A spatiotemporal molecular atlas of mouse spinal cord injury identifies a distinct astrocyte subpopulation and therapeutic potential of IGFBP2.

Spinal cord injury (SCI) triggers a cascade of intricate molecular and cellular changes that determine the outcome. In this study, we resolve the spatiotemporal organization of the injured mouse spinal cord and quantitatively assess in situ cell-cell communication following SCI. By analyzing existing single-cell RNA sequencing datasets alongside our spatial data, we delineate a subpopulation of Igfbp2-expressing astrocytes that migrate from the white matter (WM) to gray matter (GM) and become reactive upon SCI, termed Astro-GMii. Further, Igfbp2 upregulation promotes astrocyte migration, proliferation, and reactivity, and the secreted IGFBP2 protein fosters neurite outgrowth. Finally, we show that IGFBP2 significantly reduces neuronal loss and remarkably improves the functional recovery in a mouse model of SCI in vivo. Together, this study not only provides a comprehensive molecular atlas of SCI but also exemplifies how this rich resource can be applied to endow cells and genes with functional insight and therapeutic potential.

Dissipation-Induced Extended-Localized Transition.

A mobility edge (ME), representing the critical energy that distinguishes between extended and localized states, is a key concept in understanding the transition between extended (metallic) and localized (insulating) states in disordered and quasiperiodic systems. Here we explore the impact of dissipation on a quasiperiodic system featuring MEs by calculating steady-state density matrix and analyzing quench dynamics with sudden introduction of dissipation. We demonstrate that dissipation can lead the system into specific states predominantly characterized by either extended or localized states, irrespective of the initial state. Our results establish the use of dissipation as a new avenue for inducing transitions between extended and localized states and for manipulating dynamic behaviors of particles.

Effect of ultrasonic modification on the binding ability of pectin to anthocyanin.

BACKGROUND: Pectin was considered as a potential candidate to improve the thermal stability of anthocyanins, and the binding ability of pectin to anthocyanins was influenced by its structure. In this study, sunflower pectins, modified by ultrasound (40 kHz) for different periods of time, were prepared and used to bind with anthocyanins, extracted from purple sweet potato. RESULTS: Characterization and thermal stability of pectin-anthocyanin complexes were investigated. The ultrasonic modification of pectin resulted in many changes in pectin chemical structure, including degradation of neutral sugar side chains, breakage of methoxyl groups, and increased molecular flexibility. Extension of ultrasonic modification time led to greater changes in pectin chemical structure. Analysis of the binding ability, as determined by Fourier transform infrared spectroscopy and molecular dynamics simulations, revealed that the interaction between pectin and anthocyanins was driven by hydrogen bonding, electrostatic interaction, and hydrophobic interaction. Pectins with different ultrasonic modification times bound with anthocyanins to different extents, mainly resulting from an increase in the number of hydrogen bonds. According to high-performance liquid chromatographic analysis, during heating at 90 °C the stronger the binding ability of pectin and anthocyanin complex, the better was its thermal stability. CONCLUSION: Ultrasonic modification of pectin could effectively enhance its binding ability to anthocyanin. © 2023 Society of Chemical Industry.

Effects of sunflower pectin on thermal stability of purple sweet potato anthocyanins at different pH.

The present study aimed to examine the impact of sunflower pectin (SFP) on the thermal stability and antioxidant activity of purple sweet potato anthocyanins (PSPA) at varying pH levels. It was observed that the pH value significantly influenced the ability of pectin to protect anthocyanins from thermal degradation, which was found to be associated with the rate of binding between PSPA and SFP. The binding rate of PSPA-SFP was observed to be highest at pH 4.0, primarily due to the influence of electrostatic interaction and hydrogen bonding. Monoacylated anthocyanins exhibited a binding rate approximately 2-4 % higher than that of diacylated anthocyanins. The PSPA-SFP demonstrated its highest thermal stability at pH 4.0, with a corresponding half-life of 14.80 h at 100 °C. Molecular dynamics simulations indicated that pectin had a greater affinity for the flavylium cation and hemiketal form of anthocyanins. The antioxidant activity of anthocyanins in PSPA and PSPA-SFP increased with increasing pH, suggesting that anthocyanins at high pH had higher antioxidant activity than anthocyanins at low pH.

Heterochromatic silencing of immune-related genes in glia is required for BBB integrity and normal lifespan in drosophila.

Glia and neurons face different challenges in aging and may engage different mechanisms to maintain their morphology and functionality. Here, we report that adult-onset downregulation of a Drosophila gene CG32529/GLAD led to shortened lifespan and age-dependent brain degeneration. This regulation exhibited cell type and subtype-specificity, involving mainly surface glia (comprising the BBB) and cortex glia (wrapping neuronal soma) in flies. In accordance, pan-glial knockdown of GLAD disrupted BBB integrity and the glial meshwork. GLAD expression in fly heads decreased with age, and the RNA-seq analysis revealed that the most affected transcriptional changes by RNAi-GLAD were associated with upregulation of immune-related genes. Furthermore, we conducted a series of lifespan rescue experiments and the results indicated that the profound upregulation of immune and related pathways was not the consequence but cause of the degenerative phenotypes of the RNAi-GLAD flies. Finally, we showed that GLAD encoded a heterochromatin-associating protein that bound to the promoters of an array of immune-related genes and kept them silenced during the cell cycle. Together, our findings demonstrate a previously unappreciated role of heterochromatic gene silencing in repressing immunity in fly glia, which is required for maintaining BBB and brain integrity as well as normal lifespan.

Effects of coal gangue on soil property and plant growth in mining area.

With indoor and outdoor treatments, coal gangue with different ratios (10%, 20%, 30%, 40% and 50%) and different particle sizes (0-2, 2-5, 5-8 and 8-10 mm) were mixed into soil, and formed reconstructed soil with different soil bulk densities (1.3, 1.35, 1.4, 1.45 and 1.5 g·cm-3). The effects of soil reconstruction modes on soil water condition, structure stability of aggregate and the growth of Lolium perenne, Medicago sativa, and Trifolium repens were investigated. Soil saturated water (SW), capillary water (CW), and field water capacity (FC) were decreased with increasing coal gangue ratio, particle size, and bulk density of reconstructed soil. >0.25 mm particle size aggregate (R0.25), mean weight diameter (MWD), and geometric mean diameter (GMD) increased first and then decreased with the increases of coal gangue particle size, reaching the peak at 2-5 mm coal gangue particle size. R0.25, MWD and GMD were significantly and negatively correlated with coal gangue ratio. Based on boosted regression tree (BRT) model, the coal gangue ratio contributed 59.3%, 67.0% and 40.3% to the variation of SW, CW and FC, respectively, which was a main influencing factor of soil water content. The coal gangue particle size contributed 44.7%, 32.3% and 62.1% to the variation of R0.25, MWD, and GMD, respecti-vely, which was the greatest influencing factor. Coal gangue ratio had a great effect on the growth of L. perenne, M. sativa, and T. repens, which contributed to 49.9%, 17.4% and 10.3% of their variations, respectively. Soil reconstruction mode of 30% coal gangue ratio and 5-8 mm coal gangue particle size was the best condition for plant growth, indicating that coal gangue could change soil water content and structure stability of aggregate. The soil reconstruction mode of 30% coal gangue ratio and 5-8 mm coal gangue particle size was recommended.

Formulation strategies to provide oxygen-release to contrast local hypoxia for transplanted islets.

Islet transplantation refers to the transfusion of healthy islet cells into the diabetic recipients and reconstruction of their endogenous insulin secretion to achieve insulin independence. It is a minimally invasive surgery that holds renewed prospect as a therapeutic method for type 1 diabetes mellitus. However, poor oxygenation in the early post-transplantation period is considered as one of the major causes of islet loss and dysfunction. Due to the metabolism chacteristics, islets required a high supply of oxygen for cell survival while a hypoxia environment would lead to severe islet loss and graft failure. Emerging strategies have been proposed, including providing external oxygen and speeding up revascularization. From the perspective of formulation science, it is feasible and practical to protect transplanted islets by oxygen-release before revascularization as opposed to local hypoxia. In this study, we review the potential formulation strategies that could provide oxygen-release by either delivering external oxygen or triggering localized oxygen generation for transplanted islets.

Effects of different re-fermentation methods on the quality characteristics of kombucha beverages.

The effects of different re-fermentation methods on the quality characteristics of kombucha beverages were investigated. The quality characteristics of kombucha beverages included the basic physicochemical indicators (pH, total acidity, reducing sugar, total sugar, organic acids, total phenolic compound, total flavonoid compound), antioxidant activity, volatile flavor substance and sensory evaluation of the beverages. The results showed the re-fermentation methods including the mixed fermentation and the step-by-step fermentation significantly decreased total acidity and various organic acids (P < 0.05) than traditional kombucha with no re-fermentation. In addition, the contents of total phenol compounds and total flavonoid compounds for the step-by-step fermentation were 184.70 and 338.33 mg/L respectively, and were higher compared with mixed fermentation and traditional kombucha with no re-fermentation. The antioxidant activity in the step-by-step fermentation was much stronger than that of mixed fermentation and traditional kombucha with no re-fermentation. Moreover, there were 53 kinds of volatile flavor compounds produced in the step-by-step fermentation, 14 of them were unique with good sensory quality. In conclusion, the re-fermentation methods for traditional kombucha (the step-by-step fermentation and mixed fermentation) had more active ingredients and better sensory quality, and the step-by-step fermentation was better than mixed fermentation.

Evaluation of the hepatoprotective effect of naringenin loaded nanoparticles against acetaminophen overdose toxicity.

Acute liver injury is a common clinical disease, which easily leads to liver failure and endangers life, seriously threatening human health. Naringenin is a natural flavonoid that holds therapeutic potential against various liver injuries; however it has poor water solubility and bioavailability. In this study, we aimed to develop naringenin-loaded bovine serum albumin nanoparticles (NGNPs) and to evaluate their hepatoprotective effect and underlying mechanisms against acetaminophen overdose toxicity. In vitro data indicated that NGNPs significantly increased the drug solubility and also more effectively protected the hepatocyte cells from oxidative damage during hydrogen peroxide exposure or lipopolysaccharide (LPS) stimulation. In vivo results confirmed that NGNPs showed an enhanced accumulation in the liver tissue. In the murine model of acetaminophen-induced hepatotoxicity, NGNPs could effectively alleviate the progression of acute liver injury by reducing drug overdose-induced levels of oxidative stress, inflammation and apoptosis in hepatocytes. In conclusion, NGNPs has strong hepatoprotective effects against acetaminophen induced acute liver injury.

Immune-Protective Formulations and Process Strategies for Improved Survival and Function of Transplanted Islets.

Type 1 diabetes (T1D) is an autoimmune disease caused by the immune system attacking and destroying insulin-producing ß cells in the pancreas. Islet transplantation is becoming one of the most promising therapies for T1D patients. However, its clinical use is limited by substantial cell loss after islet infusion, closely related to immune reactions, including instant blood-mediated inflammatory responses, oxidative stress, and direct autoimmune attack. Especially the grafted islets are not only exposed to allogeneic immune rejection after transplantation but are also subjected to an autoimmune process that caused the original disease. Due to the development and convergence of expertise in biomaterials, nanotechnology, and immunology, protective strategies are being investigated to address this issue, including exploring novel immune protective agents, encapsulating islets with biomaterials, and searching for alternative implantation sites, or co-transplantation with functional cells. These methods have significantly increased the survival rate and function of the transplanted islets. However, most studies are still limited to animal experiments and need further studies. In this review, we introduced the immunological challenges for islet graft and summarized the recent developments in immune-protective strategies to improve the outcomes of islet transplantation.

Alantolactone-loaded chitosan/hyaluronic acid nanoparticles suppress psoriasis by deactivating STAT3 pathway and restricting immune cell recruitment.

Psoriasis is a common chronic immune-mediated skin disease characterized by hyperproliferation and aberrant differentiation of keratinocytes and massive infiltration of inflammatory immune cells. Recent studies showed that Signal Transducer and Activator of Transcription 3 (STAT3), which plays an important role in cell survival, proliferation, differentiation, angiogenesis, and immune responses, is constitutively activated in epidermal keratinocytes of human psoriatic skin lesions. In addition, STAT3 promotes the differentiation and expansion of T cells and facilitates cytokine production, thereby exacerbating the condition of psoriasis. Alantolactone (ALT) is a sesquiterpene lactone compound that could selectively suppress STAT3 activation, but its effectiveness and application in psoriasis treatment have not been determined. In this study, we developed ALT loaded chitosan/hyaluronic acid nanoparticles (CHALT), and investigated its therapeutic potential for psoriasis therapy. CHALT effectively abrogated the hyperproliferation by inducing ROS-mediated apoptosis with loss of mitochondrial membrane potential, and also inhibited IL-6-induced STAT3 signaling activation and inflammatory reaction in HaCaT cell line. In an Imiquimod (IMQ)-induced psoriasis model, the topical treatment of psoriasis lesions with CHALT effectively attenuated the STAT3 hyperactivation within keratinocytes and ameliorated the symptoms of psoriasis. In addition, it was found that CHALT restricted the recruitment of immune cells. These results indicated that ALT-based nanoformulation CHALT holds great potential for psoriasis therapy.

Method for power reduction of demodulation driver circuit in indirect time-of-flight CMOS image sensor.

To improve the depth accuracy of an indirect time-of-flight CMOS image sensor, high modulation frequency is often adopted. It will result in high power consumption of an on-chip demodulation driver, and this problem will be much more serious when the resolution of the sensor is much higher. In this paper, a power reduction method that can lower the power consumption of the demodulation driver circuit during the integration time while obtaining accurate high-resolution depth maps is proposed and analyzed theoretically. The method decreases the number of driven pixels at a high-modulation frequency by a programmable resolution adjustment circuit to obtain an accurate low-resolution depth map. A low-depth accuracy high-resolution depth map is obtained at a low modulation frequency, and then a modified super-resolution algorithm is used to obtain an accurate high resolution solution depth map. To demonstrate the effectiveness of the proposed method, a model is established based on the actual indirect time-of-flight sensor architecture, then the depth error and power consumption are analyzed by the simulation results of the model. In the simulation, 25 MHz and 100 MHz are used as the low modulation frequency and high modulation frequency, respectively. With the best scenario in depth accuracy kept, average power consumption decreases 38.47% and peak power consumption decreases 49.83% while the depth error that is represented by RMSE merely increases 8.08%.

Transplantation of a Novel Recombinant Adeno-Associated Virus (pAAV-HE1B19K-TE1A) Demonstrates Higher Anti-Tumor Effects in Tumor Cells.

BACKGROUND Oncolytic viruses (OVs) can specifically infect and kill tumor cells. Adeno-associated virus (AAV) is a widely-studied OV. This study aimed to construct a tumor-targeted recombinant AAV using genetic engineering technology. MATERIAL AND METHODS The transgene plasmid pAAV-HE1B19K-TE1A was constructed with 4 genes (hTERT, E1A, HKII, and E1B19K) and co-transfected with pAAV-RC and pHelper to tumor cells (HepG2, A549, BGC-803) and normal cells (HUVEC). rAAV was verified with fluorescence microscopy. Quantitative PCR (qPCR) assay was used to test the titer of rAAV in each cell line. Apoptosis was analyzed using qPCR and Western blot assay. MTT was used to detect the effect of rAAV on cell viability. RESULTS The pAAV-HE1B19K-TE1A transgene plasmid was successfully structured. pAAV-HE1B19K-TE1A was highly expressed in all tumor cells. The titers of pAAV-HE1B19K-TE1A in HepG2, A549, and BGC-803 were 7.4×107, 1.4×108, and 1.1×108 gc/µl, respectively. pAAV-HE1B19K-TE1A significantly decreased cell viability of tumor cells compared to that in HUVEC (p<0.05). pAAV-HE1B19K-TE1A remarkably triggered cleaved caspase 3 (C-caspase 3) activity in tumor cells compared to that in untransfected tumor cells (p<0.05). pAAV-HE1B19K-TE1A significantly induced release of cytochrome C (Cyto C) in tumor cells compared to that in untransfected tumor cells (p<0.05). pAAV-HE1B19K-TE1A demonstrated no toxicity to vital tissues of animals. CONCLUSIONS Tumor-targeted rAAV was successfully produced using the Helper-free system with recombinant plasmid, demonstrating high efficacy in decreasing viability of tumor cells without adverse effects on normal cells.

Catalytic synthesis of chloroacetates with thermoregulated ionic liquids based on vanadium-substituted polyoxometalate.

A series of polyoxometalate-based ionic liquid (POM-IL) catalysts with functional sulfonic acid groups, [TEAPS]3+n PW12-n V n O40 (n = 1, 2, 3) were synthesized and characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectrophotometry (FT-IR), UV-Vis spectrophotometry (UV), potentiometric titration and thermogravimetry-differential scanning calorimetry (TG-DSC). The catalytic ability and reusability of the POM-IL catalysts were evaluated on esterification of chloroacetic acid and n-amyl alcohol. The optimum reaction conditions, 0.2 g of the catalyst amount, 10 mL of water carrier, 140 °C of reaction temperature, and 1.2/1 of the molar ratio of alcohol/acid, were obtained by an orthogonal test. [TEAPS]5PW10V2O40 was found to be the best active catalyst with an esterification rate of 98.75% and could be reused five times without significant decrease in activity. The ionic liquid acted as a temperature-responsive catalyst, forming a homogeneous mixture with the reactants at reaction temperature, and could be precipitated and separated from products when the reaction ends at ambient temperature. Therefore, an environmentally friendly and highly efficient approach for the synthesis of chloroacetates is provided.

Synthesis and conductive performance of polyoxometalate acid salt gel electrolytes.

Two vanadium-substituted polyoxometalate acid salt gel electrolytes, [PyPS]3H4SiW9V3O40 and [PyPS]5H2SiW9V3O40, have been synthesized using a 1-(3-sulfonic group) propylpyridine (PyPS) and a Keggin vanadium-substituted heteropoly acid H7SiW9V3O40 through an ionic self-assembly method, and adjusting the ratio of cation and anion. A substitution effect of the acid salt gel electrolytes has been investigated. Interestingly, when protons of the polyoxometalate acid salt gel electrolytes are substituted, both the conductivity and the phase transformation temperature increase. The fastest conductivity of these gel electrolytes was as high as 2.57 × 10-2 S cm-1 at 110 °C.

Toxicological and biochemical basis of synergism between the entomopathogenic fungus Lecanicillium muscarium and the insecticide matrine against Bemisia tabaci (Gennadius).

The sweetpotato whitefly Bemisia tabaci (Gennadius) was challenged with different combinations of matrine (insecticide) and Lecanicillium muscarium (entomopathogenic fungus). Our results revealed a synergistic relationship between matrine and L. muscarium on mortality and enzyme activities of B. tabaci. To illustrate the biochemical mechanisms involved in detoxification and immune responses of B. tabaci against both control agents, activities of different detoxifying and antioxidant enzymes were quantified. After combined application of matrine and L. muscarium, activities of carboxylestrease (CarE), glutathione-s-transferase (GSTs) and chitinase (CHI) decreased during the initial infection period. Acetylcholinestrase (AChE) activities increased during the entire experimental period, whereas those of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) decreased during the later infection period. The increased mortality and suppression of enzymatic response of B. tabaci following matrine and L. muscarium application suggests a strong synergistic effect between both agents. The strong synergistic effect is possibly related to the disturbance of acetylcholine balance and changes in AchE activities of the whitefly as both matrine and L. muscarium target insect acetylcholine (Ach) receptors which in turn effects AchE production. Therefore, our results have revealed the complex biochemical processes involved in the synergistic action of matrine and L. muscarium against B. tabaci.

Toxic effect of destruxin A on abnormal wing disc-like (SLAWD) in Spodoptera litura fabricius (Lepidoptera: Noctuidae).

BACKGROUND: Destruxin A (DA) is a microbial insecticide with potent bioactivity against Spodoptera litura larvae. A previous proteomic analysis of S. litura (SL-1) cells exposed to DA showed the abnormal expression of wing disc-like protein of S. litura (SLAWD). To further understand the effect of DA on SLAWD expression, a functional study was carried out. PRINCIPAL FINDINGS: The SLAWD gene (SLAWD) was cloned and an open reading frame of 537 bp encoding a polypeptide of 178 amino acids was detected. Real-time fluorescence quantitative PCR (qRT-PCR) suggested that SLAWD is expressed in all developmental stages of S. litura, but expression was highest during the pupal and adult stages. RNAi knockdown of SLAWD expression in 6th-stage larvae was achieved by the microinjection of a specific double-stranded RNA (dsRNA). The results showed a significant decrease in SLAWD mRNA expression levels between the prepupal and adult stages. Interestingly, SLAWD expression was similarly down-regulated by treating 6th-stage larvae with DA. Growth- and development-related statistics confirmed the observed abnormalities in S. litura development after either RNAi or DA treatment. CONCLUSIONS: SLAWD appears to have a biosynthetic function in the pupal and adult stages of S. litura. The toxic effect of DA on S. litura development is due the negative effect of DA on SLAWD gene expression.