Engineering macrophages and their derivatives: A new hope for antitumor therapy.

Macrophages are central to the immune system and are found in nearly all tissues. Recently, the development of therapies based on macrophages has attracted significant interest. These therapies utilize macrophages' key roles in immunity, their ability to navigate biological barriers, and their tendency to accumulate in tumors. This review explores the advancement of macrophage-based treatments. We discuss the bioengineering of macrophages for improved anti-tumor effects, the use of CAR macrophage therapy for targeting cancer cells, and macrophages as vehicles for therapeutic delivery. Additionally, we examine engineered macrophage products, like extracellular vesicles and membrane-coated nanoparticles, for their potential in precise and less toxic tumor therapy. Challenges in moving these therapies from research to clinical practice are also highlighted. The aim is to succinctly summarize the current status, challenges, and future directions of engineered macrophages in cancer therapy.

Schistosoma japonicum cystatin alleviates paraquat poisoning caused acute lung injury in mice through activating regulatory macrophages.

BACKGROUND: Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated. METHODS: PQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-ß were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury. RESULT: We identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-ß from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway. CONCLUSIONS: Our study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.

Long non-coding RNAs in the nucleolus: Biogenesis, regulation, and function.

The nucleolus functions as a multi-layered regulatory hub for ribosomal RNA (rRNA) biogenesis and ribosome assembly. Long noncoding RNAs (lncRNAs) in the nucleolus, originated from transcription by different RNA polymerases, have emerged as critical players in not only fine-tuning rRNA transcription and processing, but also shaping the organization of the multi-phase nucleolar condensate. Here, we review the diverse molecular mechanisms by which functional lncRNAs operate in the nucleolus, as well as their profound implications in a variety of biological processes. We also highlight the development of emerging molecular tools for characterizing and manipulating RNA function in living cells, and how application of such tools in the nucleolus might enable the discovery of additional insights and potential therapeutic strategies.

Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: A long-term follow-up pilot study.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre- and early-symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early-onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with post-symptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over nine years. The most common adverse events (AEs) within two months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with post-symptomatic juvenile MLD.

Integrating digital design with 3D printing technology achieves customized and precise approaches for flap transplantation to facilitate fingertip defect surgery.

OBJECTIVE: This study investigates the clinical efficacy of integrating digital design with three-dimension (3D) printing technology in the transplantation of flaps for fingertip defects. METHODS: A retrospective analysis was conducted from October 2019 to June 2021 on 90 cases of patients with fingertip defects. These included 45 cases in which digital design, coupled with 3D printing, assisted the operation (3D printing group), and another 45 cases where patients underwent traditional pedicle flap transplantation and skin grafting (traditional operation group). A six-month postoperative follow-up assessed various measurements between the two groups, comparing the skin flap survival rate, aesthetic outcome, cold intolerance, sensory recovery, and overall skin flap performance. RESULTS: ① Statistical analysis utilizing the independent samples t-test revealed a significant reduction in both operation time and flap anastomosis rate for the 3D printing group compared to the traditional operation group (P < 0.05). ② Conversely, the survival rate, aesthetic outcome, and cold intolerance showed no significant disparities between the groups (P > 0.05). ③ Further, the Mann-Whitney U test indicated no significant difference in sensory recovery and overall efficacy assessment between the two cohorts (P > 0.05). CONCLUSION: Integrating digital design with 3D printing technology facilitated the surgical management of fingertip defects, achieving customized and precise approaches in flap transplantation. This precision in personalized skin flap design contributed to reduced operative time and enhanced surgical efficiency in such procedures.

High-throughput identification of gut microbiome-dependent metabolites.

A significant hurdle that has limited progress in microbiome science has been identifying and studying the diverse set of metabolites produced by gut microbes. Gut microbial metabolism produces thousands of difficult-to-identify metabolites, which present a challenge to study their roles in host biology. In recent years, mass spectrometry-based metabolomics has become one of the core technologies for identifying small metabolites. However, metabolomics expertise, ranging from sample preparation to instrument use and data analysis, is often lacking in academic labs. Most targeted metabolomics methods provide high levels of sensitivity and quantification, while they are limited to a panel of predefined molecules that may not be informative to microbiome-focused studies. Here we have developed a gut microbe-focused and wide-spectrum metabolomic protocol using liquid chromatography-mass spectrometry and bioinformatic analysis. This protocol enables users to carry out experiments from sample collection to data analysis, only requiring access to a liquid chromatography-mass spectrometry instrument, which is often available at local core facilities. By applying this protocol to samples containing human gut microbial metabolites, spanning from culture supernatant to human biospecimens, our approach enables high-confidence identification of >800 metabolites that can serve as candidate mediators of microbe-host interactions. We expect this protocol will lower the barrier to tracking gut bacterial metabolism in vitro and in mammalian hosts, propelling hypothesis-driven mechanistic studies and accelerating our understanding of the gut microbiome at the chemical level.

Cerebellar volume measures may differentiate multiple sclerosis fallers from non-fallers.

Introduction: The cerebellum is a common lesion site in persons with multiple sclerosis (PwMS). Physiologic and anatomic studies have identified a topographic organization of the cerebellum including functionally distinct motor and cognitive areas. This study implemented a recent parcellation algorithm developed by Han et al., 2020 to a sample of PwMS and healthy controls to examine relationships among specific cerebellar regions, fall status, and common clinical measures of motor and cognitive functions. Methods: Thirty-one PwMS and 29 age and sex-matched controls underwent an MRI scan and motor and cognitive testing. The parcellation algorithm was applied to all images and divided the cerebellum into 28 regions. Mann-Whitney U tests were used to compare cerebellar volumes among PwMS and controls, and MS fallers and MS non-fallers. Relationships between cerebellar volumes and motor and cognitive function was evaluated using Spearman correlations. Results: PwMS performed significantly worse on functional measures compared to controls. We found significant differences in volumetric measures between PwMS and controls in the corpus medullare, lobules I-III, and lobule V. Volumetric differences seen between PwMS and controls were primarily driven by the MS fallers. Finally, functional performance on motor and cognitive tasks was associated with cerebellar volumes. Conclusions: Using the parcellation tool, our results showed that volumes of motor and cognitive lobules impact both motor and cognitive performance, and that functional performance and cerebellar volumes distinguishes MS fallers from non-fallers. Future studies should explore the potential of cerebellar imaging to predict falls in PwMS.

Accuracy of mapping results of thoracolumbar vertebral fracture verified using finite element analysis.

OBJECTIVE: To verify the results of three-dimensional fracture mapping of T12-L2 compression fractures by the finite element method from a biomechanical point of view, and to provide clinical reference. METHODS: This study is a retrospective study. By collecting 150 patients' computerized tomography (CT) data with thoracolumbar compression fractures (T12-L2) with AO type A. Mimics was used for three-dimensional (3D) reconstruction, and 3-Matic was used to mark fracture lines in stereo images. After standardized treatment, all fracture lines were drawn in the same 3D image, and finally fracture lines and fracture map were drawn. Constructing a 3D finite element model of thoracolumbar segment to verify the fracture thermogram results from the perspective of biomechanics. RESULTS: From the fracture map, fracture lines were mainly distributed in the upper part of the vertebral body, the leading edge of the anterior column (AC), and the lateral margin of the middle column (MC). In the finite element analysis, the stress mainly was concentrated on the edge of the anterior and middle column of the vertebral body and the upper part of the vertebral body, and the stress gradually decreased from the upper endplate to the endplate, and the stress was the least in the posterior column (PC) of the vertebral body. CONCLUSION: The results of finite element analysis further confirm the accuracy of fracture mapping and explain the distribution characteristics of fracture lines. This will provide theoretical support for the selection of clinical fracture treatment, intraoperative implants, and for a standard fracture model.

Semi-supervised skin cancer diagnosis based on self-feedback threshold focal learning.

Worldwide, skin cancer prevalence necessitates accurate diagnosis to alleviate public health burdens. Although the application of artificial intelligence in image analysis and pattern recognition has improved the accuracy and efficiency of early skin cancer diagnosis, existing supervised learning methods are limited due to their reliance on a large amount of labeled data. To overcome the limitations of data labeling and enhance the performance of diagnostic models, this study proposes a semi-supervised skin cancer diagnostic model based on Self-feedback Threshold Focal Learning (STFL), capable of utilizing partial labeled and a large scale of unlabeled medical images for training models in unseen scenarios. The proposed model dynamically adjusts the selection threshold of unlabeled samples during training, effectively filtering reliable unlabeled samples and using focal learning to mitigate the impact of class imbalance in further training. The study is experimentally validated on the HAM10000 dataset, which includes images of various types of skin lesions, with experiments conducted across different scales of labeled samples. With just 500 annotated samples, the model demonstrates robust performance (0.77 accuracy, 0.6408 Kappa, 0.77 recall, 0.7426 precision, and 0.7462 F1-score), showcasing its efficiency with limited labeled data. Further, comprehensive testing validates the semi-supervised model's significant advancements in diagnostic accuracy and efficiency, underscoring the value of integrating unlabeled data. This model offers a new perspective on medical image processing and contributes robust scientific support for the early diagnosis and treatment of skin cancer.

Genome-wide investigation of lncRNAs revealed their tight association with gastric cancer.

BACKGROUND: Gastric cancer (GC) is a significant health issue globally, ranking as the fifth most common cancer with over 10,000 new cases reported annually. Long non-coding RNA (lncRNA) has emerged as a critical player in cellular functions, influencing GC's development, growth, metastasis, and prognosis. However, our understanding of lncRNA's role in the pathogenesis of GC remains limited. Therefore, it is particularly important to explore the relationship between lncRNA and gastric cancer. METHODS: we conducted a comprehensive analysis of RNA sequencing data from the GEO database and stomach adenocarcinoma (STAD) data from the TCGA database to identify lncRNAs that exhibit altered expression levels in GC and the mechanisms underlying lncRNA-mediated transcription and post-transcriptional regulation were explored. RESULTS: This study uncovered 94 lncRNAs with differential expression and, through co-expression analysis, linked these to 1508 differentially expressed genes (DEGs). GO functional enrichment analysis highlighted that these DEGs are involved in critical pathways, such as cell adhesion and the positive regulation of cell migration. By establishing a lncRNA-miRNA-mRNA regulatory network, we found that the ceRNA mechanism, particularly involving RP11-357H14.17 and CTD-2377D24.4, could play a role in GC progression. Experimental validation of selected differentially expressed lncRNAs and mRNAs (including RP11-357H14.17-CLDN1, BBOX1, TRPM2-AS, CLDN1, PLAU, HOXB7) confirmed the RNA-seq results. CONCLUSIONS: Overall, our findings highlight the critical role of the lncRNA-mRNA regulatory network in the development and progression of GC, offering potential biomarkers for diagnosis and targets for innovative treatment strategies.

AI-2 quorum sensing signal disrupts coral symbiotic homeostasis and induces host bleaching.

Symbiotic microorganisms play critical ecophysiological roles that facilitate the maintenance of coral health. Currently, information on the gene and protein pathways contributing to bleaching responses is lacking, including the role of autoinducers. Although the autoinducer AI-1 is well understood, information on AI-2 is insufficient. Here, we observed a 3.7-4.0 times higher abundance of the AI-2 synthesis gene luxS in bleached individuals relative to their healthy counterparts among reef-building coral samples from the natural environment. Laboratory tests further revealed that AI-2 contributed significantly to an increase in coral bleaching, altered the ratio of potential probiotic and pathogenic bacteria, and suppressed the antiviral activity of specific pathogenic bacteria while enhancing their functional potential, such as energy metabolism, chemotaxis, biofilm formation and virulence release. Structural equation modeling indicated that AI-2 influences the microbial composition, network structure, and pathogenic features, which collectively contribute to the coral bleaching status. Collectively, our results offer novel potential strategies for coral conservation based on a signal manipulation approach.

Hybrid U-Net and Swin-transformer network for limited-angle cardiac computed tomography.

Objective.Cardiac computed tomography (CT) is widely used for diagnosis of cardiovascular disease, the leading cause of morbidity and mortality in the world. Diagnostic performance depends strongly on the temporal resolution of the CT images. To image the beating heart, one can reduce the scanning time by acquiring limited-angle projections. However, this leads to increased image noise and limited-angle-related artifacts. The goal of this paper is to reconstruct high quality cardiac CT images from limited-angle projections.Approach. The ability to reconstruct high quality images from limited-angle projections is highly desirable and remains a major challenge. With the development of deep learning networks, such as U-Net and transformer networks, progresses have been reached on image reconstruction and processing. Here we propose a hybrid model based on the U-Net and Swin-transformer (U-Swin) networks. The U-Net has the potential to restore structural information due to missing projection data and related artifacts, then the Swin-transformer can gather a detailed global feature distribution.Main results. Using synthetic XCAT and clinical cardiac COCA datasets, we demonstrate that our proposed method outperforms the state-of-the-art deep learning-based methods.Significance. It has a great potential to freeze the beating heart with a higher temporal resolution.

Polystyrene microplastics promote intestinal colonization of Aeromonas veronii through inducing intestinal microbiota dysbiosis.

The premise that pathogen colonized microplastics (MPs) can promote the spread of pathogens has been widely recognized, however, their role in the colonization of pathogens in a host intestine has not been fully elucidated. Here, we investigated the effect of polystyrene MPs (PS-MPs) on the colonization levels of Aeromonas veronii, a typical aquatic pathogen, in the loach (Misgurnus anguillicaudatus) intestine. Multiple types of MPs were observed to promote the intestinal colonization of A. veronii, among which PS-MPs exhibited the most significant stimulating effect (67.18% increase in A. veronii colonization). PS-MPs inflicted serious damage to the intestinal tracts of loaches and induced intestinal microbiota dysbiosis. The abundance of certain intestinal bacteria with resistance against A. veronii colonization decreased, with Lactococcus sp. showing the strongest colonization resistance (73.64% decline in A. veronii colonization). Fecal microbiota transplantation was performed, which revealed that PS-MPs induced intestinal microbiota dysbiosis was responsible for the increased colonization of A. veronii in the intestine. It was determined that PS-MPs reshaped the intestinal microbiota community to attenuate the colonization resistance against A. veronii colonization, resulting in an elevated intestinal colonization levels of A. veronii.

Effectiveness of prophylactic antibacterial drugs for patients with liver cirrhosis and upper gastrointestinal bleeding: a systematic review and meta-analysis.

Background: Prophylactic antibacterial drugs are used for patients with liver cirrhosis and upper gastrointestinal bleeding, and independent studies have concluded that they can decrease the rate of infection, mortality, and rebleeding in these diseases. However, no comprehensive assessment of this effect has been reported in recent years and available data pertaining to the prognostic implications of diverse categories of antibiotic prophylaxis in individuals afflicted with cirrhosis are notably limited. The objective of this article is to assess the clinical effectiveness of prophylactic antibacterial drugs for patients with liver cirrhosis and upper gastrointestinal bleeding. Methods: Relevant randomized controlled studies and cohort studies which examined the value of prophylactic antibacterial drugs for patients with liver cirrhosis and upper gastrointestinal bleeding were retrieved via Cochrane Library, EMBASE, MedLine, and Web of Science. The search period was from database inception until 30 April 2023. Summing up the relevant data, the dichotomous variable was statistically analysed using the relative risk (RR) value and its 95% confidence interval (CI) and the continuous variable using the mean difference (MD) value and its 95% CI. All analyses were performed using Revman 5.4 software. The study has been registered on the PROSPERO website under registration number CRD42022343352. Results: Twenty-six studies (18 RCTs and 8 cohort studies, including 13,670 participants) were included to evaluate the effect of antibacterial prophylaxis versus no antibacterial prophylaxis or placebo. Prophylactic antibiotics reduced mortality rates (RR 0.66, 95% CI 0.51-0.83), infection rates (RR 0.41, 95% CI 0.35-0.49), rebleeding rates (RR 0.42, 95% CI 0.31-0.56), and length of hospital stay (MD -5.29, 95% CI -7.53, -3.04). Subgroup analysis revealed that the prophylactic administration of quinolone antimicrobials demonstrated the most favorable efficacy, followed by cephalosporins. Both interventions were effective in averting infections frequently observed in patients with liver cirrhosis and upper gastrointestinal bleeding. Conclusion: Based on our investigation, the prophylactic antibacterial drugs confers noteworthy advantages in patients afflicted by liver cirrhosis with upper gastrointestinal bleeding. It has been associated with reductions in mortality, infection incidence, rebleeding occurrences, and the duration of hospitalization. Among prophylactic antibacterial options, quinolones emerged as the foremost choice, with cephalosporins ranking closely thereafter. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022343352, identifier CRD42022343352.

Biofilm formation of Hafnia paralvei induced by c-di-GMP through facilitating bcsB gene expression promotes spoilage of Yellow River carp (Cyprinus carpio).

Hafnia paralvei, a Gram-negative foodborne pathogen, is found ubiquitously in various aquatic animals and seafoods, which can form biofilm as a dominant virulence factor that contributes to its pathogenesis. However, the biofilm formation mechanism of H. paralvei and its effect on food spoilage has not been fully characterized. Here we show that biofilm formation, is regulated by c-di-GMP which mediated by bcsB, can increase the spoilage ability of H. paralvei. We found that GTP was added exogenously to enhance the synthesis of c-di-GMP, which further promoted biofilm formation. The gene dgcC, one of 11 genes encoding GGDEF domain-containing proteins in H. paralvei, was significantly upregulated with GTP as substrate. The upregulation of dgcC contributes to a significant increase of c-di-GMP and the formation of biofilm. In addition, the overexpression of dgcC induced upregulation of bcsB, a reported effector protein encoding gene, which was further demonstrated that overexpression of bcsB can encourage the synthesis of bacterial cellulose and biofilm formation. The effect of biofilm formation induced by c-di-GMP on spoilage of Yellow River carp (Cyprinus carpio) was evaluated by sensory evaluation, the total viable count, and the total volatile basic nitrogen, which showed that biofilm formation can significantly increase the spoilage ability of H. paralvei on C. carpio. Our findings provide the regulation of c-di-GMP on expression of bcsB, that can contribute to biofilm formation and spoilage ability of H. paralvei, which is favor to understanding the pathogenesis of Hafnia paralvei and its role in food spoilage.

Structure, evolution, and roles of SWEET proteins in growth and stress responses in plants.

Carbohydrates are exported by the SWEET family of transporters, which is a novel class of carriers that can transport sugars across cell membranes and facilitate sugar's long-distance transport from source to sink organs in plants. SWEETs play crucial roles in a wide range of physiologically important processes by regulating apoplastic and symplastic sugar concentrations. These processes include host-pathogen interactions, abiotic stress responses, and plant growth and development. In the present review, we (i) describe the structure and organization of SWEETs in the cell membrane, (ii) discuss the roles of SWEETs in sugar loading and unloading processes, (iii) identify the distinct functions of SWEETs in regulating plant growth and development including flower, fruit, and seed development, (iv) shed light on the importance of SWEETs in modulating abiotic stress resistance, and (v) describe the role of SWEET genes during plant-pathogen interaction. Finally, several perspectives regarding future investigations for improving the understanding of sugar-mediated plant defenses are proposed.

Genome-wide characterization and function analysis of ginger (Zingiber officinale Roscoe) ZoGRFs in responding to adverse stresses.

Growth-regulating factors (GRFs) play crucial roles in plant growth, development, hormone signaling, and stress response. Despite their significance, the roles of GRFs in ginger remain largely unknown. Herein, 31 ginger ZoGRFs were identified and designated as ZoGRF1-ZoGRF31 according to their phylogenetic relationships. All ZoGRFs were characterized as unstable, hydrophilic proteins, with 29 predicted to be located in the nucleus. Functional cis-elements related to growth and development were enriched in ZoGRF's promoter regions. RNA-seq and RT-qPCR analysis revealed that ZoGRF12, ZoGRF24, and ZoGRF28 were highly induced in various growth and development stages, displaying differential regulation under waterlogging, chilling, drought, and salt stresses, indicating diverse expression patterns of ZoGRFs. Transient expression analysis in Nicotiana benthamiana indicated that overexpressing ZoGRF28 regulated the transcription levels of salicylic acid, jasmonic acid, and pattern-triggered immunity-related genes, increased chlorophyll content and contributed to reduced disease lesions and an increased net photosynthetic rate. This research lays the foundation for further understanding the biological roles of ZoGRFs.

Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) via regulating the synaptic plasticity in hippocampus.

TSPO, translocator protein (18 kDa) ligands have demonstrated consistent antidepression and anxiolytic effects in several preclinical studies. This study aimed to examine whether YL-IPA08[N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl) -7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, could alleviate anxiety-related behaviors induced by electric shock (ES) and investigate its underlying mechanism. As expected, we showed that chronic treatment with YL-IPA08 significantly reversed anxiety-related behaviors induced by electrical stimulation (0.5 mA, 12 times, duration 1s, interval 10s) exposure. Using the analysis of RNA-sequencing (RNA-seq) technology, it was found that the differential genes associated with the anxiolytic effect of YL-IPA08 were mainly related to synaptic plasticity. Furthermore, YL-IPA08 restored the decreased levels of brain-derived neurotrophic factor (BDNF), synapse-related protein (e.g. synapsin-1 and post-synaptic density95, PSD95), and the number of doublecortin (DCX) + neurons in the hippocampus of post-ES mice. In addition, YL-IPA08 also enhanced the dendritic complexity and dendritic spine density of hippocampal dentate gyrus (DG) granule neurons. Meanwhile, the induction of long-term potentiation (LTP) was significantly enhanced by YL-IPA08. In summary, the findings from the current study showed that YL-IPA08 exerted a clear anxiolytic effect, which might be partially mediated by promoting hippocampal neuroplasticity.

Syringo-Subarachnoid Shunt with Tube Versus T-Tube via the Dorsal Root Entry Zone Approach for Eccentric Syringomyelia.

OBJECTIVE: This study compared the clinical therapeutic efficacy of syringo-subarachnoid shunt placement with direct tube and T-tube via the dorsal root entry zone (DREZ) approach for treatment of eccentric syringomyelia. METHODS: A retrospective study was performed of 41 patients with idiopathic or secondary eccentric syringomyelia from November 2011 to December 2022. Syringo-subarachnoid shunt placement with direct tube or T-tube via the DREZ approach was performed. The modified Japanese Orthopaedic Association low back pain scale was used to investigate the severity of clinical symptoms. Magnetic resonance imaging was used to investigate therapeutic efficacy（reduction of the cavity volume by >10% was considered an improvement and 50% was considered a significant improvement). RESULTS: Incision length of the spinal cortex in the direct tube group was shorter than in the T-tube group (3.10 ± 0.28 cm vs. 5.03 ± 0.19 cm), with a significant difference between the 2 groups (t = -52.56, P < 0.001). Modified Japanese Orthopaedic Association score 3 months postoperatively was significantly better than the preoperative score in both the direct tube group（t = 40.954, P < 0.001） and the T-tube group（t = 24.769, P < 0.001）. Statistical comparison revealed there was no difference in imaging improvement between the direct tube group and T-tube group 3 months (χ2 = 0.20, P = 0.655) and 12 months (χ2 = 0.21, P = 0.647) postoperatively. CONCLUSIONS: Syringo-subarachnoid shunt placement with direct tube via the DREZ approach for treatment of eccentric syringomyelia is safer than with T-tube via the DREZ approach due to smaller incision length and less of a space-occupying effect with same therapeutic efficacy.