Inhibition of ANGPTL8 protects against diabetes-associated cognitive dysfunction by reducing synaptic loss via the PirB signaling pathway.

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS: The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS: Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION: Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Oral administration of garlic-derived nanoparticles improves cancer immunotherapy by inducing intestinal IFNγ-producing γδ T cells.

Gamma-delta (γδ) T cell-based cancer immunotherapies represent a promising avenue for cancer treatment. However, their development is challenged by the limited expansion and differentiation of the cells ex vivo. Here we induced the endogenous expansion and activation of γδ T cells through oral administration of garlic-derived nanoparticles (GNPs). We found that GNPs could significantly promote the proliferation and activation of endogenous γδ T cells in the intestine, leading to generation of large amount of interferon-γ (IFNγ). Moreover GNP-treated mice showed increased levels of chemokine CXCR3 in intestinal γδ T cells, which can drive their migration from the gut to the tumour environment. The translocation of γδ T cells and IFNγ from the intestine to extraintestinal subcutaneous tumours remodels the tumour immune microenvironment and synergizes with anti-PD-L1, inducing robust antitumour immunity. Our study delineates mechanistic insight into the complex gut-tumour interactome and provides an alternative approach for γδ T cell-based immunotherapy.

Effects of Schroth 3D Exercise on Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-Analysis.

(1) Background: This meta-analysis aims to systematically assess the effect size of Schroth three-dimensional exercise training on adolescent idiopathic scoliosis, especially for Cobb angles, angles of trunk rotation, and quality of life. (2) Methods: Randomized controlled trials (RCTs) focused on the effect of Schroth exercise on patients with adolescent idiopathic scoliosis (AIS) were retrieved from six databases, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang. All publications until July 2023 were searched. Two researchers screened and evaluated the literature. Review manager (RevMan 5.3) statistical software was used for meta-analyses, and subgroup analysis and sensitivity analysis of the literature with high heterogeneity were further conducted. (3) Results: In total, 14 studies were included, including 538 adolescent idiopathic scoliosis patients. Compared with conventional physical therapy, Schroth 3D exercise training is more effective at reducing the Cobb angle (WMD = -3.32, 95%CI [-4.15, -2.50], p < 0.001) and improving the trunk rotation angle (WMD = -2.24, 95%CI [-3.00, -1.48], p < 0.001), quality of life (SMD = 2.80, 95%CI [1.53, 4.06], p < 0.001), and WRVAS (WMD = -2.92, 95%CI [-3.25, -2.60], p < 0.001), as well as enhancing the strength of the lumbar extensor (SMD = 1.79, 95%CI [1.46, 2.12], p < 0.001). (4) Conclusion: Compared with traditional therapy, Schroth 3D exercises are more effective at decreasing the Cobb angle and ATR in adolescent idiopathic scoliosis, improving patients' quality of life, as well as enhancing the strength of the lumbar extensor.

Visible light irradiation enhanced sulfidated zero-valent iron/peroxymonosulfate process for organic pollutant degradation.

This study developed a novel process named sulfidated zero-valent iron/peroxymonosulfate/visible light irradiation (S-mZVI/PMS/vis) for enhanced organic pollutant degradation. The S-mZVI/PMS/vis process exhibited remarkable catalytic activity, achieving a 99.6% rhodamine B (RhB) removal within 10 min. The degradation rate constant of RhB by the S-mZVI/PMS/vis process was found to be 6.49 and 79.84 times higher than that by the S-mZVI/PMS and PMS/vis processes, respectively. Furthermore, the S-mZVI/PMS/vis process worked efficiently across a wide pH range (3.0-9.0), and the result of five-cycle experiments demonstrated the excellent reusability and stability of S-mZVI. Radical quenching tests and electron paramagnetic resonance analysis indicated that ·O2-, 1O2, and h+ significantly contributed to the degradation of RhB through the S-mZVI/PMS/vis process. The visible light irradiation increased the Fe2+ concentration, improved the Fe3+/Fe2+ cycle, and consequently enhanced the PMS decomposition, reactive species production, and RhB degradation. This work offers a promising strategy to highly efficiently activate PMS for organic pollutants elimination from aqueous solutions.

Isolation of anthraquinone derivatives from Rubia cordifolia (Rubiaceae) and their bioactivities against plant pathogenic microorganisms.

BACKGROUND: The discovery of antimicrobial ingredients from natural products could be an effective way to create novel fungicides. Rubia cordifolia L., a traditional Chinese herb, may have antimicrobial effects on plant pathogens according to our previous screening study. RESULTS: Rubia cordifolia L. extracts had moderate inhibitory effects on apple Valsa canker (Valsa mali) and tomato grey mould (Botrytis cinerea) at a concentration of 10 mg mL-1. With the use of bioguided isolation methods, eight compounds (1-8) were obtained, including the new compound 2,2,6-trimethyl-6-(4-methylphenyl)-tetrahydropyrano- 3-ol (7), and seven quinone derivatives. Two compounds, mollugin (1) and 1,3,6-trihydroxy-2-methylanthraquinone (6), were found to exhibit outstanding antifungal activities against V. mali and Phytophthora capsici Leon. The half maximal effective concentration (EC50) of compound 1 and compound 6 against V. mali were 79.08 and 81.78 µg mL-1, respectively, and the EC50 of compound 6 against P. capsici was 4.86 µg mL-1. Compound 1 also showed excellent activity against tobacco mosaic virus (TMV). The inactive, inductive, protective and curative activities against TMV were 84.29%, 83.38%, 86.81%, and 60.02%, respectively, at a concentration of 500 µg mL-1, which were all close to or greater than that of the positive control (100 µg mL-1 chitosan oligosaccharide, COS). CONCLUSION: Mollugin and 1,3,6-trihydroxy-2-methylanthraquinone are potentially valuable active compounds that lay a foundation for research on botanical fungicide products derived from R. cordifolia L. and provide lead structures for quinone derivative synthesis and structural modification. © 2024 Society of Chemical Industry.

A Printable Hydrogel Loaded with Medicinal Plant Extract for Promoting Wound Healing.

How to promote wound healing is still a major challenge in the healthcare while macrophages are a critical component of the healing process. Compared to various bioactive drugs, many plants have been reported to facilitate the wound healing process by regulating the immune response of wounds. In this work, a Three-dimensional (3D) printed hydrogel scaffold loaded with natural Centella asiatica extract (CA extract) is developed for wound healing. This CA@3D scaffold uses gelatin (Gel) and sodium alginate (SA) with CA extract as bio-ink for 3D printing. The CA extract contains a variety of bioactive compounds that make the various active ingredients in Centella asiatica work in concert. The printed CA@3D scaffold can fit the shape of wound, orchestrate the macrophages and immune responses within the wound, and promote wound healing compared to commercial wound dressings. The underlying mechanism of promoting wound healing is also illuminated by applying multi-omic analyses. Moreover, the CA extract loaded 3D scaffold also showed great ability to promote wound healing in diabetic chronic wounds. Due to its ease of preparation, low-cost, biosafety, and therapeutic outcomes, this work proposes an effective strategy for promoting chronic wound healing.

Mechanochemical Oxidative Coupling of Amine to Azo-based Polymers by Hypervalent Iodine Oxidant.

Among porous organic polymers (POPs), azo-linked POPs represent a crucial class of materials, making them the focus of numerous catalytic systems proposed for their synthesis. However, the synthetic process is limited to metal-catalyzed, high-temperature, and liquid-phase reactions. In this study, we employ mechanochemical oxidative metal-free systems to encompass various syntheses of azo-based polymers. Drawing inspiration from the "rule of six" principle (six or more carbons on an azide group render the organic compound relatively safe), an azo compound featuring significant steric hindrance is obtained using the hypervalent iodine oxidation strategy. Furthermore, during the polymerization process, steric hindrance is enhanced in monomers to effectively prevent explosions resulting from direct contact between hypervalent iodine oxidants and primary amines. Indeed, this approach provides a facile and innovative solid-phase synthesis method for synthesizing azo-based materials.

Self-fueling ferroptosis-inducing microreactors based on pH-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapy.

Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma (HCC) via transarterial chemoembolization (TACE). However, the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion, which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics. Therefore, the development of enhanced Lipiodol-based formulations is of great significance to enable effective and safe TACE treatment. Herein, a stable water-in-oil Lipiodol Pickering emulsion (LPE) stabilized by pH-dissociable calcium carbonate nanoparticles and hemin is prepared and utilized for efficient encapsulation of lipoxygenase (LOX). The obtained LOX-loaded CaCO3&hemin-stabilized LPE (LHCa-LPE) showing greatly improved emulsion stability could work as a pH-responsive and self-fueling microreactor to convert polyunsaturated fatty acids (PUFAs), a main component of Lipiodol, to cytotoxic lipid radicals through the cascading catalytic reaction driven by LOX and hemin, thus inducing ferroptosis of cancer cells. As a result, such LHCa-LPE upon transcatheter embolization can effectively suppress the progression of orthotopic N1S1 HCC in rats. This study highlights a concise strategy to prepare pH-responsive and stable LPE-based self-fueling microreactors, which could serve as bifunctional embolic and ferroptosis-inducing agents to enable proof-of-concept transarterial ferro-embolization therapy of HCC.

Hybrid-hybrid correction of errors in long reads with HERO.

Although generally superior, hybrid approaches for correcting errors in third-generation sequencing (TGS) reads, using next-generation sequencing (NGS) reads, mistake haplotype-specific variants for errors in polyploid and mixed samples. We suggest HERO, as the first "hybrid-hybrid" approach, to make use of both de Bruijn graphs and overlap graphs for optimal catering to the particular strengths of NGS and TGS reads. Extensive benchmarking experiments demonstrate that HERO improves indel and mismatch error rates by on average 65% (27[Formula: see text]95%) and 20% (4[Formula: see text]61%). Using HERO prior to genome assembly significantly improves the assemblies in the majority of the relevant categories.

Neural Correlation of EEG and Eye Movement in Natural Grasping Intention Estimation.

Decoding the user's natural grasp intent enhances the application of wearable robots, improving the daily lives of individuals with disabilities. Electroencephalogram (EEG) and eye movements are two natural representations when users generate grasp intent in their minds, with current studies decoding human intent by fusing EEG and eye movement signals. However, the neural correlation between these two signals remains unclear. Thus, this paper aims to explore the consistency between EEG and eye movement in natural grasping intention estimation. Specifically, six grasp intent pairs are decoded by combining feature vectors and utilizing the optimal classifier. Extensive experimental results indicate that the coupling between the EEG and eye movements intent patterns remains intact when the user generates a natural grasp intent, and concurrently, the EEG pattern is consistent with the eye movements pattern across the task pairs. Moreover, the findings reveal a solid connection between EEG and eye movements even when taking into account cortical EEG (originating from the visual cortex or motor cortex) and the presence of a suboptimal classifier. Overall, this work uncovers the coupling correlation between EEG and eye movements and provides a reference for intention estimation.

Neurological disorders after severe pneumonia are associated with translocation of endogenous bacteria from the lung to the brain.

Neurological disorders are a common feature in patients who recover from severe acute pneumonia. However, the underlying mechanisms remain poorly understood. Here, we show that the neurological syndromes after severe acute pneumonia are partly attributed to the translocation of endogenous bacteria from the lung to the brain during pneumonia. Using principal components analysis, similarities were found between the brain's flora species and those of the lungs, indicating that the bacteria detected in the brain may originate from the lungs. We also observed impairment of both the lung-blood and brain-blood barriers, allowing endogenous lung bacteria to invade the brain during pneumonia. An elevated microglia and astrocyte activation signature via bacterial infection-related pathways was observed, indicating a bacterial-induced disruption of brain homeostasis. Collectively, we identify endogenous lung bacteria that play a role in altering brain homeostasis, which provides insight into the mechanism of neurological syndromes after severe pneumonia.

PD-L1-Expressing Extracellular Vesicles for the Treatment of Pneumonia.

Acute respiratory distress syndrome (ARDS) is a severe lung condition with a high mortality rate and a lack of effective drug therapy. In this work, we developed mesenchymal stem cell (MSC)-derived extracellular vesicles with high PD-L1 expression (MSC-EVs-PD-L1) for treating lipopolysaccharide (LPS)-induced pneumonia by intratracheal administration. We found an upregulation of PD-1 expression in the inflammatory region of murine lungs; hence, MSC-EVs-PD-L1 exerted immunosuppressive effects via the PD-1/PD-L1 signaling pathway. Furthermore, we treated LPS-induced pneumonia mice by intratracheal administration, which enabled heavy drug accumulation in the lungs of mice and better therapeutic efficacy compared to systemic administration. Our results suggest that MSC-EVs-PD-L1 has the potential to provide a universal platform technology for the immunotherapy of pneumonia.

Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy.

Advances in the development of therapeutic extracellular vesicles (EVs) for cancer immunotherapy have allowed them to emerge as an alternative to cell therapy. In this proof-of-concept work, we develop bispecific EVs (BsEVs) by genetically engineering EV-producing dendritic cells (DCs) with aCD19 scFv and PD1 for targeting tumor antigens and blocking immune checkpoint proteins simultaneously. We find that these bispecific EVs (EVs-PD1-aCD19) have an impressive ability to accumulate in huCD19-expressing solid tumors following intravenous injection. In addition, EVs-PD1-aCD19 can remarkably reverse the immune landscape of the solid tumor by blocking PD-L1. Furthermore, EVs-PD1-aCD19 can also target tumor-derived EVs in circulation, which prevents the formation of a premetastatic niche in other tissues. Our technology is a demonstration of bispecific EV-based cancer immunotherapy, which may inspire treatments against various types of tumors with different surface antigens and even a patient-tailored therapy.

Severe pneumonia induces immunosenescence of T cells in the lung of mice.

Severe pneumonia may induce sequelae and accelerated aging process even after the person has recovered. However, the underline mechanism is not very clear. More research is needed to fully understand the long-term effects of severe pneumonia. In this study, we found that mice recovered from severe pneumonia showed lung immunosenescence, which was characterized by a bias naive-memory balance of T lymphocytes in the lung. The reduction of naïve T cells is associated with the diminished immune response to cancer or external new antigens, which is one of the key changes that occurs with age. Our results also indicate the link between severe pneumonia and aging process, which is mediated by the disrupted T cells homeostasis in the lungs after pneumonia.

A novel fungal-algal coupling system for slaughterhouse wastewater treatment and lipid production.

In this study, a novel fungal-algal coupling system was established for slaughterhouse wastewater treatment with Chlorella sp. DT025 and a new fungus, Penicillium sp. AHP141. With the optimization of cultivation conditions for the fungal-algal coupling system, the harvest efficiency of Chlorella sp. DT025 reached 99.79%. The mechanism of microalgae harvest of the fungal-algal system was revealed to be related to the morphological characteristics, surface charge, and the secretion of humic acid-like compounds and tryptophan on the surface of the fungi cells. For the original slaughterhouse wastewater treatment, the fungal-algal coupling system had a better removal efficiency of COD, TN, and TP than both monoculture systems. In the high-concentration artificial slaughterhouse wastewater, COD removal of the fungal-algal system reached more than 5350 mg/L. The lipid production of the fungal-algal coupling system in the high-concentration artificial slaughterhouse wastewater treatment was improved by 343.33% to 1.33 g/L compared to the microalgae monoculture treatment.

LHX2 Is a Potential Biomarker and Associated with Immune Infiltration in Breast Cancer.

Worldwide, breast cancer is the most common malignancy. LHX2, a member of the LIM homeobox gene family and a transcription factor, plays a crucial role in numerous tumors, but the function of LHX2 in breast cancer progression remains unknown. In this study, we show that LHX2 is upregulated in breast cancer tissues and positively correlated with breast cancer progression. Meanwhile, the clinical characteristics of breast cancer and LHX2 expression showed a strong correlation. GSEA showed that a high LHX2 expression may activate the T-cell activation pathway, PI3K/AKT/mTOR signaling pathway, and apoptosis pathway. Moreover, ssGSEA showed that Th1 cells and Th2 cells had a positive correlation with LHX2 expression in breast cancer. Experiments showed that LHX2 promotes the proliferation, colony formation, migration, and invasion of breast cancer cells. Immunohistochemistry and immunofluorescence assays helped to analyze LHX2-associated immune infiltration in breast cancer. A Western blot assay proved that LHX2 activated the PI3K/AKT/mTOR pathway and the apoptosis pathway. A TUNEL assay confirmed that LHX2 inhibited apoptosis. Taken together, LHX2 plays a vital role in breast cancer's progression and prognosis and could be an immune infiltration biomarker for breast cancer, and LHX2 activates the PI3K/AKT/mTOR pathway and apoptosis pathway in breast cancer.

SNHG1, a KLF4-upregulated gene, promotes glioma cell survival and tumorigenesis under endoplasmic reticulum stress by upregulating BIRC3 expression.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the resistance to endoplasmic reticulum (ER) stress in many cancers. However, ER stress-regulated lncRNAs are still unknown in glioma. In the present study, we investigated the altered lncRNAs upon ER stress in glioma and found that small nucleolar RNA host gene 1 (SNHG1) was markedly increased in response to ER stress. Increased SNHG1 suppressed ER stress-induced apoptosis and promoted tumorigenesis in vitro and in vivo. Further mechanistic studies indicated that SNHG1 elevated BIRC3 mRNA stability and enhanced BIRC3 expression. We also found that KLF4 transcriptionally upregulated SNHG1 expression and contributed to the ER stress-induced SNHG1 increase. Collectively, the present findings indicated that SNHG1 is a KLF4-regulated lncRNA that suppresses ER stress-induced apoptosis and facilitates gliomagenesis by elevating BIRC3 expression.

Post treatment and 3 month contrast enhanced MRI findings following HIFU of submucosal fibroids: a retrospective study.

PURPOSE: This study used contrast-enhanced MRI (CE-MRI) examination to assess the efficacy of high-intensity focused ultrasound (HIFU) for submucosal fibroids. METHODS: A total of 81 submucosal fibroids, including 33 cases of type 1, 29 cases of type 2, and 19 cases of type 2-5, treated by HIFU were retrospectively reviewed. CE-MRI was performed in all cases immediately after HIFU, the non-perfused volume ratio (NPVR) and the degree of endometrial impairment were recorded. Thereafter, CE-MRI was repeated in all cases after three months, and the change of fibroid volume shrinkage rate (FVSR), NPVR and the degree of endometrial impairment were recorded. RESULTS: The immediate NPVR was 86.4 ± 19.3% in type 1, 90.0 ± 13.3% in type 2 and 90.3 ± 7.2% in type 2-5. Among 81 fibroids, grades 0, 1, 2 and 3 endometrial impairments were observed in 38.3%, 16.1%, 14.8% and 30.9%, respectively. Three months later, NPVR was 68.0 ± 36.4% in type 1, 74.3 ± 27.7% in type 2 and 85.0 ± 16.1% in type 2-5. Grades 0, 1, 2 and 3 endometrial impairments were observed in 64.2%, 23.5%, 9.9% and 2.4%.FVSR was 49.0 ± 1.3% in type 1, 39.6 ± 1.7% in type 2 and 37.2 ± 2.1% in type 2-5. The FVSR in submucosal fibroid type 1 was superior to type 2 and type 2-5 (p < 0.05). The NPVR of submucosal fibroids in type 2-5 were higher than type 1 (p < 0.05) .There was no difference among different types of submucosal fibroids in endometrial impairment (p > 0.05) three months after HIFU. CONCLUSIONS: At three months after HIFU, FVSR was better for submucosal fibroid type 1 than for type 2 and type 2-5. And there was no difference in endometrial impairment among the different types of submucosal fibroid groups.