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.

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.

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.

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.

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.

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.

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.

In situ architecture and membrane fusion of SARS-CoV-2 Delta variant.

Among the current five Variants of Concern, infections caused by SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in situ structure and distribution of S on the authentic Delta variant. We also captured the virus-virus fusion events, which provided pieces of structural evidence for Delta's attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.

Nanoplastics Shape Adaptive Anticancer Immunity in the Colon in Mice.

The impact of nanoplastics (NPs) on human health is still not well understood, and more research is needed to better understand the risks associated with these particles. In this study, we found that oral administration of polyethylene (PE) NPs in a mice model significantly disrupted the intestinal microenvironment, which shapes adaptive immune response and favors the established in situ colorectal tumor growth. Using single-cell RNA sequencing technology, we show that NPs triggered colon IL-1ß-producing macrophages by inducing lysosome damage, leading to colonic Treg and Th17 differentiation associated with T cell exhaustion, which creates a colon environment that favors the tumor initiation and progress. A similar effect is also observed in polystyrene NPs. Our result provides insight into the potential link between NPs ingestion and colon tumorigenesis, and the urgency of addressing plastic pollution worldwide.

Oral feeding of nanoplastics affects brain function of mice by inducing macrophage IL-1 signal in the intestine.

Nanoplastics (NPs) as contaminants in food and water have drawn increasing public attention. However, little is known about how NPs shape the gut immune landscape after injection. In this study, we fabricate NPs (∼500 nm) and microplastics (MPs) (∼2 µm) and evaluate their in vivo effects by feeding them to mice. The results suggest that NPs show a better ability to induce gut macrophage activation than MPs. In addition, NPs trigger gut interleukin-1 (IL-1)-producing macrophage reprogramming via inducing lysosomal damage. More importantly, IL-1 signaling from the intestine can affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlates with a decline in cognitive and short-term memory in NP-fed mice. Thus, this study provides insight into the mechanism of action of the gut-brain axis, delineates the way NPs reduce brain function, and highlights the importance of fixing the plastic pollution problem worldwide.

Genomics and nitrogen metabolic characteristics of a novel heterotrophic nitrifying-aerobic denitrifying bacterium Acinetobacter oleivorans AHP123.

A novel aerobic strain of Acinetobacter oleivorans AHP123 was isolated from activated sludge, which could conduct heterotrophic nitrification and denitrification simultaneously. This strain has excellent NH4+-N removal ability, with 97.93% removal rate at 24-hour. To identify the metabolic pathways of this novel strain, genes of gam, glnA, gdhA, gltB, nirB, nasA, nar, nor, glnK and amt were detected by genome analysis. Through RT-qPCR, it was found that the expression of key genes confirmed two possible ways of nitrogen removal in strain AHP123: nitrogen assimilation and heterotrophic nitrification aerobic denitrification (HNAD). However, the absence of some common HNAD genes (amo, nap and nos) suggested that strain AHP123 might have a different HNAD pathway from other HNAD bacteria. Nitrogen balance analysis revealed that strain AHP123 assimilated most of the external nitrogen sources into intracellular nitrogen.

Research progress of child athlete’s speech sound disorders

Child athletes with speech sound disorders may experience difficulties communicating with coaches, teammates, and others in sports-related contexts. To improve communication abilities and overall athletic performance, research has made progress in exploring the impact of speech therapy and exercise programs on child athletes with speech sound disorders. These programs aim to enhance neural connections between the brain regions responsible for speech production and motor skills needed for sports, as well as boost confidence in social situations. By utilizing advanced diagnostic tools, such as speech sound assessments and imaging techniques, researchers have identified new methods for identifying and treating speech sound disorders in child athletes. This paper reviews the recent research progress on child athlete's speech sound disorders, discussing the implications for speech therapy and exercise programs in sports training, as well as the potential for improved communication and athletic performance. (AU)

Research on the Relationship between the Amylopectin Structure and the Physicochemical Properties of Starch Extracted from Glutinous Rice.

Glutinous rice has very low amylose content and is a good material for determining the structure and physicochemical properties of amylopectin. We selected 29 glutinous rice varieties and determined the amylopectin structure by high-performance anion exchange chromatography with the pulsed amperometric detection method. We also determined the correlation between amylopectin structure and the physicochemical properties of starch extracted from these varieties. The results showed that the amylopectin chain ratio Σdegree of polymerization (DP) ≤ 11/ΣDP ≤ 24 of 29 glutinous rice varieties was greater than 0.26, signifying that these varieties contained type II amylopectin. The results of the correlation analysis with gelatinization temperature showed that ΣDP 6-11 was significantly negatively correlated with the onset gelatinization temperature (GT) (TO), peak GT (TP), and conclusion GT (TC). Among the thermodynamic properties, ΣDP 12-24 was significantly positively correlated with To, Tp, and Tc, ΣDP 25-36 was significantly negatively correlated with To, Tp, and Tc, and ΣDP ≥ 37 had no correlation with the thermodynamic properties. The results of correlation analysis with RVA spectrum characteristic values showed that ΣDP 6-11 was significantly negatively correlated with hot paste viscosity (HPV), cool paste viscosity (CPV), consistency viscosity (CSV), peak time (PeT), and pasting temperature (PaT) among the Rapid Visco Analyzer (RVA) profile characteristics, ΣDP 12-24 was significantly positively correlated with HPV, CPV, CSV, PeT, and PaT, and ΣDP ≥ 25 had no correlation with the viscosity characteristics. Therefore, we concluded that the amylopectin structure had a greater effect on the TO, TP, TC, ΔH and peak viscosity, HPV, CPV, CSV, PeT, and PaT. The glutinous rice varieties with a higher distribution of short chains and a lower distribution of medium and long chains in the amylopectin structure resulted in lower GT and RVA spectrum characteristic values.