Injectable, Electroconductive, Free Radical Scavenging Silk Fibroin/Black Phosphorus/Glycyrrhizic Acid Nanocomposite Hydrogel for Enhancing Spinal Cord Repair.

Spinal cord injury (SCI) often leads to a severe permanent disability. A poor inflammatory microenvironment and nerve electric signal conduction block are the main reasons for difficulty in spinal cord nerve regeneration. In this study, black phosphorus (BP) and glycyrrhizic acid (GA) are integrated into methacrylate-modified silk fibroin (SF) to construct a bifunctional injectable hydrogel (SF/BP/GA) with appropriate conductivity and the ability to inhibit inflammation to promote neuronal regeneration after SCI. This work discovers that the SF/BP/GA hydrogel can reduce the oxidative damage mediated by oxygen free radicals, promote the polarization of macrophages toward the anti-inflammatory M2 phenotype, reduce the expression of inflammatory factors, and improve the inflammatory microenvironment. Moreover, it induces neural stem cell (NSC) differentiation and neurosphere formation, restores signal conduction at the SCI site in vivo, and ameliorates motor function in mice with spinal cord hemisection, revealing a significant neural repair effect. An injectable, electroconductive, free-radical-scavenging hydrogel is a promising therapeutic strategy for SCI repair.

CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle.

Glioblastoma (GBM) is characterized by significant heterogeneity, leading to poor survival outcomes for patients, despite the implementation of comprehensive treatment strategies. The roles of cyclin A2 (CCNA2) and NIMA related kinase 2 (NEK2) have been extensively studied in numerous cancers, but their specific functions in GBM remain to be elucidated. The present study aimed to investigate the potential molecular mechanisms of CCNA2 and NEK2 in GBM. CCNA2 and NEK2 expression and prognosis in glioma were evaluated by bioinformatics methods. In addition, the distribution of CCNA2 and NEK2 expression in GBM subsets was determined using pseudo-time analysis and tricycle position of single-cell sequencing. Gene Expression Omnibus and Kyoto Encyclopedia of Genes and Genome databases were employed and enrichment analyses were conducted to investigate potential signaling pathways in GBM subsets and a nomogram was established to predict 1-, 2- and 3-year overall survival probability in GBM. CCNA2 and NEK2 expression levels were further validated by western blot analysis and immunohistochemical staining in GBM samples. High expression of CCNA2 and NEK2 in glioma indicates poor clinical outcomes. Single-cell sequencing of GBM revealed that these genes were upregulated in a subset of positive neural progenitor cells (P-NPCs), which showed significant proliferation and progression properties and may activate G2M checkpoint pathways. A comprehensive nomogram predicts 1-, 2- and 3-year overall survival probability in GBM by considering P-NPCs, age, chemotherapy and radiotherapy scores. CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle, thus indicating the potential of novel therapy directed to CCNA2 and NEK2 in GBM.

Explainable machine learning for the prediction and assessment of complex drought impacts.

Drought is a common and costly natural disaster with broad social, economic, and environmental impacts. Machine learning (ML) has been widely applied in scientific research because of its outstanding performance on predictive tasks. However, for practical applications like disaster monitoring and assessment, the cost of the models failure, especially false negative predictions, might significantly affect society. Stakeholders are not satisfied with or do not "trust" the predictions from a so-called black box. The explainability of ML models becomes progressively crucial in studying drought and its impacts. In this work, we propose an explainable ML pipeline using the XGBoost model and SHAP model based on a comprehensive database of drought impacts in the U.S. The XGBoost models significantly outperformed the baseline models in predicting the occurrence of multi-dimensional drought impacts derived from the text-based Drought Impact Reporter, attaining an average F2 score of 0.883 at the national level and 0.942 at the state level. The interpretation of the models at the state scale indicates that the Standardized Precipitation Index (SPI) and Standardized Temperature Index (STI) contribute significantly to predicting multi-dimensional drought impacts. The time scalar, importance, and relationships of the SPI and STI vary depending on the types of drought impacts and locations. The patterns between the SPI variables and drought impacts indicated by the SHAP values reveal an expected relationship in which negative SPI values positively contribute to complex drought impacts. The explainability based on the SPI variables improves the trustworthiness of the XGBoost models. Overall, this study reveals promising results in accurately predicting complex drought impacts and rendering the relationships between the impacts and indicators more interpretable. This study also reveals the potential of utilizing explainable ML for the general social good to help stakeholders better understand the multi-dimensional drought impacts at the regional level and motivate appropriate responses.

Development of prognostic indicator based on NAD+ metabolism related genes in glioma.

Background: Studies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, the specific effects and mechanisms of NAD+ metabolism in glioma are unclear and there were no systematic researches about NAD+ metabolism related genes to predict the survival of patients with glioma. Methods: The research was performed based on expression data of glioma cases in the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Firstly, TCGA-glioma cases were classified into different subtypes based on 49 NAD+ metabolism-related genes (NMRGs) by consensus clustering. NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were gotten by intersecting the 49 NMRGs and differentially expressed genes (DEGs) between normal and glioma samples. Then a risk model was built by Cox analysis and the least shrinkage and selection operator (LASSO) regression analysis. The validity of the model was verified by survival curves and receiver operating characteristic (ROC) curves. In addition, independent prognostic analysis of the risk model was performed by Cox analysis. Then, we also identified different immune cells, HLA family genes and immune checkpoints between high and low risk groups. Finally, the functions of model genes at single-cell level were also explored. Results: Consensus clustering classified glioma patients into two subtypes, and the overall survival (OS) of the two subtypes differed. A total of 11 NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were screened by overlapping 5,995 differentially expressed genes (DEGs) and 49 NAD+ metabolism-related genes (NMRGs). Next, four model genes, PARP9, BST1, NMNAT2, and CD38, were obtained by Cox regression and least absolute shrinkage and selection operator (Lasso) regression analyses and to construct a risk model. The OS of high-risk group was lower. And the area under curves (AUCs) of Receiver operating characteristic (ROC) curves were >0.7 at 1, 3, and 5 years. Cox analysis showed that age, grade G3, grade G4, IDH status, ATRX status, BCR status, and risk Scores were reliable independent prognostic factors. In addition, three different immune cells, Mast cells activated, NK cells activated and B cells naive, 24 different HLA family genes, such as HLA-DPA1 and HLA-H, and 8 different immune checkpoints, such as ICOS, LAG3, and CD274, were found between the high and low risk groups. The model genes were significantly relevant with proliferation, cell differentiation, and apoptosis. Conclusion: The four genes, PARP9, BST1, NMNAT2, and CD38, might be important molecular biomarkers and therapeutic targets for glioma patients.

Synchronous N and P Removal in Carbon-Coated Nanoscale Zerovalent Iron Autotrophic Denitrification─The Synergy of the Carbon Shell and P Removal.

Fe0 is a promising electron donor for autotrophic denitrification in the simultaneous removal of nitrate and phosphorus in low C/N wastewater. However, P removal may inevitably inhibit bio-denitrification. It has not been well recognized and led to an overdose of iron materials. This study employed carbon-coated zerovalent iron (Fe0@C) to support autotrophic denitrification to mitigate the inhibition effects of P removal and enhance both N and P removal. The critical role of the carbon shell in Fe0@C was to block the direct contact between Fe0 and P and NO3--N, to maintain the Fe0 activity. Besides, P inhibited the chemical reduction of NO3--N by competing for Fe0 active sites. This indirectly boosted H2 generation and promoted bio-denitrification. P removal displayed negligible effects on microbial species but indirectly enhanced the nitrogen metabolic activities because of promoted H2 in Fe0@C-based autotrophic denitrification. Bio-denitrification, in turn, strengthened Fe-P co-precipitation by promoting the formation of ferric hydroxide as a secondary adsorbent for P removal. This study demonstrated an efficient method for simultaneous N and P removal in autotrophic denitrification and revealed the synergistic interactions among N and P removal processes.

Age Estimation of Faces in Videos Using Head Pose Estimation and Convolutional Neural Networks.

Age estimation from human faces is an important yet challenging task in computer vision because of the large differences between physical age and apparent age. Due to the differences including races, genders, and other factors, the performance of a learning method for this task strongly depends on the training data. Although many inspiring works have focused on the age estimation of a single human face through deep learning, the existing methods still have lower performance when dealing with faces in videos because of the differences in head pose between frames, which can lead to greatly different results. In this paper, a combined system of age estimation and head pose estimation is proposed to improve the performance of age estimation from faces in videos. We use deep regression forests (DRFs) to estimate the age of facial images, while a multiloss convolutional neural network is also utilized to estimate the head pose. Accordingly, we estimate the age of faces only for head poses within a set degree threshold to enable value refinement. First, we divided the images in the Cross-Age Celebrity Dataset (CACD) and the Asian Face Age Dataset (AFAD) according to the estimated head pose degrees and generated separate age estimates for images with different poses. The experimental results showed that the accuracy of age estimation from frontal facial images was better than that for faces at different angles, thus demonstrating the effect of head pose on age estimation. Further experiments were conducted on several videos to estimate the age of the same person with his or her face at different angles, and the results show that our proposed combined system can provide more precise and reliable age estimates than a system without head pose estimation.

Development of miniature self-powered single-chamber microbial fuel cell and its response mechanism to copper ions in high and trace concentration.

Copper ions are widely present in water environment and are involved in various biochemical reaction processes, causing irreversible damage to the human body. In this study, we design and establish a self-powered miniature single-chamber microbial fuel cell (SCMFC) reactor using xurography technology. Optimal volume of 188 µL is obtained by controlling the distance between the anode and cathode. Copper ions in two concentration gradients are tested and good linear response curves are obtained. The opposite responses to copper ions in the trace concentration range (0-0.4 mg/L) and high concentration range (1.0-8.0 mg/L) are observed. The results show that at trace concentration range, the inhibitory effect of copper ions on the biofilm activity of micro-SCMFC is dominant; while high concentration copper ions are involved in chemical reactions that produce Cu2O, which may act as a catalyst and promote electron transfer. A good linear response to trace concentration (0-0.4 mg/L) of copper ions with detection limits of 0.05 mg/L is obtained in this study. It could be used in drinking water for trace copper ion detection. The investigation of the mechanisms provides the scientific basis for the design of the efficient detection of copper ions by SCMFC.

Promotion of anammox process by different graphene-based materials: Roles of particle size and oxidation degree.

Graphene oxide (GO) and reduced graphene oxide (RGO) have been applied in the anaerobic ammonium oxidation (anammox) process for nitrogen removal as electron shuttles. However, there is still controversy about their efficacy. In this study, nine graphene-based materials with a gradient of three particle sizes (large (l), medium (m) and small (s) sizes) and oxidation degrees, were used to compare their effects on the anammox process efficiency. The graphene-based materials include GO and its reduced products (RGO250 and RGO800) obtained at temperatures of 250 °C and 800 °C respectively. It was observed that their enhancements on the anammox process were in the order of GO > RGO800 > RGO250. In detail, at the dose of 100 mg/L, specific anammox activities (SAA) were promoted by 6.7% (l-GO), 4.9% (l-RGO800), 11.5% (m-GO), 7.3% (m-RGO800), 13.2% (s-GO) and 8.3% (s-RGO800) compared to the control respectively; while RGO250 with the same dose inhibited the process. In addition, the enhancement of the anammox process was increasing with the decreasing size of GO and RGO800. The nitrite reductase (NIR) activity was greatly increased by up to 24.9% with the presence of GO, which might be attributed to organized and specific electron transport with oxygen functional groups. The finding of hydroxyl on RGO and increasing content of oxygen determined after reaction detected by Fourier transform infrared spectroscopy and energy dispersive spectrometer respectively, indicated the essential condition for RGO's function on transferring electrons for key enzymes in annamox bacteria. Most importantly, O/C (Oxygen/Carbon) ratios of graphene-based materials had greater effects on the promotion of the anammox process than the particle size and electrical conductivity.

An online participatory system for SWMM-based flood modeling and simulation.

In the context of the continuous development of urbanization and global climate change, urban flooding risk has become a well-publicized research issue. The Storm Water Management Model (SWMM) performs very well in urban rain-runoff simulations and is widely used to build flood models in specific areas. Because of the complicated and tedious processing work for urban flood modeling and simulation, multifield participants' cooperation is becoming a trend. To promote the research and application of flood modeling and simulation, some resource sharing-oriented systems and platforms have been proposed with the advantages of network technology. However, they still require a participatory environment that can help modeling participants overcome the difficulties of distributed cooperation in the process of SWMM-based flood modeling and simulation. Therefore, we designed and implemented an online participatory system to coordinate the effective collaboration of modeling participants in this process. By referring to the scenarios and specific participatory demands in the modeling process, the system provides a guiding framework that consists of multiple participatory activities and prepares a series of online auxiliary tools designed for these activities. Using the main urban area of Lishui City as the study area, it was confirmed that the process of SWMM-based flood modeling and simulation can be demonstrated collaboratively on the online participatory system developed in this study.

Comparison of robot versus fluoroscopy-assisted pedicle screw instrumentation in adolescent idiopathic scoliosis surgery: A retrospective study.

The aim of this study was to explore whether a robot-assisted (RA) technique has advantages over the conventional fluoroscopy-assisted (FA) technique in clinical and radiological outcomes and whether it could decrease the incidence of mis-implantations of pedicle screws in adolescent idiopathic scoliosis (AIS) correction surgery. A total of 101 patients with AIS were recruited (RA group: 45 patients underwent RA screw insertion; FA group: 56 patients underwent FA screw insertion). When comparing the radiological data between the two groups, the major and secondary curves were both corrected proficiently with no difference in Cobb angle comparison at the last follow-up, suggesting that both the RA technique and the FA technique could lead to efficient radiographic correction and similar clinical outcomes (all, p > 0.05). In the RA group, operation time, blood loss, and transfusion volume were significantly greater than those in the FA group, while the accuracy of screw implantations in patients with AIS with a thoracic scoliotic curve in the RA group was higher than that in the FA group. In conclusion, both the RA and FA techniques could approach proficient radiographic correction and similar clinical outcomes in AIS surgery. Compared with the conventional fluoroscopy technique, the RA technique might improve the accuracy of screw implantations in patients with AIS with a thoracic scoliotic curve, while the increased operation time, blood loss, and transfusion volume might be the disadvantages due to the preliminary stage of the learning curve.

Characteristics analysis of segmental and regional lumbar spontaneous compensation post thoracic fusion in Lenke 1 and 2 adolescent idiopathic scoliosis.

OBJECTIVE: To explore the characteristics of compensation of unfused lumbar region post thoracic fusion in Lenke 1 and 2 adolescent idiopathic scoliosis. BACKGROUND: Preserving lumbar mobility in the compensation is significant in controlling pain and maintaining its functions. The spontaneous correction of the distal unfused lumbar curve after STF has been widely reported, but previous study has not concentrated on the characteristics of compensation of unfused lumbar region post thoracic fusion. METHOD: A total of 51 Lenke 1 and2 AIS patients were included, whose lowest instrumented vertebrae was L1 from January 2013 to December 2019. For further analysis, demographic data and coronal radiographic films were collected before surgery, at immediate erect postoperatively and final follow-up. The wedge angles of each unfused distal lumbar segments were measured, and the variations in each disc segment were calculated at the immediate postoperative review and final follow-up. Meanwhile, the unfused lumbar curve was divided into upper and lower parts, and we calculated their curve angles and compensations. RESULTS: The current study enrolled 41 females (80.4%) and 10 males (19.6%). Thirty-six patients were Lenke type 1, while 15 patients were Lenke type 2. The average main thoracic Cobb angle and thoracolumbar/lumbar Cobb angle were 44.1 ± 7.7°and 24.1 ± 9.3°, preoperatively. At the final follow-up, the disc wedge angle variation of L1/2, L2/3, L3/4, L4/5 and L5/S1 was 3.84 ± 5.96°, 3.09 ± 4.54°, 2.30 ± 4.53°, - 0.12 ± 3.89° and - 1.36 ± 2.80°, respectively. The compensation of upper and lower coronal lumbar curves at final follow-up were 9.22 ± 10.39° and - 1.49 ± 5.14°, respectively. CONCLUSION: When choosing L1 as the lowest instrumented vertebrae, the distal unfused lumbar segments' compensation showed a decreasing trend from the proximal end to the distal end. The adjacent L1/2 and L2/3 discs significantly contributed to this compensation.

Photoredox ß-thiol-α-carbonylation of enones accompanied by unexpected Csp2-C(CO) bond cleavage.

An olefinic difunctionalization method of enones was presented here via aerobic visible-light catalysis. A novel reactivity was showcased in conjunction with the selective Csp2-C(CO) bond activation of enones, which provided a convenient method for the preparation of various ß-thiolated-α-functionalized compounds. Moreover, the preliminary investigation of the mechanism indicated that a ß-peroxysulfide intermediate was formed under the promotion of visible light under an oxygen atmosphere, which finally induced the unexpected C-C bond cleavage.

Factors affecting microbiological quality of household drinking water supplied by small-scale ultrafiltration systems: A field study.

Small scale ultrafiltration (UF) systems have been increasingly used in rural areas for drinking water supply, but their effectiveness in guarantying microbiological water safety at household level has rarely been assessed. Therefore, this study surveyed six representative villages where UF was utilized for full-scale drinking water supply for at least four years. At each village, the influent and the effluent from every stages of the treatment, as well as household tap water, were sampled and analyzed for microbiological indicating parameters, including total coliform count, Escherichia coli count, and heterotrophic plate count. The results were further assessed against current drinking water quality guidelines and standards. It was found that: (1) the qualification rate of household tap water samples varied substantially in the studied villages (0-75%), mainly due to the lack of post-disinfection and the occurrence of fecal contamination during water distribution; (2) UF appeared to be effective in controlling microbial contamination for small-scale systems with high-quality source water, while for systems using inferior source water, fecal contamination during water distribution necessitated continuous post-disinfection; and, (3) existing monitoring of membrane operational parameters cannot ensure microbial quality of treated water, and therefore, routine monitoring of microbial indicators in household water is recommended.

[Control of Coagulant Dosing for Humic Substances Based on Ultraviolet Spectrum Analysis].

Humic substance (HS) is a main component of dissolved organic matter in the aquatic environment and significantly affects water treatment processes. To investigate the applicability and principle of UV spectrum analysis for coagulation control, laboratory jar tests were conducted with synthetic waters that had varying concentrations of HS and kaolinite. Thus, the influence of water quality conditions on the optimal coagulant dose (OCD) was determined and further correlated to Specific Ultraviolet Absorbance (SUVA254) and the ultraviolet spectral slopes of the coagulated water. Subsequently, the relationship between the UV spectral slopes and organic fractionation was further identified by using size exclusion chromatography (SEC). The results showed that the coagulant demands of the synthetic waters were positively related to dissolved organic carbon (DOC). Consequently, a stoichiometric relationship (0.61 mg·mg-1 calculated as Al/DOC) was found between the coagulant demand and initial DOC of the synthetic water. As the coagulant dose increased, SUVA254 decreased from 8.9 L·(mg·m)-1 to a steady level of 2.0 L·(mg·m)-1 and the removal efficiency of DOC was positively correlated with SUVA254. Spectral slopes in different wavelength ranges had showed similar tendencies, with S275-295 having the best correlation with SUVA254 (R2=0.81). Furthermore, SEC results demonstrated that coagulation preferentially removed humic substances, leading to reduced humification. As a result, S275-295 had the highest correlation with the portion of UVA254 contributed by humic substances in water. Therefore, online measurement of ultraviolet spectral slopes was an important aspect in the control of coagulant dosing.

Discovery of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as novel, potent and selective c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.

A series of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives were designed, synthesized and evaluated for their biological activity. Most of these compounds showed potent activities against c-Met kinase and cell growth inhibition. The most promising compound, 7d, has the IC50 values of 2.02 and 88 nM to inhibit c-Met kinase activity and cell growth in the MKN45 cell line, respectively. In addition, 7d is highly selective to c-Met and exhibits over 2500-fold selective inhibition to 16 tyrosine kinases evaluated.

Observations of the step-like accelerating processes of cold ions in the reconnection layer at the dayside magnetopause.

Cold ions of plasmaspheric origin have been observed to abundantly appear in the magnetospheric side of the Earth's magnetopause. These cold ions could affect the magnetic reconnection processes at the magnetopause by changing the Alfvén velocity and the reconnection rate, while they could also be heated in the reconnection layer during the ongoing reconnections. We report in situ observations from a partially crossing of a reconnection layer near the subsolar magnetopause. During this crossing, step-like accelerating processes of the cold ions were clearly observed, suggesting that the inflow cold ions may be separately accelerated by the rotation discontinuity and slow shock inside the reconnection layer.

Structure-based design, synthesis, and evaluation of 4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine derivatives as novel c-Met inhibitors.

c-Met was emerging as an attractive target for cancer-targeted therapy because deregulation of c-Met has been observed in multiple tumor types. A series of 4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine derivatives were designed, synthesized and evaluated for their enzymatic inhibitory activity against c-Met kinase and cellular potency against MKN45, EBC-1 and PC-3 cell lines. Nine of them showed better activity than lead compound 1 which was found via computer-aided drug design. Among them, compound 8c showed inhibitory activity of 68 nM against c-Met and low micromole cellular potency against MKN45 and EBC-1 cell lines. Moreover, 8c demonstrated more than 50-fold selectivity against other tyrosine kinases tested. The result of western blot indicated that compound 8c was capable of inhibiting the phosphorylation of c-Met kinase in MKN45 cell line in a dose-dependent manner.

Direct observations of the evolution of polar cap ionization patches.

Patches of ionization are common in the polar ionosphere, where their motion and associated density gradients give variable disturbances to high-frequency (HF) radio communications, over-the-horizon radar location errors, and disruption and errors to satellite navigation and communication. Their formation and evolution are poorly understood, particularly under disturbed space weather conditions. We report direct observations of the full evolution of patches during a geomagnetic storm, including formation, polar cap entry, transpolar evolution, polar cap exit, and sunward return flow. Our observations show that modulation of nightside reconnection in the substorm cycle of the magnetosphere helps form the gaps between patches where steady convection would give a "tongue" of ionization (TOI).