LINC00472 regulates ferroptosis of neurons in Alzheimer's disease via FOXO 1.

OBJECTIVE: To explore the molecular mechanism of long non-coding RNA (lncRNA) LINC00472 in Alzheimer's Disease (AD). METHOD: Ferroptosis-related lncRNAs were screened by GEO database. AD mouse model was constructed for in vivo experimental. The content of Aß protein and Tau protein hyperphosphorylation were examined in Hippocampal tissue samples of mice. Subsequently, HT22 cells were induced with Aß25-35 to establish a neuronal injury model of AD in vitro. The expression of FOXO1, a key gene for ferroptosis, was verified by overexpressing/knocking down the LINC00472. The effects of LINC00472 on ROS and lipid peroxidation content, GPX4, and Tau protein in AD model cells were examined by ROS assay, MDA assay, Western Blot and qRT-PCR. Subsequently, the expression of iron ion, FTH, TfRC, and Fpn protein were detected in AD cells. RESULTS: The level of FOXO1 was positively correlated with the degree of AD. In vivo experiments showed that the expression of Aß and Tau hyperphosphorylated were significantly reduced in the inhibitor group and iron was significantly reduced relative to the AD group. In the AD cell model, the content of lipid peroxide was up-regulated, GPX4 protein and mRNA were decreased, and phosphorylation of Tau protein was enhanced in the AD cell model relative to the control group. Whereas knocking down LINC00472 inhibited the up-regulation of lipid peroxide, decreased the level of GPX4, and enhancement of Tau protein phosphorylation, and it reduced iron accumulation, in AD cells. CONCLUSIONS: LINC00472 affects ferroptosis in AD by regulating iron accumulation, in neuronal cells.

Effect of phenolics on soil microbe distribution, plant growth, and gall formation.

Phenolic compounds, abundant secondary metabolites in plants, profoundly influence soil ecosystems, plant growth, and interactions with herbivores. In this study, we explore the intricate relationships between phenolics, soil microbes, and gall formation in Ageratina adenophora (A. adenophora), an invasive plant species in China known for its allelopathic traits. Using metabolomic and microbial profiling, significant differences in soil microbial composition and metabolite profiles were observed between bulk and rhizosphere soil samples. Phenolics influenced bacterial communities, with distinct microbial populations enriched in each soil type. Additionally, phenolics impacted soil metabolic processes, with variations observed in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis between different soil treatments. Analysis of phenolic content in plant and soil samples revealed considerable variations, with higher concentrations observed in certain plant tissues and soil types. Bioactive phenols extracted from plant and soil samples were identified using gas chromatography/mass spectrometry (GC-MS), providing insights into the diverse chemical composition of these compounds. Furthermore, the effects of phenolics on plant growth and gall formation were investigated. Phenols exhibited both stimulatory and inhibitory effects on plant growth, with optimal concentrations promoting emergence but higher concentrations hindering growth. Gall formation was influenced by phenolic concentrations, leading to structural alterations in stem tissue and gall morphology. Histochemical analysis revealed starch and lipid accumulation in gall tissues, indicating metabolic changes induced by phenolics. The presence of phenolics disrupted tissue structures and influenced vascular bundle orientation in gall tissues. Overall, our study highlights the multifaceted roles of phenolic compounds in soil ecosystems, plant development, and gall formation, facilitating the utilization of secondary metabolites in agriculture.

Functional analysis of adipokinetic hormone signaling in reproductive diapause of Coccinella septempunctata.

BACKGROUND: The ladybeetle, Coccinella septempunctata, an important predator, is widely used to control aphids, whiteflies, mites, thrips, and lepidopteran pests. Diapause control technology is key to extending C. septempunctata shelf-life and commercialization. Lipid accumulation is a major feature of reproductive diapause, but the function of AKH signaling as a regulator of lipid mobilization in reproductive diapause remains unclear. This study aimed to identify and characterize AKH and AKHR genes, and clarify their functions in reproductive diapause. RESULTS: The relative expression levels of CsAKH and CsAKHR were the highest in the head and fat body, respectively, and were significantly decreased under diapause conditions, both in developmental stages and tissues (head, midgut, fat body, and ovary). Furthermore, CsAKH and CsAKHR expression was increased significantly after juvenile hormone (JH) injection, but CsMet silencing significantly inhibited CsAKH and CsAKHR expression, whereas CsMet knockdown blocked the induction effect of JH. CsAKH and CsAKHR knockdown significantly reduced water content, increased lipid storage, and promoted the expression of genes related to lipid synthesis, but significantly blocked ovarian development, and induced forkhead box O (FOXO) gene expression in C. septempunctata under reproduction conditions. By contrast, injection of AKH peptide significantly inhibited FOXO expression, reduced lipid storage, and increased water content in C. septempunctata under diapause conditions. CONCLUSION: These results indicate that CsAKH and CsAKHR are involved in the regulation of lipid accumulation and ovarian development during diapause in C. septempunctata, and provide a promising target for manipulating C. septempunctata diapause. © 2024 Society of Chemical Industry.

Regulation of forkhead box O transcription factor by insulin signaling pathway controls the reproductive diapause of the lady beetle, Coccinella septempunctata.

In biological control programs, knowledge about diapause regulation in natural enemy insects provides important insight for improving long-term storage, transportation, and field adoption of these biological control agents. As a natural predator of agricultural pests, the lady beetle Coccinella septempunctata has been commercially mass-cultured and widely employed in pest management. In some insects, insulin signaling, in conjunction with the downstream transcription factor Forkhead box O (FoxO), are master regulators of multiple physiological processes involved in diapause, but it is unclear whether insulin signaling and FoxO affect the diapause of C. septempunctata. In this study, we use a combination of approaches to demonstrate that insulin signaling and FoxO mediate the diapause response in C. septempunctata. In diapausing beetles, application of exogenous insulin and knocking down expression of CsFoxo with RNA interference (RNAi) both rescued beetles from developmental arrest. In non-diapausing beetles, knocking down expression of the insulin receptor (CsInR) with RNA interference (RNAi) arrested ovarian development and decreased juvenile hormone (JH) content to levels comparable to the diapause state. Taken together, these results suggest that a shutdown of insulin signaling prompts the activation of the downstream FoxO gene, leading to the diapause phenotype.

Male vitellogenin regulates gametogenesis through a testis-enriched big protein in Chrysopa pallens.

In insects, vitellogenin (Vg) is generally viewed as a female-specific protein. Its primary function is to supply nutrition to developing embryos. Here, we reported Vg from the male adults of a natural predator, Chrysopa pallens. The male Vg was depleted by RNAi. Mating with Vg-deficient male downregulated female Vg expression, suppressed ovarian development and decreased reproductive output. Whole-organism transcriptome analysis after male Vg knockdown showed no differential expression of the known spermatogenesis-related regulators and seminal fluid protein genes, but a sharp downregulation of an unknown gene, which encodes a testis-enriched big protein (Vcsoo). Separate knockdown of male Vg and Vcsoo disturbed the assembly of spermatid cytoplasmic organelles in males and suppressed the expansion of ovary germarium in mated females. These results demonstrated that C. pallens male Vg signals through the downstream Vcsoo and regulates male and female reproduction.

Adsorption of azoxystrobin and pyraclostrobin onto degradable and non-degradable microplastics: Performance and mechanism.

Microplastics (MPs) exist after agricultural operations and thus present potential hazards to the environment and human health. However, the ecological risks posed by MPs carrying pesticides remain unclear. In this study, the adsorption and desorption behaviors of two pesticides, azoxystrobin and pyraclostrobin, on degradable and non-degradable MPs of poly(butylene adipate-co-terephthalate) (PBAT) and polyethylene (PE) were compared before and after UV aging. Additionally, the bioaccessibility of MPs carrying pesticides within a condition simulating gastrointestinal fluids was evaluated. The results showed that, after UV aging, the adsorption capacity of PBAT for pesticides decreased, while that of PE increased. Moreover, PBAT possessed higher adsorption ability towards both the pesticides due to its higher specific surface area, pore volume, contact angle, and lower crystallinity, as well as stronger van der Waals forces, electrostatic interactions, and hydrogen bonding indicated by theoretical calculation. Bioaccessibility experiments showed that azoxystrobin and pyraclostrobin had a higher risk of desorption from PBAT than PE, which is mainly dependent on the LogKow of pesticides according to the random forest analysis. In brief, the study highlights the potential risks of degradable MPs carrying pesticides to human health and the ecosystem, especially when compared to their non-degradable counterparts, manifesting that the ecological risk posed by degradable MPs should not be ignored.

Preliminary study on a novel biological scaffold loaded with Apelin-13 sustained-release microcapsules for promoting fallopian tube recanalization in rabbits. / è½½Apelin-13ç¼“é‡Šå¾®å›Šçš„æ–°åž‹ç”Ÿç‰©æ”¯æž¶ä¿ƒå ”è¾“åµç®¡å†é€šçš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: Tubal factor infertility severely impairs the natural fertility of women, and there is for genuine tubal recanalization, including restoration of both the anatomy and function of the diseased fallopian tubes. Currently, there is no effective treatment available. This study aims to explore methods for promoting the repair and recanalization of fallopian tubes from these 2 aspects. METHODS: Apelin-13 sustained-release microspheres and poly (lactic-co-glycolic acid) (PLGA) three-dimensional (3D) biodegradable scaffolds were prepared. The basic characteristics and in vivo degradation (mass loss rate) of the biodegradable scaffolds were tested, along with the in vitro drug release (cumulative release rate), the in vivo drug release (Apelin-13 plasma concentration), and in vitro degradation (degradation rate) of the microspheres. The Apelin-13 microspheres (microsphere group)/PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres (scaffold-microcapsule group) were injected/placed into the fallopian tubes of New Zealand rabbit of chronic salpingitis models. The patency, microscopic structure, and positive expression of estrogen receptor and progesterone receptor of the fallopian tubes in the control group, the model group, the microcapsule group, and the scaffold-microcapsule group was observed and compared. RESULTS: At the 4th week post-operation, the mass loss rate of the PLGA 3D scaffolds, the degradation rate of the microspheres, and the Apelin-13 sustained-release microspheres-generated cumulative release rate in vitro over 30 days were 98.66%, 70.58%, and 98.68% respectively. The plasma concentration of Apelin-13 reached its peak within 5 days and remained stable for 25 days. Compared with the model and microsphere groups, the scaffold-microsphere group showed a milder inflammatory reaction within the tubal lumen, a higher rate of fallopian tube patency, and higher expression levels of estrogen and progesterone receptors (all P<0.05). The indicators of the scaffold-microsphere group were close to those of the control group. CONCLUSIONS: The PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres can comprehensively repair the anatomical structure and physiological function of the fallopian tubes and hold promise for truly effective tubal recanalization.

The broadband emission of Cr3+-doped CaY2Mg2Ge3O12 and its applications for NIR detectors.

A phosphor-converted light-emitting diode (pc-LED) is a prime light source in smart broadband near-infrared (NIR) spectroscopy. The performance of NIR pc-LEDs crucially depends on the employed NIR luminescent materials. In this study, we synthesized a novel high-efficiency broadband NIR phosphor, CaY2Mg2Ge3O12:Cr3+ (CYMG:Cr3+). Under 450 nm excitation, CYMG:Cr3+ exhibited remarkable broadband NIR emission from 650 to 900 nm with a full width at half maximum (FWHM) of 115 nm. Within the CYMG lattice, the Cr3+ ion occupies Ca/Y sites in the dodecahedron Ca/YO8 and Mg sites in the octahedron MgO6, giving rise to two distinct Cr3+ luminescence centers. Remarkably, the emission at 100 °C remained at 92% of its room temperature intensity and 81% at 150 °C, showcasing its exceptional thermal stability. The internal quantum efficiency (IQE) reached an impressive 81.1%, with an activation energy ΔE of 0.324 eV. Furthermore, we integrated the CYMG:Cr3+ phosphor with a commercial 450 nm blue chip to fabricate a micro NIR pc-LED, which exhibited stable NIR emission across different driving currents, with a NIR output power of 49.65 mW@400 mA and a photoelectric conversion efficiency of 10.52% at 20 mA. All findings highlight CYMG:Cr3+ as a stable and efficient broadband luminescent material for high-performance NIR LEDs.

PET/NIR Fluorescence Bimodal Imaging for Targeted Tumor Detection.

Cancer is one of the greatest threats to human health due to late diagnosis and incomplete resection. The bimodal probe combines positron emission tomography (PET) imaging for noninvasive whole-body scanning with intraoperative near-infrared fluorescence (NIRF) surgical guidance for preoperative tumor detection, tumor resection during surgery, and postoperative monitoring. We developed a new PET/NIRF bimodal imaging agent, [68Ga]Ga-DOTA-NPC, covalently coupled to DCDSTCY and DOTA via ethylenediamine and radiolabeled with gallium-68, and investigated it in vitro and in vivo. The probe was found to be preferential for colon cancer cells due to the organic anion-transporting polypeptide1B3 (OATP1B3). PET/NIRF imaging allowed us to confirm [68Ga]Ga-DOTA-NPC as a promising probe for tumor detection, as it provides good biosafety and high-contrast tumor accumulation. Orthotopic and subcutaneous colon tumors were successfully resected under real-time NIRF guidance. [68Ga]Ga-DOTA-NPC provides highly sensitive and unlimited tissue-penetrating PET/NIRF imaging, helping to visualize and differentiate tumors from adjacent tissue.

Research on image recognition of three Fritillaria cirrhosa species based on deep learning.

Based on the deep learning method, a network model that can quickly and accurately identify the species of Fritillaria cirrhosa species was constructed. The learning method based on deep residual convolutional neural network was used to input the unprocessed original image directly as input, and the features of the image were extracted through convolution and pooling operations. On this basis, the ResNet34 model was improved, and the additional fully connected layer was added in front of the Softmax classifier to improve the learning ability of the network model. Total of 3915 images of three kinds of Fritillaria cirrhosa were used as data sources for the experiments, among which 160 images of each type were randomly selected to form the validation set. The final training set recognition accuracy rate was 95.8%, the validation set accuracy rate reached 92.3%, and the test set accuracy rate was 88.7%. The image recognition method of Fritillaria cirrhosa based on deep learning proposed in this paper is effective and feasible, which can quickly and accurately identify the species of Fritillaria cirrhosa species, and provides a new idea for the intelligent recognition of Chinese medicinal materials.

Enhancing Coccinella Beetle Biological Pest Control via a Floral Approach in Cucumber Greenhouse.

Flower-rich habitats are crucial for promoting biodiversity and ecosystem services within agricultural ecosystems, such as pollination and pest control. The present study investigates the efficacy of employing floral structures as a criterion for the selection of plant species in order to enhance the attraction of natural enemies within cucumber greenhouses, consequently augmenting floral resources. The results of our study provide evidence that flower strips have a beneficial effect on the fitness of critical natural predators, while not facilitating the proliferation of detrimental insect species. These findings exhibit potential for enhancing pest-management services in the agricultural sector. The findings of our study demonstrate that pest levels within greenhouse environments closely resemble those observed in real-world commercial cropping systems. As a result, the introduction of Coccinella septempunctata and Menochilus sexmaculatus biocontrol agents is confirmed to be a reliable and efficient method for pest management. The phenomenon of predator-prey density dependency is recognized as a crucial element in the implementation of biological control strategies. Furthermore, we investigate the impact of floral resources on the reproductive capacity of indigenous predators. The impact of Coriandrum sativum on fertility is substantial, indicating that the presence of a varied plant assortment with overlapping flowering periods can prolong the availability of floral resources. This study highlights the significance of flower-rich habitats and deliberate plant selection in augmenting biodiversity, ecosystem services, and pest management within agricultural settings. The implementation of conservation biological control technologies presents supplementary ecological advantages, thus offering practical implications for the promotion of sustainable agricultural practices.

Context-aware single-cell multiome approach identified cell-type specific lung cancer susceptibility genes.

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, the genetic mechanisms and target genes underlying these loci are largely unknown, as most risk-associated-variants might regulate gene expression in a context-specific manner. Here, we generated a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Accessible chromatin peak detection identified cell-type-specific candidate cis-regulatory elements (cCREs) from each lung cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs prioritized the variants for 68% of the GWAS loci, a subset of which was also supported by transcription factor abundance and footprinting. cCRE colocalization and single-cell based trait relevance score nominated epithelial and immune cells as the main cell groups contributing to lung cancer susceptibility. Notably, cCREs of rare proliferating epithelial cell types, such as AT2-proliferating (0.13%) and basal cells (1.8%), overlapped with CCVs, including those in TERT. A multi-level cCRE-gene linking system identified candidate susceptibility genes from 57% of lung cancer loci, including those not detected in tissue- or cell-line-based approaches. cCRE-gene linkage uncovered that adjacent genes expressed in different cell types are correlated with distinct subsets of coinherited CCVs, including JAML and MPZL3 at the 11q23.3 locus. Our data revealed the cell types and contexts where the lung cancer susceptibility genes are functional.

Hexameric polyoxotantalate with proton conduction properties.

The first Fe-implanted polyoxotantalate (POTa), K12Na14H7.4[Fe10.7Ta1.3O8(OH)8(H2O)2(Ta6O19)6]·114.5H2O (1), has been obtained by self-assembly in alkaline solution. The polyanion consists of six Lindqvist-type {Ta6} units linked together by {Fe10.7Ta1.3}. The compound not only possesses the highest nuclearity transition metal-oxygen cluster, but also has the highest degree of polymerization in the POTa field to date. And 1 possesses remarkable proton conduction.

Morphology of the male reproductive system and sperm ultrastructure of the green lacewing, Chrysopa pallens (Rambur, 1838) (Neuroptera: Chrysopidae).

BACKGROUND: Chrysopa pallens is one of the most beneficial and effective natural predators, and is famous for its extensive distribution, wide prey spectrum, and excellent reproductive performance. This study examined the anatomy and fine structure of the C. pallens reproductive system and spermatogenesis. RESULTS: The male reproductive system of C. pallens comprises a pair of testes, a vas deferens, seminal vesicles, accessory glands, and short ejaculatory ducts. The testes were already mature on the day of emergence, but the accessory glands did not mature until 5 days post-emergence. In early spermatids, the flagellum had an axoneme on one side of the two mitochondrial derivatives. The nucleus was surrounded by parallel crystalline and paracrystalline materials. The spermatid envelope extends towards the paracrystalline material in a tail-shaped wing. In mature spermatids, the axoneme is located between the two accessory bodies and mitochondrial derivative sets. The parallel-crystalline and paracrystalline materials disappeared. In the testes, the wall of seminal cysts consists of a layer of epithelium, a muscular-connective sheath, and several vesicles of different sizes. The mature seminal cysts contained 128 spermatozoa. The accessory gland is composed of six parts: ventral papilla-like protuberance, anterior glandular lobe, lateral glandular lobe, seminal cyst, posterior kidney-shaped lobe, and posterior papilla-like protuberance. Muscle fibers and secretory granules are extensive. CONCLUSIONS: This study provides information on the reproductive system of C. pallens and offers a resource for taxonomy and reproductive biology.

Identification and validation of immune-associated NETosis subtypes and biomarkers in anti-neutrophil cytoplasmic antibody associated glomerulonephritis.

Background: NETosis is a new form of cell death, marked by DNA chromatin release from dead neutrophils. While it aids in microbe defense, it may worsen inflammation in autoimmune diseases, causing tissue harm. The impact of NETosis on Anti-neutrophil Cytoplasmic Antibody-associated Glomerulonephritis (ANCA-GN) remains unexplored and requires investigation. Methods: First, a weighted gene co-expression network analysis (WGCNA) was conducted to uncover differential expression of neutrophil extranuclear trap-associated genes (DE-NETs) in ANCA-GN. The NETosisScore model was established through the single sample gene set enrichment analysis (ssGSEA), which categorized all patients into high-risk and low-risk groups. The accuracy of model was assessed by ROC curve. The biological function of various subgroups was explored through Gene Set Variation Analysis (GSVA), while the abundance of immune cell infiltration was measured with CIBERSORT. Furthermore, the key NETosis-related genes (NRGs) were identified using three machine learning algorithms, and their relationship with renal function was analyzed through the NephroseqV5 database. Through the application of qPCR and immunohistochemical staining techniques, the mRNA and protein expression levels of NRGs were determined in patients with ANCA-GN and control. Results: A NETosisScore model was developed from 18 DE-NETs using the ssGSEA algorithm. The model's ability to predict ANCA-GN patients with a ROC AUC of 0.921. The high-risk group in ANCA-GN showed enrichment of immune-related pathways and greater infiltration of immune cells, as revealed by KEGG enrichment analysis and CIBERSORT. Using three machine learning algorithms, we identified six NRGs. Significant positive correlations were found between NRGs and CCR, macrophages, T-cell co-inhibition, and TIL. Further KEGG analysis revealed that the functions of NRGs may be closely related to the toll-like receptor signaling pathway. The levels of NRGs increased as kidney function declined and were positively correlated with Scr (serum creatinine) and negatively correlated with GFR (glomerular filtration rate), qPCR analysis showed increased expression of most NRGs in ANCA-GN patients. Furthermore, immunohistochemical staining confirmed higher expression of all NRGs in ANCA-GN patients. Conclusion: NETosisScore model accurately predicts high-risk patients in ANCA-GN with enriched immune pathways, 6 NRGs identified as potential biomarkers.

Non-contact thermometer behavior of (Y0.5In0.5)2O3:Yb3+,Er3+ solid solution.

Oxides are physically and chemically stable. Non-contact thermometer-Yb3+-Er3+ ions co-doped solid solution (Y0.5In0.5)2O3, is prepared by the regular solid method. The structural results obtained by XRD indicate that a pure phase solid solution (Y0.5In0.5)2O3 has been obtained. The solid solution (Y0.5In0.5)2O3 has a similar crystal structure, especially Y2O3 and In2O3 with the same space group (Ia3̄). Green emission from 500 to 600 nm is due to Er3+ 4f-4f transitions: 4S3/2 → 4I15/2 at 567 nm and 2H11/2 → 4I15/2 at 528 nm. Red emissions from 630 to 720 nm are attributed to Er3+: 4F9/2 → 4I15/2. UC luminescence changes greatly with laser diode power and Er3+ and Yb3+ content. Furthermore, the two-photon process is confirmed to be dominant between Yb3+ and Er3+ in oxide solid solution (Y0.5In0.5)2O3. Optical temperature sensitivity is also investigated systematically in order to explore the application of the oxide solid solution (Y0.5In0.5)2O3. The temperature-dependent green fluorescence at 528 and 567 nm was investigated with the range of 313-573 K. 0.316% K-1 is the maximum absolute sensitivity at 503 K, which is higher than most Yb3+/Er3+ co-doped systems. In addition, the solid solution (Y0.5In0.5)2O3:Yb3+,Er3+ has better thermal stability and stronger UC emission than a simple substance with excellent temperature sensing performance. It indicates that Yb3+-Er3+ ions co-doped (Y0.5In0.5)2O3 solid solution is a good candidate for optical temperature sensing.

Regulating highly photoelectrochemical activity of Zr-based mixed-linker metal-organic frameworks toward sensitive electrogenerated chemiluminescence sensing of α-glucosidase.

The conductivity and emission efficiency of metal-organic frameworks (MOFs) remain challenging factors that limit their electrogenerated chemiluminescence (ECL) sensing applications. Herein, we report a facile approach to address these challenges by integrating an electroactive linker (H2-TCPP) with an ECL active electrogenerated chemiluminescence linker (H4-TBAPy) to construct a highly photoelectrochemical active mixed-linker MOFs (ML-MOFs). ECL results revealed a remarkable 15.4-fold enhancement for the top-performing ML-MOFs (M6-MOFs), surpassing the single linker MOFs. In addition, M6-MOFs also exhibit a remarkable 73-fold enhancement in ECL efficiency compared to commercial Ru (bpy)32+. This improvement should be attributed to the synergistic effects resulting from the combination of two linkers. Furthermore, M6-MOFs are found to be served as a model ECLphore for sensitive and selective detection of α-glucosidase for the first time with good potential practicability in human serum samples. This work represents a promising direction to guide for designing good conductivity and high ECL efficiency MOFs in terms of linker functionalization and thus bandgap modulation for advancing their ECL sensing applications.

Myeloid-Specific SIRT6 Deletion Protects Against Particulate Matter (PM2.5)-Induced Airway Inflammation.

Purpose: Particulate matter (PM2.5) is a common risk factor for airway inflammation. Alveolar macrophages play a critical role in airway inflammation. Sirtuin 6 (SIRT6) is a class Ill histone deacetylase that exerts an anti-inflammatory effect in airway diseases. However, the role of SIRT6 on PM2.5-induced airway inflammation in macrophages remains unclear. We aimed to determine whether SIRT6 protects against PM2.5-induced airway inflammation in macrophages. Methods: The effect of SIRT6 on PM2.5-induced airway inflammation was assessed by using THP1 cells or bone marrow-derived macrophages (BMDMs) exposed to PM2.5 in vitro and myeloid cell-specific SIRT6 conditional knockout mice (Sirt6fl/fl-LysMCre) in vivo. Results: PM2.5 increased SIRT6 expression in THP1 cells, but SIRT6 gene silencing decreased PM2.5 induced inflammatory cytokines in THP1 cells. Moreover, the expression of SIRT6 and inflammatory cytokines was also decreased in BMDMs with myeloid-specific deletion of SIRT6 after stimulation of PM2.5. In vivo, Sirt6fl/fl-LysMCre mice substantially decreased airway inflammation in response to PM2.5 exposure. Conclusion: Our results revealed that SIRT6 promotes the PM2.5-induced airway inflammation in macrophages and indicated that inhibition of SIRT6 in macrophages may represent therapeutic strategy for airway disorders induced by airborne particulate pollution.

Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional MRI.

The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high-response rate. Simultaneous functional MRI (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) were correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy.

Controllable self-assembly of cellulose nanospheres through phosphoric acid triggered dissolution-regeneration and degradation.

Phosphoric acid has been utilized as a favorable alternative to strong acids for the production of cellulose nanospheres (CNS) in recent years, partly owing to the reduced reliance on mechanical assistance. In the present study, phosphoric acid hydrolysis was applied to synthesize CNS from natural cotton pulp. Compared to reported long-time hydrolysis over 12 h, reduced time of 4 h is achieved for CNS production. Particle size from 530 nm to 1.3 µm was further controlled by changing the hydrolysis time in 4-11 h. Powdered sample was obtained after freeze-drying. CNS prepared in this work exhibits a cellulose II structure. Crystallinity index of the samples locates in 70-75 % which is higher than the reported 43-60 % for the acid-hydrolyzed medical cotton. Moreover, compared to the sulphuric-acid hydrolyzed CNS with higher crystallinity, thermal stability of the CNS generated from phosphoric-acid hydrolysis is significantly greater. A cooperative dissolution-regeneration and degradation is proposed to induce CNS self-assembly. Initial cellulose microfibrils are completely dissolved as exposed to phosphoric acid. Partial chains aggregate as a result while the remaining chains assemble onto the aggregates in a layer-by-layer manner. Acid degradation to cellulose with time affects length of the molecular chains. CNS size is controlled accordingly.