Functional Characterization of PoEP1 in Regulating the Flowering Stage of Tree Peony.

The tree peony, a traditional flower in China, has a short and concentrated flowering period, restricting the development of the tree peony industry. To explore the molecular mechanism of tree peony flowering-stage regulation, PoEP1, which regulated the flowering period, was identified and cloned based on the transcriptome and degradome data of the early-flowering mutant Paeonia ostii 'Fengdan' (MU) and Paeonia ostii 'Fengdan' (FD). Through bioinformatics analysis, expression pattern analysis, and transgene function verification, the role of PoEP1 in the regulation of tree peony flowering was explored. The open-reading frame of PoEP1 is 1161 bp, encoding 386 amino acids, containing two conserved domains. PoEP1 was homologous to the EP1 of other species. Subcellular localization results showed that the protein was localized in the cell wall and that PoEP1 expression was highest in the initial decay stage of the tree peony. The overexpression of PoEP1 in transgenic plants advanced and shortened the flowering time, indicating that PoEP1 overexpression promotes flowering and senescence and shorten the flowering time of plants. The results of this study provide a theoretical basis for exploring the role of PoEP1 in the regulation of tree peony flowering.

Exploring Citronella's inhibitory mechanism against Listeria monocytogenes and its utilization in preserving cheese.

Listeria monocytogenes presents significant risk to human health due to its high resistance and capacity to form toxin-producing biofilms that contaminate food. The objective of this study was to assess the inhibitory effect of citronella aldehyde (CIT) on L. monocytogenes and investigate the underlying mechanism of inhibition. The results indicated that the minimum inhibitory concentration (MIC) and Minimum sterilisation concentration (MBC) of CIT against L. monocytogenes was 2 µL/mL. At this concentration, CIT was able to effectively suppress biofilm formation and reduce metabolic activity. Crystalline violet staining and MTT reaction demonstrated that CIT was able to inhibit biofilm formation and reduce bacterial cell activity. Furthermore, the motility assessment assay revealed that CIT inhibited bacterial swarming and swimming. Scanning electron microscopy (SEM) and laser confocal microscopy (LSCM) observations revealed that CIT had a significant detrimental effect on L. monocytogenes cell structure and biofilm integrity. LSCM also observed that nucleic acids of L. monocytogenes were damaged in the CIT-treated group, along with an increase in bacterial extracellular nucleic acid leakage. The proteomic results also confirmed the ability of CIT to affect the expression of proteins related to processes including metabolism, DNA replication and repair, transcription and biofilm formation in L. monocytogenes. Consistent with the proteomics results are ATPase activity and ATP content of L. monocytogenes were significantly reduced following treatment with various concentrations of CIT. Notably, CIT showed good inhibitory activity against L. monocytogenes on cheese via fumigation at 4 °C.This study establishes a foundation for the potential application of CIT in food safety control.

The mechanism of miR-665 targeting GNB3 in aluminum-induced neuronal apoptosis.

BACKGROUND: Aluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function. METHODS: Forty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)3] groups. Cell experiments are divided into 0, 100, 200, and 400 µM Al(mal)3 dose group and control, Al(mal)3, Al(mal)3+inhibitor NC, Al(mal)3+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment. RESULTS: In vivo experimental results showed that with the increase of Al(mal)3 concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)3 concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased. CONCLUSION: MiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.

Erratum: Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al.

[This corrects the article DOI: 10.1016/j.omtn.2021.11.010.].

MRI-only based material mass density and relative stopping power estimation via deep learning for proton therapy: a preliminary study.

Magnetic Resonance Imaging (MRI) is increasingly being used in treatment planning due to its superior soft tissue contrast, which is useful for tumor and soft tissue delineation compared to computed tomography (CT). However, MRI cannot directly provide mass density or relative stopping power (RSP) maps, which are required for calculating proton radiotherapy doses. Therefore, the integration of artificial intelligence (AI) into MRI-based treatment planning to estimate mass density and RSP directly from MRI has generated significant interest. A deep learning (DL) based framework was developed to establish a voxel-wise correlation between MR images and mass density as well as RSP. To facilitate the study, five tissue substitute phantoms were created, representing different tissues such as skin, muscle, adipose tissue, 45% hydroxyapatite (HA), and spongiosa bone. The composition of these phantoms was based on information from ICRP reports. Additionally, two animal tissue phantoms, simulating pig brain and liver, were prepared for DL training purposes. The phantom study involved the development of two DL models. The first model utilized clinical T1 and T2 MRI scans as input, while the second model incorporated zero echo time (ZTE) MRI scans. In the patient application study, two more DL models were trained: one using T1 and T2 MRI scans as input, and another model incorporating synthetic dual-energy computed tomography (sDECT) images to provide accurate bone tissue information. The DECT empirical model was used as a reference to evaluate the proposed models in both phantom and patient application studies. The DECT empirical model was selected as the reference for evaluating the proposed models in both phantom and patient application studies. In the phantom study, the DL model based on T1, and T2 MRI scans demonstrated higher accuracy in estimating mass density and RSP for skin, muscle, adipose tissue, brain, and liver. The mean absolute percentage errors (MAPE) were 0.42%, 0.14%, 0.19%, 0.78%, and 0.26% for mass density, and 0.30%, 0.11%, 0.16%, 0.61%, and 0.23% for RSP, respectively. The DL model incorporating ZTE MRI further improved the accuracy of mass density and RSP estimation for 45% HA and spongiosa bone, with MAPE values of 0.23% and 0.09% for mass density, and 0.19% and 0.07% for RSP, respectively. These results demonstrate the feasibility of using an MRI-only approach combined with DL methods for mass density and RSP estimation in proton therapy treatment planning. By employing this approach, it is possible to obtain the necessary information for proton radiotherapy directly from MRI scans, eliminating the need for additional imaging modalities.

Diffeomorphic Transformer-based Abdomen MRI-CT Deformable Image Registration.

Background: Stereotactic body radiotherapy (SBRT) is a well-established treatment modality for liver metastases in patients unsuitable for surgery. Both CT and MRI are useful during treatment planning for accurate target delineation and to reduce potential organs-at-risk (OAR) toxicity from radiation. MRI-CT deformable image registration (DIR) is required to propagate the contours defined on high-contrast MRI to CT images. An accurate DIR method could lead to more precisely defined treatment volumes and superior OAR sparing on the treatment plan. Therefore, it is beneficial to develop an accurate MRI-CT DIR for liver SBRT. Purpose: To create a new deep learning model that can estimate the deformation vector field (DVF) for directly registering abdominal MRI-CT images. Methods: The proposed method assumed a diffeomorphic deformation. By using topology-preserved deformation features extracted from the probabilistic diffeomorphic registration model, abdominal motion can be accurately obtained and utilized for DVF estimation. The model integrated Swin transformers, which have demonstrated superior performance in motion tracking, into the convolutional neural network (CNN) for deformation feature extraction. The model was optimized using a cross-modality image similarity loss and a surface matching loss. To compute the image loss, a modality-independent neighborhood descriptor (MIND) was used between the deformed MRI and CT images. The surface matching loss was determined by measuring the distance between the warped coordinates of the surfaces of contoured structures on the MRI and CT images. To evaluate the performance of the model, a retrospective study was carried out on a group of 50 liver cases that underwent rigid registration of MRI and CT scans. The deformed MRI image was assessed against the CT image using the target registration error (TRE), Dice similarity coefficient (DSC), and mean surface distance (MSD) between the deformed contours of the MRI image and manual contours of the CT image. Results: When compared to only rigid registration, DIR with the proposed method resulted in an increase of the mean DSC values of the liver and portal vein from 0.850±0.102 and 0.628±0.129 to 0.903±0.044 and 0.763±0.073, a decrease of the mean MSD of the liver from 7.216±4.513 mm to 3.232±1.483 mm, and a decrease of the TRE from 26.238±2.769 mm to 8.492±1.058 mm. Conclusion: The proposed DIR method based on a diffeomorphic transformer provides an effective and efficient way to generate an accurate DVF from an MRI-CT image pair of the abdomen. It could be utilized in the current treatment planning workflow for liver SBRT.

Diffeomorphic transformer-based abdomen MRI-CT deformable image registration.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is a well-established treatment modality for liver metastases in patients unsuitable for surgery. Both CT and MRI are useful during treatment planning for accurate target delineation and to reduce potential organs-at-risk (OAR) toxicity from radiation. MRI-CT deformable image registration (DIR) is required to propagate the contours defined on high-contrast MRI to CT images. An accurate DIR method could lead to more precisely defined treatment volumes and superior OAR sparing on the treatment plan. Therefore, it is beneficial to develop an accurate MRI-CT DIR for liver SBRT. PURPOSE: To create a new deep learning model that can estimate the deformation vector field (DVF) for directly registering abdominal MRI-CT images. METHODS: The proposed method assumed a diffeomorphic deformation. By using topology-preserved deformation features extracted from the probabilistic diffeomorphic registration model, abdominal motion can be accurately obtained and utilized for DVF estimation. The model integrated Swin transformers, which have demonstrated superior performance in motion tracking, into the convolutional neural network (CNN) for deformation feature extraction. The model was optimized using a cross-modality image similarity loss and a surface matching loss. To compute the image loss, a modality-independent neighborhood descriptor (MIND) was used between the deformed MRI and CT images. The surface matching loss was determined by measuring the distance between the warped coordinates of the surfaces of contoured structures on the MRI and CT images. To evaluate the performance of the model, a retrospective study was carried out on a group of 50 liver cases that underwent rigid registration of MRI and CT scans. The deformed MRI image was assessed against the CT image using the target registration error (TRE), Dice similarity coefficient (DSC), and mean surface distance (MSD) between the deformed contours of the MRI image and manual contours of the CT image. RESULTS: When compared to only rigid registration, DIR with the proposed method resulted in an increase of the mean DSC values of the liver and portal vein from 0.850 ± 0.102 and 0.628 ± 0.129 to 0.903 ± 0.044 and 0.763 ± 0.073, a decrease of the mean MSD of the liver from 7.216 ± 4.513 mm to 3.232 ± 1.483 mm, and a decrease of the TRE from 26.238 ± 2.769 mm to 8.492 ± 1.058 mm. CONCLUSION: The proposed DIR method based on a diffeomorphic transformer provides an effective and efficient way to generate an accurate DVF from an MRI-CT image pair of the abdomen. It could be utilized in the current treatment planning workflow for liver SBRT.

QTc prolongation after aneurysmal subarachnoid hemorrhage might be associated with worse neurologic outcome in patients receiving microsurgical clipping or embolization of the intracranial aneurysms: a retrospective observational study.

PURPOSE: QT interval prolongation is one of the most common electrocardiographic (ECG) abnormalities in patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether corrected QT interval (QTc) prolongation is associated with perioperative cardiac events and dismal neurological outcome in mid to long-term follow-up in patients after aSAH is insufficiently studied and remains controversial. METHODS: We retrospectively studied the adult (≥ 18 years) patients admitted to our institution between Jan 2018 and Dec 2020 for aSAH who underwent intracranial aneurysm clipping or embolization. The patients were divided into 2 groups (normal and QTc prolongation groups) according to their QTc. To minimize the confounding bias, a propensity score matching (PSM) analysis was performed to compare the neurologic outcomes between patients with normal QTc and QTc prolongation. RESULTS: After screening, 908 patients were finally included. The patients were divided into 2 groups: normal QTc groups (n = 714) and long QTc group (n = 194). Female sex, hypokalemia, posterior circulation aneurysm, and higher Hunt-Hess grade were associated with QTc prolongation. In multiple regression analysis, older age, higher hemoglobin level, posterior circulation aneurysm, and higher Hunt-Hess grade were identified to be associated with worse outcome during 1-year follow-up. Before PSM, patients with QTc prolongation had higher rate of perioperative cardiac arrest or ventricular arrhythmias. After PSM, there was no statistical difference between normal and QTc prolongation groups in perioperative cardiac events. However, patients in the QTc prolongation group still had worse neurologic outcome during 1-year follow-up. CONCLUSIONS: QTc prolongation is associated with worse outcome in patients following SAH, which is independent of perioperative cardiac events.

UNVEILING THE PROTECTIVE MECHANISMS OF PUERARIN AGAINST ACUTE LUNG INJURY: A COMPREHENSIVE EXPLORATION OF THE ROLES AND MECHANISMS OF MST1/ERS SIGNALING.

ABSTRACT: Objectives: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). Methods: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines. Identification of target proteins was conducted through western blotting. Histological alterations and apoptosis were scrutinized using hematoxylin-eosin staining and TUNEL staining, respectively. The ultrastructure of the endoplasmic reticulum was observed via transmission electron microscopy. Results: Puerarin significantly protected mice from LPS-induced ALI, reducing lung interstitial width, neutrophil and lymphocyte infiltration, pulmonary interstitial and alveolar edema, and lung apoptosis. Puerarin treatment also markedly attenuated levels of TNF-α and IL-1ß in both alveolar lavage fluid and serum. Furthermore, puerarin significantly attenuated LPS-induced increases in Mst1, GRP78, CHOP, and Caspase12 protein expression and blunted LPS-induced decrease in ZO-1 protein expression in lung tissues. Puerarin obviously reduced endoplasmic reticulum expansion and vesiculation. Similarly, puerarin significantly mitigated the LPS-induced reduction in HUVEC cell viability and ZO-1 expression. Puerarin also attenuated LPS-induced increase in apoptosis, TNF-α and IL-1ß, FD40 flux, and Mst1, GRP78, CHOP, and Caspase12 expression in HUVEC cells. Nevertheless, the inhibitory impact of puerarin on vascular endothelial cell injury, lung injury, and endoplasmic reticulum stress (ERS) was diminished by Mst1 overexpression. Conclusion: These findings demonstrated that the Mst1/ERS signaling pathway played a pivotal role in the development of LPS-induced vascular endothelial cell dysfunction and ALI. Puerarin exhibited the ability to attenuate LPS-induced vascular endothelial cell dysfunction and ALI by inhibiting the Mst1/ERS signaling pathway.

m6A methyltransferase AflIme4 orchestrates mycelial growth, development and aflatoxin B1 biosynthesis in Aspergillus flavus.

Aflatoxin B1 (AFB1), a highly toxic secondary metabolite produced by Aspergillus flavus, poses a severe threat to agricultural production, food safety and human health. The methylation of mRNA m6A has been identified as a regulator of both the growth and AFB1 production of A. flavus. However, its intracellular occurrence and function needs to be elucidated. Here, we identified and characterized a m6A methyltransferase, AflIme4, in A. flavus. The enzyme was localized in the cytoplasm, and knockout of AflIme4 significantly reduced the methylation modification level of mRNA. Compared with the control strains, ΔAflIme4 exhibited diminished growth, conidial formation, mycelial hydrophobicity, sclerotium yield, pathogenicity and increased sensitivity to CR, SDS, NaCl and H2O2. Notably, AFB1 production was markedly inhibited in the A. flavus ΔAflIme4 strain. RNA-Seq coupled with RT-qPCR validation showed that the transcriptional levels of genes involved in the AFB1 biosynthesis pathway including aflA, aflG, aflH, aflK, aflL, aflO, aflS, aflV and aflY were significantly upregulated. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) analysis demonstrated a significant increase in m6A methylation modification levels of these pathway-specific genes, concomitant with a decrease in mRNA stability. These results suggest that AflIme4 attenuates the mRNA stability of genes in AFB1 biosynthesis by enhancing their mRNA m6A methylation modification, leading to impaired AFB1 biosynthesis. Our study identifies a novel m6A methyltransferase AflIme4 and highlights it as a potential target to control A. flavus growth, development and aflatoxin pollution.

MiR-29a-3p mediates phosphatase and tensin homolog and inhibits osteoarthritis progression.

Despite substantial progress in clinical trials of osteoarthritis (OA) gene therapy, the prevalence of OA is still on the rise. MiRNAs have a potential biomarker and therapeutic target for OA. OA cartilage and chondrosarcoma cells were studied to determine the role of miR-29a-3p and PTEN. OA cartilage and human chondrosarcoma cells (SW1353) were obtained. miR-29a-3p and PTEN signature expression was determined by RT-qPCR. The binding relationship between miR-29a-3p and PTEN was investigated by dual-luciferase reporter gene and western blot assay. TUNEL, immunohistochemistry, CCK-8, and flow cytometry were utilized to determine the proliferation and apoptosis of SW1353 cells. This study indicated downregulation of miR-29a-3p expression and upregulation of PTEN expression in human OA primary chondrocytes or OA tissue samples, compared with the normal cartilage cells or tissues. PTEN expression was negatively correlated with miR-29a-3p expression, and miR-29a-3p targeted PTEN mechanistically. miR-29a-3p reduced SW1353 cell activity and proliferation and promoted cell apoptosis. However, the aforementioned effects could be reversed by downregulating PTEN. miR-29a-3p can stimulate chondrocyte proliferation and inhibit apoptosis by inhibiting PTEN expression.

A Novel Control Strategy for Soft Open Point to Address Terminal Voltage Violations and Load Rate Imbalance in Low-Voltage Power Distribution Station Areas.

In low-voltage power distribution station areas (DSAs), sensor devices and communication networks are often inadequate. Therefore, the control strategies mainly used for soft open points (SOPs) based on global information in medium-voltage distribution networks are difficult to be directly applied to low-voltage DSAs. This paper proposes a novel control strategy for SOP that only requires collecting the local information of SOP and the load rate of transformers. It aims to address the issues faced of voltage violations at the end of feeders and the load rate imbalance among adjacent DSAs under the current high penetration of renewable energy sources. In this paper, first, a sensor network consisting of sensor devices located at the transformers and each port of the SOP is introduced for information collection. Then, based on the sensitivity relationship between the node voltage and the injected power, considering capacity and voltage safety constraints, the adjustable range of the active power output for each port of the SOP is derived. According to this range, the operating states of the DSAs are categorized into four scenarios. For each scenario, the adjustment amount of SOP output power is determined to achieve comprehensive regulation of terminal voltage and load rate of all DSAs interconnected by SOP. Finally, the effectiveness of the proposed strategy is verified based on a simulation model of three flexible interconnected DSAs established in MATLAB/Simulink.

Machine-learning-based optical spectrum feature analysis for DoS attack detection in IP over optical networks.

In this paper, we introduce a novel approach for detecting Denial of Service (DoS) attacks in software-defined IP over optical networks, leveraging machine learning to analyze optical spectrum features. This method employs machine learning to automatically process optical spectrum data, which is indicative of network security status, thereby identifying potential DoS attacks. To validate its effectiveness, we conducted both numerical simulations and experimental trials to collect relevant optical spectrum datasets. We then assessed the performance of three machine learning algorithms XGBoost, LightGBM, and the BP neural network in detecting DoS attacks. Our findings show that all three algorithms demonstrate a detection accuracy exceeding 97%, with the BP neural network achieving the highest accuracy rates of 99.55% and 99.74% in simulations and experiments, respectively. This research not only offers a new avenue for DoS attack detection but also enhances early detection capabilities in the underlying optical network through optical spectrum data analysis.

Specific fractionation of ginsenosides based on activated carbon fibers and online fast screening of ginseng extract by mass spectrometry.

Ginseng is beneficial in the prevention of many diseases and provides benefits for proper growth and development owing to the presence of various useful bioactive substances of diverse chemical heterogeneity (e.g., triterpenoid saponins, polysaccharides, volatile oils, and amino acids). As a result, understanding the therapeutic advantages of ginseng requires an in-depth compositional evaluation employing a simple and rapid analytical technique. In this work, three types of surface-activated carbon fibers (ACFs) were prepared by gas-phase oxidation, strong acid treatment, and Plasma treatment to obtain CO2-ACFs, acidified-ACFs, and plasma-ACFs, respectively. Three prepared ACFs were compared in terms of their physicochemical characterization (i.e., surface roughness and functional groups). A separation system was built using a column with modified ACFs, followed by mass spectrometry detection to investigate and determine substances of different polarities. Among the three columns, CO2-ACFs showed the optimum separation effect. 13 strong polar compounds (12 amino acids and1 oligosaccharide) and 15 lesser polar compounds (ginsenosides) were separated and identified successfully within 4 min in the ginseng sample. The data obtained by CO2-ACFs-TOF-MS/MS and UHPLC-TOF-MS/MS were compared. Our approach was found to be faster (4 min vs. 36 min) and greener, requiring much less solvent (1 mL vs. 10.8 mL), and power (0.06 vs. 0.6 kWh). The developed methodology can provide a faster, eco-friendly, and more reliable tool for the high-throughput screening of complex natural matrices and the simultaneous evaluation of several compounds in diverse samples.

Ultra-stable hollow nanotube conjugated microporous polymer incorporating fluorenyl moieties for Co-capture of PM and CO2.

Conjugated microporous polymers have a highly delocalized π-π conjugated porous skeleton connected by covalent bonds, which can combine their excellent stability with high adsorption, in order to be applied to the study of co-capture of harmful particulate matter (PM) and carbon dioxide (CO2) under high temperature and high humidity conditions. In this paper, fluorene-based coupled conjugated microporous polymers (D-CMPs) with functionalized hollow nanotubes and abundant microporous structures were proposed. Through mechanism exploration and molecular electrostatic potential (MESP) calculation, the capture efficiency, adsorption capacity and selectivity of PM and CO2 in the waste gas stream of carbon-based combustion were analyzed. The results indicate that D-CMPs, with their rigid carbon-based π-conjugated framework, exhibit excellent tolerance under prolonged high-humidity conditions, with a capture efficiency exceeding 99.87% for PM0.3 and exceeding 99.99% for PM2.5. Meanwhile, based on its chemical/thermal stability, it can realize the recycling of adsorption-regeneration. On this basis, the "slip effect" induced by the open three-dimensional hierarchical porous structure of D-CMPs significantly enhances airflow dispersion and improves gas throughput (with a minimal permeation resistance of only 15 Pa). At a pressure of 1 bar and a temperature of 273.15 K, D-CMP-2 exhibited a CO2 adsorption capacity of up to 2.69 mmol g-1. The fitting results of three isothermal adsorption models demonstrate that D-CMPs exhibit an outstanding equilibrium selectivity towards CO2. Therefore, prior to the widespread adoption of low-carbon and clean energy technologies, porous solid materials exhibiting excellent structural stability, equilibrium selectivity, environmental tolerance, and high adsorption capacity emerge as optimal candidates for the treatment of industrial waste gases.

Modulating Th1/Th2 drift in asthma-related immune inflammation by enhancing bone mesenchymal stem cell homing through targeted inhibition of the Notch1/Jagged1 signaling pathway.

Asthma, a disease intricately linked to immune inflammation, is significantly influenced by the immune regulatory effect of bone mesenchymal stem cells (BMSCs). This study aims to investigate changes in the homing of BMSCs in bronchial asthma, focusing on the Notch homolog (Notch)1/Jagged1 signaling pathway's role in regulating T helper 1(Th1)/T helper 2(Th2) drift. Additionally, we further explore the effects and mechanisms of homologous BMSCs implantation in asthma-related immune inflammation. Following intervention with BMSCs, a significant improvement in the pathology of rats with asthma was observed. Simultaneously, a reduction in the expression of inflammatory cells and inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin(IL)-4, and IL-13 was observed in bronchoalveolar lavage fluid (BALF). Furthermore, there was an increase in the expression of Th1 cytokine Interferon-γ（IFN-γ）and the transcription factor T-box expressed in T cell (T-bet), while the expression of Th2 cytokine IL-13 and transcription factor GATA binding protein (GATA)-3 decreased in lung tissue. This indicates that the Th1/Th2 drift leans towards Th1, which a crucial in ameliorating asthma inflammation. Importantly, inhibition of the Notch1 signaling pathway led to an increased expression of the Stromal cell-derived factor-1(SDF-1)/C-X-C motif chemokine receptor (CXCR)4 chemokine axis. Consequently, the homing ability of bone marrow mesenchymal stem cells to asthma-affected lung tissue was significantly enhanced. BMSCs demonstrated heightened efficacy in regulating the cytokine/chemokine network and Th1/Th2 balance, thereby restoring a stable state during the immune response process in asthma. In conclusion, inhibiting the Notch signaling pathway enhances the expression of the SDF-1 and CXCR4 chemokine axis, facilitating the migration of allogeneic BMSCs to injured lung tissues. This, in turn, promotes immune regulation and improves the Th1/Th2 imbalance, thereby enhancing the therapeutic effect on asthmatic airway inflammation.

RNA-seq combined network pharmacology reveals that Fu-Gan-Wan (FGW) inhibits liver fibrosis via NF-κB/CCL2/CCR2 and lipid peroxidation via Nrf2/HMOX1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a serious complication of liver disease characterized by excessive collagen deposition, without effective therapeutic agents in the clinic. Fu-Gan-Wan (FGW) is an empirical formula used for the clinical treatment of hepatitis and cirrhosis. It has been shown to reverse experimental liver fibrosis. However, its corresponding mechanisms remain unclear. AIM OF THE REVIEW: This study aimed to elucidate the key pathways and target genes of FGW in attenuating liver fibrosis. MATERIALS AND METHODS: The therapeutic effects of different doses of FGW on liver fibrosis were investigated using a 2 mL/kg 15% CCl4-induced mouse model. Then, RNA-seq combined with network pharmacology was used to analyze the key biological processes and signaling pathways underlying the anti-liver fibrosis exertion of FGW. These findings were validated in a TGF-ß1-induced model of activation and proliferation of mouse hepatic stellate cell line JS-1. Finally, the key signaling pathways and molecular targets were validated using animal tissues, and the effect of FGW on tissue lipid peroxidation was additionally observed. RESULTS: We found that 19.5 g/kg FGW significantly down-regulated CCl4-induced elevation of hepatic ALT and AST, decreased collagen deposition, and inhibited the expression of pro-fibrotic factors α-SMA, COL1α1, CTGF, TIMP-1, as well as pro-inflammatory factor TGF-ß1. Additionally, FGW at doses of 62.5, 125, and 250 µg/mL dose-dependently blocked JS-1 proliferation, migration, and activation. Furthermore, RNA-seq identified the NF-κB signaling pathway as a key target molecular pathway for FGW against liver fibrosis, and network pharmacology combined with RNA-seq focused on 11 key genes. Significant changes were identified in CCL2 and HMOX1 by tissue RT-PCR, Western blot, and immunohistochemistry. We further demonstrated that FGW significantly attenuated CCl4-induced increases in p-p65, CCL2, CCR2, and HMOX1, while significantly elevating Nrf2. Finally, FGW significantly suppressed the accumulation of lipid peroxidation products MDA and 4-HNE and reconfigured the oxidation-reduction balance, including promoting the increase of antioxidants GPx, GSH, and SOD, and the decrease of peroxidation products ROS and GSSG. CONCLUSIONS: This study demonstrated that FGW exhibits potential in mitigating CCl4-induced hepatic fibrosis, lipid peroxidation, and iron metabolism disorders in mice. This effect may be mediated through the NF-κB/CCL2/CCR2 and Nrf2/HMOX1 pathways.

Spinal infection caused by Aspergillus flavus in a diabetic: a case report and literature review.

Spinal infections, notably those induced by Aspergillus flavus (A. flavus), represent a complex and uncommon clinical challenge. In individuals with diabetes mellitus, the risk is exacerbated due to a compromised immune response and a heightened vulnerability to non-standard pathogens. This case report chronicles the intricate diagnostic and treatment journey of a 59-year-old diabetic patient grappling with a spinal infection attributed to A. flavus. The diagnosis was delayed due to non-specific symptoms and unclear radiological signs. The administration of voriconazole, a targeted antifungal treatment, resulted in a significant clinical and radiological improvement, underscoring its effectiveness in treating such unusual fungal spinal infections; meanwhile, we found that terbinafine hydrochloride also has a similar effect in treating fungal spinal infections. This case underscores the importance of considering fungal causes in spinal infections among diabetic patients and highlights prompt diagnosis and individualized targeted antifungal therapy.

Percutaneous kyphoplasty combined with pediculoplasty for the surgical treatment of osteoporotic thoracolumbar burst fractures.

OBJECTIVE: This study introduces a minimally invasive technique for efficient three-column reconstruction, augmentation, and stabilization of osteoporotic thoracolumbar burst fractures (OTLBFs). METHODS: Sixty-eight patients with OTLBFs and no neurological deficits were included from July 2019 to September 2020. The patients were divided into two groups: the simple percutaneous kyphoplasty (PKP) group (n = 32) and the percutaneous kyphoplasty combined with pediculoplasty (PKCPP) group (n = 36). The clinical and radiological outcomes were assessed during a minimum 1-year follow-up period. Clinical outcomes were assessed via the visual analog scale (VAS) and modified MacNab grading criteria. The radiological outcomes included the Cobb angle (CA), anterior wall height (AWH), and posterior wall height (PWH). The surgery duration, postoperative analgesic dosage, length of hospital stay, and complications were recorded. RESULTS: Surgery duration was not significantly different between the two groups (P > 0.05). The PKCPP group had a lower analgesic dosage and shorter hospital stay (P < 0.05). Postoperatively, the PKCPP group exhibited better VAS scores and modified MacNab scale scores (P < 0.05), but the differences at the last follow-up assessment were not significant (P > 0.05). Postoperative CA, AWH, and PWH correction were not significantly different on the first postoperative day (P > 0.05). However, the PKCPP group had significantly less CA and PWH loss of correction at the last follow-up visit (P < 0.05). The PKCPP group had significantly fewer complications (P < 0.05). CONCLUSIONS: The PKCPP technique complements simple PKP for OTLBFs. It quickly relieves pain, maintains the vertebral body height and Cobb angle, ensures cement stabilization, and offers more stable three-column support.