Dynamic monitoring and analysis of chlorophyll-a concentrations in global lakes using Sentinel-2 images in Google Earth Engine.

Remote estimation of Chlorophyll-a (Chl-a) has long been used to investigate the responses of aquatic ecosystems to global climate change. High-spatiotemporal-resolution Sentinel-2 satellite images make it possible to routinely monitor and trace the spatial distributions of lake Chl-a if reliable retrieval algorithms are available. In this study, Sentinel-2 images and in-situ measured data were used to develop a Chl-a retrieval algorithm based on 13 optical water types (OWTs) with a satisfying performance (R2 = 0.74, RMSE = 0.42 mg/m3, MAE = 0.33 mg/m3, and MAPE = 55.56 %). After removing the disturbance of algal blooms and other factors, the distribution of Chl-a in 3067 of the largest global lakes (≥50 km2) was mapped using the Google Earth Engine (GEE). From 2019 to 2021, the average Chl-a concentration was 16.95 ± 5.95 mg/m3 for the largest global lakes. During the COVID-19 pandemic, global lake-averaged Chl-a concentration reached its lowest value in 2020. From the perspective of spatial distribution, lakes with low Chl-a concentrations were mainly distributed in high-latitude, high-elevation, or economically underdeveloped areas. Among all the potential influencing factors, lake surface temperature had the largest contribution to Chl-a and showed a positive correlation with Chl-a in approximately 92.39 % of the lakes. Conversely, factors such as precipitation and tree cover area around the lake were negatively correlated with Chl-a concentration in nearly 61.44 % of the lakes.

Nanoplastics increase the adverse impacts of lead on the growth, morphological structure and photosynthesis of marine microalga Platymonashelgolandica.

Nanoplastics and heavy metals are common pollutants in coastal environments with high concerns, but their joint ecological risk to marine primary productivity remains unclear. In this study, the effects of 7, 70, 700 µg/L lead (Pb) single exposure and in combination with 200 µg/L polystyrene nanoplastics (NPs, 70 nm) on marine microalga Platymonas helgolandica were investigated. Pb single exposure induced a dose-dependent inhibition on the growth of P. helgolandica, which was associated with the reduced photosynthetic efficiency and nutrient accumulation. Compared to Pb single exposure, the addition of NPs significantly reduced the photosynthetic efficiency and aggravated the damage to cell structure. Reduced esterase activity and increased membrane permeability also indicated that NPs exacerbated the adverse effects of Pb on P. helgolandica. Thus, co-exposure to NPs and Pb induced more severe impacts on marine microalgae, suggesting that the joint ecological risk of NPs and heavy metals to marine primary productivity merits more attention.

Efficient As(III) removal from water by ZrO2 modified covalent organic framework under visible light irradiation.

Adsorption-oxidation is a promising technique to decontaminate As(III) polluted water. In present study, ZrO2-modified covalent organic framework (ZrO2-COF) was fabricated and used to remove arsenic from water under visible light irradiation. The results showed that ZrO2-COF (0.2 g/L) could efficiently capture As(III) (5 mg/L) from water and then oxidize the adsorbed As(III) into less toxic As(V) under visible light irradiation (60 min), achieving the complete decontamination of As(III) polluted water. Based on characterization results and theoretical calculations, we found that in ZrO2-COF composite, ZrO2 served as sites for adsorption of As(III)/the latter transformed As(V), while COF worked as photocatalytic center for As(III) oxidation. Effective As(III) removal could also be achieved by ZrO2-COF under visible light irradiation in complex water chemistry conditions including wide solution pH range (3-11), broad solution ion strength range (1-100 mM), the copresence of natural organic matter (0.1-1 mg/L humic acid) and various coexisting ions in solutions, as well as in real water samples. In addition, we found that ZrO2-COF had excellent reuse performance in 4 consecutive cycles. Our results showed that under visible light irradiation, ZrO2-COF composites could be a promising technique for efficient As(III) removal from water.

Efficient Photosynthesis of Hydrogen Peroxide by Cyano-Containing Covalent Organic Frameworks from Water, Air and Sunlight.

The insufficient exciton (e- -h+ pair) separation/transfer and sluggish two-electron water oxidation are two main factors limiting the H2 O2 photosynthetic efficiency of covalent organic frameworks (COFs) photocatalysts. Herein, we present an alternative strategy to simultaneously facilitate exciton separation/transfer and reduce the energy barrier of two-electron water oxidation in COFs via a dicyano functionalization. The in situ characterization and theoretical calculations reveal that the dicyano functionalization improves the amount of charge transfer channels between donor and acceptor units from two in COF-0CN without cyano functionalization to three in COF-1CN with mono-cyano functionalization and four in COF-2CN with dicyano functionalization, leading to the highest separation/transfer efficiency in COF-2CN. More importantly, the dicyano group activates the neighbouring C atom to produce the key *OH intermediate for effectively reducing the energy barrier of rate-determining two-electron water oxidation in H2 O2 photosynthesis. The simultaneously enhanced exciton separation/transfer and two-electron water oxidation in COF-2CN result in high H2 O2 yield (1601 µmol g-1 h-1 ) from water and oxygen without using sacrificial reagent under visible-light irradiation. COF-2CN can effectively yield H2 O2 in water with wide pH range, in different real water samples, in scaled-up reactor under natural sunlight irradiation, and in continuous-flow reactor for consecutively producing H2 O2 solution for water decontamination.

Boosting Exciton Dissociation and Charge Transfer in Triazole-Based Covalent Organic Frameworks by Increasing the Donor Unit from One to Two for the Efficient Photocatalytic Elimination of Emerging Contaminants.

As novel photocatalysts, covalent organic frameworks (COFs) have potential for water purification. Insufficient exciton dissociation and low charge mobility in COFs yet restricted their photocatalytic activity. Excitonic dissociation and charge transfer in COFs could be optimized via regulating the donor-acceptor (D-A) interactions through adjusting the number of donor units within COFs, yet relevant research is lacking. By integrating the 1,2,4-triazole or bis-1,2,4-triazole unit with quinone, we fabricated COF-DT (with a single donor unit) and COF-DBT (with double donor units) via a facile sonochemical method and used to decontaminate emerging contaminants. Due to the stronger D-A interactions than COF-DT, the exciton binding energy was lower for COF-DBT, facilitating the intermolecular charge transfer process. The degradation kinetics of tetracycline (model contaminant) by COF-DBT (k = (12.21 ± 1.29) × 10-2 min-1) was higher than that by COF-DT (k = (5.11 ± 0.59) × 10-2 min-1) under visible-light irradiation. COF-DBT could efficiently photodegrade tetracycline under complex water chemistry conditions and four real water samples. Moreover, six other emerging contaminants, both Gram-negative and Gram-positive strains, could also be effectively eliminated by COF-DBT. High tetracycline degradation performance achieved in a continuous-flow system and in five reused cycles in both laboratory and outdoor experiments with sunlight irradiation showed the stability and the potential for the practical application of COF-DBT.

Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures.

BACKGROUND & AIMS: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. METHODS: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. RESULTS: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). CONCLUSIONS: aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. IMPACT AND IMPLICATIONS: In this multicenter nationwide cohort study, we developed and externally validated two novel hepatocellular carcinoma (HCC) risk prediction models (called aMAP-2 and aMAP-2 Plus scores), using longitudinal discriminant analysis algorithm and longitudinal data (i.e., aMAP and alpha-fetoprotein) with or without the addition of cell-free DNA signatures, based on 13,728 patients from 61 centers across mainland China. Our findings demonstrated that the performance of aMAP-2 and aMAP-2 Plus scores was markedly better than the original aMAP score, and any other existing HCC risk scores across all subsets, especially for patients with cirrhosis. More importantly, the stepwise application of aMAP scores (aMAP -> aMAP-2 -> aMAP-2 Plus) provides an improved enrichment strategy, identifying patients at high risk of HCC, which could effectively guide individualized HCC surveillance.

Ideal entry point and direction of retrograde intramedullary nailing of the tibia.

PURPOSE: To determine the ideal entry point and direction of retrograde intramedullary nailing of the tibia. METHODS: The imaging data of patients with distal tibial fractures from June 2020 to December 2021 in our hospital were collected, and computer-aided design was performed. The relevant data were imported into the software for processing, so as to obtain a distal tibial fracture model and simulate the retrograde intramedullary nail placement in the tibia. The entry points and angles at which the intramedullary nail could be inserted successfully and the fracture could be maintained in good alignment were overlapped and counted to obtain the safe entry range and angle. The center of this safe range is the ideal entry point for retrograde intramedullary nailing of the tibia, and the mean value of the angle is the ideal direction of entry. RESULTS: The ideal entry point of the retrograde intramedullary nailing was located at the midpoint of the medial malleolus in the C-arm fluoroscopic anteroposterior (AP) and lateral view. The ideal nail entry direction was located at the anatomic axis of the medial malleolus in the AP position and at the anatomic axis of the distal tibial metaphysis in the lateral position. CONCLUSION: The ideal point and direction of nail insertion for retrograde tibial intramedullary nailing is a "double midpoint, double axis" approach.

An Optimized Method for Microcomputed Tomography Analysis of Trabecular Parameters of Metal Scaffolds for Bone Ingrowth.

Owing to its superior mechanical and biological properties, titanium metal is widely used in dental implants, orthopedic devices, and bone regenerative materials. Advances in 3D printing technology have led to more and more metal-based scaffolds being used in orthopedic applications. Microcomputed tomography (µCT) is commonly applied to evaluate the newly formed bone tissues and scaffold integration in animal studies. However, the presence of metal artifacts dramatically hinders the accuracy of µCT analysis of new bone formation. To acquire reliable and accurate µCT results that reflect new bone formation in vivo, it is crucial to lessen the impact of metal artifacts. Herein, an optimized procedure for calibrating µCT parameters using histological data was developed. In this study, the porous titanium scaffolds were fabricated by powder bed fusion based on computer-aided design. These scaffolds were implanted in femur defects created in New Zealand rabbits. After 8 weeks, tissue samples were collected to assess new bone formation using µCT analysis. Resin-embedded tissue sections were then used for further histological analysis. A series of deartifact two-dimensional (2D) µCT images were obtained by setting the erosion radius and the dilation radius in the µCT analysis software (CTan) separately. To get the µCT results closer to the real value, the 2D µCT images and corresponding parameters were subsequently selected by matching the histological images in the particular region. After applying the optimized parameters, more accurate 3D images and more realistic statistical data were obtained. The results demonstrate that the newly established method of adjusting µCT parameters can effectively reduce the influence of metal artifacts on data analysis to some extent. For further validation, other metal materials should be analyzed using the process established in this study.

Efficient peroxymonosulfate activation by magnetic MoS2@Fe3O4 for rapid degradation of free DNA bases and antibiotic resistance genes.

Antibiotic resistance genes (ARGs) have become as emerging contaminant with great concerns worldwide due to their threats to human health. It is thus urgent to develop techniques to degrade ARGs in water. In this study, MoS2@Fe3O4 (MF) particles were fabricated and used to activate peroxymonosulfate (PMS) for the degradation of four types of free DNA bases (T, A, C, and G, major components of ARGs) and ARGs. We found that MF/PMS system could effectively degrade all four DNA bases (T within 10 min, A within 30 min, C within 5 min, and G within 5 min) in very short time. During the reaction process, MF could activate PMS to form the reactive radicals such as ·OH, SO4·-, O2·-, and 1O2, contributing to the degradation of DNA bases. Due to the low adsorption energy, high charge transfer, and great capability for PMS cleavage, MF exhibited excellent PMS adsorption and activation performances. MoS2 in MF could enhance the cycle of Fe(III)/Fe(II), improving the catalytic performance. Excellent catalytic performances of MF/PMS system were achieved in complex water matrix (including different solution pH, coexisting of anions and natural organic matter) as well as in real water samples (including tap water, river water, sea water, and sewage) especially under high salinity conditions due to the generation of Cl· radicals and HClO species. MF/PMS system could also efficiently degrade ARGs (chromosomal kanR and plasmid gmrA) and DNA extracted from antibiotic resistant bacteria (ARB) in super-short time. Moreover, complete disinfection of two types of model ARB (E. coli K-12 MG 1655 and E. coli S17-1) could also be achieved in MF/PMS system. The high degradation performances of MF/PMS system achieved in the reused experiments and the 14-day continuous flow reactor experiments indicated the stability of MF particles. Due to the magnetic property, it would be convenient to separate MF particles from water after use via using magnet, facilitating their reuse of MF and avoiding potential water contamination by catalysts. Overall, this study not only provided a deep insight on Fe/Mo-triggered PMS activation process, but also provided an effective and reliable approach for the treatment of DNA bases, ARGs, DNA, and ARB in water.

Periodate activation by pyrite for the disinfection of antibiotic-resistant bacteria: Performance and mechanisms.

The propagation of antibiotic-resistant bacteria (ARB) greatly endangers the ecological safety and human health. This study employed pyrite (FeS2, naturally abundant mineral) for periodate (PI) activation to disinfect ARB. FeS2/PI system could disinfect 1 × 107 CFU mL-1 of kanamycin-resistant E.coli below the limit of detection in 20 min. Efficient ARB inactivation performance was achieved in pH from 3 to 9, ionic strength from 0 to 300 mM, with HA (0.1-10 mg L-1) in suspension, and in real water samples including tap water, river water and sewage. FeS2/PI system could also efficiently disinfect gentamycin-resistant E.coli and Gram-positive B. subtilis. The generated reactive species including Fe(IV), ·O2- and ·OH would attack cell membrane and overwhelmed intracellular defense system. The intracellular kanamycin resistance genes in cells would be released and then degraded in FeS2/PI system. PI preferred to be adsorbed on Fe site of FeS2 (with lower adsorption energy, more occupancy of bonding state and stronger bonding strength). The subsequent transfer of electron cloud from Fe site to PI would cleave IO bond to generate reactive species. Moreover, FeS2/PI system could also combine with sand filtration system to efficiently capture and disinfect ARB. Therefore, FeS2/PI system is a promising approach to inactivate ARB in different scenarios.

Decreased synapse-associated proteins are associated with the onset of epileptic memory impairment in endothelial CDK5-deficient mice.

Accumulating evidence indicates that epilepsy has a higher risk of inducing memory impairment and dementia. However, the underlying onset mechanism remains unclear. Here, we found that mice with spontaneous epilepsy induced by endothelial CDK5 deficiency exhibited hippocampal-dependent memory impairment at 6 months of age, but not at 2 months of age. Moreover, the persistent epileptic seizures induce aberrant changes in phosphorylation of CaMKII protein in the hippocampus of spontaneous epileptic mice. Using genome-wide RNA sequencing and intergenic interaction analysis of STRING, we found that in addition to epilepsy-related genes, there are changes in synaptic organization pathway node genes, such as Bdnf and Grin1. The synapse-related proteins by Western blot analysis, such as NMDA receptors (NR1 and NR2B), PSD95, and the phosphorylation of synapsin1, are progressively decreased during epileptic seizures in Cdh5-CreERT2;CDK5f/f mice. Notably, we found that valproate (VPA) and phenytoin (PHT) augment mRNA expression and protein levels of synapse-related genes and ameliorate memory impairment in Cdh5-CreERT2;CDK5f/f mice. Our study elucidates a potential mechanism of memory deficits in epilepsy, and pharmacological reversal of synaptic pathology targeting might provide a new therapeutic intervention for epileptic memory deficits.

Assessment of Resonant Acoustic Mixing for Low-Dose Pharmaceutical Powder Blends.

Obtaining a homogeneous low-dose pharmaceutical powder blend without multi-step processing remains a challenge. One promising technology to address this risk is resonant acoustic mixing (RAM). In this study, the performance of a laboratory resonant acoustic mixer (LabRAM) was studied at low active pharmaceutical ingredient (API) concentrations (0.1-0.5% w/w), using three commercial grades of a model API (Acetaminophen) and diluents with varying physical properties. The performance was assessed by evaluating blend uniformity (BU) and capsule content uniformity (CU) as a function of mixing time. Overall, the LabRAM achieved acceptable BU in a single step even at 0.1% w/w drug loading. A reduction in API primary particle size led to improved mixing efficiency and uniformity. Moreover, the presence of surface cavities in the diluents used appeared to have led to improved uniformity. The results demonstrated that RAM could achieve uniform powder blends without multi-step processing, for low-dose formulations.

Catalyst-Free Periodate Activation by Solar Irradiation for Bacterial Disinfection: Performance and Mechanisms.

Periodate (PI)-based advanced oxidation process has recently attracted great attention in the water treatment processes. In this study, solar irradiation was used for PI activation to disinfect waterborne bacteria. The PI/solar irradiation system could inactivate Escherichia coli below the limit of detection (LOD, 10 CFU mL-1) with initial concentrations of 1 × 106, 1 × 107, and 1 × 108 CFU mL-1 within 20, 40, and 100 min, respectively. •O2- and •OH radicals contributed to the bacterial disinfection. These reactive radicals could attack and penetrate the cell membrane, thereby increasing the amount of intracellular reactive oxygen species and destroying the intracellular defense system. The damage of the cell membrane caused the leakage of intracellular K+ and DNA (that could be eventually degraded). Excellent bacterial disinfection performance in PI/solar irradiation systems was achieved in a wide range of solution pH (3-9), with coexisting humic acid (0.1-10 mg L-1) and broad solution ionic strengths (15-600 mM). The PI/solar irradiation system could also efficiently inactivate Gram-positive Bacillus subtilis. Moreover, PI activated by natural sunlight irradiation could inactivate 1 × 107 CFU mL-1 viable E. coli below the LOD in the river and sea waters with a working volume of 1 L in 40 and 50 min, respectively. Clearly, the PI/solar system could be potentially applied to disinfect bacteria in water.

Polarized light sun position determination artificial neural network.

Our previous work has constructed a polarized light orientation determination (PLOD) artificial neural network. Although a PLOD network can determine the solar azimuth angle, it cannot determine the solar elevation angle. Therefore, this paper proposes an artificial neural network for polarized light solar position determination (PLSPD), which has two branches: the solar azimuth angle determination branch and the solar elevation angle determination branch. Since the solar elevation angle has no cyclic characteristics, and the angle range of the solar elevation angle is different from that of the solar azimuth angle, the solar elevation angle exponential function encoding is redesigned. In addition, compared with the PLOD, the PLSPD deletes a local full connection layer to simplify the network structure. The experimental results show that the PLSPD can determine not only the solar azimuth angle but also the solar elevation angle, and the solar azimuth angle determination accuracy of the PLSPD is higher than that of the PLOD.

Local administration of low doses of exogenous BMP2 and leptin promotes ectopic bone regeneration in leptin-deficient mice.

BACKGROUND: Obesity and leptin deficiency are associated with compromised bone regeneration. OBJECTIVE: This study aims to investigate the role of locally administrated low-dose BMP2+leptin on bone regeneration in leptin-deficient obese (ob/ob) mice. METHODS: Wildtype (WT) and ob/ob mice were divided into 3 groups (4 mice/group): BMP2 (5 µg) group, BMP2+low-dose leptin (1 µg) group, and BMP2+high-dose leptin (2.5 µg) group. WT mice were used as control mice. An equal size absorbable collagen sponge was prepared by loading the BMP2 or/and leptin and implanted subcutaneously. After 19 days, samples were collected and analyzed by micro-CT and H&E staining. RESULTS: No significant difference in bone regeneration among the three groups in WT mice. Quantification of newly formed bone parameters from micro-CT and H&E staining showed that low-dose BMP2 treatment formed less new bone in ob/ob mice compared to WT. BMP2+low-dose leptin treatment substantially rescued the compromised bone regeneration in ob/ob mice up to the level in WT mice. However, the BMP2 and high dose of leptin failed to rescue the compromised bone regeneration in ob/ob mice. CONCLUSION: Our findings suggest that a combination of the low-dose BMP2 and leptin could be a strategy to promote osteogenesis in obese populations with leptin deficiency.

Endothelial peroxynitrite causes disturbance of neuronal oscillations by targeting caspase-1 in the arcuate nucleus.

Severe anorexia limits the clinical application of cisplatin, and even leads to the discontinuation of treatment. However, the mechanisms underlying cisplatin-induced anorexia are unknown. Herein, we demonstrated that cisplatin could affect neuronal gamma oscillations and induce abnormal neuronal theta-gamma phase-amplitude coupling in the arcuate nucleus (Arc) of the hypothalamus, and these findings were associated with significantly decreased food intake and weight loss in mice. Chemogenetic activation of AgRP neurons in the Arc reversed the cisplatin-induced food intake reduction in mice. We further demonstrated that endothelial peroxynitrite (ONOO-) formation in the Arc induced nitrosative stress following cisplatin treatment via a previously uncharacterized pathway involving neuronal caspase-1 activation. Strikingly, treatment with the ONOO- scavenger uric acid (UA) reversed the reduced action potential (AP) frequency of AgRP neurons and increased the AP frequency of POMC neurons induced by SIN1, a donor of ONOO-, in the Arc, as determined by whole-cell patch-clamp electrophysiological recording. Consistent with these findings, UA treatment effectively alleviated cisplatin-induced dysfunction of neuronal oscillations and neuronal theta-gamma phase-amplitude coupling in the Arc of mice. Taken together, these results suggest, for the first time, that targeting the overproduction of endothelial ONOO- can regulate cisplatin-induced neurotoxicity through neuronal caspase-1, and thereby serve as a potential therapeutic approach to alleviate chemotherapy-induced anorexia and weight loss.

Multifunctional Ca-Zn-Si-based micro-nano spheres with anti-infective, anti-inflammatory, and dentin regenerative properties for pulp capping application.

While pulp capping using a variety of materials has been applied clinically to preserve the health and vitality of the dental pulp and induce dentin repair no material meets all the anti-infection, anti-inflammation, and promoting pulp tissue regeneration criteria. Micro-nano materials of bioactive glasses (BG) with the biocompatibility and osteogenesis-promoting properties were developed for this study using Zn-doped bioactive glass (BGz) micro-nano spheres for dental pulp capping to control infection and inflammation and promote tissue regeneration. Of three key findings, the co-culture of Porphyromonas gingivalis showed that the BGz had an excellent antibacterial effect, and after being stimulated with BGz in vitro, macrophages showed a significant decrease of pro-inflammatory M1 markers compared with the undoped BG group. It is also noted that the conditioned medium derived from BGz-stimulated macrophages could significantly promote mineralized dentin formation of dental pulp cells (DPCs). In rats, acute pulp restoration experiments proved that BGz used as a pulp capping agent had excellent dentin regenerative properties. This work may provide a novel strategy to promote osteo/dentinogenic differentiation through regulating early inflammation, with potential applications in pulp capping.

Circ_0016347 Promotes Osteosarcoma Progression by Regulating miR-1225-3p/KCNH1 Axis.

Background: Osteosarcoma (OS) is a common malignant bone cancer and usually occurs in adolescents and children. Circular RNAs (circRNAs) play essential roles in tumor development and progression. This study aimed to explore the function and molecular basis of circ_0016347 in OS progression. Materials and Methods: The levels of circ_0016347, miR-1225-3p, and ether à go-go 1 (KCNH1) were measured by quantitative real-time polymerase chain reaction or western blot assay. Cell proliferation was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony formation assay. Cell migration and invasion were evaluated by transwell assay. Glucose consumption and lactate production were detected by glucose detection and lactic acid detection kits. The levels of Ki-67, matrix metalloproteinase-9 (MMP-9), and hexokinase-2 (HK2) were examined by western blot assay. The interaction among circ_0016347, miR-1225-3p, and KCNH1 was validated by dual-luciferase reporter assay. Xenograft assay was conducted to analyze tumor growth in vivo. Results: Circ_0016347 and KCNH1 were upregulated, while miR-1225-3p was downregulated in OS tissues or cells. Circ_0016347 and KCNH1 promoted proliferation, migration, invasion, and glycolysis of OS cells. Circ_0016347 regulated OS progression by modulating KCNH1. Circ_0016347 was a sponge of miR-1225-3p, and miR-1225-3p targeted KCNH1. Circ_0016347 regulated KCNH1 expression via sponging miR-1225-3p. Moreover, silencing of circ_0016347 inhibited tumor growth in vivo. Conclusion: Circ_0016347 contributed to OS progression through the miR-1225-3p/KCNH1 axis, which might provide a promising biomarker for OS therapy.

Impacts of contracted endodontic cavities compared to traditional endodontic cavities in premolars.

BACKGROUND: This study aims to compare the percentage of dentin removed, instrumentation efficacy, root canal filling and load at fracture between contracted endodontic cavities, and traditional endodontic cavities on root canal therapy in premolars. METHODS: Forty extracted intact human first premolars were imaged with micro-CT and randomly assigned to the contracted endodontic cavity (CEC) or traditional endodontic cavity (TEC) groups. CEC was prepared with the aid of a 3D-printed template, canals were prepared with a 0.04 taper M-Two rotary instrument, and cavities were restored with resin. Specimens were loaded to fracture in an Instron Universal Testing Machine after a fatigue phase. The data were analyzed by the independent samples T test and Mann-Whitney U test, appropriate post hoc tests. RESULTS: In the premolars tested in vitro, the percentage of dentin removed in the premolars with two dental roots in the CEC group (3.85% ± 0.42%) was significantly smaller (P < 0.05) than in the TEC group (4.94% ± 0.5%). The untouched canal wall (UCW) after instrumentation for TECs (16.43% ± 6.56%) was significantly lower (P < .05) than the UCW (24.42% ± 9.19%) for CECs in single-rooted premolars. No significant differences were observed in the increased canal volume and surface areas in premolars between the TEC and CEC groups (P > 0.05). CECs conserved coronal dentin in premolars with two dental roots but no impact on the instrument efficacy. There were no differences between the CEC groups and the TEC groups in the percentage of filling material and voids (P > 0.05). In addition, the mean load at failure of premolars did not significantly differ between the CEC and TEC groups and there was no significant difference in the type of fracture (P > 0.05). CONCLUSION: The results of this study suggest that CEC could not improve the fracture resistance of the endodontically treated premolars. The instrumentation efficacy and the percentage of filling material did not significantly differ between CECs and TECs in premolars.

Valproic acid affects neuronal fate and microglial function via enhancing autophagic flux in mice after traumatic brain injury.

In recent years, many studies have focused on autophagy, an evolutionarily conserved mechanism that relies on lysosomes to achieve cellular metabolic requirements and organelle turnover, and revealed its important role in animal models of traumatic injury. Autophagy is a double-edged sword. Appropriate levels of autophagy can promote the removal of abnormal proteins or damaged organelles, while hyperactivated autophagy can induce autophagic apoptosis. However, recent studies suggest that autophagic flux seems to be blocked after traumatic brain injury (TBI), which contributes to the apoptosis of brain cells. In this study, valproic acid (VPA), which was clinically used for epilepsy treatment, was used to treat TBI. The Morris water maze test, hematoxylin & eosin staining and Nissl staining were first conducted to confirm that VPA treatment had a therapeutic effect on mice after TBI. Western blotting, enzyme-linked immunosorbent assay and immunofluorescence staining were then performed to reveal that VPA treatment reversed TBI-induced blockade of autophagic flux, which was accompanied by a reduced inflammatory response. In addition, the variations in activation and phenotypic polarization of microglia were observed after VPA treatment. Nevertheless, the use of the autophagy inhibitor 3-methyladenine partially abolished VPA-induced neuroprotection and the regulation of microglial function after TBI, resulting in the deterioration of the central nervous system microenvironment and neurological function. Collectively, VPA treatment reversed the TBI-induced blockade of autophagic flux in the mouse brain cortex, subsequently inhibiting brain cell apoptosis and affecting microglial function to achieve the promotion of functional recovery in mice after TBI. Cover Image for this issue: doi: 10.1111/jnc.14755.