose, fasting insulin, D-D and HbA1c levels were significantly greater in the FGR group than in the normal group, while the homeostasis model assessment of insulin resistance values were lower (P < 0.05). Regarding the diagnosis of FGR based on serum D-D and HbA1c levels, the areas under the curves (AUCs) were 0.826 and 0.848, the cutoff values were 3.04 mg/L and 5.80%, the sensitivities were 81.0% and 79.4%, and the specificities were 88.1% and 87.1%, respectively. The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928, and the sensitivity and specificity were 84.1% and 91.1%, respectively. High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients (P < 0.05). CONCLUSION: D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent, and their combination can be used as an important index for the early prediction of FGR.

Enabling High Reversibility of Zn anode via Interfacial Engineering Induced by Amino acid Electrolyte Additive.

Despite possessing substantial benefits of enhanced safety and cost-effectiveness, the aqueous zinc ion batteries (AZIBs) still suffers with the critical challenges induced by inherent instability of Zn metal in aqueous electrolytes. Zn dendrites, surface passivation, and corrosion are some of the key challenges governed by water-driven side reactions in Zn anodes. Herein, a highly reversible Zn anode is demonstrated via interfacial engineering of Zn/electrolyte driven by amino acid D-Phenylalanine (DPA) additions. The preferential adsorption of DPA and the development of compact SEI on the Zn anode suppressed the side reactions, leading to controlled and uniform Zn deposition. As a result, DPA added aqueous electrolyte stabilized Zn anode under severe test environments of 20.0 mA cm-2 and 10.0 mAh cm-2 along with an average plating/stripping Coulombic efficiency of 99.37%. Under multiple testing conditions, the DPA-incorporated electrolyte outperforms the control group electrolyte, revealing the critical additive impact on Zn anode stability. This study advances interfacial engineering through versatile electrolyte additive(s) toward development of stable Zn anode, which may lead to its practical implementation in aqueous rechargeable zinc batteries.

pH-Dependent Reversible Self-Assembly of ß-Lactoglobulin-Derived Reducing Peptides.

Peptide-based self-assembled nanostructures are emerging vehicles for nutrient delivery and interface engineering. The present study screened eight ß-lactoglobulin (ß-Lg) derived peptides and found that two reducing peptides [EQSLVCQCLV (EV-10) and VCQCLVR (VR-7)] demonstrated pH-dependent reversible fibrilization. EV-10 formed fibrils at pH 2.0 but became unordered aggregates at pH 7.0. VR-7 showed the opposite trend. Both peptides could undergo repetitive transitions between fibrils and unordered aggregates during consecutive pH-cycling. Fibrilization of both peptides was dominated by charges carried by N- and C-terminals. Both fibrils were characterized by a cross-ß sheet structure where the ß-sheet was arranged in an antiparallel manner. Fe3+ was reduced by Cys and EV-10 (pH 5.0 and 7.0) simultaneously upon mixing. In contrast, EV-10 fibrils released Fe3+ reducing capacity progressively, which were beneficial to long-term protection Fe2+. The EV-10 fibrils remained intact after simulated gastric digestion and finally dissociated after intestinal digestion. The results shed light on the mechanisms of fibrilization of ß-Lg derived peptides. This study was beneficial to the rational design of smart pH-responsive materials for drug delivery and antioxidants for nutrients susceptible to oxidation.

A Novel Network Pharmacology Strategy Based on the Universal Effectiveness-Common Mechanism of Medical Herbs Uncovers Therapeutic Targets in Traumatic Brain Injury.

Purpose: Many herbs can promote neurological recovery following traumatic brain injury (TBI). There must lie a shared mechanism behind the common effectiveness. We aimed to explore the key therapeutic targets for TBI based on the common effectiveness of the medicinal plants. Material and methods: The TBI-effective herbs were retrieved from the literature as imputes of network pharmacology. Then, the active ingredients in at least two herbs were screened out as common components. The hub targets of all active compounds were identified through Cytohubba. Next, AutoDock vina was used to rank the common compound-hub target interactions by molecular docking. A highly scored compound-target pair was selected for in vivo validation. Results: We enrolled sixteen TBI-effective medicinal herbs and screened out twenty-one common compounds, such as luteolin. Ten hub targets were recognized according to the topology of the protein-protein interaction network of targets, including epidermal growth factor receptor (EGFR). Molecular docking analysis suggested that luteolin could bind strongly to the active pocket of EGFR. Administration of luteolin or the selective EGFR inhibitor AZD3759 to TBI mice promoted the recovery of body weight and neurological function, reduced astrocyte activation and EGFR expression, decreased chondroitin sulfate proteoglycans deposition, and upregulated GAP43 levels in the cortex. The effects were similar to those when treated with the selective EGFR inhibitor. Conclusion: The common effectiveness-based, common target screening strategy suggests that inhibition of EGFR can be an effective therapy for TBI. This strategy can be applied to discover core targets and therapeutic compounds in other diseases.

Femtosecond Laser Maskless Optical Projection Lithography of Cartilage PCM Inspired 3D Protein Matrix to Chondrocyte Phenotype.

Hydrogels containing chondrocytes have exhibited excellent potential in regenerating hyaline cartilage. However, chondrocytes are vulnerable to dedifferentiation during in vitro culture, leading to fibrosis and mechanical degradation of newly formed cartilage. It is proposed to modulate cartilage formation via the developed chondrocyte pericellular matrix (PCM) -like scaffolds for the first time, in which the S, M, and L-sized scaffolds are fabricated by femtosecond laser maskless optical projection lithography (FL-MOPL) of bovine serum albumin-glyceryl methacrylate hydrogel. Chondrocytes on the M PCM-like scaffold can maintain round morphology and synthesize extracellular matrix (ECM) to induce regeneration of hyaline cartilage microtissues by geometrical restriction. A series of M PCM-like scaffolds is fabricated with different stiffness and those with a high Young's modulus are more effective in maintaining the chondrocyte phenotype. The proposed PCM-like scaffolds are effective in modulating cartilage formation influenced by pore size, depth, and stiffness, which will pave the way for a better understanding of the geometric cues of mechanotransduction interactions in regulating cell fate and open up new avenues for tissue engineering.

Bu zhong Yiqi Decoction ameliorates mild cognitive impairment by improving mitochondrial oxidative stress damage via the SIRT3/MnSOD/OGG1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Zhong-Yi-Qi Decoction(BZYQD) is a traditional formula commonly used in China, known for its effects in tonifying Qi and raising Yang. It can relieve symptoms of cognitive impairment such as forgetfulness and lack of concentration caused by qi deficiency, which is common in aging and debilitating. However, much of the current research on BZYQD has been focused on its impact on the digestive system, leaving its molecular mechanisms in improving cognitive function largely unexplored. AIM OF THE STUDY: Cognitive decline in the aging central nervous system is intrinsically linked to oxidative damage. This study aims to investigate the therapeutic mechanism of BZYQD in treating mild cognitive impairment caused by qi deficiency, particularly through repair of mitochondrial oxidative damage. MATERIALS AND METHODS: A rat model of mild cognitive impairment (MCI) was established by administering reserpine subcutaneously for two weeks, followed by a two-week treatment with BZYQD/GBE. In vitro experiments were conducted to assess the effects of BZYQD on neuronal cells using a H2O2-induced oxidative damage model in PC12 cells. The open field test and the Morris water maze test evaluated the cognitive and learning memory abilities of the rats. HE staining and TEM were employed to observe morphological changes in the hippocampus and its mitochondria. Mitochondrial activity, ATP levels, and cellular viability were measured using assay kits. Protein expression in the SIRT3/MnSOD/OGG1 pathway was analyzed in tissues and cells through western blotting. Levels of 8-OH-dG in mitochondria extracted from tissues and cells were quantified using ELISA. Mitochondrial morphology in PC12 cells was visualized using Mito Red, and mitochondrial membrane potential was assessed using the JC-1 kit. RESULTS: BZYQD treatment significantly improved cognitive decline caused by reserpine in rats, as well as enhanced mitochondrial morphology and function in the hippocampus. Our findings indicate that BZYQD mitigates mtDNA oxidative damage in rats by modulating the SIRT3/MnSOD/OGG1 pathway. In PC12 cells, BZYQD reduced oxidative damage to mitochondria and mtDNA in H2O2-induced conditions and was associated with changes in the SIRT3/MnSOD/OGG1 pathway. CONCLUSION: BZYQD effectively counteracts reserpine-induced mild cognitive impairment and ameliorates mitochondrial oxidative stress damage through the SIRT3/MnSOD/OGG1 pathway.

Xuefu Zhuyu decoction promotes synaptic plasticity by targeting miR-191a-5p/BDNF-TrkB axis in severe traumatic brain injury.

BACKGROUND: Xuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal formula known for its ability to eliminate blood stasis and improve blood circulation, providing neuroprotection against severe traumatic brain injury (sTBI). However, the underlying mechanism is still unclear. PURPOSE: We aim to investigate the neuroprotective effects of XFZYD in sTBI from a novel mechanistic perspective of miRNA-mRNA. Additionally, we sought to elucidate a potential specific mechanism by integrating transcriptomics, bioinformatics, and conducting both in vitro and in vivo experiments. METHODS: The sTBI rat model was established, and the rats were treated with XFZYD for 14 days. The neuroprotective effects of XFZYD were evaluated using a modified neurological severity score, hematoxylin and eosin staining, as well as Nissl staining. The anti-inflammatory effects of XFZYD were explored using quantitative real-time PCR (qRT-PCR), Western blot analysis, and immunofluorescence. Next, miRNA sequencing of the hippocampus was performed to determine which miRNAs were differentially expressed. Subsequently, qRT-PCR was used to validate the differentially expressed miRNAs. Target core mRNAs were determined using various methods, including miRNA prediction targets, mRNA sequencing, miRNA-mRNA network, and protein-protein interaction (PPI) analysis. The miRNA/mRNA regulatory axis were verified through qRT-PCR or Western blot analysis. Finally, morphological changes in the neural synapses were observed using transmission electron microscopy and immunofluorescence. RESULTS: XFZYD exhibited significant neuroprotective and anti-inflammatory effects on subacute sTBI rats' hippocampus. The analyses of miRNA/mRNA sequences combined with the PPI network revealed that the therapeutic effects of XFZYD on sTBI were associated with the regulation of the rno-miR-191a-5p/BDNF axis. Subsequently, qRT-PCR and Western blot analysis confirmed XFZYD reversed the decrease of BDNF and TrkB in the hippocampus caused by sTBI. Additionally, XFZYD treatment potentially increased the number of synaptic connections, and the expression of the synapse-related protein PSD95, axon-related protein GAP43 and neuron-specific protein TUBB3. CONCLUSIONS: XFZYD exerts neuroprotective effects by promoting hippocampal synaptic remodeling and improving cognition during the subacute phase of sTBI through downregulating of rno-miR-191a-5p/BDNF axis, further activating BDNF-TrkB signaling.