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Abstract: A novel series of 3-arylsulfonylamino-5,6-dihydro-6-substituted-1H-pyrazolo[3,4-c]pyridine-7-ones was designed and synthesized as 5-HT6 ligands. Among the derivatives synthesized, the lead compound, 12b, having piperidine functionality at the 6-position and (1-naphthyl)sulfonamino at the 3-position of the core structure showed the most potent 5-HT6 inhibitory activity in vitro, good stability without CYP liability, and good neuropathic pain alleviation activity in a rat animal model. [Copyright &y& Elsevier]

This study introduces an implantable scaffold-free (SF) cartilage tissue construct that is composed of chondrocytes and their self-produced extracellular matrix (ECM). Chondrocytes were isolated from the articular cartilages from knees of domestic pigs (2-week old) and monolayer-cultured for 3–4 days in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal calf serum and 50 µg/mL of ascorbic acid. Briefly treated with 0.25% trypsin–ethylenediaminetetraacetic acid (EDTA), an intact chondrocytes/ECM membrane, as a cell sheet was released from the plate bottom and subsequently centrifuged into a pellet-type construct. Each was grown in vitro for up to 5 weeks and subjected to various assays at different time points (1, 7, 14, 21, and 35 days). For in vivo implantation, full-thickness defects ( n = 4) were manually created on the femoro-patellar groove of the left porcine knee and 1-week-cultured SF construct was implanted as an allograft for a month. One defect (♯1) was an empty control and the remaining three received different recipes; construct only (♯2) or 0.25% trypsin/EDTA-treated first and then construct and collagen gel (♯3) or construct and collagen gel (♯4). While the total cell numbers significantly increased by 2 weeks and then remained stable, cell viability stayed in the mid-70% range through the entire culture period. Biochemical assay found continuous glycosaminoglycan (GAG) accumulation. Histology exhibited that cell distribution was even in the construct and GAG intensity became stronger and uniform with time. Real-time reverse transcription polymerase chain reaction (RT-PCR) results showed that phenotypic stability peaked at 2 weeks, which was arable to that of freshly isolated chondrocytes. Upon analysis of the retrieved implants, some promising results were witnessed in the defects (♯3) retaining not only their intact mass but also chondrocytic morphology with lacuna formation. [ABSTRACT FROM AUTHOR]

The water conservation (WC) function of ecosystems is related to regional ecological security and the sustainable development of water resources, and the assessment of WC and its influencing factors is crucial for ecological and water resource management. The Tumen River Basin (TRB) is located in the core of the Northeast Asian ecological network and has been experiencing severe ecological crises and water shortages in recent years due to climate change and human activities. However, these crises have not been fully revealed to the extent that corresponding scientific measures are lacking. This study analyzed the spatial and temporal evolution characteristics and drivers of WC in the TRB from 1990 to 2019 based on the water yield module of the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model. The results showed that: 1) under the combined effect of nature and socioeconomics, the WC depth of the TRB has slowly increased at a rate of 0.11 mm/yr in the past 30 years, with an average WC depth of 36.14 mm. 2) The main driving factor of the spatial variation in WC is precipitation, there is a significant interaction between precipitation and velocity, the interaction between each factor is higher than the contribution of a single factor, and the interactions between factors all have nonlinear enhancement and two-factor enhancement. 3) Among the seven counties and municipalities in the study area, the southern part of Helong City and the southeastern part of Longjing City are extremely important areas for WC (> 75 mm), and they should be regarded as regional water resources and ecological priority protection areas. It is foreseen that under extreme climate conditions in the future, the WC of the watershed is under great potential threat, and protection measures such as afforestation and forestation should begin immediately. Furthermore, the great interannual fluctuations in WC depth may place more stringent requirements on the choice of time scales in the ecosystem service assessment process. [ABSTRACT FROM AUTHOR]

A series of sulfonated polyimide copolymers as novel proton exchange materials were synthesized by the polycondensation of 1,4,5,8-naphthalene-tetracarboxylic dianhydride (NTDA), sulfonated diamine based on pyridine group and diamine containing N-phenyl-1,2,4-triazole moiety. Flexible, transparent and tough membranes with high thermal stability and good mechanical properties were obtained. They exhibited good stability in boiling water and Fenton's reagent at 80 °C. More interestingly, a nonlinear relationship between proton conductivities of the resulting membranes and the degree of sulfonation (DS) was observed. The membrane with 50% DS exhibited the maximum proton conductivity, which was due to the combinational contributions of sulfonic acid and N-pheny-1,2,4-triazole groups. Thus, the N-phenyl-1,2,4-triazole moiety in this study not only can depress water absorption but also increase proton conductivity, especially at low DS. [ABSTRACT FROM AUTHOR]

Cerebellar parallel fiber-Purkinje cell ( PF- PC) long-term synaptic plasticity is important for the formation and stability of cerebellar neuronal circuits, and provides substrates for motor learning and memory. We previously reported both presynaptic long-term potentiation ( LTP) and long-term depression ( LTD) in cerebellar PF- PC synapses in vitro. However, the expression and mechanisms of cerebellar PF- PC synaptic plasticity in the cerebellar cortex in vivo are poorly understood. In the present study, we studied the properties of 4 Hz stimulation-induced PF- PC presynaptic long-term plasticity using in vivo the whole-cell patch-clamp recording technique and pharmacological methods in urethane-anesthetised mice. Our results demonstrated that 4 Hz PF stimulation induced presynaptic LTD of PF- PC synaptic transmission in the intact cerebellar cortex in living mice. The PF- PC presynaptic LTD was attenuated by either the N-methyl-D-aspartate receptor antagonist, D-aminophosphonovaleric acid, or the group 1 metabotropic glutamate receptor antagonist, JNJ16259685, and was abolished by combined D-aminophosphonovaleric acid and JNJ16259685, but enhanced by inhibition of nitric oxide synthase. Blockade of cannabinoid type 1 receptor activity abolished the PF- PC LTD and revealed a presynaptic PF- PC LTP. These data indicate that both endocannabinoids and nitric oxide synthase are involved in the 4 Hz stimulation-induced PF- PC presynaptic plasticity, but the endocannabinoid-dependent PF- PC presynaptic LTD masked the nitric oxide-mediated PF- PC presynaptic LTP in the cerebellar cortex in urethane-anesthetised mice. [ABSTRACT FROM AUTHOR]

• A new function for computing local self-organizing clustering center with SOM clustering algorithm. • An adaptive sign function is presented to replace the constant of the area term in the level set method that enables model to change motion direction of the level set. • An improved double-well potential function is proposed to improve the stability of curve evolution. • The proposed model shows better segmentation accuracy and robustness. Supervised active contour models can use information extracted from supervised samples to guide contour evolution. However, their applicability is limited by the accuracy of the probabilistic models they use, especially when processing images with intensity inhomogeneity. In this paper, an unsupervised activity contour model with Self Organizing Maps (SOM) is proposed. The proposed model employs the self-organizing neural network to perform clustering calculation and the clustering center is called local self-organizing clustering center. An adaptive sign function is used to control the direction of curve evolution. To improve the stability of curve evolution, an improved double-well potential function is proposed. The experiment results show that our model can effectively segment images with intensity inhomogeneity. [ABSTRACT FROM AUTHOR]

• A MS probe N13CS-OTPP for chiral separating of thiol compounds was developed. • The D/L-thiol compounds in human urine were monitored in different states. • Fitted curves of the D/L-thiol compound in different states were plotted. • This study provided a method for monitoring the dynamics of chiral thiol compounds. Monitoring changes in the content of chiral thiol compounds in the human body is crucial for the early diagnosis of oxidative stress-related diseases and the exploration of their pathogenesis. To address this, we synthesized a novel isotope mass spectrometry (MS) probe, denoted as (R)-(5-(3-isothiocyanato (13C) pyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium (N13CS-OTPP), with triphenylphosphine as its parent structure. In this study, we established a new ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC HRMS) relative quantitative method to monitor chiral thiol compounds in human urine under varying oxidative stress conditions. This method relies on the ratio of 12C/13C isotope-labeled peak areas. To assess the chiral separation efficiency of N13CS-OTPP, we employed three types of thiol compounds (D/L-GSH, D/L-Cys, and D/L-Hcy) and observed separation degrees (Rs) ranging from 1.82 to 1.89. We further validated the accuracy and feasibility of our relative quantitative methods using D/L-Cys-as a model compound. N12C/13CS-OTPP-Cys-exhibited excellent linearity (R2 = 0.9993–0.9994) across different molar ratios (D/L-Cys = 10:1, 4:1, 2:1, 1:1, 1:2, 1:4, 1:10) and achieved a low limit of detection (LOD) of 2.5 fmol. Additionally, we monitored the dynamic changes in urine D/L-Cys-and D/L-Hcy ratios in 12 healthy volunteers (six males and six females) under various oxidative stress states. We generated fitting curves and investigated the trends in chiral thiol compounds in vivo. This study introduces a novel method for the relative quantitative monitoring of chiral thiol compounds in different oxidative stress states within the human body. It also presents a new strategy for understanding the pathogenesis of related diseases resulting from the abnormal metabolism of thiol compounds. [ABSTRACT FROM AUTHOR]

• DPSIRM model derived from 23 factors was used to assess wetland ecological security • The weights were determined by combining the AHP and entropy weight method • Ecological security has improved in most areas Ecological safety evaluation is a key tool that reflects changes in the quality of the ecological environment and provides a scientific basis for land use policies and ecological environment construction. This study used the Changbaishan region as the study area, selected 23 indicators from natural and socioeconomic aspects, adopted the Driving Force-Pressure-State-Impact-Response-Management (DPSIRM) model, and used hierarchical analysis and entropy value methods to determine the weights and comprehensively evaluate the ecological security of wetlands. The results showed that the ecological safety value increased from 0.1754 to 0.2933 from 1990–2020 in the Changbai Mountains area, moving the critical safety state to the safety state. The value was lower in the center and higher in the east, north, and southwest. In addition, the wetlands in the north recovered faster. During the study period, the driver, response, and management indices increased, whereas the pressure, state, and impact were relatively stable. The Changbai Mountain region has achieved success in wetland management, education, environmental protection expenditure, ecological compensation, and natural wetland protection; however, rational planning is still needed for urbanization, construction and development, and wetland tourism. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate correlation between three-dimensional medial longitudinal arch joint complex mobility and medial arch angle in stage II posterior tibial tendon dysfunction flatfoot under loading.Methods: CT scans of 15 healthy feet and 15 feet with stage II posterior tibial tendon dysfunction flatfoot were taken both in non- and simulated weight-bearing condition. The CT images of the hindfoot and medial longitudinal arch bones were reconstructed into three-dimensional models with Mimics and Geomagic reverse engineering software. The three-dimensional complex mobility of each joint in the medial longitudinal arch and their correlation with the medial arch angle change were calculated.Results: From non- to simulated weight-bearing condition, the medial arch angle change and the medial longitudinal arch joints mobility were significant larger in stage II posterior tibial tendon dysfunction flatfoot (p<0.05). The eversion of the talocalcaneal joint, the proximal translation of the calcaneus relative to the talus, the dorsiflexion of the talonavicular joint, the dorsiflexion and abduction of the medial cuneonavicular joint, and the lateral translation of the medial cuneiform relative to the navicular, and the dorsiflexion of the first tarsometatarsal joint were all significantly correlated to the medial arch angle change in stage II posterior tibial tendon dysfunction flatfoot (all r>0.5, p<0.05).Conclusions: There is increased mobility in the medial longitudinal arch joints in stage II posterior tibial tendon dysfunction flatfoot and the medial arch angle change under loading causes displacement not only at hindfoot joints but also involve midfoot and forefoot joint. [ABSTRACT FROM AUTHOR]

• Radiation use efficiency, growth module and temperature of trees were modified. • Modified SWAT provides improved forest nutrient simulation and ALP. • Model performance of the import and export of nutrients in litter was evaluated. • Climatic factors and dynamics involved in litter nutrient export were identified. Nutrient release from litter significantly contributes to the global nutrient cycle and the nutritional status of river systems. Simulating the diffuse nutrients from litterfall at the watershed scale is extremely uncertain, owing partly to a lack of measurements covering a variety of features and underlying terrain and insufficient modeling methods. We quantified annual litter production (ALP) simulation at the basin and sub-basin scales by improving the Soil and Water Assessment Tool (SWAT) for forest nutrient cycling, including the forest growth module, tree biomass accumulation, and parametrization scheme. The modified model was comprehensively constrained and calibrated for tree biomass, ALP, monthly dynamics of nutrient mineralization, monthly stream flow, sediment yield, nitrate nitrogen (NO 3 -N), dissolved organic nitrogen (DON), and total phosphorus (TP) in the Tumen River Basin (TRB). Results showed that the modified SWAT increases the ALP simulation from 132.13 ± 21.73 g/m2 to 351.88 ± 18.28 g/m2 and the relative error of spatial ALP decreased from −50.65 %∼66.59 % to −11.18 %∼27.62 %. The accuracy of nitrate improved notably (coefficient of determination (R2) increased by 0.2–0.25, Nash-Sutcliffe Efficiency (NSE) increased by 0.09–0.19), and that of runoff simulation improved modestly (R2 increased by 0.05 and NSE increased by 0.08 for validation period). A comparison with the original simulation of nutrient dynamics also indicated that the modified SWAT model could reasonably identify the dynamics and interactions between litter nutrients and climate factors. Increased mineralization caused by warming and snow melting in spring is the main factor contributing to nitrate accumulation and soluble phosphorus (soluble P) loss in the soil. Improved forest nutrient cycles are expected to help enhance future applications of SWAT for investigating the biogeochemical consequences of climate change. [ABSTRACT FROM AUTHOR]

• Contribution of diffuse nutrients export from forest litterfall in low temperature watershed were quantified. • Critical factors and dynamics involved in the export of nutrients were identified. • Litterfall is a key contributor to spatial nutrients discharge during rainy periods. • Low temperature decreases the litterfall decomposition rate and diffuse nutrient exports. Nutrients exported from forest litterfall significantly contribute to the global cycling of elements and the water quality in watersheds. Simulating the watershed discharge load is challenging because of the combined effects of the decomposing litterfall and topographic heterogeneity. We quantified the contribution of diffuse nutrient export from forest litterfall in a low temperature watershed using artificial rainfall experiments and watershed territorial modeling with remote sensing data, and therefore, the critical spatial factors and corresponding nutrient export dynamics were identified. Rainfall intensity and terrain slope were found to be the key factors for nutrient export under different litterfall decomposition conditions. Based on the moderate resolution imaging spectroradiometer data and field observations, the temporal patterns of litterfall biomass of two types of dominant forests (broad-leaved and mixed) were interpreted. The spatial patterns of total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP) exports from watershed litterfall were simulated by coupling the observed discharge parameters under artificial rainfall conditions and watershed surface flow modeling with the hydrological characteristics of the forested areas. The average watershed TOC, TN, and TP loads exported from the litterfall were approximately 58.22, 7.89, and 0.37 kg ha−1 a−1, respectively. The exported loads of TOC, TN, and TP varied with the forest types, and the loads from the litterfall of deciduous broad-leaved forest were found to be ∼50–70% of loads from the litterfall of mixed forest. A comparison with similar studies worldwide also indicated that low temperature decreased the litterfall decomposition rate and diffuse nutrient export. This study indicated that litterfall nutrients were a key contributor to watershed water pollution, and their spatial discharge trend varied intensively with the terrestrial conditions. The modified simulation methods were found to accurately assess the cycling of nutrients from the forest litterfall on a watershed scale. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, we examined the luminescent properties of uncured and cured samarium tris-(2-thenoyltrifluoroacetone)-1,10-phenanthroline/nitrile rubber composites (Sm(TTA)3phen/NBR, i.e. Sm-complex/NBR). The formula of Sm-complex was determined by infrared spectroscopy (IR) and elementary analysis. The composites were investigated and characterized by photoluminescent (PL) spectroscopy, scanning electron microscopy (SEM) and X-rays diffraction (XRD). The characteristic emission fluorescent intensities of the Sm3+ in both uncured and cured composites increase with the increase of Sm-complex content. For the nitrile rubber composites with the same content of Sm(TTA)3phen, the uncured composites are found to have lower luminescent intensity than that of cured composites. To explain this result, we propose that the cross-linking network structure can help to stabilize the coordination environment of the Sm3+ ion and improve the energy transfer efficiency from the outside energy to the central Sm3+ ion. In our study, the rare earth organic complexes were dispersed homogeneously into the NBR matrix. The fluorescent intensity of the composites was high and no fluorescent quenching had been observed until the complexes concentration was up to 14.3%. [Copyright &y& Elsevier]

[Display omitted] • Carbon dioxide emission source was observed in a forest wetland catchment during rainy season. • NEE variation was influenced by hydrologic DOC and DON exports from surrounding land uses. • Wetland might play an important role in local positive NEE during rainy season. Forest wetland catchments are widely distributed in middle-high latitude and their hydrological and biogeochemical processes are sensitive to climate change. The net ecosystem exchange (NEE), meteorological forcing, and hydrological data in the Shuidong forest wetland catchment (SFWC) were continuously measured by eddy covariance (EC) tower and water monitoring instruments from 2019 to 2020. During rainy season, large carbon dioxide emission was detected with mean NEE value of 1.85 g C m−2 d-1 from local footprint area. Significant positive correlation was observed between daily NEE and air temperature (T air), relative humidity (RH). We further found that the NEE was mainly controlled by ecosystem respiration (RE) instead of gross primary production (GPP), which might be caused by local high Q 10 value. In addition, dissolved organic carbon (DOC) and dissolved organic (DON) concentrations near the stream outlet also had significant positive relationship with NEE, indicating the hydrological transport from upland forests may trigger the soil priming effect and result in higher CO 2 emission within the local footprint area. Soil CO 2 flux measurements from different land uses suggested that wetland may be the primary CO 2 emission source during rainy season. Under the Representative Concentration Pathway (RCP) 8.5 scenario, the CO 2 emission hotspot was expected to occur in this forest wetland catchment due to more frequent rainfall events predicted in this region. [ABSTRACT FROM AUTHOR]

• Diffuse nitrogen export in forest-dominated watersheds is analyzed. • Forests are the main source for diffuse dissolved organic nitrogen export. • Dominant transport path of diffuse dissolved organic nitrogen export from forests is lateral flow. • Returning forest to wetland is helpful for diffuse nitrogen load removal. Along with gradually controlled point source discharges, diffuse nitrogen pollution has become an important cause of eutrophication. Diffuse nitrogen export from forests is an inherent characteristic, and increasing human disturbance aggravates this process. To control diffuse nitrogen pollution effectively, it is of great significance to determine the source, transport path and removal method of diffuse nitrogen export in forest-dominated watersheds. Long-term variations in the nitrogen concentrations indicate that nitrate and dissolved organic nitrogen (DON) are the main diffuse nitrogen export forms in the Buerhatong River watershed (BRW). Thus, the Soil and Water Assessment Tool (SWAT) hydrological model is conducted to simulate diffuse nitrate and DON export. First, main source of diffuse nitrate and DON export is determined by the fitting results of nitrogen contribution and forest/farmland cover. Then, the relationship between nitrogen export from forest/farmland and main hydrologic streamflow is explored. Finally, the role of wetlands in the diffuse nitrogen load removal is analyzed, and sensitivity results by Monte Carlo simulation of nitrogen export from wetlands, forests and farmlands are compared. The average annual diffuse nitrate and DON export values are 1.19 and 0.43 kg ha−1 yr−1, respectively, from 2014 to 2017. When forest cover and farmland cover are higher than 70% and 5%, farmlands and forests are the main sources of diffuse nitrate and DON export, respectively. Lateral flow is the dominant transport path of DON export from forests and nitrate export from farmlands, with correlation coefficient of 0.73 and proportion of 98%, respectively. Wetlands have the ability to reduce the diffuse nitrogen load, and their efficiency is related to the relative geographic location. The in situ experimental results show that the nitrate and DON removal rates by wetlands are 24.46% and 11.71%, respectively. The sensitivity of forest and wetland for diffuse nitrate and DON load removal is 0.31, −0.12 and 0.2, −0.21, respectively. Returning forests to wetlands is a good method for diffuse nitrogen removal with food production taken into consideration. [ABSTRACT FROM AUTHOR]

This study was conducted to compare the changes in different clinical scores and imaging indexes of patients who underwent robot-assisted total knee arthroplasty (RA-TKA) and manual total knee arthroplasty (M-TKA). PubMed, Web of Science, Cochrane Library and Embase were searched according to PRISMA guidelines in June 2024. Search terms included "robot-assisted", "manual" and "total knee arthroplasty". Outcome indicators included American Knee Society Score (KSS), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), range of motion (ROM), Hospital for Special Surgery (HSS) score, Forgotten Joint Score (FJS), 36-Item Short Form Health Survey (SF-36), operation duration (min), intraoperative blood loss (ml), pain score, patient's satisfaction scores, hip-knee-ankle (HKA) angle, frontal femoral component angle, frontal tibia component angle, lateral femoral component angle and lateral tibia component angle. A total of 1,033 articles were obtained after removing duplicates, and 12 studies involving 2,863 patients (1,449 RA-TKAs and 1,414 M-TKAs) were finally meta-analyzed (22-32). The baseline data of both groups were similar in all results. Meta-analysis suggested a better performance of the RA-TKA group than the M-TKA group regarding the HKA angle. The manual TKA reduced the operation time and significantly improved the range of motion. The results of > 6 months follow-up showed that M-TKA was better than RA-TKA in terms of KSS score and WOMAC. Compared with M-TKA, RA-TKA can produce more accurate prosthetic alignment, but it does not lead to better clinical results. Orthopedic surgeons should choose between two surgical procedures according to their own experience and patients' characteristics., (© 2024. The Author(s).)

Landscape patterns affect river water quality by influencing hydrological processes. However, with changes in spatial scale and season, landscape factors may have different effects on water pollution. Therefore, quantitative analysis of the scale effect of each landscape index was carried out to determine the mutation point of river water quality and its index relationship, which is of great significance to landscape planning and water quality protection. Based on the water quality monitoring data of 19 sampling points in the Tumen River Basin, we used redundant methods to quantify the spatial scale effects and seasonal dependencies of various landscape indicators on river water quality, then determined the mutation point of the water quality along the landscape-scale gradient. The results showed that different types of landscape indicators have different effects on river water quality, and the spatial-scale effect of landscape composition affects a river's water quality, while landscape configuration indicators had the highest sensitivity. The landscape characteristics of river straps better explained the overall water quality, a phenomenon that is more obvious in the wet season than the dry season. We identified a key landscape indicator of urban area proportion (Urban%) and a contagion index (CONTAG) as the river strap scale. An Urban% < 30% and a CONTAG > 70% suggest effective landscape planning parameters that effectively protect water quality. The results indicated that, to protect water quality, landscape regulation should follow scale-adaptability measures and consider landscape thresholds, which cause abrupt changes in water quality., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The endothelial inflammatory response plays an important role in atherogenesis by inducing nuclear factor (NF)κB-dependent cell adhesion molecule expression and monocyte recruitment. Here, we screened for natural ligands and investigated the ability of shinjulactone A to inhibit interleukin-1β (IL-1β)-induced endothelial inflammatory signaling., Methods: The natural compound library included 880 single compounds isolated from medicinal plants by the Korean Medicinal Material Bank. Primary endothelial cells were pretreated with single compounds before stimulation with IL-1β to induce endothelial inflammation. Endothelial inflammation was measured by assaying NFκB activation and monocyte adhesion. The endothelial-mesenchymal transition (EndMT) was evaluated using cell type-specific marker protein expression and morphology., Results: Shinjulactone A was identified as an efficient blocker of IL-1β -induced NFκB activation, with a half-maximal inhibitory concentration of approximately 1 µM, and monocyte recruitment in endothelial cells. However, it did not affect lipopolysaccharide-induced NFκB activation in macrophages. Compared to Bay 11-782, a well-known NFκB inhibitor that shows considerable cytotoxicity during long-term treatment, shinjulactone A did not affect endothelial cell viability. Furthermore, it also significantly inhibited the EndMT, which is known to promote atherosclerosis and plaque instability., Conclusion: We suggest that shinjulactone A may be an effective and safe drug candidate for atherosclerosis because it targets and inhibits both endothelial inflammation and the EndMT, without impairing NFκB-dependent innate immunity in macrophages., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2022 The Korean Society of Lipid and Atherosclerosis.)

Phosphoglycerate mutase (PGAM) is a critical enzyme in glycolysis. PGAM2 is abundant in several types of tissues and malignant tumours. However, there is limited information regarding their clinicopathological significance in dysplastic nodules and hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of PGAM2 as a new biomarker for HCC. The PGAM2 expression level was evaluated by immunohistochemistry in liver cirrhosis (n = 10), low-grade dysplastic nodules (n = 15), high-grade dysplastic nodules (n = 15) and HCCs (n = 20) and 178 pairs of HCC and adjacent peritumoral liver tissues. We selected X-tile software for counting cut-point based on the outcomes for prognosis analysis, and used Kaplan-Meier analysis and Cox regression analysis can assess the prognosis of clinicopathologic parameters. Nuclear PGAM2 was significantly overexpressed in peritumoral liver tissues compared with HCC tissues (P = 0.0010). Kaplan-Meier analyses of 178 HCC samples revealed that nuclear PGAM2's high expression level, but not cytoplasmic PGAM2, was significantly related to good overall survival rate (OS). In addition, univariate and multivariate Cox analyses indicated nuclear PGAM2 expression could be regarded as valuable predictors for OS in HCC. PGAM2 was highly expressed in HCC tissues than liver cirrhosis tissues, and nuclear PGAM2's high expression might demonstrate HCC patients have poor postoperative results. Thus, nuclear PGAM2 can be regarded as valuable predictors for OS in HCC patients after surgery., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial neoplasm of the central nervous system, which is difficult to distinguish from other neoplastic and non-neoplastic entities. Herein, we report 2 cases of PXA that had been misdiagnosed as an inflammatory granuloma., Patient Concerns: The first case was a 22-year-old man who originally presented with a generalized seizure 7 years previously. Magnetic resonance imaging (MRI) revealed a lesion in the right parietal lobe, leading to a diagnosis of inflammatory granuloma. The second case was a 43-year-old man who presented with repeated generalized seizures. MRI revealed a nodular lesion in the left temporal lobe. The magnetic resonance spectrum showed elevated Cho and NAA peaks and a decreased Cr peak. An inflammatory granuloma was suspected., Diagnosis: After surgical treatment, histopathological examination revealed PXA., Interventions: In the first case, after 10 months of anti-inflammatory treatment, the lesion was significantly reduced in size. During the following 7 years, the patient experienced generalized seizures 3 to 4 times annually. To control intractable epilepsy, the lesion was resected. In the second case, conservative treatment provided no benefit, and then the lesion was resected., Outcomes: In the first case, during a follow-up period of 14 months, the patient was seizure-free with no tumor recurrence. In the second case, after a 6 months of follow-up, the patient remained seizure-free with no tumor recurrence., Lessons: The preoperative differential diagnosis of PXA is challenging due to the nonspecific symptoms and imaging manifestations. Considering the potential risk of malignant transformation of PXA, early surgery should be highlighted, and gross total resection is associated with a favorable prognosis.

Rhodamine B (RhB), widely used as an industrial dye, is a toxic organic that is hazardous to human health and can cause water pollution. In this study, the removal rate of RhB was investigated by the following methods: hydrodynamic cavitation (HC) operated individually, and HC combined with oxidants H 2 O 2 or ClO 2 . The effect of different operating parameters including pressure (2-6 bar) and initial pH (2-8) on the extent of degradation was investigated using an orifice plate as the cavitation device to achieve maximum removal of RhB. Under the parameters of HC, the effect of different loadings was investigated: H 2 O 2 (n(RhB):n(H 2 O 2 ) was varied from 1:17.60 to 1:211.28) and ClO 2 (n(RhB):n(ClO 2 ) was varied from 1:8.87 to 1:177.53). A combination of cavitation and H 2 O 2 or ClO 2 resulted in degradations of 80.6% and 95.3%. The results indicated that the combination of HC and oxidants was better than the individual HC process for the degradation of RhB. When combining HC with H 2 O 2 or ClO 2 , the synergistic coefficients of 62.54 and 74.79 were obtained. The combination of HC and ClO 2 was proven to be more effective for the removal of RhB compared to HC alone and the hybrid process of HC and H 2 O 2 .

Propofol is a widely used intravenous sedative-hypnotic agent, which causes rapid and reliable loss of consciousness via activation of γ -aminobutyric acid A (GABA A ) receptors. We previously found that propofol inhibited cerebellar Purkinje cells (PC) activity via both GABA A and glycine receptors in vivo in mice. We here examined the effect of propofol on the cerebellar parallel fiber (PF)-PC synaptic transmission in mouse cerebellar slices by whole-cell recording technique and pharmacological methods. We found that following blockade of GABA A and glycine receptors activity, propofol reversely decreased the amplitude of PF-PC excitatory postsynaptic currents (PF-PC EPSCs), and significantly increased paired-pulse ratio (PPR). The propofol-induced decrease in amplitude of PF-PC EPSCs was concentration-dependent. The half-inhibitory concentration (IC 50 ) of propofol for inhibiting PF-PC EPSCs was 4.7 μM. Notably, the propofol-induced changes in amplitude and PPR of PF-PC EPSCs were abolished by GABA B receptor antagonist, saclofen (10 μM), but not blocked by N-methyl-D-aspartate receptor (NMDA) receptor antagonist, D-APV (50 μM). Application of the GABA B receptor agonist baclofen induced a decrease in amplitude and an increase in PPR of PF-PC EPSCs, as well masked the propofol-induced changes in PF-PC EPSCs. Moreover, the propofol-induced changes in amplitude and PPR of PF-PC EPSCs were abolished by a specific protein kinase A (PKA) inhibitor, KT5720. These results indicate that application of propofol facilitates presynaptic GABA B receptors, resulting in a depression of PF-PC synaptic transmission via PKA signaling pathway in mouse cerebellar cortex. The results suggest that the interaction with GABA B receptors may contribute to the general anesthetic action of propofol.

Colorectal cancer (CRC) is one of the most common cancers worldwide. B cell-associated protein 31 (BAP31) was shown to participate in the apoptosis, and to be an immunotherapy target and a, prognostic factor for cancer, but its role in CRC has not been elucidated. In this study, we examined the expression of BAP31 in CRC to evaluate its prognostic values. We investigated the BAP31 expression level in 142 tissues (108 CRC and 17 paired human adjacent normal mucosa, and 17 liver metastatic CRC tissues) from 108 patients, using tissue microarray-based immunohistochemistry. We further investigated the association between BAP31 expression and overall survival (OS) and disease-free survival (DFS) in 77 CRC patients using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were applied to evaluate the potential prognostic value of BAP31 in CRC patients. BAP31 expression level was significantly increased in CRC tissues (p = 0.0014) and liver metastatic CRC tissues (p < 0.0001) compared with corresponding adjacent normal mucosa. BAP31 expression was also significantly increased in liver metastatic CRC tissues compared with corresponding primary CRC tissues (p = 0.0116). Kaplan-Meier analyses showed that CRC patients with low BAP31 expression had significantly lower survival rate (p = 0.001) and lower disease-free survival rate (P = 0.009). Furthermore, multivariate Cox analysis showed that BAP31 was an independent prognostic factor for OS (hazard ratio = 0.410, 95% confidence interval = 0.195-0.862, p = 0.019)., Conclusions: Our study demonstrated that BAP31 is a potential prognostic marker for CRC patients after surgery., (Copyright © 2018. Published by Elsevier GmbH.)

A novel series of fused-benzensulfonamide 2-N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives was designed and synthesized as metabolically stable T-type calcium channel inhibitors. Several compounds, 9, 10, and 17, displayed potent T-type channel inhibitory activity. Among them, compounds 10 and 17 showed good metabolic stability in human liver microsomes, and low hERG channel and CYP450 inhibition. Compound 10 exhibited diabetic neuropathic pain-alleviating effects in a streptozotocin-induced peripheral diabetic neuropathy (PDN) model. The maximum efficacy of compound 10, which was 3-fold more potent than gabapentin, was observed at 1h after administration, and co-administration of compound 10 with gabapentin showed a considerable synergic effect., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background and Objective: Ultrashort time-to-echo (UTE) MRI scanning has been applied to observe the cartilaginous endplate (CEP) in intervertebral disc. CEP plays a critical role in IVD health and disease. Nevertheless, current measurements of CEP based on UTE MRI technique are still by manual segmentation, and observation of signal abnormality was usually time-consuming and often disturbed by subjective bias. This study hence proposed an efficient way to harvest the global parameters of CEP after UTE MRI scanning., Methods: Ex-vivo UTE-MRI scanning was performed using 12 goat lumbar spine specimens. After the UTE-MRI data were collected, the computational method for CEP segmentation and assessment was developed. Global view of CEP, e.g., surface morphology as well as distributions of thickness and signal intensity, were measured. Histological staining of the CEP as well as manual CEP segmentation was then conducted to validate the accuracy., Results: Segmentation of CEP by the proposed method presented a good agreement with manual measurement, with mean Jaccard index of 0.7296 and mean Cohen's Kappa coefficient of 0.8286. The processing time for CEP segmentation and property measurements was 59.2s which was much shorter than the manual measurement., Conclusions: This newly-developed technique is able to qualitatively and quantitatively assess the CEP structure, which is very valuable for the clinicians and researchers to accurately evaluate the endplate health after UTE MRI scanning., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Gliomas are the most common primary intracranial tumors of the central nervous system (CNS), accounting for about one third of all brain tumors. Glioblastoma multiforme (GBM) is the aggressive grade IV glioma with survival as low as 2-5% in the second year post-diagnosis, hence necessitating efficient diagnostic markers. More than 50% of the non-small cell lung cancer (NSCLC) brain metastases are solitary lesions, often difficult to differentiate from gliomas by conventional imaging diagnostics. Here, we explored the utility of measuring serum expression levels of Micro-RNAs (miRs) 221, 608 and 504 as biomarkers for differentiating primary GBMs from solitary metastatic lesions of NSCLC., Methods: Serum expression level of miRs 221, 608 and 504 were determined in 49 GBM, 27 NSCLC brain metastasis patients, and 30 cancer-free normal controls by real time PCR using commercially available miR specific primers. Mann-Whitney U test was used to compare the expression of each miR between each group. Receiver operating characteristics (ROC) curve analysis was also carried out to determine the feasibility of using miR expression as differential diagnosis test., Results: Our results indicated that serum expression of mir-221 was upregulated in GBM as well as in metastatic NSCLC patients. Although both miR-608 and 504 were specifically downregulated only in the GBM patient group, ROC curve analysis showed that only miR-504 serum expression can be utilized as reliable differential diagnosis marker (sensitivity and specificity; 100 and 88.89% respectively)., Conclusions: Serum expression level of miR-504 is a reliable biomarker to be used for differentiating primary GBM from solitary brain metastasis of NSCLC.

Propofol is an intravenous sedative-hypnotic agen, which causes rapid and reliable loss of consciousness. Under in vitro conditions, propofol activates GABAA and glycine receptors in spinal cord, hippocampus and hypothalamus neurons. However, the effects of propofol on the cerebellar neuronal activity under in vivo conditions are currently unclear. In the present study, we examined the effects of propofol on the spontaneous activity of Purkinje cells (PCs) in urethane-anesthetized mice by cell-attached recording and pharmacological methods. Our results showed that cerebellar surface perfusion of propofol (10-1000 μM) induced depression of the PC simple spike (SS) firing rate in a dose-dependent manner, but without significantly changing the properties of complex spikes (CS). The IC50 of propofol for inhibiting SS firing of PCs was 144.5 μM. Application of GABAA receptor antagonist, SR95531 (40 μM) or GABAB receptor antagonist, saclofen (20 μM), as well as glycine receptor antagonist, strychnine (10 μM) alone failed to prevent the propofol-induced inhibition of PCs spontaneous activity. However, application the mixture of SR95531 (40 μM) and strychnine (10 μM) completely blocked the propofol-induced inhibition of PC SS firing. These data indicated that cerebellar surface application of propofol depressed PC SS firing rate via facilitation of GABAA and functional glycine receptors activity in adult cerebellar PCs under in vivo conditions. Our present results provide a new insight of the anesthetic action of propofol in cerebellar cortex, suggesting that propofol depresses the SS outputs of cerebellar PCs which is involved in both GABAA and glycine receptors activity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate clinical significance of microRNA-130b (miR-130b) in osteosarcoma and its role in cell growth and invasion., Methods: miR-130b expression was detected in 68 samples of surgically resected osteosarcoma and matched normal tumor-adjacent tissues by qRT-PCR. The expression of miR-130b was altered by corresponding vectors in osteosarcoma cells, and then Western blot was used to detect the expression of PPARγ. BrdU cell proliferation and Transwell assays were performed to determine cell proliferation and invasion., Results: The expression of miR-130b in osteosarcoma tissues was significantly higher than that in normal tumor-adjacent tissues. Its expression in patients with metastasis was significantly higher than that in those without metastases. miR-130b expression in tumor tissues was significantly associated with tumor size, clinical stage and distant metastasis. And its expression was significantly correlated with overall survival and disease free survival. miR-130b overexpression obviously repressed the expression of PPARγ, and resulted in significant increase of Saos-2 cell proliferation and invasion. On the contrast, repressing miR-130b expression with its inhibitor significantly increased PPARγ expression, and inhibited MG-63 cell proliferation and invasion., Conclusions: The high-expression of miR-130b is correlated with the adverse clinicopathological features and poor prognosis in osteosarcoma. miR-130b may regulate proliferation and invasion of osteosarcoma cells by targeting PPARγ, suggesting miR-130b may play a key role in the progression of osteosarcoma., (Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: To investigate the effectiveness of anterior knee incision by the patellar longitudinal approach for osteotomy in treating type C fractures of the distal femur., Methods: Between March 2010 and June 2014, 36 patients with type C fractures of the distal femur underwent fracture reduction and internal fixation by patellar longitudinal approach for osteotomy. There were 25 males and 11 females, aged 26-72 years (mean, 49 years). Injury causes included traffic accident injury (19 cases), falling injury from height (8 cases), and crushing injury (9 cases). There were 34 cases of closed fracture and 2 cases of open fracture. Associated fractures included 2 cases of patellar fracture and 4 cases of clavicular fracture; combined injuries included 4 cases of anterior cruciate ligament injury, 1 case of posterior cruciate ligament injury, 12 cases of meniscus injury, and 9 cases of medial and lateral collateral ligament injuries. It was 3-11 days from injury to operation (mean, 6 days)., Results: Among 36 patients, 29 were followed up 12-24 months (mean, 18 months). Primary healing of incision was obtained, without infection or lower limb deep venous thrombosis. X-ray films showed fracture healing at 12-32 weeks (mean, 16.4 weeks). Neither loosening of screw and plate breakage nor valgus and varus knee occurred. Pain and stiff of the knee joint were observed in 4 and 2 cases, respectively; 4 cases walked with a cane. According to Hospital for Special Surgery (HSS) scoring system, the results were excellent in 21 cases, good in 7 cases, and fair in 1 case; and the excellent and good rate was 96.55%. The internal fixation was removed at 10-14 months after operation, and there was no re-fracture., Conclusion: The patellar longitudinal approach has the advantages of sufficient exposure, easy reduction, short operation time, good internal fixation, less damage of soft tissue, and less complication. So it is the appropriate approach to treat type C fractures of the distal femur.

Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae family, is an enveloped, positive-sense, single-stranded RNA virus, which causes severe diarrhea and dehydration in suckling pigs. We detected three PEDV strains from ten small intestine samples from piglets with acute diarrhea and we determined the complete genome sequences of the reemerging Korean PEDV field isolates, except for the noncoding regions from both ends. The complete genome sequences of the strains were identical or almost identical (one synonymous single-nucleotide polymorphism (SNP) in the ORF1a/1b genomic sequence). Interestingly, comparative genome analysis of recent Korean PEDV isolates and other strains revealed that the complete genome sequences of recent Korean strains were almost identical (99.9%) to those of the US PEDV strains isolated in 2013. These results suggest that the three reemerging Korean strains are distinct from previous endemic Korean PEDV strains and has been recently introduced into Korea from oversea with high likelihood., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To investigate the migration of fluorescent dye PKH26-labeled BM-MSC in the Alzheimer's model rats., Methods: Normal human bone marrow extracted for isolation of BM-MSC was cultured in vitro. The 5th passaged BM-MSC was labeled with PKH26, and observed under a fluorescence microscope for PKH26 labeling efficiency, and using flow cytometry BM-MSC surface markers was checked. The PKH26 labeled BM-MSC injected into the tail vein of the normal control group and AD animal model group, 14 days after finding the PKH26-labeled BM-MSC cells in the rat hippocampus using fluorescence microscopy. Using the Morris water maze experiment comparison of AD model and BM-MSC transplantation group of spatial learning and memory ability., Results: TFlow cytometry showed BM-MSC surface markers CD73 and CD105 were positive. In vitro, PKH26-labeled rate of BM-MSC was 100 %. The Morris water maze experiment comparison of BM-MSC transplantation group and AD group of animals, BM-MSC transplantation group at 13, 14 days of spatial learning and memory ability than AD animal group had significantly improved. 14 days after BM-MSCs in rat hippocampus could be found which were PKH26-positive, consistent with DAPI staining. PKH26-positive cells in animal models of AD were significantly more than those in the normal control group., Conclusion: BM-MSC in AD rats not only migrates through the blood-brain barrier, but also mainly survives in the hippocampus of AD rats, and it can improve AD rat model of learning disabilities.