One-Stone-for-Two-Birds Strategy for VSe2 to Enable High Capacity and Long-Life Zinc Storage.

Based on a specific zinc storage mechanism and excellent electronic conductivity, transition metal dichalcogenides, represented by vanadium diselenide, are widely used in aqueous zinc-ion battery (AZIB) energy storage systems. However, most vanadium diselenide cathode materials are presently limited by low specific capacity and poor cycling life. Herein, a simple hydrothermal process has been proposed for obtaining a vanadium diselenide cathode for an AZIB. The interaction of defects and crystal planes enhances zinc storage capacity and reduces the migration energy barrier. Moreover, abundant lamellar structure greatly increases reaction sites and alleviates volume expansion during the electrochemical process. Thus, the as-obtained vanadium diselenide AZIB exhibits an excellent reversible specific capacity of 377 mAh g-1 at 1 A g-1, and ultralong cycle stability of 291 mAh g-1 after 3200 cycles, with a nearly negligible capacity loss. This one-stone-for-two-birds strategy would be expected to be applied to large-scale synthesis of a high-performance zinc-ion battery cathode in the future.

Prediction of sulfate concentrations in groundwater in areas with complex hydrogeological conditions based on machine learning.

The persistent and increasing levels of sulfate due to a variety of human activities over the last decades present a widely concerning environmental issue. Understanding the controlling factors of groundwater sulfate and predicting sulfate concentration is critical for governments or managers to provide information on groundwater protection. In this study, the integration of self-organizing map (SOM) approach and machine learning (ML) modeling offers the potential to determine the factors and predict sulfate concentrations in the Huaibei Plain, where groundwater is enriched with sulfate and the areas have complex hydrogeological conditions. The SOM calculation was used to illustrate groundwater hydrochemistry and analyze the correlations among the hydrochemical parameters. Three ML algorithms including random forest (RF), support vector machine (SVM), and back propagation neural network (BPNN) were adopted to predict sulfate levels in groundwater by using 501 groundwater samples and 8 predictor variables. The prediction performance was evaluated through statistical metrics (R2, MSE and MAE). Mine drainage mainly facilitated increase in groundwater SO42- while gypsum dissolution and pyrite oxidation were found another two potential sources. The major water chemistry type was Ca-HCO3. The dominant cation was Na+ while the dominant anion was HCO3-. There was an intuitive correlation between groundwater sulfate and total dissolved solids (TDS), Cl-, and Na+. By using input variables identified by the SOM method, the evaluation results of ML algorithms showed that the R2, MSE and MAE of RF, SVM, BPNN were 0.43-0.70, 0.16-0.49 and 0.25-0.44. Overall, BPNN showed the best prediction performance and had higher R2 values and lower error indices. TDS and Na+ had a high contribution to the prediction accuracy. These findings are crucial for developing groundwater protection and remediation policies, enabling more sustainable management.

Fine-tuning of p-coumaric acid synthesis to increase (2S)-naringenin production in yeast.

(2S)-Naringenin is a key precursor for biosynthesis of various high-value flavonoids and possesses a variety of nutritional and pharmaceutical properties on human health. Systematic optimization approaches have been employed to improve (2S)-naringenin production in different microbial hosts. However, very few studies have focused on the spatiotemporal distribution of (2S)-naringenin and the related pathway intermediate p-coumaric acid, which is an important factor for efficient production. Here, we first optimized the (2S)-naringenin biosynthetic pathway by alleviating the bottleneck downstream of p-coumaric acid and increasing malonyl-CoA supply, which improved (2S)-naringenin production but significant accumulation of p-coumaric acid still existed extracellularly. We thus established a dual dynamic control system through combining a malonyl-CoA biosensor regulator and an RNAi strategy, to autonomously control the synthesis of p-coumaric acid with the supply of malonyl-CoA. Furthermore, screening potential transporters led to identification of Pdr12 for improved (2S)-naringenin production and reduced accumulation of p-coumaric acid. Finally, a titer of 2.05 g/L (2S)-naringenin with negligible accumulation of p-coumaric acid was achieved in a fed batch fermentation. Our work highlights the importance of systematic control of pathway intermediates for efficient microbial production of plant natural products.

Engineering Interface Defects and Interdiffusion at the Degenerate Conductive In2O3/Al2O3 Interface for Stable Electrodes in a Saline Solution.

A low-temperature Al2O3 deposition process provides a simplified method to form a conductive two-dimensional electron gas (2DEG) at the metal oxide/Al2O3 heterointerface. However, the impact of key factors of the interface defects and cation interdiffusion on the interface is still not well understood. Furthermore, there is still a blank space in terms of applications that go beyond the understanding of the interface's electrical conductivity. In this work, we carried out a systematic experimental study by oxygen plasma pretreatment and thermal annealing post-treatment to study the impact of interface defects and cation interdiffusion at the In2O3/Al2O3 interface on the electrical conductance, respectively. Combining the trends in electrical conductance with the structural characteristics, we found that building a sharp interface with a high concentration of interface defects provides a reliable approach to producing such a conductive interface. After applying this conductive interface as electrodes for fabricating a field-effect transistor (FET) device, we found that this interface electrode exhibited ultrastability in phosphate-buffered saline (PBS), a commonly used biological saline solution. This study provides new insights into the formation of conductive 2DEGs at metal oxide/Al2O3 interfaces and lays the foundation for further applications as electrodes in bioelectronic devices.

Construction of a fecal immune-related protein-based biomarker panel for colorectal cancer diagnosis: a multicenter study.

Purpose: To explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis. Patients and methods: Three independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC). Results: In the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue. Conclusion: A novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

Exploring the mechanism of MP gel against skin photoaging based on network pharmacology, molecular docking, and experimental validation.

OBJECTIVE: Long-term and high exposure to UV radiation can lead to the development of skin photoaging diseases. Therefore, there is an ongoing need for more natural and safe drugs to prevent or treat skin photoaging diseases. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database were used to collect the active compounds and corresponding targets of Cnidii Fructus, Arnebiae Radix, Angelicae Sinensis Radix, Poria, and Borneolum. The GeneCards database and the NCBI Gene database were used to collect the targets of skin photoaging diseases. The STRING database was used to construct a protein-protein interaction network formed by the intersecting targets of drugs and diseases. The Metascape database was applied for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the targets. Molecular docking between active compounds and targets was verified by Autodock. After that, the skin photoaging model of mice was established and treated with MP gel. The skin characterization on the back of mice was observed, and the ameliorative effect of MP gel on skin photoaging was evaluated by histological and epidermal thickness assays. The MDA content and SOD activity were measured. Caspase-3 expression in mouse skin tissues was detected by immunohistochemistry, quantitative real-time polymerase chain reaction assay, and Western blot. RESULTS: The results of network pharmacology experiments showed that the natural drugs have multi-component, multi-target therapeutic disease characteristics. The results of animal studies showed that MP gel improved the health of photoaged skin, promoted skin structural integrity, had antioxidant properties and significantly inhibited caspase-3 expression. CONCLUSION: The experimental validation of the results of the preliminary network pharmacology analysis was carried out in animal experiments, which confirmed part of the mechanism of action of MP gel in the prevention and treatment of skin photoaging.

Inexact fuzzy-flexible left-hand-side chance-constrained programming for agricultural nonpoint-source water quality management.

In this study, an inexact fuzzy-flexible left-hand-side chance-constrained programming (IFLCCP) method is proposed for optimizing an agricultural nonpoint-source water quality management problem under uncertainty. The developed method can address complex uncertainties resulted from system fuzzy flexible under various level of decision-making requirements and randomness parameters appeared on the left-hand side of the constraints, and deal with the conflict between water quality protection and agricultural system economic development. The IFLCCP model is formulated through incorporating inexact left-hand-sided chance-constrained programming into interval fuzzy flexible programming framework. The decision schemes obtained by the IFLCCP are analyzed under scenarios at different confidence level of environmental constraint. The results demonstrate that the scale of crop planting and breeding industries reduces as the confidence coefficient of environmental constraint (1-pi) increases, in order to satisfy pollutant discharge constraints, which results in the reduction of the system net benefit from scenarios 1 to 3. Meanwhile, the interval control variables λ± are introduced for quantifying the degrees of overall satisfaction for the objective function and the constraints, which get optimal adjustment to guarantee the net benefit to be as close as possible to the upper bound. The IFLCCP is able to provide management schemes with high system benefits under different levels of acceptable environmental risk, taking full consideration of decision makers' environmental management requirements. This study is a new application of the IFLCCP model to agricultural water quality management problem, demonstrating its applicability to practical environmental problems with high complexity and uncertainty.

Customizable assembly of free-standing integrated electronics for wearables by phase separation.

The non-solvent induced phase separation method is utilized to produce a free-standing electrode with good conductivity retention during 1000 bending/stretching cycles. The as-prepared electrode has been fabricated for an integrated device consisting of an ethanol fuel cell, a supercapacitor and a motion sensor. This method for fabricating free-standing electronics reveals a cost-effective approach towards wearable devices.

Metabolic reconfiguration enables synthetic reductive metabolism in yeast.

Cell proliferation requires the integration of catabolic processes to provide energy, redox power and biosynthetic precursors. Here we show how the combination of rational design, metabolic rewiring and recombinant expression enables the establishment of a decarboxylation cycle in the yeast cytoplasm. This metabolic cycle can support growth by supplying energy and increased provision of NADPH or NADH in the cytosol, which can support the production of highly reduced chemicals such as glycerol, succinate and free fatty acids. With this approach, free fatty acid yield reached 40% of theoretical yield, which is the highest yield reported for Saccharomyces cerevisiae to our knowledge. This study reports the implementation of a synthetic decarboxylation cycle in the yeast cytosol, and its application in achieving high yields of valuable chemicals in cell factories. Our study also shows that, despite extensive regulation of catabolism in yeast, it is possible to rewire the energy metabolism, illustrating the power of biodesign.

Highly Selective Wearable Alcohol Homologue Sensors Derived from Pt-Coated Truncated Octahedron Au.

Unhealthy alcohol inhalation is among the top 10 causes of preventable death. However, the present alcohol sensors show poor selectivity among alcohol homologues. Herein, Pt-coated truncated octahedron Au (Ptm@Auto) as the electrocatalyst for a highly selective electrochemical sensor toward alcohol homologues has been designed. The alcohol sensor is realized by distinguishing the electro-oxidation behavior of methanol (MeOH), ethanol (EtOH), or isopropanol (2-propanol). Intermediates from alcohols are further oxidized to CO2 by Ptm@Auto, resulting in different oxidation peaks in cyclic voltammograms and successful distinction of alcohols. Ptm@Auto is then modified on wearable glove-based sensors for monitoring actual alcohol samples (MeOH fuel, vodka, and 2-propanol hand sanitizer), with good mechanical performance and repeatability. The exploration of the Ptm@Auto-based wearable alcohol sensor is expected to be suitable for environmental measurement with high selectivity for alcohol homologues or volatile organic compounds.

Monoclinic Bimetallic Prussian Blue Analog Cathode with High Capacity and Long Life for Advanced Sodium Storage.

Prussian blue analogs (PBAs) are regarded as promising cathode materials for sodium-ion batteries (SIBs), but most of them suffer from an incompatibility between capacity and structural stability. Herein, an innovative disodium ethylenediaminetetraacetate (Na2EDTA)-assisted hydrothermal method is proposed to synthesize monoclinic Fe-substituted Ni-rich PBA (H-PBA) cathodes for Na-ion storage. The as-designed H-PBA cathode combines the merits of the low strain of a Ni-based PBA framework and the enhanced capacity of N-Fe3+/Fe2+ redox sites. It can achieve superior sodium-storage performance in terms of capacity, rate capability, and cycle stability. Moreover, ex situ measurements reveal that solid solution (2.0-3.0 V) and phase-transition (3.0-4.0 V) reactions occur during the charge/discharge process to allow almost 1.5 Na+ storage in the H-PBA lattice. Meanwhile, the H-PBA//NaTi2(PO4)3@C full cell also delivers remarkable electrochemical properties. Prospectively, this work would promote the practical application of SIBs in grid-scale electric energy storage.

Heavy metal enrichment in drinking water pipe scales and speciation change with water parameters.

Pipe scales that form in drinking water distribution systems (DWDS) can accumulate pollutants that may be re-released into bulk water, posing a significant threat to water safety. This study aims to evaluate the pollutant enrichment capacity of the pipe scale and identify speciation changes in heavy metals under variations in water quality. When the water quality conditions changed, the forms of inorganic metal elements in drinking water pipe scales also changed and the proportion of unstable forms increased, thereby increasing the risk of secondary pollution. Morphological analysis showed that the pipe scale samples had porous structures and large specific surface areas (the maximum was 52.94 m2/g, which is higher than that of many natural adsorbents), which could promote the accumulation of contaminants. XRD profiles also showed that the pipe scale samples were rich in substances with heavy metal adsorption capacities, such as Fe3O4. As the pH changed from 6 to 10, no significant difference in the release of heavy metals was found. The maximum release of Cu, Cr, As, Pb, and Cd at pH 8 was 0.56, 0.51, 1.82, 0.84, and 0.72 µg/g, respectively. Although the amounts were small, the speciation distribution of the heavy metals changed significantly. In addition, the proportion of unstable fractions increased, which increased the release risk of the pipe scale. The presence of humic acid accelerated the dissolution of organic matter and metals in the pipe scale, which further proved that the pipe scales were unstable and susceptible to water quality conditions. The pipe scales could not maintain stability when the water quality changed, and the DWDS should be regularly monitored and cleaned when necessary.

Metabolomics reveal the mechanism for anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica.

To reveal the mechanism of anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica, renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an n-butanol extract (BUT) from Amygdalus mongolica (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg-1) and BUT-treated (1.75, 1.5 and 1.25 g kg-1) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. A. mongolica BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.

Wearable Motion Smartsensors Self-Powered by Core-Shell Au@Pt Methanol Fuel Cells.

A wearable self-powered sensor is a promising frontier in recent flexible electronic devices. In this work, a wearable fuel cell (FC)-type self-powering motion smartsensor has been fabricated, particularly in choosing methanol vapor as a target fuel for the first time. The core-shell structure of Pt@Au/N-rGO and the porous carbon network act as methanol oxidation and oxygen reduction reaction catalysts, with a highly conductive alkaline hydrogel as a solid-state electrolyte. As a result, a wearable FC for a self-powered sensing system demonstrates excellent sensing performance toward 2-20% (v/v) methanol vapor with a maximum power density of 2.26 µW cm-1 and good mechanical behaviors during the bending or twisting process. Significantly, this wearable FC device could power strain sensors of human motion, and real-time signals can be easily remotely detected via a cellphone. With attractive biocompatibility and self-powering performance, wearable FCs for a self-powering system would provide new opportunities for next-generation flexible smartsensing electronics and initiate a developed self-powering platform in future practical application of wearable smart monitoring.

De novo biosynthesis of bioactive isoflavonoids by engineered yeast cell factories.

Isoflavonoids comprise a class of plant natural products with great nutraceutical, pharmaceutical and agricultural significance. Their low abundance in nature and structural complexity however hampers access to these phytochemicals through traditional crop-based manufacturing or chemical synthesis. Microbial bioproduction therefore represents an attractive alternative. Here, we engineer the metabolism of Saccharomyces cerevisiae to become a platform for efficient production of daidzein, a core chemical scaffold for isoflavonoid biosynthesis, and demonstrate its application towards producing bioactive glucosides from glucose, following the screening-reconstruction-application engineering framework. First, we rebuild daidzein biosynthesis in yeast and its production is then improved by 94-fold through screening biosynthetic enzymes, identifying rate-limiting steps, implementing dynamic control, engineering substrate trafficking and fine-tuning competing metabolic processes. The optimized strain produces up to 85.4 mg L-1 of daidzein and introducing plant glycosyltransferases in this strain results in production of bioactive puerarin (72.8 mg L-1) and daidzin (73.2 mg L-1). Our work provides a promising step towards developing synthetic yeast cell factories for de novo biosynthesis of value-added isoflavonoids and the multi-phased framework may be extended to engineer pathways of complex natural products in other microbial hosts.

Metabolomics reveals the renoprotective effect of n-butanol extract and amygdalin extract from Amygdalus mongolica in rats with renal fibrosis.

Renal fibrosis (RF) is a pathological process of progression from chronic kidney disease to end-stage renal disease. Amygdalus mongolica is a traditional Chinese medicine, and our previous studies demonstrated that the n-butanol extract (BUT) and amygdalin extract (AMY) from its seeds can prevent RF. However, the underlying mechanism remains unclear. The present study investigated the exact mechanism of the protective effect of A. mongolica on RF. A renal fibrosis rat model was induced with unilateral ureteral obstruction. Biochemical indicators were measured and combined with histopathology of renal tissue to evaluate the anti-RF effects. A serum metabonomic method was used to clarify the changes in the metabolic profile. The tubulointerstitial damage and fibrosis were significantly improved and metabolic perturbations were restored after treatment with BUT and AMY. Thirty-eight metabolites associated with RF progression and related to the regulation of arginine and proline metabolism, nicotinate and nicotinamide metabolism, and histidine metabolism were identified. They were restored to levels similar to those in controls after treatment. Moreover, no significant differences in efficacy were observed between the BUT and AMY groups. This study reveals and compares the potential mechanisms of the renoprotective effects after treatment with BUT and AMY from a metabolomic perspective.

Fabrication of a Robust In2O3 Nanolines FET Device as a Biosensor Platform.

Field-effect transistors (FETs) are attractive biosensor platforms for rapid and accurate detection of various analytes through surface immobilization of specific bio-receptors. Since it is difficult to maintain the electrical stability of semiconductors of sensing channel under physiological conditions for long periods, passivation by a stable metal oxide dielectric layer, such as Al2O3 or HfO2, is currently used as a common method to prevent damage. However, protecting the sensing channel by passivation has the disadvantage that the distance between the target and the conductive channel increases, and the sensing signal will be degraded by Debye shielding. Even though many efforts use semiconductor materials directly as channels for biosensors, the electrical stability of semiconductors in the physiological environments has rarely been studied. In this work, an In2O3 nanolines FET device with high robustness in artificial physiological solution of phosphate buffered saline (PBS) was fabricated and used as a platform for biosensors without employing passivation on the sensing channel. The FET device demonstrated reproducibility with an average threshold voltage (VTH) of 5.235 V and a standard deviation (SD) of 0.382 V. We tested the robustness of the In2O3 nanolines FET device in PBS solution and found that the device had a long-term electrical stability in PBS with more than 9 days' exposure. Finally, we demonstrated its applicability as a biosensor platform by testing the biosensing performance towards miR-21 targets after immobilizing the phosphonic acid terminated DNA probes. Since the surface immobilization of multiple bioreceptors is feasible, we demonstrate that the robust In2O3 FET device can be an excellent biosensor platform for biosensors.

Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica.

CONTEXT: The petroleum ether extract (PET) of Amygdalus mongolica (Maxim.) Ricker (Rosaceae) has an ameliorative effect on renal fibrosis (RF). OBJECTIVE: To evaluate the antifibrotic effects of A. mongolica seeds PET on RF by serum metabolomics, biochemical and histopathological analyses. MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, RF model, benazepril hydrochloride-treated model (1.5 mg/kg) and PET-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. Biochemical indicators including BUN, Scr, HYP, SOD, and MDA were measured. Haematoxylin and eosin and Masson staining were used for histological examination. The serum metabolomic profiles were determined by UPLC-Q-TOF/MS and metabolism network analysis. Acute toxicity test was performed to validate biosafety. RESULTS: The PET LD50 was >23.9 g/kg in rats. PET significantly alleviated fibrosis by reducing the levels of Scr (from 34.02 to 32.02), HYP (from 403.67 to 303.17) and MDA (from 1.84 to 1.73), and increasing that of SOD (from 256.42 to 271.85). Metabolomic profiling identified 10 potential biomarkers, of which three key markers were significantly associated with RF-related pathways including phenylalanine, tyrosine and tryptophan biosynthesis, amino sugar and nucleotide sugar metabolism and tyrosine metabolism. In addition, three key biomarkers were restored to baseline levels following PET treatment, with the medium dose showing optimal effect. CONCLUSIONS: These findings revealed the mechanism of A. mongolica PET antifibrotic effects for RF rats on metabolic activity and provided the experimental basis for the clinical application.

Microheater-integrated zinc oxide nanowire microfluidic device for hybridization-based detection of target single-stranded DNA.

Detection of cell-free DNA (cfDNA) has an impact on DNA analysis in liquid biopsies. However, current strategies to detect cfDNA have limitations that should be overcome, such as having low sensitivity and requiring much time and a specialized instrument. Thus, non-invasive and rapid detection tools are needed for disease prevention and early-stage treatment. Here we developed a device having a microheater integrated with zinc oxide nanowires (microheater-ZnO-NWs) to detect target single-stranded DNAs (ssDNAs) based on DNA probe hybridization. We confirmed experimentally that our device realizedin-situannealed DNA probes by which we subsequently detected target ssDNAs. We envision that this device can be utilized for fundamental studies related to nanobiodevice-based DNA detection.