Response of water quality in major tributaries to the difference of multi-scale landscape indicators in Dongting Lake basin, China.

River water quality has been increasingly deteriorated because of the influence of natural process and anthropogenic activities. Quantifying the influence of landscape metrics, namely topography and land use pattern, which encompass land use composition and landscape configuration, across different spatial and seasonal scales that reflect natural process and anthropogenic activities, is highly beneficial for water quality protection. In this study, we focused on investigating the effects of topography, landscape configuration and land use composition on water quality at different spatial scales, including 1-km buffer and sub-watershed, and seasonal scales, including wet and dry season, based on the monthly water quality data in 2016 of Dongting Lake in China. Multivariate statistical analysis of redundancy analysis and partial redundancy analysis was used to quantify the contributions of these factors under different scales. Our results showed that among the three environmental groups, topography made the greatest pure contribution to water quality, accounting for 11.4 to 30.9% of the variation. This was followed by landscape configuration, which accounted for 9.4 to 23.0%, and land use composition, which accounted for 5.9 to 15.7%. More specifically, water body made the greatest contribution to the water quality variation during dry season at both spatial scales, contributing 16.6 to 17.2% of the variation. In contrast, edge density was the primary interpreter of the variability in water quality during wet season at both spatial scales, accounting for 9.9 to 11.1% of the variation. The spatial variability in the influence of landscape metrics on water quality was not markedly distinct. However, these metrics have a minimal impact difference on water quality at the buffer scale and the sub-watershed scale. Moreover, the contribution of landscape configuration varied the most from the buffer to sub-watershed scales, indicating its importance for the spatial scale difference in water quality. The findings of this study offer useful insights into enhancing water quality through improved handling of landscape metrics.

Identify the seasonal differences in water quality and pollution sources between river-connected and gate-controlled lakes in the Yangtze River basin.

The river-connected Dongting Lake (DT) and Poyang Lake (PY), and the gate-controlled Taihu Lake (TH) and Chaohu Lake (CH) are the four important lakes in the Yangtze River Basin. The comprehensive Water Quality Index (WQI), the Eutrophication Integrated Index (TLI(Σ)), and the Positive Matrix Factorization (PMF) model were employed to evaluate water quality and the contribution of pollution sources for these lakes. The results show that WQI for all lakes indicated generally good water quality, with DT scoring 73.52-86.18, the highest among them. During the wet season, the eutrophication degree of river-connected lake was medium, and that of gate-controlled lakes was high. The surface runoff and agricultural non-point sources are the main pollution sources for both types of lakes, but their impact is more pronounced in gate-controlled lakes during the wet season. The study provides evidence support for scientific understanding of water quality problems and management strategies in these areas.

Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis.

In eukaryotes, the nucleolus is the critical non-membranous organelle within nuclei that is responsible for ribosomal DNA (rDNA) transcription and ribosome biogenesis. The transcription of rDNA, a rate-limiting step for ribosome biogenesis, is tightly regulated to meet the demand for global protein synthesis in response to cell physiology, especially in neurons, which undergo rapid changes in morphology and protein composition during development and synaptic plasticity. However, it is unknown how the pre-initiation complex for rDNA transcription is efficiently assembled within the nucleolus in neurons. Here, we report that the nucleolar protein, coronin 2B, regulates rDNA transcription and maintains nucleolar function through direct interaction with upstream binding factor (UBF), an activator of RNA polymerase I transcriptional machinery. We show that coronin 2B knockdown impairs the formation of the transcription initiation complex, inhibits rDNA transcription, destroys nucleolar integrity, and ultimately induces nucleolar stress. In turn, coronin 2B-mediated nucleolar stress leads to p53 stabilization and activation, eventually resulting in neuronal apoptosis. Thus, we identified that coronin 2B coordinates with UBF to regulate rDNA transcription and maintain proper nucleolar function in neurons.

Health and ecological risk of heavy metals in agricultural soils related to Tungsten mining in Southern Jiangxi Province, China.

Background: Dayu County, a major tungsten producer in China, experiences severe heavy metal pollution. This study evaluated the pollution status, the accumulation characteristics in paddy rice, and the potential ecological risks of heavy metals in agricutural soils near tungsten mining areas of Dayu County. Furthermore, the impacts of soil properties on the accumulation of heavy metals in soil were explored. Methods: The geo-accumulation index (Igeo), the contamination factor (CF), and the pollution load index (PLI) were used to evaluate the pollution status of metals (As, Cd, Cu, Cr, Pb, Mo, W, and Zn) in soils. The ecological risk factor (RI) was used to assess the potential ecological risks of heavy metals in soil. The health risks and accumulation of heavy metals in paddy rice were evaluated using the health risk index and the translocation factor (TF), respectively. Pearson's correlation coefficient was used to discuss the influence of soil factors on heavy metal contents in soil. Results: The concentrations of metals exceeded the respective average background values for soils (As: 10.4, Cd: 0.10, Cu: 20.8, Cr: 48.0, Pb: 32.1, Mo: 0.30, W: 4.93, Zn: 69.0, mg/kg). The levels of As, Cd, Mo, and tungsten(W) exceeded the risk screening values for Chinese agricultural soil contamination and the Dutch standard. The mean concentrations of the eight tested heavy metals followed the order FJ-S > QL > FJ-N > HL > CJ-E > CJ-W, with a significant distribution throughout the Zhangjiang River basin. Heavy metals, especially Cd, were enriched in paddy rice. The Igeo and CF assessment indicated that the soil was moderately to heavily polluted by Mo, W and Cd, and the PLI assessment indicated the the sites of FJ-S and QL were extremely severely polluted due to the contribution of Cd, Mo and W. The RI results indicated that Cd posed the highest risk near tungsten mining areas. The non-carcinogenic and total carcinogenic risks were above the threshold values (non-carcinogenic risk by HQ > 1, carcinogenic risks by CR > 1 × 10-4 a-1) for As and Cd. Correlation analysis indicated that K2O, Na2O, and CaO are main factors affecting the accumulation and migration of heavy metals in soils and plants. Our findings reveal significant contamination of soils and crops with heavy metals, especially Cd, Mo, and W, near mining areas, highlighting serious health risks. This emphasizes the need for immediate remedial actions and the implementation of stringent environmental policies to safeguard health and the environment.

Sulfuric acid-assisted ball milling for the preparation of Si-O-enriched straw biochar: removal efficiency of rhodamine B and adsorption mechanism.

Traditional pyrolysis biochar has been widely employed to treat dye wastewater. However, there are some problems in the pyrolysis process, such as the generation of harmful gases and the low content of silico-oxygen functional groups to promote adsorption. Straw biochar (Ac-BCbm) was prepared by sulfuric acid co-ball milling method. The adsorption performance and adsorption mechanism of rhodamine B (RhB) under different preparation conditions and factors were investigated. The results showed that the adsorption rate of Ac-BCbm on RhB was up to 94.9%, which was 60.5% and 55.8% higher than that of ball-milling straw (STbm) and biochar prepared by pyrolysis (STBC600), respectively. The Ac-BCbm had better adaptability under different pH and common interfering ions for remove RhB. Characterization and DFT simulation analysis revealed that the sulfuric acid co-ball milling process promoted the formation of Si-OH and Si-O-CH3 oxygen-containing functional groups of Si component in straw, which enhanced the hydrogen bonding interactions and effectively improved the adsorption efficiency. This study investigated a new strategy for biochar preparation by sulfuric acid co-ball milling, which provides an additional development direction for the efficient resource utilization of straw.

Analyzing the phosphorus flow characteristics in the largest freshwater lake (Poyang Lake) watershed of China from 1950 to 2020 through a bottom-up approach of watershed-scale phosphorus substance flow model.

Understanding the historical patterns of phosphorus (P) cycling is essential for sustainable P management and eutrophication mitigation in watersheds. Currently, there is a lack of long-term watershed-scale models that analyze the flow of P substances and quantify the socioeconomic patterns of P flow. This study adopted a watershed perspective and incorporated crucial economic and social subsystems related to P production, consumption, and emissions throughout the entire life cycle. Based on this approach, a bottom-up watershed P flow analysis model was developed to quantify the P cycle for the first time in the Poyang Lake watershed from 1950 to 2020 and to explore the driving factors that influence its strength by analyzing multi-year P flow results. In general, the P cycle in the Poyang Lake watershed was no longer a naturally dominated cycle but significantly influenced by human activities during the flow dynamics between 1950 and 2015. Agricultural intensification and expansion of large-scale livestock farming continue to enhance the P flow in the study area. Fertilizer P inputs from cultivation account for approximately 60% of the total inputs to farming systems, but phosphate fertilizer utilization continues to decline. Feed P inputs have continued to increase since 2007. The expansion of large-scale farming and the demand for urbanization are the main factors leading to changes in feed P input patterns. The P utilization rate for livestock farming (PUEa) is progressively higher than international levels, with PUEa increasing from 0.64% (1950) to 9.7% (2020). Additionally, per capita food P consumption in the watershed increased from 0.67 kg to 0.80 kg between 1950 and 2020. The anthropogenic P emissions have increased from 1.67 × 104 t (1950) to 8.73 × 104 t (2020), with an average annual growth rate of 2.41%. Watershed-wide P pollution emissions have increased by more than five-fold. Population growth and agricultural development are important drivers of structural changes in P flows in the study area, and they induce changes in social conditions, including agricultural production, dietary structure, and consumption levels, further dominating the cyclic patterns of P use, discharge, and recycling. This study provides a broader and applicable P flow model to measure the characteristics of the P cycle throughout the watershed social system as well as provides methodological support and policy insights for large lakes in rapidly developing areas or countries to easily present P flow structures and sustainably manage P resources.

[Evaluation of Shallow Groundwater Quality and Optimization of Monitoring Indicators in Nanchang].

In the process of groundwater environmental monitoring, while ensuring the representativeness of groundwater quality evaluation, the number of monitoring indicators should be optimized as much as possible, which is of great significance to groundwater environmental management. Based on monitoring data of shallow groundwater in Nanchang in 2014 and 2019, the chemical characteristics of water and the changes in water quality were analyzed via statistical analysis, a Piper three-line diagram, and the entropy-weighted water quality index (EWQI). Furthermore, a key indicator optimization method based on water quality evaluation was constructed by coupling stepwise multiple linear regression analysis. The feasibility of this method was also evaluated. The results showed that the water chemistry type of groundwater in 2014 and 2019 was mainly HCO3-Ca, and the five abnormal indicators pH value, NO3-, I-, Fe, and Mn were the main influencing factors of water quality change. The water quality in 2019 was generally higher than that in 2014, which was considered as overall "moderate," and the average EWQI values of the two years were 53.72 and 82.34, respectively. The optimal model EWQImin-4 constructed based on the key indicator optimization method could better represent the actual EWQI; the key indicators included Mn, NO3-, TH, Fe, pH value, and I-; and the determination coefficient (R2) and percentage error (PE) values were 0.865 and 10.61%, respectively. Therefore, the optimization method of groundwater monitoring indicators based on entropy-weighted water quality evaluation could be used as an important reference for optimizing monitoring indicators and provide a method for regional groundwater environmental management.

Pollution and health risk assessment of rare earth elements in Citrus sinensis growing soil in mining area of southern China.

Background: Analyzing the pollution and health risk of rare earth elements (REEs) in crop-growing soils around rare earth deposits can facilitate the improvement of REE mining-influenced area. In this study, pollution status, fraction and anomaly, plant accumulation characteristics, and potential risks of REEs (including heavy and light rare earth elements, HREEs and LREEs) in C. sinensis planting soil near ion-adsorption deposits in southern Ganzhou were analyzed. The influence of the soil environment on REEs in soil and fruit of C. sinensis was also explored. Methods: The geo-accumulation index (Igeo) and ecological risk index(RI) were used to analyze the pollution potential and ecological risks of REEs in soils, respectively. Health risk index and translocation factor (TF) were applied to analyze the accumulation and health risks of REEs in fruit of C. sinensis. The influence of soil factors on REEs in soil and fruit of C. sinensis were determined via correlation and redundancy analysis. Results: Comparison with background values and assessment of Igeo and RI indicated that the soil was polluted by REEs, albeit at varying degrees. Fractionation between LREEs and HREEs occurred, along with significant positive Ce anomaly and negative Eu anomaly. With TF values < 1, our results suggest that C. sinensis has a weak ability to accumulate REEs in its fruit. The concentrations of REEs in fruit differed between LREEs and HREEs, with content of HREE in fruit ordered as Jiading > Anxi > Wuyang and of LREE in fruit higher in Wuyang. Correlation and redundancy analysis indicated that K2O, Fe2O3 and TOC are important soil factors influencing REE accumulation by C. sinensis, with K2O positively related and Fe2O3 and TOC negatively related to the accumulation process.

Strategy for cost-effective BMPs of non-point source pollution in the small agricultural watershed of Poyang Lake: A case study of the Zhuxi River.

In recent years, Poyang Lake has been affected by severe agricultural non-point source (NPS) pollution, a global water pollution problem. The most recognized and effective control measure for agricultural NPS pollution is the strategic selection and placement of best management practices (BMPs) for critical source areas (CSAs). The present study employed the Soil and Water Assessment Tool (SWAT) model to identify CSAs and evaluate the effectiveness of different BMPs in reducing agricultural NPS pollutants in the typical sub-watersheds of the Poyang Lake watershed. The model performed well and satisfactorily in simulating the streamflow and sediment yield at the outlet of the Zhuxi River watershed. The results indicated that urbanization-oriented development strategies and the Grain for Green program (returning the grain plots to forestry) had certain effects on the land-use structure. The proportion of cropland in the study area decreased from 61.45% (2010) to 7.48% (2018) in response to the Grain for Green program, which was mainly converted to forest land (58.7%) and settlements (36.8%). Land-use type changes alter the occurrence of runoff and sediment, which further affect the nitrogen (N) and phosphorus (P) loads since sediment load intensity is a key factor affecting the P load intensity. Vegetation buffer strips (VBSs) proved the most effective BMPs for NPS pollutant reduction, and the cost of 5-m VBSs proved the lowest. The effectiveness of each BMP in reducing N/P load ranked as follows: VBS > grassed river channels (GRC) > 20% fertilizer reduction (FR20) > no-tillage (NT) > 10% fertilizer reduction (FR10). All combined BMPs had higher N and P removal efficiencies than the individual measures. We recommend combining FR20 and VBS-5m or NT and VBS-5m, which could achieve nearly 60% pollutant removal. Depending on the site conditions, the choice between FR20+VBS and NT + VBS is flexible for targeted implementation. Our findings may contribute to the effective implementation of BMPs in the Poyang Lake watershed and provide theoretical support and practical guidance for agricultural authorities to perform and direct agricultural NPS pollution prevention and control.

Role of phosphite in the environmental phosphorus cycle.

In modern geochemistry, phosphorus (P) is considered synonymous with phosphate (Pi) because Pi controls the growth of organisms as a limiting nutrient in many ecosystems. The researchers therefore realised that a complete P cycle is essential. Limited by thermodynamic barriers, P was long believed to be incapable of redox reactions, and the role of the redox cycle of reduced P in the global P cycling system was thus not ascertained. Nevertheless, the phosphite (Phi) form of P is widely present in various environments and participates in the global P redox cycle. Herein, global quantitative evidences of Phi are enumerated and the early origin and modern biotic/abiotic sources of Phi are elaborated. Further, the Phi-based redox pathway for P reduction is analysed and global multienvironmental Phi redox cycle processes are proposed on the basis of this pathway. The possible role of Phi in controlling algae in eutrophic lakes and its ecological benefits to plants are proposed. In this manner, the important role of Phi in the P redox cycle and global P cycle is systematically and comprehensively identified and confirmed. This work will provide scientific guidance for the future production and use of Phi products and arouse attention and interest on clarifying the role of Phi in the environmental phosphorus cycle.

Tunable circular conversion dichroism of single-layer twisted graphene-patterned metasurface.

Two-dimensional (2D) chirality-induced asymmetric transmission/reflection has great potential for polarization applications. Usually, asymmetric effects resulting from circular conversion dichroism (CCD) occur in chiral metasurfaces. Here, we propose a single-layer twisted graphene-patterned (with tilted elliptical hole arrays) metasurface and theoretically reveal its tunable CCD in the terahertz (THz) region. The unit cell of the metasurface is achiral. Merely by altering the in-plane orientation of holes for structural 2D chirality, a tunable CCD can be achieved at normal incidence. Interestingly, the reflection phase can be considered an intuitive method to show this metasurface's anisotropy, which complements the conventional CCD measurement in characterizing chiral materials. Furthermore, we can achieve active CCD based on the tunability of graphene. Due to the Fabry-Pérot resonance, a multiband enhancement of CCD spectrum will happen by changing the dielectric layer thickness. The proposed metasurface provides more flexible opportunities for designing active THz devices for polarization manipulation.

Xanthones from securidaca inappendiculata antagonizes the anti-rheumatic effect of methotrexate by inhibiting reduced folate carrier 1.

BACKGROUND: The first-line anti-rheumatic drug methotrexate (MTX) is used in the combination. Because of the unpredictable adverse reactions, optimization of relevant regimens is necessary and meaningful. This study aimed to study the possible interaction between Securidaca inappendiculate Hassk. Derived xanthones and MTX. METHODS: We established adjuvant-induced arthritis (AIA) model, which was treated with MTX and MTX + xanthone-rich fraction (XRF). The clinical efficacy was evaluated by histopathological examination, and LC-MS was used to monitor the blood concentration of MTX. Western blotting and immunohistochemistry were used to detect protein expression. In vitro, we assessed the activity of related transporters by cellular uptake assay based on HEK-293T cells. RESULTS: Compared with MTX-treated rats, inflammation in the immunized rats in the MTX + XRF group was obvious, indicating that XRF antagonized the anti-rheumatic effect of MTX. Meanwhile, XRF reduced liver and kidney injuries caused by MTX in addition to MTX. Results from immunohistochemical and nappendiculat assays suggested that XRF may reduce uptake of MTX by down-regulating reduced folate carrier 1 (RFC1). CONCLUSION: This study indicated that XRF could reduce the plasma concentration of MTX by inhibiting the expression of RFC1, antagonize the therapeutic effect of MTX on AIA rats, and reduce its oral bioavailability. The combination of S. inappendiculate and MTX should be further optimized to achieve the goal of increasing efficiency and reducing toxicity.

Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions.

BACKGROUND: Brain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen-glucose deprivation (OGD). METHODS: We examined astrocytic NDRG2 expression after middle cerebral artery occlusion (MCAO) using western blot and immunofluorescence staining. Under hypoxia conditions, we added exogenous L-lactate sodium (lactate) to cultured primary astrocytes to explore the effects of lactate on the ubiquitination modification of NDRG2. We profiled the transcriptomic features of NDRG2 silencing in astrocytes after 8 h of OGD conditions as well as exogenous lactate treatment by performing RNA-seq. Finally, we evaluated the molecular mechanisms of NDRG2 in regulating TNFα under OGD conditions using western blot and immunohistochemistry. RESULTS: Reactive astrocytes strongly expressed NDRG2 in a rat model of MCAO. We also showed that lactate stabilizes astrocytic NDRG2 by inhibiting its ubiquitination. NDRG2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways. NDRG2 knockdown induced TNFα expression and secretion via c-Jun phosphorylation. CONCLUSIONS: We revealed that under OGD conditions, lactate plays an important anti-inflammatory role and inhibits TNFα expression by stabilizing NDRG2, which is beneficial for neurological functional recovery. NDRG2 may be a new therapeutic target for cerebral ischemia.

Soft substrates promote direct chemical reprogramming of fibroblasts into neurons.

Fibroblasts can be directly reprogrammed via a combination of small molecules to generate induced neurons (iNs), bypassing intermediate stages. This method holds great promise for regenerative medicine; however, it remains inefficient. Recently, studies have suggested that physical cues may improve the direct reprogramming of fibroblasts into neurons, but the underlying mechanisms remain to be further explored, and the physical factors reported to date do not exhibit the full properties of the extracellular matrix (ECM). Previous in vitro studies mainly used rigid polystyrene dishes, while one of the characteristics of the native in-vivo environment of neurons is the soft nature of brain ECM. The reported stiffness of brain tissue is very soft ranging between 100 Pa and 3 kPa, and the effect of substrate stiffness on direct neuronal reprogramming has not been explored. Here, we show for the first time that soft substrates substantially improved the production efficiency and quality of iNs, without needing to co-culture with glial cells during reprogramming, producing more glutamatergic neurons with electrophysiological functions in a shorter time. Transcriptome sequencing indicated that soft substrates might promote glutamatergic neuron reprogramming through integrins, actin cytoskeleton, Hippo signalling pathway, and regulation of mesenchymal-to-epithelial transition, and competing endogenous RNA network analysis provided new targets for neuronal reprogramming. We demonstrated that soft substrates may promote neuronal reprogramming by inhibiting microRNA-615-3p-targeting integrin subunit beta 4. Our findings can aid the development of regenerative therapies and help improve our understanding of neuronal reprogramming. STATEMENT OF SIGNIFICANCE: First, we have shown that low stiffness promotes direct reprogramming on the basis of small molecule combinations. To the best of our knowledge, this is the first report on this type of method, which may greatly promote the progress of neural reprogramming. Second, we found that microRNA (miR)-615-3p may interact with integrin subunit beta 4 (ITGB4), and the soft substrates may promote neural reprogramming by inhibiting miR-615-3p targeting ITGB4. We are the first to report on this mechanism. Our findings will provide more functional neurons for subsequent basic and clinical research in neurological regenerative medicine, and will help to improve the overall understanding of neural reprogramming. This work also provides new ideas for the design of medical biomaterials for nerve regeneration.

Giant 2D-chiroptical response in an achiral metasurface integrated with black phosphorus.

In this work, we proposed a black phosphorus (BP) achiral metasurface and theoretically study the chiroptical response arising from extrinsic 2D-chirality in the mid-infrared regime. The achiral metasurface is composed of a monolayer BP sheet sandwiched by a silver ring array and dielectric spacer stacking on a silver substrate. The giant circular conversion dichroism (CCD) of the achiral metasurface is allowed at oblique incidence for the cooperative interaction of BP anisotropic surface plasmon modes and localized surface plasmons in metal rings, and the integrated BP can dynamically modulate the chiroptical response by controlling the doping concentration of BP. Furthermore, we found that a multiband phenomenon for CCD response occurs when tuning the thickness of the spacer. The proposed hybrid achiral metasurface provides more flexible opportunities to realize active polarization modulator, biosensor and chiral detection.

α-Mangostin Treats Early-Stage Adjuvant-Induced Arthritis of Rat by Regulating the CAP-SIRT1 Pathway in Macrophages.

BACKGROUND: Studies have found that α-mangostin (MG) can relieve experimental arthritis by activating cholinergic anti-inflammatory pathway (CAP). It affects the polarization of macrophages and the balance of related immune cell subpopulations, but the specific mechanism is still unclear. It has been found that silent information regulator 1 (SIRT1) is closely related to macrophage activity. The purpose of this study is to explore the mechanism of MG intervening in macrophage polarization during treatment of early adjuvant-induced (AIA) rats through the CAP-SIRT1 pathway. METHODS: We investigated the polarization of M1 macrophages and the differentiation of Th1 in AIA rats by flow cytometry. Activity of acetylcholinesterase (AChE) and the level of nicotinic adenine dinucleotide (NAD+) in serum were also detected, and immunohistochemical was used to detect the levels of α7 nicotinic cholinergic receptor (α7nAChR) and SIRT1. Then in macrophages, the molecular mechanism of MG regulating the abnormal activation of macrophages in rats with early AIA through the CAP-SIRT1 pathway was studied. RESULTS: MG can significantly inhibit the polarization of M1 macrophages and the differentiation of Th1 in AIA rats in the acute phase of inflammation. MG can significantly inhibit the activity of AChE and increase the level of NAD+, thereby further up-regulated the expression levels of α7nAChR and SIRT1. Meanwhile, MG inhibited nuclear factor-κB (NF-κB)-mediated inflammation by activating the CAP-SIRT1 pathway in macrophages. CONCLUSION: In summary, the stimulation of MG induced CAP activation, which up-regulated SIRT1 signal, and thereby inhibited M1 polarization through the NF-κB pathway, and improved the pathological immune environment of early-stage AIA rats.

Extramedullary Osseointegration-A Novel Design of Percutaneous Osseointegration Prosthesis for Amputees.

The percutaneous osseointegrated (OI) prostheses have greatly improved the overall quality of life for amputees. However, the long-term maintenance of the OI prostheses is still challenging. A major problem is bone resorption around the bone-implant-skin interface, which might cause implant loosening or osteomyelitis. Another problem is the breakage of connecting components between the intramedullary implant and external prosthesis due to excessive stress. We designed a novel osseointegration implant by changing the bone-implant contact from the inner cortex to the outer surface of cortical bone. In the current study, we compared the extramedullary cap-shaped implants with the intramedullary screw-type implants in rabbits. Osteointegration was confirmed at the interface of bone to implant contact (BIC) in both implant types. The external implant induced intramedullary bone regeneration in the medullary canal and increased the cortical bone density at the end of the stump. This study provides a new perspective on the design of osseointegration implants which might prevent the currently reported complications of the intramedullary OI systems.

miR-124: A Promising Therapeutic Target for Central Nervous System Injuries and Diseases.

Central nervous system injuries and diseases, such as ischemic stroke, spinal cord injury, neurodegenerative diseases, glioblastoma, multiple sclerosis, and the resulting neuroinflammation often lead to death or long-term disability. MicroRNAs are small, non-coding, single-stranded RNAs that regulate posttranscriptional gene expression in both physiological and pathological cellular processes, including central nervous system injuries and disorders. Studies on miR-124, one of the most abundant microRNAs in the central nervous system, have shown that its dysregulation is related to the occurrence and development of pathology within the central nervous system. Herein, we review the molecular regulatory functions, underlying mechanisms, and effective delivery methods of miR-124 in the central nervous system, where it is involved in pathological conditions. The review also provides novel insights into the therapeutic target potential of miR-124 in the treatment of human central nervous system injuries or diseases.

Retinal Dysfunction in Alzheimer's Disease and Implications for Biomarkers.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that manifests as cognitive deficits and memory decline, especially in old age. Several biomarkers have been developed to monitor AD progression. Given that the retina and brain share some similarities including features related to anatomical composition and neurological functions, the retina is closely associated with the progression of AD. Herein, we review the evidence of retinal dysfunction in AD, particularly at the early stage, together with the underlying molecular mechanisms. Furthermore, we compared the retinal pathologies of AD and other ophthalmological diseases and summarized potential retinal biomarkers measurable by existing technologies for detecting AD, providing insights for the future development of diagnostic tools.

Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders.

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.