High-mass loaded redox-active lignin functionalized carbonized wood collector to construct sustainable and high-performance supercapacitors.

Traditional electrode materials for supercapacitors often face issues like high toxicity, cost, and non-renewability. To address these drawbacks, biomass-based alternatives are being explored, aligning with green development trends. Herein, carbonized wood (CW) with rich pore structure and redox-active lignin are combined to fabricate an all-wood-based sustainable supercapacitor electrode material. Due to its inherent porous structure, CW provides a larger surface area for accommodating active materials ion, enabling the electrode to achieve a higher lignin loading capacity of 2.82-11.68 mg/cm2. Furthermore, the utilization of lignin as a substitute for conventional transition metal-based pseudocapacitor material functionalized CW endows the electrode with exemplary electrochemical performance while guaranteeing the comprehensive sustainability of the electrode. This synergy confers the electrode with exceptional electrical performance, yielding an areal capacitance of 960.7 mF/cm2 at a current density of 1 mA/cm2. The symmetric supercapacitors (SSC) manufactured by this composite electrode can achieve a notable areal energy density of 0.14 mWh/cm2 and a power density of 15.98 mW/cm2, while maintaining an outstanding capacitance retention rate of 81 % after 50,000 cycles at 20 mA/cm2. The manufacture of CW-lignin electrode underscores the potential of utilizing renewable biomass resources as alternatives for developing high-performance energy storage applications, thereby reducing negative environmental impacts.

Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.

Emerging evidence shows that psychological stress promotes the progression of Parkinson's disease (PD) and the onset of dyskinesia in non-PD individuals, highlighting a potential avenue for therapeutic intervention. We previously reported that chronic restraint-induced psychological stress precipitated the onset of parkinsonism in 10-month-old transgenic mice expressing mutant human α-synuclein (αSyn) (hαSyn A53T). We refer to these as chronic stress-genetic susceptibility (CSGS) PD model mice. In this study we investigated whether ginsenoside Rg1, a principal compound in ginseng notable for soothing the mind, could alleviate PD deterioration induced by psychological stress. Ten-month-old transgenic hαSyn A53T mice were subjected to 4 weeks' restraint stress to simulate chronic stress conditions that worsen PD, meanwhile the mice were treated with Rg1 (40 mg· kg-1 ·d-1, i.g.), and followed by functional magnetic resonance imaging (fMRI) and a variety of neurobehavioral tests. We showed that treatment with Rg1 significantly alleviated both motor and non-motor symptoms associated with PD. Functional MRI revealed that Rg1 treatment enhanced connectivity between brain regions implicated in PD, and in vivo multi-channel electrophysiological assay showed improvements in dyskinesia-related electrical activity. In addition, Rg1 treatment significantly attenuated the degeneration of dopaminergic neurons and reduced the pathological aggregation of αSyn in the striatum and SNc. We revealed that Rg1 treatment selectively reduced the level of the stress-sensitive protein RTP801 in SNc under chronic stress conditions, without impacting the acute stress response. HPLC-MS/MS analysis coupled with site-directed mutation showed that Rg1 promoted the ubiquitination and subsequent degradation of RTP801 at residues K188 and K218, a process mediated by the Parkin RING2 domain. Utilizing αSyn A53T+; RTP801-/- mice, we confirmed the critical role of RTP801 in stress-aggravated PD and its necessity for Rg1's protective effects. Moreover, Rg1 alleviated obstacles in αSyn autophagic degradation by ameliorating the RTP801-TXNIP-mediated deficiency of ATP13A2. Collectively, our results suggest that ginsenoside Rg1 holds promise as a therapeutic choice for treating PD-sensitive individuals who especially experience high levels of stress and self-imposed expectations.

Diet affects inflammatory arthritis: a Mendelian randomization study of 30 dietary patterns causally associated with inflammatory arthritis.

Background: The causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown. Objective: In this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR). Methods: We analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran's Q tests. FDR correction was used to correct the p-values. Results: IVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360-6.021, p = 0.006, p_fdr < 0.05] was positively associated with rheumatoid arthritis(RA); Dried fruit intake (OR = 0.522; 95% CI, 0.349-0.781, p = 0.002, p_fdr < 0.05), and Iron intake (OR = 0.864; 95%CI, 0.777-0.960, p = 0.007, p_fdr < 0.05) were negatively associated with RA, all of which were evidence of significance. Fresh fruit intake (OR = 2.528. 95% CI, 1.063-6.011, p = 0.036, p_fdr > 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367-0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100-0.565, p = 0.001, p_fdr < 0.05) was negatively associated with reactive arthritis (ReA), a protective factor, and significant evidence. All exposure data passed the heterogeneity check (Cochrane's Q test p > 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results. Conclusion: Our study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.

Biomimetic concentric microgrooved titanium surfaces influence bone marrow-derived mesenchymal stem cell osteogenic differentiation via H3K4 trimethylation epigenetic regulation.

Material surface micromorphology can modulate cellular behavior and promote osteogenic differentiation through cytoskeletal rearrangement. Bone reconstruction requires precise regulation of gene expression in cells, a process governed by epigenetic mechanisms such as histone modifications, DNA methylation, and chromatin remodeling. We constructed osteon-mimetic concentric microgrooved titanium surfaces with different groove sizes and cultured bone marrow-derived mesenchymal stem cells (BMSCs) on the material surfaces to study how they regulate cell biological behavior and osteogenic differentiation through epigenetics. We found that the cells arranged in concentric circles along the concentric structure in the experimental group, and the concentric microgrooved surface did not inhibit cell proliferation. The results of a series of osteogenic differentiation experiments showed that the concentric microgrooves facilitated calcium deposition and promoted osteogenic differentiation of the BMSCs. Concentric microgrooved titanium surfaces that were 30 µm wide and 10 µm deep promoted osteogenic differentiation of BMSC by increasing WDR5 expression via H3K4 trimethylation upregulation.

Farmland hydrological cycle under agroforestry systems and efficient use of water resources in the karst desertification environment.

In karst desertification (KD) regions, surface water (SW) easily enters underground through pore fissures and sinkholes despite the presence of abundant precipitation. Such regions have a typical distribution of "soil above and water below", and, thus, the unique "karst drought" occurs. Hence, an urgent and primary problem in combating KD is to reach highly efficient utilization of water resources in these regions. We selected three karst research areas with different levels of karst desertification and different geomorphic types. By monitoring the storage and transformation of five types of water in the agroforestry system-precipitation, SW, groundwater (GW), soil water (SoW), plant water (PW), the following results were obtained: (1) In KD regions, a positive correlation was found among available precipitation, rainfall, and land evapotranspiration (LE), and LE was approximately equivalent to soil evaporation. (2) To varying degrees, agroforestry brings ecological benefits, including reducing surface runoff, increasing soil infiltration, lowering the transpiration rate, and reducing soil evaporation, thus achieving efficient use of water resources. (3) From 100 % rainfall, the transformation rates of SW, GW, PW, and SoW reached 0.14-12.71 %, 9.43-30.20 %, 9.79-49.97 %, and 40.72-82.58 %, respectively, and SoW showed a larger reserve than the other three types. (4) Drought stress contributes to the improvement of water use efficiency (WUE). Affected by drought stress, WUE was found to be the highest in a medium-intensity karst desertification environment. The transformation mechanisms of the five types of water observed in the agroforestry system provide a reference for efficient utilization of water resources in KD regions as well as theoretical support for addressing karst drought. They are also essential in helping to advance the ecological derivative industry, boosting the economy in karst mountainous areas, and controlling karst desertification.

Lignin containing cellulose nanofiber/Ag2Se nanocomposite films: a promising material for thermoelectric film generators.

This work deals with the fabrication of lignin containing cellulose nanofiber (LCNF)/Ag2Se films for thermoelectric applications. Ag2Se nanoparticles were synthesized within the LCNF network through in situ methods, employing Na2SeO3 and AgNO3 along with microwave energy treatment. LCNF/Ag2Se films fabricated with two LCNF : Ag2Se weight percent ratios (i.e., 50 : 50 and 30 : 70) were used to construct a flexible thermoelectric module. The obtained Ag2Se nanoparticles displayed a uniform size distribution in the LCNF network with smaller dimensions from the microwave energy treated group. The microstructure of LCNF/Ag2Se films was improved by hot-pressing, leading to enhanced film density thermoelectric properties. At a differential temperature of 50 K, films with 50% and 70% of Ag2Se exhibited output voltages of 18 and 21 mV; and Seebeck coefficients of -60 and -70 µV K-1 at 350 K, respectively. When microwave energy was applied, the films at 50% and 70% Ag2Se showed highest output voltages of 19 and 33 mV, respectively, and Seebeck coefficients of -63.3 and -110 µV K-1 at 350 K. The low-cost fabrication process associated with this module opens a pathway for applications such as energy harvesting.

Soil quality enhancement by multi-treatment in the abandoned land of dry-hot river valley hydropower station construction area under karst desertification environment.

The medium-intensity karst desertification environment is typically characterized by more rocks and less soil. The abandoned land in the construction areas of the dry-hot river valley hydropower station has more infertile soil, severe land degradation, and very low land productivity. Therefore, it is urgent to improve the soil quality to curb the increasingly degrading land and reuse the construction site. Few studies have focused on the effect of soil restoration and comprehensive evaluation of soil quality with multi-treatment in abandoned land in the dry-hot valley hydropower station construction area. Here, 9 soil restoration measures and 1 control group were installed at the Guangzhao Hydropower Station construction in Guizhou Province, China, for physical and chemical property analysis. In total, 180 physical and 90 chemical soil samples were collected on three occasions in May, August, and December 2022. Soil fertility and quality were evaluated under various measures using membership functions and principal component analysis (PCA). This study showed that almost all measures could enhance soil water storage capacity (The average total soil porosity of 9 soil treatments was 57.56%, while that of the control group was 56.37%). With the increase in soil porosity, soil evaporation became stronger, and soil water content decreased. Nevertheless, no decrease in soil water content was observed in the presence of vegetation cover (soil water content: 16.46% of hairy vetch, 13.99% of clover, 13.77% of the control). They also proved that manure, synthetic fertilizer, and straw could promote total and available nutrients (Soil total nutrient content, or the total content of TN、TP、TK,was presented as: synthetic fertilizer (11.039g kg-2)>fowl manure (10.953g kg-2)>maize straw (10.560g kg-2)>control (9.580g kg-2);Total available nutrient content in soil, or the total content of AN,AP,A,was shown as:fowl manure (1287.670 mg kg-1)>synthetic fertilizer (925.889 mg kg-1)>sheep manure (825.979 mg kg-1)>control (445.486 mg kg-1). They could also promote soil fertility, among which the first two reached the higher comprehensive soil quality. Fertilizer was conducive to improve soil quality and fertility, yet long-term application could cause land degradation like soil non-point source pollution, compaction, and land productivity decline. Ultimately, combining fertilizer with biochar or manure is recommended to improve soil fertility. Biochar and green manure could play an apparent role in soil improvement only when there is abundant soil water. The above views provide theoretical support for curbing soil degradation, improving soil fertility and quality, enhancing land productivity, and promoting the virtuous cycle of the soil ecosystem.

Oral citrate supplementation mitigates age-associated pathological intervertebral disc calcification in LG/J mice.

Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. Here, we investigate the efficacy of long-term oral K3Citrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. K3Citrate successfully reduced the incidence of disc calcification in LG/J mice without deleterious effects on vertebral bone structure, plasma chemistry, and locomotion. Notably, a positive effect on grip strength was evident in treated mice. Spectroscopic investigation of the persisting calcified nodules indicated K3Citrate did not alter the mineral composition and revealed that reactivation of an endochondral differentiation program in endplates may drive LG/J disc calcification. Importantly, K3Citrate reduced calcification incidence without altering the pathological endplate chondrocyte hypertrophy, suggesting mitigation of disc calcification primarily occurred through Ca2+ chelation, a conclusion supported by chondrogenic differentiation and Seahorse metabolic assays. Overall, this study underscores the therapeutic potential of K3Citrate as a systemic intervention strategy for disc calcification.

Recycling Functional Fillers from Waste Tires for Tailored Polystyrene Composites: Mechanical, Fire Retarding, Electromagnetic Field Shielding, and Acoustic Insulation Properties-A Short Review.

Polymer waste is currently a big and challenging issue throughout the world. Waste tires represent an important source of polymer waste. Therefore, it is highly desirable to recycle functional fillers from waste tires to develop composite materials for advanced applications. The primary theme of this review involves an overview of developing polystyrene (PS) composites using materials from recycled tires as fillers; waste tire recycling in terms of ground tire rubbers, carbon black, and textile fibers; surface treatments of the fillers to optimize various composite properties; and the mechanical, fire retarding, acoustic, and electromagnetic field (EMI) shielding performances of PS composite materials. The development of composite materials from polystyrene and recycled waste tires provides a novel avenue to achieve reductions in carbon emission goals and closed-loop plastic recycling, which is of significance in the development of circular economics and an environmentally friendly society.

Suitability of agronomic water saving in karst areas and its enlightenment in the karst desertification control.

The special "dual" hydrogeological structure in karst areas causes rainfall easily "leaking" into the ground, resulting a unique "karst drought". In these areas, drought and insufficient water resources seriously restrict the sustainable development of agriculture. In order to restore the ecology of karst desertification, develop ecological industries, improve the utilization efficiency of water resources, and advance water-saving agriculture in such areas, literature review method was applied to discuss the suitability of agronomic water-saving measures in karst areas. The results are as follows. (1) Agronomic water-saving measures including tillage, mulching, water-fertilizer coupling, chemical regulation, crop allocation and deficit irrigation can all enhance the crop WUE. For example, deep tillage and deep loosening increased the WUE by 15.1 % and 15.9 % respectively. The WUE of spring wheat under straw mulching increased by 17.17 %-43.01 % compared with that under mulching film. Increased density of intercropping corn and wheat saved 9.85 % of water. (2) The cultural or natural particularity of karst areas limits the application of all agronomic water-saving measures in karst areas, and therefore choices and adjustments are necessary according to local conditions: ① No tillage should be adopted because of the high output of labor force; ② straw mulching need to be crushed; ③ the coupling of water and fertilizer reaches better effect when applied to crops several hours before rainfall; ④ the shallow soil layer and the complexity of preparing water retaining agent make it unsuitable to use water retaining agent; ⑤ agroforestry with dwarf and dense planting is more suitable; ⑥ crop deficit irrigation can be carried out by using ecological small pools. Based on the above results, proposes are offered in the following. First, it is necessary to construct the optimal model of regional water and fertilizer coupling in karst areas, and apply composite agronomic water-saving measures. Second, it is suggested to establish a model of coordinating forest, grain and grass, and vigorously develop ecologically derivative agroforestry. Third, there is a necessity to strengthen the research and development of technology about soil and water leakage monitoring and resistance, and intensify studies on "five waters" transformation at the basin scale. The research results and implication are an important reference for developing water-saving agriculture, solving the shortage of agricultural water resources, ensuring the sustainability of agriculture and improving farmers' living standards. Rational use of agronomic water-saving measures is of great significance to enhance the utilization efficiency of water resources and boost regional economy in karst desertification areas.

Nanocellulose-mediated bilayer hydrogel actuators with thermo-responsive, shape memory and self-sensing performances.

Inspired by creatures, abundant stimulus-responsive hydrogel actuators with diverse functionalities have been manufactured for applications in soft robotics. However, constructing a shape memory and self-sensing bilayer hydrogel actuator with high mechanical strength and strong interfacial bonding still remains a challenge. Herein, a novel bilayer hydrogel with a stimulus-responsive TEMPO-oxidized cellulose nanofibers/poly(N-isopropylacrylamide) (TOCN/PNIPAM) layer and a non-responsive TOCN/polyacrylamide (TOCN/PAM) layer is proposed as a thermosensitive actuator. TOCNs as a nano-reinforced phase provide a high mechanical strength and endow the hydrogel actuator with a strong interfacial bonding. Due to the incorporation of TOCNs, the TOCN/PNIPAM hydrogel exhibits a high compressive strength (~89.2 kPa), elongation at break (~170.7 %) and tensile strength (~24.0 kPa). The prepared PNIPAM/TOCN/PAM hydrogel actuator performs the roles of an encapsulation, jack, temperature-controlled fluid valve and temperature-control manipulator. The incorporation of Fe3+ further endows the bilayer hydrogel actuator with a synergistic performance of shape memory and temperature-driven, which can be used as a temperature-responsive switch to detect ambient temperature. The PNIPAM/TOCN/PAM-Fe3+ conductive hydrogel can be assembled into a flexible sensor and generate sensing signals when driven by temperature changes to achieve real-time feedback. This research may lead to new insights into the design and manufacturing of intelligent flexible soft robots.

Early application of awake extracorporeal membrane oxygenation in pneumocystis jirovecii pneumonia complicated with severe acute respiratory distress syndrome: a case report.

Introduction: Patients suffering from severe acute respiratory distress syndrome (ARDS) are usually treated with mechanical ventilation. Extracorporeal membrane oxygenation (ECMO) has traditionally been considered a life-saving therapy and was reserved as a last resort when other treatment options were exhausted. However, this report outlines our successful initial experience with early implementation of awake venovenous extracorporeal membrane oxygenation (VV-ECMO) in a case of pneumocystis jirovecii pneumonia complicated by severe acute respiratory distress syndrome (ARDS), offering a promising new approach for recovery. Case presentation: We present a case report of the effective application of awake VV-ECMO in a 29 years-old man with severe ARDS caused by pneumocystis jirovecii pneumonia. The patient initially received antibiotic treatment and non-invasive ventilation (NIV) for respiratory distress, but these interventions failed to improve the worsening dyspnea that occurred in the patient. Following the combined antifungal therapy, high-flow nasal cannula (HFNC) oxygen therapy, and VV-ECMO for a duration of 7 days, the patient's symptoms improved, showing relief. Conclusion: Awake VV-ECMO proved to be an effective treatment for critically ill patients with ARDS, avoiding the need for invasive mechanical ventilation. However, increased clinical evidence is needed to verify whether awake ECMO could be widely used in severe ARDS caused by other diseases or conditions.

Comparison of ecosystem health in different geomorphic regions of Chishui River Basin, Southwest China.

Ecosystem health of the Chishui River Basin (CRB, a crucial ecological barrier in the upper reaches of the Yangtze River) is vital for the ecological security and sustainability of the Yangtze River Basin. We used RUSLE model, SWAT model, Fragstats and geographic detectors to construct a theoretical framework of ecosystem health assessment for CRB, and examined the spatiotemporal variations and driving factors of ecosystem health in CRB under ecological restoration from 2010 to 2020. The results showed that ecosystem service in the CRB decreased and then increased during 2010-2020 and the overall trend was downward. The overall ecosystem service function was higher in the Danxia (non-karst) area than that in the karst area. The ecosystem health was generally subhealthy, with the Danxia area being mostly extremely healthy and healthy, whereas the karst area mostly subhealthy and unhealthy. There were differences in the dominant drivers of ecosystem health between karst and Danxia areas. Vegetation, precipitation, and bedrock bareness rate were the dominant drivers in the karst area, while vegetation, land use, and precipitation were the dominant factors in Danxia area. After interaction detection, the explanatory power of impact factors increased, and the dominant interaction factor combinations in different geomorphological type regions had shown great differences. Among them, precipitation∩normalized difference vegetation index (NDVI), precipitation∩digital elevation model (DEM) and precipitation ∩ bedrock bareness rate were the dominant interaction factor combinations in the karst area, and NDVI∩precipitation, NDVI∩land use and NDVI∩DEM were the dominant interaction factor combinations in Danxia area. These results would provide scientific support for health maintenance and conservation of CRB ecosystem.

Highly Flexible, Self-Bonding, Self-Healing, and Conductive Soft Pressure Sensors Based on Dicarboxylic Cellulose Nanofiber Hydrogels.

Conductive hydrogels have gained a great deal of interest in the flexible electronics industry because of their remarkable inherent properties. However, a significant challenge remains for balancing hydrogel's conductivity, self-healing, and strength properties. Herein, double network ionic hydrogels were fabricated by concurrently introducing borax into dicarboxylic cellulose nanofiber (DCNFs) and polyacrylamide (PAM) hydrogels. The incorporation of borax provided a superabsorbent feature to the PAM/DCNF hydrogels (without borax) with the equilibrium water absorption rate increased from 552 to 1800% after 42 h. The compressive strength of the prepared hydrogel was 935 kPa compared to 132 kPa for the PAM hydrogel, with high cycling stability (stable after 1000 compression cycles with 50% strain). The hydrogel pressure sensor had a very sensitive response (gauge factor = 1.36) in the strain range from 10 to 80%, which made it possible to detect mechanical motion accurately and reliably. The developed hydrogels with high-performance, environmentally friendly properties are promising for use in future artificial skin and human-machine interface applications.

Efficacy of acupotomy combined with sodium hyaluronate versus sodium hyaluronate alone in the treatment of knee osteoarthritis: A meta-analysis.

BACKGROUND: The efficacy of acupotomy combined with hyaluronic sodium acid in the treatment of knee osteoarthritis (KOA) is unclear. Therefore, this meta-analysis aims to evaluate the efficacy of acupotomy combined with hyaluronic sodium acid compared with hyaluronic sodium acid alone in the treatment of KOA. METHODS: Studies from 8 Online databases were searched on KOA treatment using acupotomy combined with sodium hyaluronate until May 2022. The primary outcome indicator was clinical effectiveness, and the secondary outcome indicators included the visual analogue scale scores and Lysholm scores. We calculated the weighted mean difference (WMD) or relative risk for all relevant outcomes. RESULTS: Nine studies were identified, involving 644 cases. The results showed that acupotomy combined with intra-articular sodium hyaluronate injection for KOA was superior to sodium hyaluronate injection alone in terms of clinical effectiveness (relative risk = 1.17, 95% confidence interval [CI]: 1.09-1.25, P < .001) and visual analogue scale (WMD = -2.1, 95% CI: -2.25 to 1.95, P < .001), Lysholm score (WMD = 13.83, 95% CI: 3.47-24.19, P = .009). CONCLUSION: Acupotomy combined with intra-articular sodium hyaluronate injection for KOA is superior to sodium hyaluronate injection alone. Limited by the number and quality of included studies, this conclusion still needs to be verified by more high-quality Research. INPLASY REGISTRATION NUMBER: INPLASY202350029.

A novel small-molecular CCR5 antagonist promotes neural repair after stroke.

Chemokine receptor 5 (CCR5) is one of the main co-receptors of HIV-1, and has been found to be a potential therapeutic target for stroke. Maraviroc is a classic CCR5 antagonist, which is undergoing clinical trials against stroke. As maraviroc shows poor blood-brain barrier (BBB) permeability, it is of interest to find novel CCR5 antagonists suitable for neurological medication. In this study we characterized the therapeutic potential of a novel CCR5 antagonist A14 in treating ischemic stroke mice. A14 was discovered in screening millions compounds in the Chemdiv library based on the molecular docking diagram of CCR5 and maraviroc. We found that A14 dose-dependently inhibited the CCR5 activity with an IC50 value of 4.29 µM. Pharmacodynamic studies showed that A14 treatment exerted protective effects against neuronal ischemic injury both in vitro and vivo. In a SH-SY5Y cell line overexpressing CCR5, A14 (0.1, 1 µM) significantly alleviated OGD/R-induced cell injury. We found that the expression of CCR5 and its ligand CKLF1 was significantly upregulated during both acute and recovery period in focal cortical stroke mice; oral administration of A14 (20 mg·kg-1·d-1, for 1 week) produced sustained protective effect against motor impairment. A14 treatment had earlier onset time, lower onset dosage and much better BBB permeability compared to maraviroc. MRI analysis also showed that A14 treatment significantly reduced the infarction volume after 1 week of treatment. We further revealed that A14 treatment blocked the protein-protein interaction between CCR5 and CKLF1, increasing the activity of CREB signaling pathway in neurons, thereby improving axonal sprouting and synaptic density after stroke. In addition, A14 treatment remarkably inhibited the reactive proliferation of glial cells after stroke and reduced the infiltration of peripheral immune cells. These results demonstrate that A14 is a promising novel CCR5 antagonist for promoting neuronal repair after ischemic stroke. A14 blocked the protein-protein interaction between CKLF1 and CCR5 after stroke by binding with CCR5 stably, improved the infarct area and promoted motor recovery through reversing the CREB/pCREB signaling which was inhibited by activated CCR5 Gαi pathway, and benefited to the dendritic spines and axons sprouting.

A breakdown of metabolic reprogramming in microglia induced by CKLF1 exacerbates immune tolerance in ischemic stroke.

Ischemic stroke is characterized by the presence of reactive microglia. However, its precise involvement in stroke etiology is still unknown. We used metabolic profiling and showed that chemokine like factor 1 (CKLF1) causes acute microglial inflammation and metabolic reprogramming from oxidative phosphorylation to glycolysis, which was reliant on the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR)-hypoxia inducible factor 1α (HIF-1α) signaling pathway. Once activated, microglia enter a chronic tolerant state as a result of widespread energy metabolism abnormalities, which reduces immunological responses, including cytokine release and phagocytosis. Metabolically dysfunctional microglia were also found in mice using genome-wide RNA sequencing after chronic administration of CKLF1, and there was a decrease in the inflammatory response. Finally, we showed that the loss of CKLF1 reversed the defective immune response of microglia, as indicated by the maintenance its phagocytosis to neutrophils, thereby mitigating the long-term outcomes of ischemic stroke. Overall, CKLF1 plays a crucial role in the relationship between microglial metabolic status and immune function in stroke, which prepares a potential therapeutic strategy for ischemic stroke.

Effect of graphene-oxide-modified osteon-like concentric microgrooved surface on the osteoclastic differentiation of macrophages.

OBJECTIVES: This study aimed to investigate the effect of new biomimetic micro/nano surfaces on the osteoclastic differentiation of RAW264.7 macrophages by simulating natural osteons for the design of concentric circular structures and modifying graphene oxide (GO). METHODS: The groups were divided into smooth titanium surface group (SS), concentric microgrooved titanium surface group (CMS), and microgroove modified with GO group (GO-CMS). The physicochemical properties of the material surfaces were studied using scanning electron microscopy (SEM), contact-angle measurement, atomic force microscopy, X-ray photoelectron spectroscopy analysis, and Raman spectroscopy. The effect of the modified material surface on the cell biological behavior of RAW264.7 was investigated by cell-activity assay, SEM, and laser confocal microscopy. The effect on the osteoclastic differentiation of macrophages was investiga-ted by tartrate-resistant acid phosphatase (TRAP) immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR) experiments. RESULTS: Macrophages were arranged in concentric circles along the microgrooves, and after modification with GO, the oxygen-containing groups on the surface of the material increased and hydrophilicity increased. Osteoclasts in the GO-CMS group were small in size and number and had the lowest TRAP expression. Although it promoted the proliferation of macrophages in the GO-CMS group, the expression of osteoclastic differentiation-related genes was lower than that in the SS group, and the difference was statistically significant (P<0.05). CONCLUSIONS: Concentric circular microgrooves restricted the fusion of osteoclasts and the formation of sealing zones. Osteomimetic concentric microgrooves modified with GO inhibited the osteoclastic differentiation of RAW 264.7 macrophages.

Ice-Crystal-Templated "Accordion-Like" Cellulose Nanofiber/MXene Composite Aerogels for Sensitive Wearable Pressure Sensors.

Exfoliated MXene nanosheets are integrated with cellulose nanofibers (CNFs) to form composite aerogels with high electric conductivity. The combination of CNFs and MXene nanosheets forms a unique "accordion-like" hierarchical architecture with MXene-CNF pillared layers through ice-crystal templating. Benefiting from the special "layer-strut" structure, the MXene/CNF composite aerogels have low density (50 mg/cm3), excellent compressibility and recoverability, as well as superior fatigue resistance (up to 1000 cycles). When being used as a piezoresistive sensor, the composite aerogel exhibits high sensitivity upon different strains, stable sensing performance with various compressive frequencies, broad detection range, and quick responsiveness (0.48 s). Moreover, the piezoresistive sensors are shown to have an excellent real-time sensing ability for human motions such as swallowing, arm bending, walking, and running. The composite aerogels also have a low environmental impact with the natural biodegradability of CNFs. The designed composite aerogels can serve as a promising sensing material for developing next-generation sustainable and wearable electronic devices.