The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.

AIMS/HYPOTHESIS: Glomerular lipid accumulation is a defining feature of diabetic kidney disease (DKD); however, the precise underlying mechanism requires further elucidation. Recent evidence suggests a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in intracellular lipid homeostasis. Although PCSK9 is present in kidneys, its role within kidney cells and relevance to renal diseases remain largely unexplored. Therefore, we investigated the role of intracellular PCSK9 in regulating lipid accumulation and homeostasis in the glomeruli and podocytes under diabetic conditions. Furthermore, we aimed to identify the pathophysiological mechanisms responsible for the podocyte injury that is associated with intracellular PCSK9-induced lipid accumulation in DKD. METHODS: In this study, glomeruli were isolated from human kidney biopsy tissues, and glomerular gene-expression analysis was performed. Also, db/db and db/m mice were used to perform glomerular gene-expression profiling. We generated DKD models using a high-fat diet and low-dose intraperitoneal streptozocin injection in C57BL/6 and Pcsk9 knockout (KO) mice. We analysed cholesterol and triacylglycerol levels within the kidney cortex. Lipid droplets were evaluated using BODIPY staining. We induced upregulation and downregulation of PCSK9 expression in conditionally immortalised mouse podocytes using lentivirus and siRNA transfection techniques, respectively, under diabetic conditions. RESULTS: A significant reduction in transcription level of PCSK9 was observed in glomeruli of individuals with DKD. PCSK9 expression was also reduced in podocytes of animals under diabetic conditions. We observed significantly higher lipid accumulation in kidney tissues of Pcsk9 KO DKD mice compared with wild-type (WT) DKD mice. Additionally, Pcsk9 KO mouse models of DKD exhibited a significant reduction in mitochondria number vs WT models, coupled with a significant increase in mitochondrial size. Moreover, albuminuria and podocyte foot process effacement were observed in WT and Pcsk9 KO DKD mice, with KO DKD mice displaying more pronounced manifestations. Immortalised mouse podocytes exposed to diabetic stimuli exhibited heightened intracellular lipid accumulation, mitochondrial injury and apoptosis, which were ameliorated by Pcsk9 overexpression and aggravated by Pcsk9 knockdown in mouse podocytes. CONCLUSIONS/INTERPRETATION: The downregulation of PCSK9 in podocytes is associated with lipid accumulation, which leads to mitochondrial dysfunction, cell apoptosis and renal injury. This study sheds new light on the potential involvement of PCSK9 in the pathophysiology of glomerular lipid accumulation and podocyte injury in DKD.

Manganese-based nanomaterials in diagnostics and chemodynamic therapy of cancers: new development.

In the realm of cancer treatment, traditional modalities like radiotherapy and chemotherapy have achieved certain advancements but continue to grapple with challenges including harm to healthy tissues, resistance to treatment, and adverse drug reactions. The swift progress in nanotechnology recently has opened avenues for investigating innovative approaches to cancer therapy. Especially, chemodynamic therapy (CDT) utilizing metal nanomaterials stands out as an effective cancer treatment choice owing to its minimal side effects and independence from external energy sources. Transition metals like manganese are capable of exerting anti-tumor effects through a Fenton-like mechanism, with their distinctive magnetic properties playing a crucial role as contrast agents in tumor diagnosis and treatment. Against this backdrop, this review emphasizes the recent five-year advancements in the application of manganese (Mn) metal ions within nanomaterials, particularly highlighting their unique capabilities in catalyzing CDT and enhancing MRI imaging. Initially, we delineate the biomedical properties of manganese, followed by an integrated discussion on the utilization of manganese-based nanomaterials in CDT alongside multimodal therapies, and delve into the application and future outlook of manganese-based nanomaterial-mediated MRI imaging techniques in cancer therapy. By this means, the objective is to furnish novel viewpoints and possibilities for the research and development in future cancer therapies.

Gemfibrozil Alleviates Cognitive Impairment by Inhibiting Ferroptosis of Astrocytes via Restoring the Iron Metabolism and Promoting Antioxidant Capacity in Type 2 Diabetes.

Diabetes-associated cognitive dysfunction (DACD) is considered a significant complication of diabetes and manifests as cognitive impairment. Astrocytes are vital to the brain energy metabolism and cerebral antioxidant status. Ferroptosis has been implicated in cognitive impairment, but it is unclear whether the ferroptosis of astrocytes is involved in the progression of DACD. PPARA/PPARα (peroxisome proliferator-activated receptor alpha) is a transcription factor that regulates glucose and lipid metabolism in the brain. In this study, we demonstrated that high glucose promoted ferroptosis of astrocytes by disrupting iron metabolism and suppressing the xCT/GPX4-regulated pathway in diabetic mice and astrocytes cultured in high glucose. Administration of gemfibrozil, a known PPARα agonist, inhibited ferroptosis and improved memory impairment in db/db mice. Gemfibrozil also prevented the accumulation of lipid peroxidation products and lethal reactive oxygen species induced by iron deposition in astrocytes and substantially reduced neuronal and synaptic loss. Our findings demonstrated that ferroptosis of astrocytes is a novel mechanism in the development of DACD. Additionally, our study revealed the therapeutic effect of gemfibrozil in preventing and treating DACD by inhibiting ferroptosis.

Bioinspired, Robust, and Absorbable Cellulose Nanofibrils/Chitosan Filament with Remarkable Cytocompatibility and Wound Healing Properties.

Surgical threads are of great importance to prevent wound infection and accelerate tissue healing in surgical treatment. Cellulose nanofibrils (CNF) and chitosan (CS) are attracting increasing attention to be employed as biomedicine materials due to their nontoxicity, cytocompatibility, and biodegradability. However, a robust and absorbable cellulose-based surgical thread has not been explored. Therefore, in this work, a bioinspired CNF/CS composite thread containing 5% cationic polyacrylamide (CPAM) by the mass of CS was prepared, and the obtained CNF/CS-5C thread exhibited excellent mechanical properties and low swelling ratio in water due to the high cross-link degree. Especially, the tensile strength (1877 ± 107 MPa) of this thread was much higher than that of most reported CNF-based threads. Meanwhile, compared with commercial silk and Vicryl surgical threads, the CNF/CS-5C thread exhibited better in vitro cytocompatibility toward endothelial and fibroblast cells and lower inflammatory response in vivo to subcutaneous tissues of rats. In addition, the obtained thread could be regarded as a promising absorbable suture, which exhibited excellent wound healing performances in vivo. Therefore, the prepared absorbable thread will open a new window to prepare novel and advanced cellulose-based threads for medical applications.

Renalase regulates renal tubular injury in diabetic nephropathy via the p38MAPK signaling pathway.

Diabetic nephropathy (DN) is an important complication of diabetes and the leading cause of end-stage renal disease globally. Renal tubular damage occurs to varying degrees in the early stages of DN prior to glomerular damage. Renalase (RNLS) is an amine oxidase, which is produced and secreted by the renal tubular epithelial cells. RNLS is reportedly closely related to renal tubular injury in acute and chronic kidney diseases. Herein, we aimed to evaluate the changes in tubular RNLS expression in DN and its correlation with DN-associated renal tubular injury. Conditional permanent renal tubular epithelial rat-cell line NRK-52E was transfected with pcDNA3-RNLS plasmid or administered recombinant rat RNLS protein and high glucose (HG) dose. A total of 22 adult Sprague-Dawley rats were randomly divided into the control (CON, n = 10) or diabetic nephrology (DN, n = 12) group. Random blood glucose levels of the rats were measured by sampling of the caudal vein weekly. After 8 weeks, the rat's body weight, 24-h urinary albumin concentration, and right kidney were evaluated. Our study suggested the decreased expression levels of RNLS in renal tissue and renal tubular epithelial cells in DN rats, accompanied by renal tubulointerstitial fibrosis, apoptosis of renal tubular epithelial cells, and activation of the p38MAPK signal pathway. Reversing the low RNLS expression can reduce the level of p38MAPK phosphorylation and delay renal tubular injury. Thus, the reduction of renal tubular RNLS expression in DN mediates tubulointerstitial fibrosis and cell apoptosis via the activation of the p38MAPK signal pathway. RNLS plays a key mediating role in DN-associated tubular injury via p38MAPK, which provides new therapeutic targets and a theoretical basis for early prevention and treatment of DN.

Fabrication of cationic cellulose nanofibrils/sodium alginate beads for Congo red removal.

Congo red is hard to remove from dye wastewater due to its structure stability and high chemical oxygen demand. In this study, cationic cellulose nanofibrils (CCNF) prepared from herb residues was physically crosslinked with sodium alginate (SA) in the presence of calcium ions, and the obtained CCNF/SA beads were used to adsorb Congo red. Results showed that CCNF/SA beads with porous internal structure were beneficial to adsorption. The maximum adsorption capacity of Congo red could reach to 518.4 mg/g, which was superior to most cellulose-based adsorption materials. Furthermore, the equilibrium adsorption isotherms and XPS analysis indicated the adsorption for Congo red was a physical process, and hydrogen bond and electrostatic adsorption were proposed as dominant adsorption mechanism. In addition, the Congo red removal efficiency of the beads was still higher than 70% after three cycles. Therefore, this high efficiency and green beads have great potential as adsorbents for anionic dyes removal.

Integrated transcriptome and proteome analysis reveals molecular responses of soybean anther under high-temperature stress.

It is well documented that high temperature (HT) severely affects the development of soybean male reproductive organs. However, the molecular mechanism of thermo-tolerance in soybean remains unclear. To explore the candidate genes and regulatory mechanism of soybean response to HT stress and flower development, here, the anthers of two previously identified HT-tolerant (JD21) and HT-sensitive (HD14) varieties were analyzed by RNA-seq. In total, 219 (172 upregulated and 47 downregulated), 660 (405 upregulated and 255 downregulated), and 4,854 (2,662 upregulated and 2,192 downregulated) differentially expressed genes (DEGs) were identified between JD21 anthers treated with HT stress vs. JD21 anthers in the natural field conditions (TJA vs. CJA), HD14 anthers treated with HT stress vs. HD14 anthers in the natural field conditions (THA vs. CHA), and JD21 vs. HD14 anthers treated with HT stress (TJA vs. THA), respectively. The results showed that there were more DEGs upregulated in JD21; this might be the reason why JD21 was more HT-resistant than the HT-sensitive variety HD14. GO annotation and KEGG enriched analysis showed that many DEGs are mainly involved in defense response, response to biological stimuli, auxin-activated signaling pathway, plant hormone signal transduction, MAPK signaling pathway-plant, starch and sucrose metabolism, etc. The conjoint analysis of RNA-seq and previous iTRAQ results found that there were 1, 24, and 54 common DEGs/DAPs showing the same expression pattern and 1, 2, and 13 common DEGs/DAPs showing the opposite pattern between TJA vs. CJA, THA vs. CHA, and TJA vs. THA at the protein and gene level, respectively, among which HSPs, transcription factor, GSTU, and other DEGs/DAPs participated in the response to HT stress and flower development. Notably, the qRT-PCR analysis and physiological index change results coincided with the sequencing results of RNA-seq and iTRAQ. In conclusion, the HT-tolerant cultivar performed better under stress than the HT-sensitive cultivar through modulation of HSP family proteins and transcription factors, and by keeping key metabolic pathways such as plant hormone signal transduction normal. This study provided important data and some key candidate genes to better study the effect and molecular basis of HT on anther in soybean at a transcription and translation level.

Reprogramming astrocytic NDRG2/NF-κB/C3 signaling restores the diabetes-associated cognitive dysfunction.

BACKGROUND: Dementia is a serious complication in patients with diabetes-associated cognitive dysfunction (DACD). In this study, we aim to explore the protective effect of exercise on DACD in diabetic mice, and the role of NDRG2 as a potential guarder for reversing the pathological structure of neuronal synapses. METHODS: Seven weeks of standardized exercise at moderate intensity was carried out using an animal treadmill in the vehicle + Run and STZ + Run groups. Based on quantitative transcriptome and tandem mass tag (TMT) proteome sequencing, weighted gene co-expression analysis (WGCNA) and gene set enrichment analysis (GSEA) were used to investigate the activation of complement cascades to injury neuronal synaptic plasticity. Golgi staining, Western blotting, immunofluorescence staining, and electrophysiology were used to verify the reliability of sequencing data. The role of NDRG2 was assessed by overexpressing or inhibiting the NDRG2 gene in vivo. Moreover, we estimated the cognitive function in diabetic or normal patients using DSST scores. FINDINGS: Exercise reversed the injury of neuronal synaptic plasticity and the downregulation of astrocytic NDRG2 in diabetic mice, which succeeded in attenuating DACD. The deficiency of NDRG2 aggravated the activation of complement C3 by accelerating the phosphorylation of NF-κB, ultimately leading to synaptic injury and cognitive dysfunction. Conversely, the overexpression of NDRG2 promoted astrocytic remodeling by inhibiting complement C3, thus attenuating synaptic injury and cognitive dysfunction. Meanwhile, C3aR blockade rescued dendritic spines loss and cognitive deficits in diabetic mice. Moreover, the average DSST score of diabetic patients was significantly lower than that of non-diabetic peers. Levels of complement C3 in human serum were elevated in diabetic patients compared to those in non-diabetic patients. INTERPRETATION: Our findings illustrate the effectiveness and integrative mechanism of NDRG2-induced improvement of cognition from a multi-omics perspective. Additionally, they confirm that the expression of NDRG2 is closely related to cognitive function in diabetic mice and the activation of complement cascades accelerated impairment of neuronal synaptic plasticity. NDRG2 acts as a regulator of astrocytic-neuronal interaction via NF-κB/C3/C3aR signaling to restore synaptic function in diabetic mice. FUNDING: This study was supported by the National Natural Science Foundation of China (No. 81974540, 81801899, 81971290), the Key Research and Development Program of Shaanxi (Program No. 2022ZDLSF02-09) and Fundamental Research Funds for the Central Universities (Grant No. xzy022019020).

Tailoring Functionality of Nanocellulose: Current Status and Critical Challenges.

Nanocellulose (NC) isolated from natural cellulose resources, which mainly includes cellulose nanofibril (CNF) and cellulose nanocrystal (CNC), has garnered increased attention in recent decades due to its outstanding physical and chemical properties. Various chemical modifications have been developed with the aim of surface-modifying NC for highly sophisticated applications. This review comprehensively summarizes the chemical modifications applied to NC so far in order to introduce new functionalities to the material, such as silanization, esterification, oxidation, etherification, grafting, coating, and others. The new functionalities obtained through such surface-modification methods include hydrophobicity, conductivity, antibacterial properties, and absorbability. In addition, the incorporation of NC in some functional materials, such as films, wearable sensors, cellulose nanospheres, aerogel, hydrogels, and nanocomposites, is discussed in relation to the tailoring of the functionality of NC. It should be pointed out that some issues need to be addressed during the preparation of NC and NC-based materials, such as the low reactivity of these raw materials, the difficulties involved in their scale-up, and their high energy and water consumption. Over the past decades, some methods have been developed, such as the use of pretreatment methods, the adaptation of low-cost starting raw materials, and the use of environmentally friendly chemicals, which support the practical application of NC and NC-based materials. Overall, it is believed that as a green, sustainable, and renewable nanomaterial, NC is will be suitable for large-scale applications in the future.

All-Tunicate Cellulose Film with Good Light Management Properties for High-Efficiency Organic Solar Cells.

Tunicate nanocellulose with its unique properties, such as excellent mechanical strength, high crystallinity, and good biodegradability, has potential to be used for the preparation of light management film with tunable transmittance and haze. Herein, we prepared a whole tunicate cellulose film with tunable haze levels, by mixing tunicate microfibrillated cellulose (MFC) and tunicate cellulose nanofibrils (CNF). Then, the obtained whole tunicate cellulose film with updated light management was used to modify the organic solar cell (OSC) substrate, aiming to improve the light utilization efficiency of OSC. Results showed that the dosage of MFC based on the weight of CNF was an important factor to adjust the haze and light transmittance of the prepared cellulose film. When the dosage of MFC was 3 wt.%, the haze of the obtained film increased 74.2% compared to the pure CNF film (39.2%). Moreover, the optimized tunicate cellulose film exhibited excellent mechanical properties (e.g., tensile strength of 168 MPa, toughness of 5.7 MJ/m3) and high thermal stability, which will be beneficial to the workability and durability of OSC. More interestingly, we applied the obtained whole tunicate cellulose film with a high haze (68.3%) and high light transmittance (85.0%) as an additional layer to be adhered to the glass substrate of OSC, and a notable improvement (6.5%) of the power conversion efficiency was achieved. With the use of biodegradable tunicate cellulose, this work provides a simple strategy to enhance light management of the transparent substrate of OSC for improving power conversion efficiency.

Robust, Scalable, and Cost-Effective Surface Carbonized Pulp Foam for Highly Efficient Solar Steam Generation.

Recently, a solar-driven evaporator has been applied in seawater desalination, but the low stability, high cost, and complex fabrication limit its further application. Herein, we report a novel, low-cost, scalable, and easily fabricated pulp-natural rubber (PNR) foam with a unique porous structure, which was directly used as a solar-driven evaporator after facile surface carbonization. This surface carbonized PNR (CPNR) foam without interface adhesion or modification was composed of a top photothermal layer with light absorption ability and a bottom hydrophilic foam layer with a porous and interconnected network structure. Due to the strong light absorption ability (93.2%) of the carbonized top layer, together with the low thermal conductivity (0.1 W m K-1) and good water adsorption performance (9.9 g g-1) of the bottom layer, the evaporation rate and evaporation efficiency of the pulp foam evaporator under 1 sun of illumination attained 1.62 kg m-2 h-1 and 98.09%, respectively, which were much higher than those of most cellulose-based solar-driven evaporators. Furthermore, the CPNR foam evaporator with high cost-effectiveness presented high light-thermal conversion, heat localization, and good salt rejection properties due to the unique porous structure. Additionally, the CPNR foam evaporator exhibited potential applications in the treatments of simulated sewage, metal ion concentration, and seawater desalination. Its cost-effectiveness was clearly higher than that of most reported evaporators as well. Therefore, this novel, low-cost, and stable pulp foam evaporator demonstrated here can be a very promising solution for water desalination and purification.

Core-Shell Filament with Excellent Wound Healing Property Made of Cellulose Nanofibrils and Guar Gum via Interfacial Polyelectrolyte Complexation Spinning.

Natural polymer-based sutures have attractive cytocompatibility and degradability in surgical operations. Herein, anionic cellulose nanofibrils (ACNF) and cationic guar gum (CGG) are employed to produce nontoxic CGG/ACNF composite filament with a unique core-shell structure via interfacial polyelectrolyte complexation (IPC) spinning. The comprehensive characterization and application performance of the resultant CGG/ACNF filament as a surgical suture are thoroughly investigated in comparison with silk and PGLA (90% glycolide and 10% l-lactide) sutures in vitro and in vivo, respectively. Results show that the CGG/ACNF filament with the typical core-shell structure and nervation pattern surface exhibits a high orientation index (0.74) and good mechanical properties. The tensile strength and knotting strength of CGG/ACNF suture prepared by twisting CGG/ACNF filaments increase by 69.5%, and CGG/ACNF suture has a similar friction coefficient to silk and PGLA sutures. Moreover, CGG/ACNF suture with antibiosis and cytocompatibility exhibits better growth promotion of cells than silk suture, similar to PGLA suture in vitro. In addition, the stitching experiment of mice with the CGG/ACNF suture further confirms better healing properties and less inflammation in vivo than silk and PGLA sutures do. Hence, the CGG/ACNF suture with a simple preparation method and excellent application properties is promising in surgical operations.

Performance of urinary liver-type fatty acid-binding protein in diabetic nephropathy: A meta-analysis.

Aims: Diabetic nephropathy (DN) is one of the main causes of chronic kidney disease (CKD), which increases the risk of cardiovascular diseases and progresses to end-stage renal failure. Thus, early diagnostic markers for diabetic patients are urgently needed to improve the prognosis of DN and predict DN progression. Materials and methods: PubMed, MEDLINE, EMBASE, and Scopus were searched for publications until February 24, 2021. Review Manager 5.4 software was used for meta-analysis. We performed the heterogeneity test using the I2 statistic: P < 0.1 and I2> 50% meant statistical significance. Results: We included 13 studies. The urinary liver-type fatty acid-binding protein (uL-FABP) concentrations in the normal albuminuria group were significantly higher than those in the normal control group without diabetes mellitus (DM) [P = 0.009, SMD 1.72, 95% CI (0.44, 2.99)]. Urinary F-LABP levels were elevated in the macroalbuminuria group compared with those in the microalbuminuria group with DM [P = 0.002, SMD 2.82, 95% CI (1.03, 4.61)]. Urinary L-FABP levels were also significantly increased in the progression and CKD groups compared with non-progression and CKD subjects with DM [P = 0.02, P < 0.00001, respectively]. Furthermore, uL-FABP concentrations were positively correlated with the albumin-to-creatinine ratio and systolic blood pressure in patients with DM [Summary Fisher's Z = 0.58 P < 0.00001; Summary Fisher's Z = 0.24 P < 0.0001, respectively] and negatively correlated with estimated glomerular filtration rate in patients with DM [Summary Fisher's Z = -0.36, P < 0.0001]. Conclusion: Urinary L-FABP may be a potential marker for the detection of all stages of DN and for the prediction of the progression and severity of DN in patients with type 1 and 2 DM.

Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in maintenance dialysis: a meta-analysis.

BACKGROUND: Anaemia is a common complication of end-stage renal disease (ESRD) that relies on dialysis. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) is a new class of small-molecule oral drugs for the treatment of anaemia in chronic kidney disease. They demonstrate several advantages over traditional exogenous erythropoietin (EPO). We conducted a meta-analysis of studies that compared the efficacy of HIF-PHI in erythropoiesis and iron metabolism, and its safety with EPO in maintenance dialysis patients. METHODS: A sensitive search strategy in the PubMed, EMBASE and Cochrane databases identified all citations for randomised controlled trials (RCTs) comparing HIF-PHI agents with EPO/placebo through December 2021. RESULTS: Fourteen RCTs were identified, which included 2738 patients. No statistical difference was found in haemoglobin increase (p = 0.37) between HIF-PHI treatment and EPO using the random-effects model. HIF-PHI administration upregulated transferrin (MD 36.12, 95% CI 27.04-45.20) and soluble transferrin receptors (sTfR) (MD 1.28, 95% CI 0.44-2.13), but did not statistically reduce hepcidin level (p = 0.37). Total and LDL-cholestrol levels were suppressed by HIF-PHI (MD - 0.99, 95% CI - 1.34 to - 0.63) (MD - 0.99, 95% CI - 1.34 to - 0.64), while triglyceride (TG) was not different between HIF-PHI and EPO (p = 0.74). The total incident rates of treatment-emergent adverse events (TEAE) (p = 0.20) from HIF-PHI treatment were not different from those of erythropoietin, while the treatment-emergent serious adverse events (TSAE) (p = 0.02) were higher in the HIF-PHI group than those in the EPO controls with the fixed-effect model. CONCLUSION: HIF-PHI could effectively upregulate and maintain haemoglobin levels in patients with anaemia receiving maintenance dialysis. Furthermore, HIF-PHI could elevate iron metabolism activity and utility without inducing treatment-associated serious adverse events. Robust data from larger RCTs with longer treatment duration and follow-up are needed.

Facile Fabrication of Cellulose Nanofibrils/Chitosan Beads as the Potential pH-Sensitive Drug Carriers.

It is highly desirable to develop a safe, highly efficient, and biodegradable drug carrier with an enhanced drug transport efficiency. Cellulose nanofibrils (CNF) and chitosan (CS) composite hydrogels are promising candidate carriers with biological compatibility and non-cytotoxicity. Herein, the CNF/CS composite beads were prepared by dissolving cellulose and CS in LiBr molten salt hydrate and regenerating in ethanol. This preparation method is facile and efficient, and the obtained porous CNF/CS beads with the weight ratio of 8:2 exhibited a large specific surface area, uniform micro-nano-sized pores, strong mechanical property, and water absorption-resistance. Moreover, these beads as drug (tetracycline hydrochloride, TH) carriers showed a higher encapsulation efficiency (47.4%) at the TH concentration of 5 mg/mL in 24 h, and a higher drug loading rate (12.0%) than pure CNF and other CNF/CS beads prepared with different ratios. In addition, the TH releasing behavior of CNF/CS (8:2) beads fitted well into the zero-order, first-order, and Higuchi models under an acid condition, indicating that the drug release of these pH-sensitive beads was mainly affected by drug concentration under an acid condition. Therefore, these CNF/CS beads have great potential to be used as drug carriers for medical applications.

Therapeutic targeting of STING-TBK1-IRF3 signalling ameliorates chronic stress induced depression-like behaviours by modulating neuroinflammation and microglia phagocytosis.

Stress is well known to contribute to the development of both neurological and psychiatric diseases. In the central nervous system, a role for STING (stimulator of interferon genes) in modulating immunological responses has been widely suggested, and this protein possesses both neurotoxic and neuroprotective properties. However, the potential role of the STING signalling pathway and the underlying regulatory mechanism in chronic stress have not been well established. In this study, C57BL/6 mice were subjected to intermittent restraint stress for 14 days (6 h/day), and sucrose preference, elevated plus maze, and tail suspension tests were performed by mice subjected to chronic restraint stress (RST). Here, we showed that RST mice displayed depression-like behaviours, accompanied by increased levels of proinflammatory cytokines in the brain. We also observed remarkably decreased levels of the pathway components STING, p-TBK1 (phospho-TANK-binding kinase-1), and p-IRF3 (phospho-interferon regulatory factor-3) in the hippocampus and the prefrontal cortex of RST mice. Significant reductions in STING fluorescence intensity were also observed in the hippocampus and the prefrontal cortex of RST mice. Next, fluorescently labelled latex beads, flow cytometry, and CD68-positive cell counts were utilized to evaluate the phagocytic abilities of microglia in vivo and in vitro. Importantly, our results first indicated that activation of the STING pathway by administration of the STING agonist 2'3-cGAMP enhanced microglial phagocytosis and suppressed the release of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß in the brains of RST mice, which further led to antidepressant effects. Based on the results of our study, the amelioration of stress-driven depression-like behaviours by activation of the STING pathway is associated with the suppression of neuroinflammation and enhanced phagocytosis.

Nitrogen application practices to reduce cadmium concentration in rice (Oryza sativa L.) grains.

Cadmium (Cd) pollution in paddy soils creates challenges in rice grain production, thereby threatening food security. The effectiveness of different base-tillering-panicle urea application ratios and the combined basal application of urea and Chinese milk vetch (CMV, Astragalus sinicus L.) in minimizing Cd accumulation in rice grains was explored in a Cd-contaminated acidic soil via a field experiment. The results indicated that under similar nitrogen (N) application rates, an appropriate amount of urea applied at the panicle stage or the combined basal application of urea and CMV decreased Cd absorption by rice roots and its accumulation in rice grains, as compared with that of conventional N application (control). Furthermore, under a 3:4:3 base-tillering-panicle urea application ratio or under a high basal application of CMV (37,500 kg hm-2), Cd concentrations in brown rice were significantly lower (40.7% and 34.1%, respectively) than that of control. Cadmium transport coefficient from root to straw was significantly higher than that of control when an appropriate amount of urea was applied at the panicle stage or when urea and CMV were applied basally, whereas the Cd transport coefficient from straw to brown rice was relatively lower. Moreover, soil pH, or the CEC and CaCl2-Cd concentrations under different N fertilizer treatment was not significantly different. However, the rice grain yield increased by 29.4% with basal application of a high CMV amount compared with that of control. An appropriate amount of urea applied at the panicle stage or the combined basal application of urea and CMV decreased Cd absorption by rice roots and inhibited its transport from straw to brown rice, thus reducing Cd concentration in brown rice. Therefore, combined with the key phase of Cd accumulation in rice, a reasonable urea application ratio or a basal application of high CMV amounts could effectively reduce Cd concentration in brown rice.

Ultrafast improvement of cellulose accessibility via non-dissolving pretreatment with LiBr·3H2O under room temperature.

The development of sustainable and effective pretreatment methods to improve the accessibility of cellulose is of vital importance for its utilization. Herein, a novel high-efficiency pretreatment method based on lithium bromide trihydrate (LBTH) was established, which realized the fast improvement of cellulose accessibility under ambient conditions without dissolution of cellulose. The cellulose I structure of microcrystalline cellulose (MCC) was transformed into amorphous structure just within 5 min of LBTH pretreatment, and the crystallinity was reduced from 79.1 to 19.9%. After pretreatment for 30 min, the BET surface area of MCC increased from 2.1 to 125.9 m2/g. Particularly, the pretreated cellulose could be near-completely saccharified to glucose (98.3%) with ultra-low enzyme dosage (2.5 mg protein/g-glucan) just within 24 h, while the conversion of untreated MCC under the same conditions was only 16.7%. Additionally, this non-dissolving pretreatment is beneficial to the separation and recycling of LBTH, guaranteeing a clean and sustainable process.

Label-free in vivo assessment of brain mitochondrial redox states during the development of diabetic cognitive impairment using Raman spectroscopy.

Mitochondrial redox imbalance has been recognized as a unifying cause for diabetic cognitive impairment. Currently, a robust method for the in vivo assessment of brain mitochondrial redox imbalance is still lacking. Here, we conducted a spectral study to assess brain mitochondrial redox imbalance in the process of diabetic cognitive impairment by using label-free resonance Raman spectroscopy (RRS). Our findings showed that mitochondrial redox imbalance in cultured neurons and organotypic cortical slices exposed to high glucose were quantified by the reduction of Raman peak area at 750 cm-1 and 1128 cm-1, which were also associated with synaptic injury and neuron apoptosis. Raman peak area at 750 cm-1 and 1128 cm-1 were also decreased in db/db mice at the age of 8, 16 and 24 weeks, and had a high correlation with the mitochondrial NAD+/NADH redox couple. Of note, this mitochondrial redox imbalance occurred before measurable cognitive decline in 8-week-old diabetic mice, and might signal impending diabetic cognitive impairment. In summary, RRS-based mitochondrial redox states assay enabled the in vivo assessment of brain mitochondrial redox imbalance, and might provide an early indicator to enhance the prediction of diabetic cognitive impairment and inform on the response to therapies targeting mitochondrial redox imbalance.

A pulp foam with highly improved physical strength, fire-resistance and antibiosis by incorporation of chitosan and CPAM.

Bio-inspired borate cross-linked pulp foam (PF) with high porosity and low density can be widely used in many fields. However, PF is flammable, and lack of mechanical strength and antibacterial activity. To solve these issues, an ultra-strong PF was prepared by incorporation of chitosan and cationic polyacrylamide (CPAM). Results showed that the obtained PF exhibited highly improved mechanical properties (the compressive strength (485 kPa at a strain of 50%) was over 6 times higher compared with the borate cross-linked PF without chitosan and CPAM, and it was even higher than most of the reported cellulose-based porous materials). Also, the prepared PF has good performance on fire-retardance (hard to light), thermal insulation, antibiosis and sound absorption, due to the synergistic actions of borate, chitosan and CPAM. Additionally, spent liquor in preparing PF could be fully recycled, and thus this sustainable approach has potential for large-scale production of high-performance PF.