Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

Effects of Curcumin on Neuroinflammation and the Nrf2/HO-1 Pathway in Rat Brains Following Gas Explosion

Gas explosions,a major occupational hazard in China’s coal industry,endanger the lives and health of miners.These explosions cause a specific type of traumatic brain injury with complex mechanisms,leading to disability and death.A study by Zhao et al.using magnetic resonance imaging on 49 gas explosion survivors revealed significant damage to brain regions like the hippocampus and cerebral cortex.

The HOXC10/NOD1/ERK axis drives osteolytic bone metastasis of pan-KRAS-mutant lung cancer

While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients,effective treatments are still lacking.Here,we identified homeobox C10(HOXC10)as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis.

Instant trachea reconstruction using 3D-bioprinted C-shape biomimetic trachea based on tissue-specific matrix hydrogels

Currently,3D-bioprinting technique has emerged as a promising strategy to offer native-like tracheal substitutes for segmental trachea reconstruction.However,there has been very limited breakthrough in tracheal repair using 3D-bioprinted biomimetic trachea owing to the lack of ideal bioinks,the requirement for precise structural biomimicking,and the complexity of multi-step surgical procedures by mean of intramuscular pre-implantation.Herein,we propose a one-step surgical technique,namely direct end-to-end anastomosis using C-shape 3D-bioprinted biomimetic trachea,for segmental trachea defect repair.First,two types of tissue-specific matrix hydrogels were exploited to provide mechanical and biological microenvironment conducive to the specific growth ways of cartilage and fibrous tissue respectively.In contrast to our previous O-shape tracheal design,the tubular structure of alternating C-shape cartilage rings and connecting vascularized-fibrous-tissue rings was meticulously designed for rapid 3D-bioprinting of tracheal constructs with optimal printing paths and models.Furthermore,in vivo trachea regeneration in nude mice showed satisfactory mechanical adaptability and efficient physiological regeneration.Finally,in situ segmental trachea reconstruction by direct end-to-end anastomosis in rabbits was successfully achieved using 3D-bioprinted C-shape biomimetic trachea.This study demonstrates the potential of advanced 3D-bioprinting for instant and efficient repair of segmental trachea defects.

Degradation of pyrene by immobilized microorganisms in saline-alkaline soil

Biodegradation of polycyclic aromatic hydrocarbons （PAHs） is very difficult in saline-alkaline soil due to the inhibition of microbial growth under saline-alkaline stress. The microorganisms that can most effectively degrade PAHs were screened by introducing microorganisms immobilized on farm byproducts and assessing the validity of the immobilizing technique for PAHs degradation in pyrene-contaminated saline-alkaline soil. Among the microorganisms examined, it was found that Mycobacterium sp. B2 is the best, and can degrade 82.2% and 83.2% of pyrene for free and immobilized cells after 30 days of incubation. The immobilization technique could increase the degradation of pyrene significantly, especially for fungi. The degradation of pyrene by the immobilized microorganisms Mucor sp. F2, fungal consortium MF and co-cultures of MB＋MF was increased by 161.7% （P 〈 0.05）, 60.1% （P 〈 0.05） and 59.6% （P 〈 0.05） after 30 days, respectively, when compared with free F2, MF and MB＋ME Scanning electron micrographs of the immobilized microstructure proved the positive effects of the immobilized microbial technique on pyrene remediation in saline- alkaline soil, as the interspace of the carder material structure was relatively large, providing enough space for cell growth. Co-cultures of different bacterial and fungal species showed different abilities to degrade PAHs. The present study suggests that Mycobacterium sp. B2 can be employed for in situ bioremediation of PAHs in saline-alkaline soil, and immobilization of fungi on farm byproducts and nutrients as carriers will enhance fungus PAil-degradation ability in saline-alkaline soil.

Influence of kaolinite and montmorillonite on benzo[a]pyrene biodegradation by Paracoccus aminovorans HPD-2 and the underlying interface interaction mechanisms

Clay minerals play an important role in biogeochemical cycling.Here,kaolinite and montmorillonite,the two most abundant and widespread clay minerals with typical layered structures,were selected to investigate and compare their effects on the biodegradation of benzo[a]pyrene(BaP)by Paracoccus aminovorans HPD-2 and to investigate the underlying interface mechanisms.Overall,the BaP degradation efficiency was significantly higher 7 d after montmorillonite addition,reaching 68.9%(P<0.05),when compared with that of the control without addition of clay minerals(CK,61.4%);however,the addition of kaolinite significantly reduced the BaP degradation efficiency to 45.8%.This suggests that kaolinite inhibits BaP degradation by inhibiting the growth of strain HPD-2,or its strong hydrophobicity and readily agglomerates in the degradation system,resulting in a decrease in the bio-accessibility of BaP to strain HPD-2.Montmorillonite may buffer some unfavorable factors,and cells may be fixed on the surface of montmorillonite colloidal particles across energy barriers.Furthermore,the adsorption of BaP on montmorillonite may be weakened after swelling,reducing the effect on the bio-accessibility of BaP,thus promoting the biodegradation of BaP by strain HPD-2.The experimental results indicate that differential bacterial growth,BaP bio-accessibility,interface interaction,and the buffering effect may explain the differential effects of the different minerals on polycyclic aromatic hydrocarbon biodegradation.These observations improve our understanding of the mechanisms by which clay minerals,organic pollutants,and degrading bacteria interact during the biodegradation process and provide a theoretical basis for increasing the biodegradation of soil pollutants by native microorganisms under field conditions.

Theoretical kinetic quantitative calculation predicted the expedited polysulfides degradation

The performance of lithium-sulfur battery is restricted by the lower value of electrode conductance and the sluggish LiPSs degradation kinetics.Unfortunately,the degradation rate of polysulfides was mostly attributed to the catalytic energy barrier in previous,which is unable to give accurate predictions on the performance of lithium-sulfur battery.Thereby,a quantitative framework relating the battery performance to catalytic energy barrier and electrical conductivity of the cathode host is developed here to quantitate the tendency.As the model compound,calculated-Ti_(4)O_(7)(c-Ti_(4)O_(7))has the highest comprehensive index with excellent electrical conductivity,although the catalytic energy barrier is not ideal.Through inputting the experimental properties such as impedance and charge/discharge data into the as-build model,the final conclusion is still in line with our prediction that Ti_(4)O_(7)host shows the most excellent electrochemical performance.Therefore,the accurate model here would be attainable to design lithium-sulfur cathode materials with a bottom–up manner.

高硫高硅铝土矿焙烧–溶出性能研究

采用悬浮焙烧对高硫高硅铝土矿进行处理,考察了不同焙烧温度对矿石中硫含量的影响,通过X射线衍射和扫描电子显微镜分析了不同温度条件下焙烧对铝土矿中物相变化及微观形貌的影响,研究了焙烧温度对矿石中氧化铝溶出性能的影响。结果表明,悬浮焙烧温度600℃及以上时,能够使铝土矿硫化型硫含量降至0.2wt%以下。焙烧使铝土矿中高岭石相发生分解生成非晶态的偏高岭石,同时破坏矿颗粒致密结构,出现晶粒细化,但温度过高(650℃)会出现局部烧结现象。焙烧使一水硬铝石晶体破坏而活化,600℃时晶体破坏最完全,使600℃焙烧矿在相同溶出条件下溶出效果较原矿及其他焙烧矿优势明显,在溶出温度270℃、苛碱浓度245 g/L、石灰添加量14wt%的条件下,相对溶出率能达96%以上。

Spatial and temporal distribution of acetochlor in sediments and riparian soils of the Songhua River Basin in northeastern China

The Songhua River Basin is a burgeoning agricultural area in the modern times in China. Particularly in recent years, increasing chemical fertilizers and pesticides have been applied with the development of agricultural production. However, the situation of non- point source pollution （NSP） from agricultural production in this basin is still obscure. In order to solve the problem, the occurrence and distribution of acetochlor in sediments and riparian soils of the Songhua River Basin before rain season and after rain season were investigated. In addition, total organic carbon was analyzed. The result showed that the concentration of acetochlor ranged from 0.47 to 11.76 μg/kg in sediments and 0.03 to 709.37 μg/kg in riparian soils. During the high flow period in 2009, the mean concentration was 4.79 μg/kg in sediments and 0.75 μg]kg in riparian soils, respectively. Similarly, the mean concentration was 2.53 μg/kg in sediments and 61.36μg/kg in riparian soils, during the average flow period in 2010. There was a significant correlation between the concentration of acetochlor and total organic carbon in surface sediments. Moreover, the distribution of acetochlor in sediments of the Songhua River was significantly correlated to land use and topography of the watershed. The investigated data suggested that the concentration of acetochlor in the Songnen Plain and the Sanjiang Plain was higher than that in the other areas of the basin, and riparian buffering zones in these areas bad been destroyed by human activities. The optimal agricultural measures to alleviate the contamination of pesticides should be adopted, including controlling agricultural application of acetochlor and ecological restoration of riparian buffering strips.

Large-sized bone defect repair by combining a decalcified bone matrix framework and bone regeneration units based on photo-crosslinkable osteogenic microgels

Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaffold,but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration.To address these problems,we proposed a novel strategy of bone regeneration units(BRUs)based on microgels produced by photo-crosslinkable and microfluidic techniques,containing both the osteogenic ingredient DBM and vascular endothelial growth factor(VEGF)for accurate biomimic of an osteoinductive microenvironment.The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.BRUs were successfully constructed by seeding BMSCs onto microgels,which achieved reliable bone regeneration in vivo.Finally,by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength,a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia.The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.

A highly effective polycyclic aromatic hydrocarbon-degrading bacterium,Paracoccus sp.HPD-2,shows opposite remediation potential in two soil types

Bioaugmentation is an efficient and eco-friendly strategy for the bioremediation of polycyclic aromatic hydrocarbons(PAHs).Since the degrading abilities of soils can greatly alter the abilities of PAH-degrading bacteria,illustrating the potential and mechanism of highly efficient degrading bacteria in different soil environments is of great importance for bioremediation.A PAH-degrading bacterium,Paracoccus aminovorans HPD-2,and two soil types,red and paddy soils,with distinct PAH-degrading abilities,were selected for this study.A soil microcosm experiment was performed by adding pyrene(PYR)and benzo[a]pyrene(B[a]P).Illumina sequencing was used to examine bacterial community structure.The results showed that inoculation with HPD-2 significantly elevated PYR and B[a]P degradation rates by 44.7%and 30.7%,respectively,in the red soil,while it only improved the degradation rates by 1.9%and 11%,respectively,in the paddy soil.To investigate the underlying mechanism,the fate of strain HPD-2 and the response of the indigenous bacterial communities were determined.Strain HPD-2 occupied certain niches in both soils,and the addition of the bacterium changed the native community structure more noticeably in the red soil than in the paddy soil.The addition of PAHs and strain HPD-2 significantly changed the abundances of 7 phyla among the 15 detected phyla in the red soil.In the paddy soil,5 of the 12 dominant phyla were significantly affected by PAHs and the inoculation of HPD-2,while 6new phyla were detected in the low-abundance phyla(<0.1%).The abundances of Massilia,Burkholderia,and Rhodococcus genera with PAH degradation efficiency were significantly increased by the inoculation of HPD-2 in the red soil during 42 d of incubation.Meanwhile,in the paddy soil,the most dominant effective genus,Massilia,was reduced by HPD-2 inoculation.This research revealed the remediation ability and inherent mechanism of the highly effective PAH-degrading strain HPD-2 in two different soil types,which would provide a theoretical basis for the application of degrading bacteria in different soils.

Legacy of herbicides in water from Hailun City,Northeast China:Occurrence,source,and ecological risk assessment

Herbicides(HBCs)are extensively used in modern agriculture.However,their potential negative impacts on environmental media have emerged as a significant environmental concern.In this study,we employed positivematrix factorization(PMF)to identify the potential sources of HBCs.Furthermore,we utilized amulti-matrix ecological riskmodel to assess the risks associated with HBCs in both surface water and groundwater in the black soil region of Northeast China.The findings revealed that the levels of15HBCs in surface water and groundwater ranged from585.84 to 6466.96 ng/L and 4.80 to 11,774.64 ng/L,respectively.The PMF results indicated that surface runoff and erosion accounted for 50%of the total HBCs in water,serving as the primary sources.All tested HBCs exhibited acute risk values within acceptable levels.The risk index for the∑15HBCs was categorized as“moderate risk”in 31%of the surface waters and 13%of the groundwaters.However,4%of the groundwater sampling sites reached the“high risk”level.The chronic risk quotient of∑15HBCs in surface water and groundwater was 92%and 62%at the“high risk”level,respectively.Interestingly,noncarcinogenic HBCs contributed more significantly to the ecotoxicology of the aquatic system than carcinogenic HBCs.This study provides comprehensive information on the legacy of HBCs in water bodies and emphasizes the potential risks posed by HBCs to aquatic systems.The results obtained from this study could help relevant management authorities in developing and implementing effective regulations tomitigate the ecological and environmental risks associated with HBCs.