Exploring the mechanisms of organic fertilizers on Cd bioavailability in rice fields: Environmental behavior and effect factors.

The problem of paddy Cadmium (Cd) contamination is currently the focus of global research. Earlier researches have confirmed that utilization of organic fertilizers regulates Cd chemical fraction distribution by increases organic bound Cd. However, environmental behaviours of organic fertilizers in paddy are still lack exploration. Here, we critical reviewed previous publications and proposed a novel research concept to help us better understand it. Three potential impact pathways of utilization of organic fertilizers on the bioavailability of Cd are presented: (i) use of organic fertilizers changes soil physicochemical properties, which directly affects Cd bioavailability by changing chemical form of Cd(II); (ii) use of organic fertilizers increases soil nutrient content, which indirectly regulates Cd supply and bioaccumulation through ion adsorption and competition for ion-transport channels between nutrients and Cd; and (iii) use of organic fertilizers increases activity of microorganisms and efflux of rice root exudates, which indirectly affects Cd bioavailability of through complexation and sequestration of these organic materials with Cd. Meanwhile, dissolved organic matter (DOM) in the rhizosphere of rice is believed to be the key to revealing the effects of organic fertilizers on Cd. DOM is capable of adsorption and complexation-chelation reactions with Cd and the fractionation of Cd(II) is regulated by DOM. Molecular mass, chemical composition, major functional groups and reaction sequence of DOM determine the formation and solubilization of DOM-Cd complexes.

Radiomics prediction models of left atrial appendage hypercoagulability based on machine learning algorithms: an exploration about cardiac computed tomography angiography imaging.

Transesophageal echocardiography (TEE) is the standard method for diagnosing left atrial appendage (LAA) hypercoagulability in patients with atrial fibrillation (AF), which means LAA thrombus/sludge, dense spontaneous echo contrast and slow LAA blood flow velocity (< 0.25 m/s). Based on machine learning algorithms, cardiac computed tomography angiography (CCTA) radiomics features were adopted to construct prediction models and explore a suitable approach for diagnosing LAA hypercoagulability and adjusting anticoagulation. This study included 652 patients with non-valvular AF. The univariate analysis were used to select meaningful clinical characteristics to predict LAA hypercoagulability. Then 3D Slicer software was adopted to extract radiomics features from CCTA imaging. The radiomics score was calculated using the least absolute shrinkage and selection operator logistic regression analysis to predict LAA hypercoagulability. We then combined clinical characteristics and radiomics scores to construct a nomogram model. Finally, we got prediction models based on machine learning algorithms and logistic regression separately. The area under the receiver operating characteristic curve of radiomics score was 0.8449 in the training set and 0.7998 in the validation set. The nomogram model had a concordance index of 0.838. The final machine-learning based prediction models had good performances (best f1 score = 0.85). Radiomics features of long maximum diameter and high uniformity of Hounsfield unit in left atrial were significant predictors of the hypercoagulable state in LAA, with better predictive efficacy than clinical characteristics. Our combined models based on machine learning were reliable for hypercoagulable state screening and anticoagulation adjustment.

The primary systemic vasculitis associated optic neuritis: a retrospective analysis in a single center over 10 years.

OBJECTIVES: To investigate the clinical and image characteristics of primary systemic vasculitis-associated optic neuritis patients. METHODS: This is a retrospective study. The patients clinically diagnosed with primary system vasculitis-induced optic neuritis were recruited from March 2013 to December 2023. All cases received orbital magnetic resonance imaging scans were analyzed. The ocular findings, systemic manifestations, laboratory data and prognosis were reviewed retrospectively. In addition, the related literature was reviewed. RESULTS: Fourteen patients (21 eyes), including 10 men and 4 women, were enrolled in this study. The ages ranged from 30 to 86 years in this cohort. Orbits MRI detects the enlargement and/or enhancement of the optic nerve. Cases 1-5 reported a confirmed diagnosis of Takayasu's arteritis, and cases 6-8 had giant cell arteritis. Cases 9-13 were antineutrophil cytoplasmic antibody-associated vasculitis. Case 14 was Cogan's syndrome. Mult organs and tissues, such as the kidneys, heart, paranasal sinuses, meninges, and respiratory system, were involved. In all of the 14 involved patients, the disease onset was either during the fall or winter season. There were no or only slight improvements in visual activity after conventional therapies. CONCLUSIONS: The autoantibodies' attack on the optic nerve, ischemic damage, or destruction of the blood-brain barrier may be the potential pathogenesis of vasculitis-associated optic neuritis. Even with prompt and aggressive clinical interventions, the prognosis remains unsatisfactory.

Rich-silicon rice husk ash increases iron plaque formation and decreases cadmium and arsenic accumulation in rice seedlings.

Combined Cd (cadmium) and As (arsenic) pollution in cultivated land affects the safety of crops production and endangers human health. Rice (Oryza sativa L.) is a crop that uptakes Si (silicon), and Si can effectively promote rice growth and mitigate heavy metal toxicity. This study examined the effect and mechanism of Si-rich amendment (HA) prepared by aerobic combustion of rice husk on Cd and As accumulation in iron plaque and rice seedlings via hydroponic experiments. HA enhanced the vitality of rice growth because of its Si content and increased the amount of amorphous fraction iron plaques, furthermore, Cd content was decreased while the As was increased in both amorphous fraction and crystalline fraction iron plaques, resulting in the contents of Cd and As decreases by 10.0%-38.3% and 9.6%-42.8% for the shoots, and by 13.4%-45.2% and 9.9%-20.0% for the roots, respectively. In addition, X-ray diffraction and X-ray photoelectron spectroscopy illustrated significantly more Fe2O, MnO2 and MnO in the iron plaque after HA supply and the simultaneous existence of Mn-As and Mn-Si compounds. This result revealed less Cd from iron plaque and more As retention with HA supply, reducing the amount of Cd and As up taking and accumulation by rice seedlings. HA is beneficial to rice growth and reduce the absorption of heavy metals in plants. At the same time, HA is environmentally friendly, it can be used for the remediation of paddy fields contaminated by Cd and As.

Novel Therapeutic Mechanisms and Strategies for Intracerebral Hemorrhage: Focusing on Exosomes.

Intracerebral hemorrhage (ICH) is a primary, non-traumatic cerebral event associated with substantial mortality and disability. Despite advancements in understanding its etiology and refining diagnostic techniques, a validated treatment to significantly improve ICH prognosis remains elusive. Exosomes, a subtype of extracellular vesicles, encapsulate bioactive components, predominantly microRNAs (miRNAs), facilitating and regulating intercellular communication. Currently, exosomes have garnered considerable interests in clinical transformation for their nanostructure, minimal immunogenicity, low toxicity, inherent stability, and the ability to traverse the blood-brain barrier. A wealth of studies has demonstrated that exosomes can improve the prognosis of ICH through anti-apoptosis, neurogenesis, angiogenesis, anti-inflammation, immunomodulation, and autophagy, primarily via the transportation or overexpression of selected miRNAs. More importantly, exosomes can be easily customized with specific miRNAs or bioactive compounds to establish delivery systems, broadening their potential applications. This review focuses on the therapeutic potential of exosomes in ICH, reviewing the mechanisms of molecular biology mediated by certain miRNAs, discussing the benefits, challenges, and future prospects in ICH treatment. We hope comprehensive understanding of exosomes based on miRNAs will provide new insights into the treatment of ICH and guide the translation of exosome's research from laboratory to clinical practice.

Prenatal diagnosis of 17q12 copy number variants in fetuses via chromosomal microarray analysis - A retrospective cohort study and literature review.

Purpose: 17q12 copy number variants (CNVs) have variable presentations and incomplete penetrance, challenging prenatal counseling and management. This study aims to investigate the intrauterine phenotype. Methods: We included 48 fetuses diagnosed with 17q12 microdeletion or microduplication by chromosomal microarray analysis. Results: For 17q12 deletion, renal anomalies were found in 35 fetuses (35/37, 94.6 %), with hyperechogenic kidneys (HEK, 28/37, 75.7 %) and multicystic dysplastic kidneys (17/37, 45.9 %) being the most common findings. Duodenal obstruction (DO) was most frequently combined in 17q12 duplication fetuses. In addition, cardiac abnormalities were the first reported prenatal phenotype in 17q12 duplication fetuses. Conclusion: Our study shows that HEK and DO are the most predominant presentations of 17q12 deletion and duplication, respectively, and cardiac structural abnormalities may be associated with the latter. Although 17q12 CNVs have incomplete penetrance and variable expressivity and may be mainly involved in neurodevelopmental disorders, their short-term prognosis appears positive.

Potassium indole-3-butyric acid affects rice's adaptability to salt stress by regulating carbon metabolism, transcription factor genes expression, and biosynthesis of secondary metabolites.

Soil salinity pollution is increasing worldwide, seriously affecting plant growth and crop production. Existing reports on how potassium indole-3-butyric acid (IBAK) regulates rice salt stress adaptation by affecting rice carbon metabolism, transcription factor (TF) genes expression, and biosynthesis of secondary metabolites still have limitations. In this study, an IBAK solution at 40 mg L-1 was sprayed on rice leaves at the seedling stage. The results showed that the IBAK application could promote shoot and root growth, decrease sucrose and fructose content, increase starch content, and enhance acid invertase (AI) and neutral invertase (NI) activity under salt stress, indicating altered carbon allocation. Furthermore, the expression of TF genes belonging to the ethylene responsive factor (ERF), WRKY, and basic helix-loop-helix (bHLH) families was influenced by IBAK. Many key genes (OsSSIIc, OsSHM1, and OsPPDKB) and metabolites (2-oxoglutaric acid, fumaric acid, and succinic acid) were upregulated in the carbon metabolism pathway. In addition, this study highlighted the role of IBAK in regulating the biosynthesis of secondary metabolites pathway, potentially contributing to rice stress adaptability. The results of this study can provide new sustainable development solutions for agricultural production.

AB091. Establishment and application of brainstem glioma organoids.

BACKGROUND: Traditional preclinical experiments on brainstem gliomas mainly rely on patient-derived primary cell lines, but there are problems such as low success rate in establishment and inability to preserve tumor heterogeneity, which limit the clinical transformation. As a new type of in vitro tumor model, organoids have similar structure and function to the original tumor, requiring less tissue for cultivation, with short cycle and high success rate, which is particularly suitable for brainstem glioma biopsy. There is currently no precedent for the successful construction of brainstem glioma organoid models. This new established organoid provides us a more robust preclinical tool for comprehending the pathogenesis and conducting drug screening for this kind of disease. METHODS: Cultivate patient-derived brainstem glioma organoids in vitro, verify the genetic fidelity and consistency of the organoids through morphological experiments as well as sequencing technology. Then explore the evolutionary direction of multiple types of brainstem gliomas through pseudo-time series analysis. Complete drug screening, natural killer (NK) cell co-culture, oncolytic virus therapy, and other treatments based on organoids in vitro, and evaluate the efficacy. Complete co-culture of organoids and Institute of Cancer Research (ICR) mouse brain slices in vitro. Establish patient-derived organoid xenograft (PDOX) mouse models derived from organoids in vivo. RESULTS: The establishment of organoids of all types of brainstem gliomas was completed for the first time in the world, with a total of 41/48 organoid models derived from patients, with a success rate of 85.4%, covering all segments and pathological types. The results of morphological experiments and sequencing showed that the genetic characteristics of organoids were highly consistent with those of tumor tissues. Drug screening tests for temozolomide and panobinostat were completed in vitro, and NK cell co-culture and oncolytic virus therapy testing were achieved. Co-culture of brainstem glioma organoids and mouse brain slices was achieved in vitro. Furthermore, a PDOX model of brainstem glioma was established. CONCLUSIONS: Brainstem glioma organoids can be established maturely, stably, and reliably, and can be used for preclinical drug testing for patients. Animal models derived from brainstem glioma organoids have broad preclinical experimental value.

Reviving Multivalent-metal Anodes in Simple Salt Electrolytes via Component Modifier Design.

Using combinatory electrolyte blends represents an imperative avenue to achieve good magnesium (Mg)-metal anode compatibility and commercial feasibility in fields of promising rechargeable Mg batteries. However, fundamental challenges of how to manipulate component modifier reactivity on molecule level still remain to be solved. Here, molecular structure design concepts towards seeking bromophenyl complex-based component modifiers has been proposed according to implications of electron-donating and/or electron-withdrawing substituents on Br-C bond dissociation reactivity. Exceptional Mg electro-plating/stripping properties (a stable cycle life of 250 days in Mg//Cu asymmetric cells) have been firstly achieved in a simple salt electrolyte with 1-(3-bromophenyl)-N,N-dimethylmethanamine (BPDMA) as optimal component modifier. Comprehensive analyses disclose the unique electrochemically-active Br-containing ion-pairs formation, such as [(Mg2+)2(TFSI-)Br-]2+ and [(Mg2+)2(TFSI-)(Br-)(G2)2]2+, which results in the much thinner Br- containing and organic-inorganic mixed interphases on Mg-metal anodes. Furthermore, conventional MgSO4-based electrolytes and even calcium (Ca)-ion electrolytes can also be revived by similar strategy, demonstrating its generality and superiority.

Epidemiology and genetic characterization of human parainfluenza virus-1 infection in pediatric patients from Hangzhou China, 2021-2022.

BACKGROUND: Human parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021-2022. METHODS: A cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing. RESULTS: The highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643). CONCLUSION: In conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.

Efficient Capture and Traceless Release of Functional CD8+ T Cells with a Microfluidic Chip for Enhanced In Vitro and In Vivo CD4-CAR Transduction.

The chimeric antigen receptor (CAR) T cells targeting CD4 expressed cells in acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) could reduce the risk of off target effects in normal tissues. However, the efficacy of adoptive cell therapy is predominantly attributed to CD8+ T cells, necessitating their purification before lentivirus transfection to enhance the production of CD4-CAR-T cells. In this study, we developed a microfluidic chip functionalized with an optimized CD8 aptamer, A3t-MU, to facilitate the enrichment and purification of CD8+ T cells. The presented chip showed efficient capture and seamless release of CD8+ T cells from cultured T cells and peripheral blood mononuclear cells (PBMCs). The purity of the released CD8+ T cells reached 98.1%, representing a 13% improvement over the conventional magnetic bead separation method. CD4-CAR was efficiently transduced into the purified CD8+ T cells to construct CAR-T cells. We evaluated the antitumor capability of the CD4-CAR transduced CD8+ T cells (anti-CD4 CD8-CAR T cells) both in vitro and in vivo. The anti-CD4 CD8-CAR T cells exhibited significant cancer-cell-killing capacity across multiple tumor cell lines, including CEM, Jurkat, and MV4-11. Meanwhile, anti-CD4 CD8-CAR T cells significantly inhibited tumor growth in vivo. In conclusion, the presented microfluidic chip offers a cost-effective and high-purity approach for CD8+ T cell separation, enhancing CD4-CAR transduction and achieving efficient antitumor capability both in vitro and in vivo.

Ex Situ Production and Storage of Exciton-Polariton Vortices in Higher-Order Topological Corner Modes.

We propose a scheme for producing and manipulating quantized exciton-polariton vortices in the higher-order topological corner modes of a two-dimensional array of micropillars. By nonresonantly exciting p-orbital condensates with different orientations at two input corners, polariton vortices carrying the required topological charges can be controllably created at output corners away from the pumping spots. Besides, polariton vortices formed at input corners can be copied to the output corners through the topological edge states. Our scheme provides topological double insurance for intrinsic binary information memory and holds potential applications in remote information processing.

Investigating the Inhibition of Diindolylmethane Derivatives on SARS-CoV-2 Main Protease.

The SARS-CoV-2 main protease (Mpro) is an essential enzyme that promotes viral transcription and replication. Mpro conserved nature in different variants and its nonoverlapping nature with human proteases make it an attractive target for therapeutic intervention against SARS-CoV-2. In this work, the interaction mechanism between Mpro and diindolylmethane derivatives was investigated by molecular docking, enzymatic inhibition assay, UV-vis, fluorescence spectroscopy, and circular dichroism spectroscopy. Results of IC50 values show that 1p (9.87 µM) was the strongest inhibitor for Mpro in this work, which significantly inhibited the activity of Mpro. The binding constant (4.07 × 105 Lmol-1), the quenching constant (5.41 × 105 Lmol-1), and thermodynamic parameters indicated that the quenching mode of 1p was static quenching, and the main driving forces between 1p and Mpro are hydrogen bond and van der Waals force. The influence of molecular structure on the binding is investigated. Chlorine atoms and methoxy groups are favorable for the diindolylmethane derivative inhibitors of Mpro. This work confirms the changes in the microenvironment of Mpro by 1p, and provides clues for the design of potential inhibitors.

Association of prenatal Cleft Lip and Palate ultrasound abnormalities with copy number variants at a single Chinese tertiary center.

BACKGROUD: A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes. METHODS: In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes. RESULTS: Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001). Within the remaining 20 twin pregnancies, three clinically significant variants (15%) were observed. CONCLUSIONS: This study provides powerful evidence supporting the efficacy of CMA as a valuable tool for facilitating the prenatal genetic diagnosis of fetal CL/P. The presence of CP and CLP in fetal cases demonstrated a relatively higher incidence of pathogenic/likely pathogenic CNVs. Moreover, when these cases were accompanied by additional ultrasound abnormalities, the likelihood of identifying diagnostic CNVs significantly increased. Conversely, cases of CL alone might not be associated with positive CNVs. The present data may significantly enhance prenatal diagnosis accuracy and facilitate informed genetic counseling for cases of fetal CL/P.

Human genetics and epigenetics of alcohol use disorder.

Alcohol use disorder (AUD) is a prominent contributor to global morbidity and mortality. Its complex etiology involves genetics, epigenetics, and environmental factors. We review progress in understanding the genetics and epigenetics of AUD, summarizing the key findings. Advancements in technology over the decades have elevated research from early candidate gene studies to present-day genome-wide scans, unveiling numerous genetic and epigenetic risk factors for AUD. The latest GWAS on more than one million participants identified more than 100 genetic variants, and the largest epigenome-wide association studies (EWAS) in blood and brain samples have revealed tissue-specific epigenetic changes. Downstream analyses revealed enriched pathways, genetic correlations with other traits, transcriptome-wide association in brain tissues, and drug-gene interactions for AUD. We also discuss limitations and future directions, including increasing the power of GWAS and EWAS studies as well as expanding the diversity of populations included in these analyses. Larger samples, novel technologies, and analytic approaches are essential; these include whole-genome sequencing, multiomics, single-cell sequencing, spatial transcriptomics, deep-learning prediction of variant function, and integrated methods for disease risk prediction.

Focused ultrasound-induced cell apoptosis for the treatment of tumours.

Cancer is a serious public health problem worldwide. Traditional treatments, such as surgery, radiotherapy, chemotherapy, and immunotherapy, do not always yield satisfactory results; therefore, an efficient treatment for tumours is urgently needed. As a convenient and minimally invasive modality, focused ultrasound (FUS) has been used not only as a diagnostic tool but also as a therapeutic tool in an increasing number of studies. FUS can help treat malignant tumours by inducing apoptosis. This review describes the three apoptotic pathways, apoptotic cell clearance, and how FUS affects these three apoptotic pathways. This review also discusses the role of thermal and cavitation effects on apoptosis, including caspase activity, mitochondrial dysfunction, and Ca2+ elease. Finally, this article reviews various aspects of FUS combination therapy, including sensitization by radiotherapy and chemotherapy, gene expression upregulation, and the introduction of therapeutic gases, to provide new ideas for clinical tumour therapy.

Hyperbaric oxygen promotes bone regeneration by activating the mechanosensitive Piezo1 pathway in osteogenic progenitors.

Background: Hyperbaric oxygen (HBO) therapy is widely used to treat bone defects, but the correlation of high oxygen concentration and pressure to osteogenesis is unclear. Methods: Bilateral monocortical tibial defect surgeries were performed on 12-week-old Prrx1-Cre; Rosa26-tdTomato and Prrx1-Cre; Piezo1fl/+ mice. Daily HBO treatment was applied on post-surgery day (PSD) 1-9; and daily mechanical loading on tibia was from PSD 5 to 8. The mice were euthanized on PSD 10, and bone defect repair in their tibias was evaluated using µCT, biomechanical testing, and immunofluorescence deep-tissue imaging. The degree of angiogenesis-osteogenesis coupling was determined through spatial correlation analysis. Bone marrow stromal cells from knockout mice were cultured in vitro, and their osteogenic capacities of the cells were assessed. The activation of genes in the Piezo1-YAP pathway was evaluated using RNA sequencing and quantitative real-time polymerase chain reaction. Results: Lineage tracing showed HBO therapy considerably altered the number of Prrx1+ cells and their progeny in a healing bone defect. Using conditional knockdown mice, we found that HBO stimulation activates the Piezo1-YAP axis in Prrx1+ cells and promotes osteogenesis-angiogenesis coupling during bone repair. The beneficial effect of HBO was similar to that of anabolic mechanical stimulation, which also acts through the Piezo1-YAP axis. Subsequent transcriptome sequencing results revealed that similar mechanosensitive pathways are activated by HBO therapy in a bone defect. Conclusion: HBO therapy promotes bone tissue regeneration through the mechanosensitive Piezo1-YAP pathway in a population of Prrx1+ osteogenic progenitors. Our results contribute to the understanding of the mechanism by which HBO therapy treats bone defects. The Translational Potential of this Article: Hyperbaric oxygen therapy is widely used in clinical settings. Our results show that osteogenesis was induced by the activation of the Piezo1-YAP pathway in osteoprogenitors after HBO stimulation, and the underlying mechanism was elucidated. These results may help improve current HBO methods and lead to the formulation of alternative treatments that achieve the same functional outcomes.

IL-32 aggravates metabolic disturbance in human nucleus pulposus cells by activating FAT4-mediated Hippo/YAP signaling.

Extracellular matrix (ECM) metabolism disorders in the inflammatory microenvironment play a key role in the pathogenesis of intervertebral disc degeneration (IDD). Interleukin-32 (IL-32) has been reported to be involved in the progression of various inflammatory diseases; however, it remains unclear whether it participates in the matrix metabolism of nucleus pulposus (NP) cells. Therefore, this study aimed to investigate the mechanism of IL-32 on regulating the ECM metabolism in the inflammatory microenvironment. RNA-seq was used to identify aberrantly expressed genes in NP cells in the inflammatory microenvironment. Western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence analysis were performed to measure the expression of IL-32 and metabolic markers in human NP tissues or NP cells treated with or without tumor necrosis factor-α (TNF-α). In vivo, an adeno-associated virus overexpressing IL-32 was injected into the caudal intervertebral discs of rats to assess its effect on IDD. Proteins interacting with IL-32 were identified via immunoprecipitation and mass spectrometry. Lentivirus overexpressing IL-32 or knocking down Fat atypical cadherin 4 (FAT4), yes-associated protein (YAP) inhibitor-Verteporfin (VP) were used to treat human NP cells, to explore the pathogenesis of IL-32. Hippo/YAP signaling activity was verified in human NP tissues. IL-32 expression was significantly upregulated in degenerative NP tissues, as indicated in the clinical samples. Furthermore, IL-32 was remarkably overexpressed in TNF-α-induced degenerative NP cells. IL-32 overexpression induced IDD progression in the rat model. Mechanistically, the elevation of IL-32 in the inflammatory microenvironment enhanced its interactions with FAT4 and mammalian sterile 20-like kinase1/2 (MST1/2) proteins, prompting MST1/2 phosphorylation, and activating the Hippo/YAP signaling pathway, causing matrix metabolism disorder in NP cells. Our results suggest that IL-32 mediates matrix metabolism disorders in NP cells in the inflammatory micro-environment via the FAT4/MST/YAP axis, providing a theoretical basis for the precise treatment of IDD.

Acupuncture Modulation of Chronic Neuropathic Pain and Its Association With Brain Functional Properties.

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn.