Wearable Sensing Device Integrated with Prestored Reagents for Cortisol Detection in Sweat.

Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.

Efficient phosphate removal by Mg-La binary layered double hydroxides: synthesis optimization, adsorption performance, and inner mechanism.

Layered double hydroxides (LDH) hold great promise as phosphate adsorbents; however, the conventional binary LDH exhibits low adsorption rate and adsorption capacity. In this study, Mg and La were chosen as binary metals in the synthesis of Mg-La LDH to enhance phosphate efficient adsorption. Different molar ratios of Mg to La (2:1, 3:1, and 4:1) were investigated to further enhance P adsorption. The best performing Mg-La LDH, with Mg to La ratio is 4:1 (LDH-4), presented a larger adsorption capacity and faster adsorption rate than other Mg-La LDH. The maximum adsorption capacity (87.23 mg/g) and the rapid adsorption rate in the initial 25 min of LDH-4 (70 mg/(g·h)) were at least 1.6 times and 1.8 times higher than the others. The kinetics, isotherms, the effect of initial pH and co-existing anions, and the adsorption-desorption cycle experiment were studied. The batch experiment results proved that the chemisorption progress occurred on the single-layered LDH surface and the optimized LDH exhibited strong anti-interference capability. Furthermore, the structural characteristics and adsorption mechanism were further investigated by SEM, BET, FTIR, XRD, and XPS. The characterization results showed that the different metal ratios could lead to changes in the metal hydroxide layer and the main ions inside. At lower Mg/La ratios, distortion occurred in the hydroxide layer, resulting in lower crystallinity and lower performance. The characterization results also proved that the main mechanisms of phosphate adsorption are electrostatic adsorption, ion exchange, and inner-sphere complexation. The results emphasized that the Mg-La LDH was efficient in phosphate removal and could be successfully used for this purpose.

Partial nitrification-denitrification and enrichment of paracoccus induced by iron-chitosan beads addition in an intermittently-aerated activated sludge system.

Insufficient carbon source has become the main limiting factor for efficient nitrogen removal in wastewater treatment. In this study, an intermittently-aerated activated sludge system with iron-chitosan (Fe-CS) beads addition was proposed for nitrogen removal from low C/N wastewater. By adding Fe-CS beads, partial nitrification-denitrification (PND) process and significant enrichment of Paracoccus (with ability of iron reduction/ammonium oxidation/aerobic denitrification) were observed in the reactor. The accumulation rate of NO2--N reached 81.9 %, and the total nitrogen removal efficiency was improved to 93.9 % by shortening the aeration time. The higher activity of ammonium oxidizing bacteria and inhibited activity of nitrite-oxidizing bacteria in Fe-CS assisted system mediated the occurrence of PND. In contrast, the traditional nitrification and denitrification process occurred in the control group. The high-throughput sequencing analysis and metagenomic results confirmed that the addition of Fe-CS induced 77.8 % and 54.9 % enrichment of Paracoccus in sludge and Fe-CS beads, respectively, while almost no enrichment was observed in control group. Furthermore, with the addition of Fe-CS beads, the expression of genes related to outer membrane porin, cytochrome c, and TCA was strengthened, thereby enhancing the electron transport of Fe(Ⅱ) (electron donor) and Fe(Ⅲ) (electron acceptor) with pollutants in the periplasm. This study provides new insights into the direct enrichment of iron-reducing bacteria and its PND performance induced by the Fe-CS bead addition. It therefore offers an appealing strategy for low C/N wastewater treatment.

Achieving simultaneous nitrification and endogenous denitrifying phosphorus removal in anaerobic/intermittently-aerated moving bed biofilm reactor for low carbon-to-nitrogen ratio wastewater treatment.

In this study, an anaerobic/intermittently-aerated moving bed biofilm reactor (AnIA-MBBR) was proposed to realize simultaneous nitrification and endogenous denitrifying phosphorus removal (SNEDPR) in treating low carbon-to-nitrogen (C/N) ratio wastewater. The effect of different intermittent aeration modes (short and long aeration) on nutrients' removal was investigated. With the C/N ratio around 3, the removal efficiencies of total nitrogen and phosphorus were 90% and 74%, 88% and 59%, respectively, for short aeration and long aeration. The different aeration time also altered the nutrients' degradation pathway, biofilm characteristics, microbial community, and functional metabolic pathways. The results confirmed the occurrence of aerobic denitrifiers, anoxic denitrifiers, phosphorus accumulating organisms, glycogen accumulating organisms in AnIA-MBBR systems and their synergistic performance induced the SNEDPR. These results indicated that the application of AnIA in MBBR systems was an effective strategy to achieve SNEDPR, providing better simultaneous removal performance of nitrogen and phosphorus from low C/N ratio wastewater.

Effect of anaerobic duration on biological phosphorus removal in reversed AAO process (anoxic-anaerobic-oxic).

In this study, the effect of anaerobic duration on phosphorus (P) removal in reversed AAO (anoxic-anaerobic-oxic) process was investigated using synthetic wastewater (with different volatile fatty acid (VFA) ratios) and real wastewater. The P, poly-hydroxyalkanoates (PHAs), dehydrogenase activity (DHA), polyphosphate kinases (PPK), electron transfer system (ETS), and adenosine 5'-triphosphate (ATP) were determined as indicators. The highest P removal efficiencies were achieved at an anaerobic duration of 3, 4, and 6 h for 15, 30, and 60% VFA ratio in synthetic wastewater. The amount of the released P and stored PHAs can be manipulated by different anaerobic durations, but the P removal efficiency cannot be guaranteed with higher stored PHAs. Additionally, the energy metabolism confirmed the significance of anaerobic duration extension on microbial activity. The highest values of four indicators were all achieved at anaerobic duration of 4 h with 30% VFAs ratio which achieved the highest P removal efficiency. Real wastewater experiments also proved the reproductivity of these results. We defined this phenomenon as the "hunger response" where microorganisms responded to suppression (anaerobic duration extension) with higher activity after the end of the anaerobic condition. These results can provide references for better design and operation of biological phosphorus removal in RAAO process.

Enhanced nitrogen removal in immersed rotating self-aerated biofilm reactor: Nitrogen removal pathway and microbial mechanism.

To achieve energy-efficient treatment of the rural wastewater with satisfying performance, a novel immersed rotating self-aerated biofilm reactor (iRSABR) was proposed in this study. The iRSABR system showed better biofilm renewal performance and higher microbial activity. The effect of different regulation strategies on the iRSABR system was investigated in this study. The 70% immersion ratio and 4 r/min rotation speed (stage III) exhibited the best performance, with a total nitrogen removal efficiency of 86% and a simultaneous nitrification-denitrification (SND) rate of 76%, along with the highest electron transport system activity. The nitrogen removal pathway revealed that the SND was achieved through autotrophic/heterotrophic nitrification and aerobic/anoxic denitrification. The regulation strategy in the iRSABR system established a synergistic microbial community with main functional bacteria of nitrification (Nitrosomonas), anoxic denitrification (Flavobacterium, Pseudoxanthomonas), and aerobic denitrification (Thauera). This study highlighted the feasibility and adaptability of the iRSABR system toward energy-efficient rural wastewater treatment.

Portable detection of multiple mycotoxins based on a sonic toothbrush, microfluidic chip and smartphone.

A portable method for on-site detection of three mycotoxins was developed based on a sonic toothbrush, microfluidic chip and smartphone. Our method could complete all procedures, including sample pretreatment, signal conversion and processing, without any sophisticated instruments. The limits of detection for these mycotoxins were lower than the limit values in cereals in the standards of China and the European Union.

Simultaneous nitrification and denitrification in a novel rotating self-aerated biofilm reactor for decentralized wastewater treatment.

Decentralized wastewater pollution in rural areas has become a serious problem for the rural environment. In this study, a novel rotating self-aerated biofilm reactor was developed for decentralized wastewater treatment without any aeration equipment. After the long-term operation of 110 days, the removal efficiency reached to 96.06 % (COD), 98.06 % (NH4+-N), and 62.58 % (TN) in the last phase. Under high dissolved oxygen level, the simultaneous nitrification-denitrification (SND) maintained at a stable ratio of 62.53 % and the denitrification rates reached over 28.37 mg/L/h. With the organic loading rate increased, key nitrogen functional bacterial communities such as anoxic denitrifiers (Thiothrix, Flavobacterium, Pseudoxanthomonas, Aquimonas and Azoarcus) and aerobic denitrifiers (Hydrogenophaga, Zoogloea and Terrimonas) increased obviously. Overall, microbial analysis and nitrogen metabolism pathway indicated that an integration of SND process was achieved in this single reactor by the combined action of nitrification, denitrification and comammox without any aeration equipment.

Investigation of an intermittently-aerated moving bed biofilm reactor in rural wastewater treatment under low dissolved oxygen and C/N condition.

An intermittently-aerated moving bed biofilm reactor (MBBR) was proposed for nitrogen and carbon removal from low C/N synthetic rural wastewater. In purposes of low energy consumption and costs, the intermittent aeration modes were changed and the dissolved oxygen was reduced gradually during the operation. The results showed that effluent concentrations of ammonia nitrogen and chemical oxygen demand were lower than 15 and 50 mg/L, respectively, even under microaerobic condition (0.1-1.0 mg/L). Meanwhile, the simultaneous nitrification-denitrification was achieved by intermittent aeration. The activity of functional bacteria was still high and the proportion of autotrophic biomass increased significantly under intermittent micro-aeration mode, which improved the nitrification performance. Aerobic denitrifier Hydrogenophaga, anoxic denitrifier Thiothrix, and heterotrophic nitrifier such as Rhodobacter were enriched in the intermittently micro-aerated MBBR, which will provide an applicable solution for rural wastewater treatment under low C/N and costs.

Freeze substitution Hi-C, a convenient and cost-effective method for capturing the natural 3D chromatin conformation from frozen samples.

Chromatin interactions functionally affect genome architecture and gene regulation, but to date, only fresh samples must be used in High-through chromosome conformation capture (Hi-C) to keep natural chromatin conformation intact. This requirement has impeded the advancement of 3D genome research by limiting sample collection and storage options for researchers and severely limiting the number of samples that can be processed in a short time. Here, we develop a freeze substitution Hi-C (FS-Hi-C) technique that overcomes the need for fresh samples. FS-Hi-C can be used with samples stored in liquid nitrogen (LN2): the water in a vitreous form in the sample cells is replaced with ethanol via automated freeze substitution. After confirming that the FS step preserves the natural chromosome conformation during sample thawing, we tested the performance of FS-Hi-C with Drosophila melanogaster and Gossypium hirsutum. Beyond allowing the use of frozen samples and confirming that FS-Hi-C delivers robust data for generating contact heat maps and delineating A/B compartments and topologically associating domains, we found that FS-Hi-C outperforms the in situ Hi-C in terms of library quality, reproducibility, and valid interactions. Thus, FS-Hi-C will probably extend the application of 3D genome structure analysis to the vast number of experimental contexts in biological and medical research for which Hi-C methods have been unfeasible to date.

REST-repressed lncRNA NPPA-AS1 regulates cervical cancer progression by modulating miR-302e/DKK1/Wnt/ß-catenin signaling pathway.

Long noncoding RNAs (lncRNAs), a group of transcripts, have been revealed to be critical participants in regulating multiple biological processes of malignant tumors. The knowledge of NPPA-AS1 (a new lncRNA) in cancer research is hardly known. Thus, it is of urgent need to study the underlying role of NPPA antisense RNA 1 (NPPA-AS1) in cervical cancer (CC). In this study, NPPA-AS1 was discovered to be lowly expressed and upregulation of it impaired cell proliferation and migration in CC. Besides, downregulation of it led to opposite results. Molecular mechanism assays uncovered that increased expression of NPPA-AS1 could inactivate Wnt/ß-catenin signaling pathway in CC. In addition, NPPA-AS1 was found to negatively interact with miR-302e whereas positively correlate with dickkopf-1 (DKK1, an inhibitor of Wnt pathway) in CC. Besides, loss of function assay illuminated that miR-302e inhibition restrained cell proliferation and migration in CC. Subsequent rescue assays confirmed that NPPA-AS1 acted as a competing endogenous RNA in CC by sponging miR-302e to upregulate DKK1 expression. Finally, the RE-1 silencing transcription factor (REST) was testified to function as a transcription suppressor of NPPA-AS1 in CC. In brief, REST-repressed NPPA-AS1 regulates CC progression by modulating miR-302e/DKK1/Wnt/ß-catenin signaling pathway.

Development of biodegradable Zn-1Mg-0.1RE (RE = Er, Dy, and Ho) alloys for biomedical applications.

Zinc (Zn) and its alloys are receiving great attention as promising biodegradable materials due to their suitable corrosion resistance, good biocompatibility, and highly desirable biofunctionality. Nevertheless, the low mechanical strength of pure Zn impedes its practical clinical application and there have been calls for further research into the Zn alloys and thermomechanical processes to enhance their mechanical properties and biocompatibility. Here, we report on the alloying efficacy of rare earth elements (REEs) including erbium (Er), dysprosium (Dy), and holmium (Ho) on the microstructure, mechanical properties, corrosion and wear behavior, and in vitro biological properties of Zn-1Mg-0.1RE alloys. Microstructural characterization revealed that the addition of 0.1 wt.% REEs had a significant refining effect on the grain size of the α-Zn matrix and the second phases of the alloys. Alloying of the REEs and hot-rolling effectively improved the mechanical properties due to both precipitation strengthening of the second phases of ErZn5, DyZn5, and Ho2Zn17 and grain-refinement strengthening. The highest ultimate tensile strength of 259.4 MPa and yield strength of 234.8 MPa with elongation of 16.8% were achieved in the hot-rolled Zn-1Mg-0.1Ho. Alloying of REEs also improved the wear and corrosion resistance, and slowed down the degradation rate in Hanks' solution. Zn-1Mg-0.1Er showed the highest cytocompatibility of MC3T3-E1 cells cultured directly on the alloy surface and of MG-63 cells cultured in the alloy extract. Zn-1Mg-0.1Dy showed the best anticoagulant property among all the alloys. Overall, these Zn-1Mg-0.1RE (Er, Dy, and Ho) alloys can be considered promising biodegradable metallic materials for orthopedic applications.

Biodegradable ternary Zn-3Ge-0.5X (X=Cu, Mg, and Fe) alloys for orthopedic applications.

Biodegradable zinc (Zn) and its alloys have great potential to be used for orthopedic applications due to their suitable degradation rate and good biocompatibility. However, pure Zn has insufficient mechanical properties, such as low strength and hardness, and poor plasticity, which limits its clinical applications. Here, we report on a new series of ternary Zn-3Ge-0.5X (X=Cu, Mg, and Fe) alloys aiming to achieve good corrosion resistance and biocompatibility, and enhanced mechanical properties via micro-alloying with copper (Cu), magnesium (Mg), and iron (Fe). Hot-rolling has also been applied to the new ternary alloys to further enhance their mechanical properties. Mechanical testing results indicate that both the strength and hardness of hot-rolled Zn-3Ge are significantly improved with micro-alloying of Cu, Mg, and Fe; of which the hot-rolled Zn-3Ge-0.5Mg exhibits the highest ultimate tensile strength of 253.4 MPa and yield strength of 208.5 MPa among all the alloys, 25.9% and 44.7% higher than those of the hot-rolled Zn-3Ge. The degradation rate of the as-cast alloys is lower than that of the hot-rolled alloys in Hanks' solution for 1 month and the hot-rolled Zn-3Ge-0.5Mg alloy exhibits the highest degradation rate of 0.075 mm/y. CCK-8 assay using MG-63 cells indicates that the diluted extracts of Zn-3Ge-0.5X (X=Cu, Mg, and Fe) alloys with concentrations of 12.5% and 25% exhibit no or slight cytotoxicity, and the diluted extracts of Zn-3Ge-0.5Cu alloys show high cell viability of over 100%, showing the best cytocompatibility.

Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum.

Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine-a strongly protective environment factor as suggested by epidemiological evidence-may represent a novel pharmacological therapy for PD by targeting autophagy pathway.

Spatiotemporal Control of GPR37 Signaling and Its Behavioral Effects by Optogenetics.

Despite the progress in deorphanization of G Protein-Coupled Receptors (GPCRs), ≈100 GPCRs are still classified as orphan receptors without identified endogenous ligands and with unknown physiological functions. The lack of endogenous ligands triggering GPCR signaling has hampered the study of orphan GPCR functions. Using GPR37 as an example, we provide here the first demonstration of the channelrhodopsin 2 (ChR2)-GPCR approach to bypass the endogenous ligand and selectively activate the orphan GPCR signal by optogenetics. Inspired by the opto-XR approach, we designed the ChR2-GPR37 chimera, in which the corresponding parts of GPR37 replaced the intracellular portions of ChR2. We showed that optogenetic activation of ChR2/opto-GPR37 elicited specific GPR37 signaling, as evidenced by reduced cAMP level, enhanced ERK phosphorylation and increased motor activity, confirming the specificity of opto-GPR37 signaling. Besides, optogenetic activation of opto-GPR37 uncovered novel aspects of GPR37 signaling (such as IP-3 signaling) and anxiety-related behavior. Optogenetic activation of opto-GPR37 permits the causal analysis of GPR37 activity in the defined cells and behavioral responses of freely moving animals. Importantly, given the evolutionarily conserved seven-helix transmembrane structures of ChR2 and orphan GPCRs, we propose that opto-GPR37 approach can be readily applied to other orphan GPCRs for their deorphanization in freely moving animals.