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The Strength and toughness trade-off is a long-term dilemma in structural materials. Here, we report a new strategy for synergistically improving the strength and toughness of Nb/Nb 5 Si 3 composites by incorporating high-performance graphene to tailor the interfacial coherency and strengthen the matrix. The fabricated graphene reinforced Nb/Nb 5 Si 3 composite stands out from available reports on Nb/Nb 5 Si 3 composites. The medium mismatch Nb–Nb 5 Si 3 interface is transformed into the low mismatch Nb–Nb 4 C 3 –Nb 5 Si 3 multi-interfaces because of the incorporation of graphene and the formation of nano-sized interfacial Nb 4 C 3 phases. These low mismatch interfaces facilitate the multiplication of dislocations and the formation of long-range dislocations to annihilate, thereby leading to a superior combination of strength and toughness. Importantly, the low mismatch of Nb 4 C 3 –Nb and -Nb 5 Si 3 interfaces are beneficial for forming a strong interfacial bonding and effectively promoting the anchoring effect to inhibit the pull-out of graphene, resulting in increasing the load transfer from matrix to graphene. The deflecting and bridging of cracks, as well as microcracks, are recognized as the toughening mechanisms in this composite. The present study reveals a strategy to evade the strength and toughness trade-off in Nb/Nb 5 Si 3 composites by incorporating high-performance graphene to tailor the interfacial coherency and strengthen the matrix. • A new strategy for synergistically improving the strength and toughness of Nb/Nb 5 Si 3 composites is reported. • The fabricated graphene reinforced Nb/Nb 5 Si 3 composite stands out from available reports on Nb/Nb 5 Si 3 composites. • Nano-sized interfacial Nb 4 C 3 phases decrease the interfacial mismatch of Nb/Nb 5 Si 3 composite. [ABSTRACT FROM AUTHOR]

[Display omitted] • Traditional RSM and ANN models were evaluated to optimize fungal fermentations. • Multi-parameter optimized ANN models outperformed traditional RSM models. • Data stratifying, internal adjustments, and metaheuristic algorithms optimized ANN. • ANN models shown great robustness across various fungi and experimental designs. Filamentous fungi's secondary metabolites (SMs) possess significant application owing to their distinct structure and diverse bioactivities, yet their restricted yield levels often hinder further research and application. The study developed a response surface methodology-artificial neural network (RSM-ANN) strategy with multi-parameter optimizations of the ANN model to optimize medium for the production of two high-value fungal SMs, echinocandin E and paraherquamide A. Multi-parameter optimization of the ANN model was achieved through stratifying experimental data, fully adjusting neural network internals, and evaluating metaheuristic algorithms for optimal initial weights and biases. Experimental validation of models revealed that ANN-genetic algorithm models outperformed traditional RSM models in terms of determination coefficients, accuracy, and mean squared errors. ANN models showed outstanding robustness across a variety of fungal species, mediums, and experimental designs (Central Composite Design or Box-Behnken Design). This work refines the RSM-ANN optimization technique to increase fungal SM production efficiency, enabling industrial-scale production and applications. [ABSTRACT FROM AUTHOR]

Na 0.5 Bi 0.5 TiO 3 -based solid solutions are one of the most promising lead-free piezoelectric candidates since they can be easily tailored to exhibit large electrostrain. However, the large hysteresis and temperature-dependence of the electrostrain response are longstanding obstacles for their practical applications. In the present study, 0–3 type composites were developed with 0.97(0.94Na 0.5 Bi 0.5 TiO 3 -0.06BaTiO 3)-0.03AgNbO 3 (NBT-6BT-3AN) matrix phase and ZnO inclusions. The optimum addition of 5 wt.% ZnO in the composites leads to reduction in hysteresis of electrostrain by 35% in comparison with pure NBT-6BT-3AN at room temperature. Meanwhile, electrostrain of the composites maintains superior temperature stability, with a variance of less than ±10% in the temperature range between 25 and 125 °C. The reason for the improvement of electrostrain is proposed to be attributed to the ergodic/nonergodic mixture phases induced by residual stress between the inclusion and matrix, as well as the phase evolution caused by the incorporation of Zn2+ into the matrix. Therefore, this work provides a new strategy to improve the electromechanical properties of Na 0.5 Bi 0.5 TiO 3 -based ceramics. [ABSTRACT FROM AUTHOR]

Most polymers used in coatings are thermosetting resins because of their good adhension, protective capability, thermal and mechanical properties. Prepolymerization is a common procedure in the application of thermosetting resins, in order to adapt the specific processing condition, processing equipment or to achieve desired performance. However, the effects of prepolymerization on the curing behavior, chemical structure and properties of the resultant resins haven't been systematically studied. Among various thermosetting resins used as coatings, benzoxazine is a relatively new member, but it is being intensively studied due to its good processability, adhesive strength, low water absorption, as well as good anticorrosive property. Hence, in this work, 1,3-benzoxazine, a kind of high-performance thermosetting resin, was used as an example to probe the influence of prepolymerization. The chemical structure variation was characterized, the curing activity and the rheological behavior were investigated, and the thermal, mechanical and dielectric properties of the resultant polymers were also studied. It was found that the content of benzoxazine groups decreased while the molecular weight and the melt viscosity increased with prelonged prepolymerization time, which may release more active phenolic hydroxyls that could promote the curing of benzoxazine, but also caused worse molecular moveability. The glass transition temperature, initial decomposition temperature and char yield of most polymers decreased consequently, with few exceptions. However, the mechanical property was improved, as suggested by higher tensile strength and elongation at break value after prepolymerization. [Display omitted] • 1,3-benzoxazine was used as an example to probe the influence of prepolymerization; • Prepolymerization led to consumption of functional groups, increased molecular weight and higher melt viscosity; • Prepolymerization led to lower crosslinking density; • Prepolymerization led to lower glass transition temperature; • Prepolymerization led to higher mechanical strength. [ABSTRACT FROM AUTHOR]

• Diurnal and seasonal cycles of PE rate over three different saturated soil textures were assessed using a unique lysimeter. • The textures showed different PE sums, with the largest differences during daytime in spring and summer. • PE differences over textures were reproduced well by the energy balance method. • Simplifying the estimate of ground heat flux results in large deviations from measured PE. Calculating actual bare soil evaporation (E a) based on potential evaporation (PE) is a widely followed approach in many disciplines such as hydrogeology, hydrology and agricultural sciences. The influence of soil texture on PE is rarely considered in these approaches. In this work, seasonal and diurnal cycles of PE over saturated bare soils were assessed using a unique lysimeter experiment in the Guanzhong Basin, China. The assessment was made for three different soil textures including fine sand (PE fine), coarse sand (PE coarse) and gravel (PE gravel). Meteorological variables, soil heat flux and soil temperatures were measured at a high temporal resolution for more than 14 consecutive months. Potential evaporation rates over saturated bare soil showed clear differences between fine sand, coarse sand and gravel on an annual basis. PE fine was higher than PE coarse and PE gravel (7.3 % and 11.0 % respectively). The differences between measured PE rates over different surfaces were especially pronounced during daytime in spring and summer, but showed minor differences in autumn and winter. These results are quantitatively explained with detailed calculations of the surface energy balance and it is found that differences in available energy over the soil textures, related to different albedos, as well as different porosities and thermal properties for the materials (which influence soil temperatures) explain the differences. This shows that PE is different for different soil textures, which is neglected in most hydrological studies. Nevertheless, the full-form Penman-Monteith equation can reproduce the PE differences over soil textures quite well in autumn and winter, but a simplified approach to calculate the ground heat flux does not allow to reproduce PE differences between textures. [ABSTRACT FROM AUTHOR]

Salient object detection has achieved great success in natural scene images, but there is big room for exploration in steel defect images (SDIs). Moreover, the unique characteristic of SDIs makes salient object detection in SDIs (SDI-SOD) a challenging task, and many representative methods for natural scene images struggle to get satisfactory results in SDI-SOD. Existing SDI-SOD methods usually ignore the edge information, and focus only on enhancing the feature interaction of different layers. To this end, we propose a specialized Cross-Scale Edge Purification Network (CSEPNet) to explore the correlations of features at different scales for SDI-SOD. To be specific, our CSEPNet is based on the general encoder–decoder architecture. First, we adopt a generic Convolutional Block Attention Module (CBAM) to refine and enhance the features from the encoder. Then, we propose the Cross-Scale Calibration Module (CSCM) and Cross-Scale Feature Interweaving Module (CSFIM) to capture the relationship of inter-layer features and intra-layer features, respectively. In CSCM, adjacent features of different scales are effectively calibrated by each other and are re-calibrated by their collective weight map to generate informative features. In CSFIM, two branches of features interweave and fuse with their corresponding edge information purified to generate robust features. Besides, we employ deep supervision and use a hybrid loss to guide the training process. We perform comprehensive experiments on the public SD-saliency-900 dataset, and demonstrate that our method is superior to 26 state-of-the-art methods, including both traditional and CNN-based ones. The code and results of our method are available at https://github.com/showmaker369/CSEPNet. • We propose the CSEPNet for salient object detection of steel defect images. • We propose the CSCM to capture the relationship of features from different layers. • We propose the CSFIM to explore the complementarity of intra-layer features. • Our CSEPNet achieves the best performance as compared with 26 SOTA methods. [ABSTRACT FROM AUTHOR]

• 2,3-Dihydroxyisovalerate production by Enterobacter cloacae was set up. • budA disrupted strain exhibited 2,3-dihydroxyisovalerate producing ability. • Disruption of ilvD further increased 2,3-dihydroxyisovalerate level. • 31.2 g/L of 2,3-Dihydroxyisovalerate was produced in fed-batch fermentation. 2,3-Dihydroxyisovalerate is an intermediate of the valine synthesis pathway. However, neither natural microorganisms nor valine producing engineered strains have been reported yet to produce this chemical. Based on the 2,3-butanediol synthesis pathway, a biological route of 2,3-dihydroxyisovalerate production was developed using a budA and ilvD disrupted Klebsiella pneumoniae strain in our previous research. We hypothesised, that other 2,3-butanediol producing bacteria could be used for 2,3-dihydroxyisovalerate production. Here a budA disrupted Enterobacter cloacae was constructed, and this strain exhibited a high 2,3-dihydroxyisovalerate producing ability. Disruption of ilvD in E. cloacae Δ budA further increased 2,3-dihydroxyisovalerate level. The disruption of budA, encoding an acetolactate decarboxylase, resulted in the acetolactate synthesized in the 2,3-butanediol synthesis pathway to flow into the valine synthesis pathway. The additional disruption of ilvD, encoding a dihydroxy acid dehydratase, prevented the 2,3-dihydroxyisovalerate to be further metabolized in the valine synthesis pathway. Thus, the disruption of both budA and ilvD in 2,3-butanediol producing strains might be an universal strategy for 2,3-dihydroxyisovalerate accumulation. After optimization of the medium components and culture parameters 31.2 g/L of 2,3-dihydroxyisovalerate was obtained with a productivity of 0.41 g/L h and a substrate conversion ratio of 0.56 mol/mol glucose in a fed-batch fermentation. This approach provides an economic way for 2,3-dihydroxyisovalerate production. [ABSTRACT FROM AUTHOR]

Organic ultralong room temperature phosphorescence (OURTP) materials capable of combining various emission behaviors for diversified optoelectronic properties and applications have recently gained a vigorous development, but it remains a forbidden challenge in designing OURTP molecules with hybrid local and charge-transfer (HLCT) feature, possibly due to the elevated difficulties in simultaneously meeting the stringent requirements of both HLCT and OURTP emitters. Here, through introducing multiple heteroatoms into one-dimensional fused ring of coumarin with moderate charge transfer perturbation in donor-π-acceptor architecture, we demonstrate a HLCT-featured OURTP molecule showing both promoted fluorescence with a quantum yield of 77 % in solution and long-lived OURTP with a lifetime of 251 ms in conventional host material used in electroluminescent device. Thus, efficient OURTP organic light-emitting diodes (OLEDs) were fabricated, exhibiting bright electroluminescence with an exciton utilization efficiency of 85 % and yellow OURTP lasting over 2 s for afterglow. Impressively, the HLCT OURTP-OLEDs can be further optimized to reach an unprecedented total external quantum efficiency (EQE) of ~12 % and OURTP EQE up to 3.11 %, representing the highest performance among the reported OURTP-OLEDs. These impressive results highlight the significance to fuse HLCT and OURTP together in enriching OURTP materials and improving the afterglow OLED performances., (© 2024 Wiley-VCH GmbH.)

Quantifying the impacts of climate change and wetland area dynamics on methane (CH 4 ) emissions in the Qinghai-Tibetan Plateau (QTP) is crucial for enhancing our understanding of regional and global CH 4 budgets. However, a major source of uncertainty in estimating wetland methane emissions stems from the limited delineation of wetland area dynamics. In this study, we integrated dynamic wetland inundation schemes into a process-based model to quantify the contributions of wetland area variations to natural wetland CH 4 emissions on the QTP, both historically and in the future. The results revealed that climate change significantly influenced the spatiotemporal distribution of wetland CH 4 emissions, with wetland inundation dynamics contributing between 21.84 % and 27.18 % of the increase in CH 4 emissions from 1960 to 2020. Under future climate change scenarios, wetland CH 4 emissions are projected to exhibit a more pronounced increasing trend, with wetland inundation dynamics projected to contribute 18.94 % to 21.80 % of the increase in CH 4 emissions in the QTP under seven Shared Socioeconomic Pathways scenarios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The water ecological security pattern is a core factor. A scientific, accurate, and practical evaluation of water ecological security provides a theoretical basis for regional water ecological management. Using water resource data from five cities in the Hexi Corridor of Gansu Province (Jiuquan (JQ), Jiayuguan (JYG), Zhangye (ZY), Jinchang (JC), and Wuwei (WW)) from 2006 to 2021, a water ecological security evaluation index system based on the PSR (pressure-state-response) framework was constructed, covering 27 factors related to water resources, socio-economics, and the ecological environment. The main obstacle factors of water ecological security were identified using the obstacle degree model, and the grey GM(1,1) model was employed to predict water ecological security. Results indicated that the comprehensive assessment index of water ecology in the Hexi Corridor increased from 2006 to 2021, showing a transition from relatively unsafe (0.319) to basic safety and then to relatively safe (0.672). The pressure and response systems were the main limiting factors affecting water ecological security in the Hexi Corridor. After a slight decline in 2008, the overall spatial distribution continued to rise, with WW City and ZY City leading since 2016. ZY had a higher safety grade proportion (25%) compared to other areas in the Hexi region. The pressure system was the most significant obstacle to water ecological security after 2006. Prediction results indicated that the comprehensive evaluation index of water ecological security would continue to rise annually from 2022 to 2031, reaching a very safe level by 2025. The evaluation results provide a scientific basis for ecological security and risk decision-making in the study area., (© 2024. The Author(s).)

Introduction: The utilization of denosumab in treating osteoporosis highlights promising prospects for osteoporosis intervention guided by gene targets. While omics-based research into osteoporosis pathogenesis yields a plethora of potential gene targets for clinical transformation, identifying effective gene targets has posed challenges., Methods: We first queried the omics data of osteoporosis clinical samples on PubMed, used International Mouse Phenotyping Consortium (IMPC) to screen differentially expressed genes, and conducted preliminary functional verification of candidate genes in human Saos2 cells through osteogenic differentiation and mineralization experiments. We then selected the candidate genes with the most significant effects on osteogenic differentiation and further verified the osteogenic differentiation and mineralization functions in mouse 3T3-E1 and bone marrow mesenchymal stem cells (BMSC). Finally, we used RNA-seq to explore the regulation of osteogenesis by the target gene., Results: We identified PPP2R2A , RRBP1 , HSPB6 , SLC22A15 , ADAMTS4 , ATP8B1 , CTNNB1 , ROBO1 , and EFR3B , which may contribute to osteoporosis. ROBO1 was the most significant regulator of osteogenesis in both human and mouse osteoblast. The inhibitory effect of Robo1 knockdown on osteogenic differentiation may be related to the activation of inflammatory signaling pathways., Conclusion: Our study provides several novel molecular mechanisms involved in the pathogenesis of osteoporosis. ROBO1 is a potential target for osteoporosis intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wang, Zheng, Wei, Zhang, Zhu, Zhai and Xu.)

Organic afterglow with long-persistent luminescence (LPL) after photoexcitation is highly attractive, but the realization of narrowband afterglow with small full-width at half-maximum (FWHM) is a huge challenge since it is intrinsically contradictory to the triplet- and solid-state emission nature of organic afterglow. Here, narrow-band, long-lived, and full-color organic LPL is realized by isolating multi-resonant thermally activated delayed fluorescent (MR-TADF) fluorophores in a glassy steroid-type host through a facile melt-cooling treatment. Such prepared host becomes capable of exciton dissociation and recombination (EDR) upon photoirradiation for both long-lived fluorescence and phosphorescence; and, the efficient Förster resonance energy transfer (FRET) from the host to various MR-TADF emitters leads to high-performance LPL, exhibiting small FWHM of 33 nm, long persistent time over 10 s, and facile color-tuning in a wide range from deep-blue to orange (414-600 nm). Moreover, with the extraordinary narrowband LPL and easy processability of the material, centimeter-scale flexible optical waveguide fibers and integrated FWHM/color/lifetime-resolved multilevel encryption/decryption devices have been designed and fabricated. This novel EDR and singlet/triplet-to-singlet FRET strategy to achieve excellent LPL performances illustrates a promising way for constructing flexible organic afterglow with easy preparation methods, shedding valuable scientific insights into the design of narrow-band emission in organic afterglow., (© 2024 Wiley‐VCH GmbH.)

Riparian zones play a crucial role in reducing nitrate pollution in both terrestrial and aquatic environments. Complex deposition action and dynamic hydrological processes will change the grain size distribution of riparian sediments, affect the residence time of substances, and have a cascade effect on the biogeochemical process of nitrate nitrogen (NO 3 - -N). However, simultaneous studies on NO 3 - -N transformation and the potential drivers in riparian zones are still lacking, especially neglecting the effect of sediment grain size (SGS). To fill this knowledge gap, we first systematically identified and quantified NO 3 - -N biogeochemical processes in the riparian zone by integrating molecular biotechnology, 15 N stable isotope tracing, and microcosmic incubation experiments. We then evaluated the combined effects of environmental variables (including pH, dissolved organic carbon (DOC), oxidation reduction potential, SGS, etc.) on NO 3 - -N transformation through Random Forest and Structural Equation Models. The results demonstrated that NO 3 - -N underwent five microbial-mediated processes, with denitrification, dissimilatory nitrate reduction to ammonium (DNRA) dominated the NO 3 - -N attenuation (69.4 % and 20.1 %, respectively), followed by anaerobic ammonia oxidation (anammox) and nitrate-dependent ferric oxidation (NDFO) (8.4 % and 2.1 %, respectively), while nitrification dominated the NO 3 - -N production. SGS emerged as the most critical factor influencing NO 3 - -N transformation (24.96 %, p < 0.01), followed by functional genes (nirS, nrfA) abundance, DOC, and ammonia concentrations (14.12 %, 16.40 %, 13.08 %, p < 0.01). SGS influenced NO 3 - -N transformation by regulating microbial abundance and nutrient concentrations. RF predicted that a 5 % increase in the proportion of fine grains (diameter < 50 μm) may increase the NO 3 - -N transformation rate by 3.8 %. This work highlights the significance of integrating machine learning and geochemical analysis for a comprehensive understanding of nitrate biogeochemical processes in riparian zones, contributing valuable references for future nitrogen management strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ultrasound localization microscopy is a super-resolution vascular imaging technique which has garnered substantial interest as a tool for small animal neuroimaging, neuroscience research, and the characterization of vascular pathologies. In the pursuit of increasingly high-fidelity reconstructions of microvasculature, there remains several outstanding questions concerning this sub-diffraction imaging technology, including the accurate reconstruction of microvessels approaching the capillary scale and the pragmatic challenges associated with long data acquisition times. In the context of small animal neurovascular imaging, we posit that increasing the ultrasound imaging frequency is a straightforward approach to enable higher concentrations of microbubble contrast agents, thus increasing the likelihood of microvascular/capillary mapping and decreasing the imaging duration. We demonstrate that higher frequency imaging results in improved ULM fidelity and more efficient microbubble localization due to a smaller microbubble point-spread function that is easier to localize, and which can achieve a higher localizable concentration within the same unit volume of tissue. A select example of in vivo capillary-level vascular reconstruction is demonstrated for the highest frequency imaging probe, which has substantial implications for neuroscientists investigating microvascular function in disease states, regulation, and brain development. High frequency ULM yielding a spatial resolution of 7.1μm, as measured by Fourier ring correlation, throughout the entire depth of the brain, highlighting this technology as a highly relevant tool for neuroimaging research.

The primary tumor ("root") and circulating tumor cells (CTCs; "seeds") are vital factors in tumor progression. However, current treatment strategies mainly focus on inhibiting the tumor while ignoring CTCs, resulting in tumor metastasis. Here, we design a multifunctional 3D scaffold with interconnected macropores, excellent photothermal ability and perfect bioaffinity as a blood vessel implantable device. When implanted upstream of the primary tumor, the scaffold intercepts CTCs fleeing back to the primary tumor and then forms "micro-thrombi" to block the supply of nutrients and oxygen to the tumor for embolization therapy. The scaffold implanted downstream of the tumor efficiently captures and photothermally kills the CTCs that escape from the tumor, thereby preventing metastasis. Experiments using rabbits demonstrated excellent biosafety of this scaffold with 86% of the CTC scavenging rate, 99% of the tumor inhibition rate and 100% of CTC killing efficiency. The multifunctional 3D scaffold synergistically inhibits the "root" and eliminates the "seeds" of the tumor, demonstrating its potential for localized cancer therapy with few side effects and high antitumor efficacy.

To improve the spatial resolution of power Doppler (PD) imaging, we explored null subtraction imaging (NSI) as an alternative beamforming technique to delay-and-sum (DAS). NSI is a nonlinear beamforming approach that uses three different apodizations on receive and incoherently sums the beamformed envelopes. NSI uses a null in the beam pattern to improve the lateral resolution, which we apply here for improving PD spatial resolution both with and without contrast microbubbles. In this study, we used NSI with three types of singular value decomposition (SVD)-based clutter filters and noise equalization to generate high-resolution PD images. An element sensitivity correction scheme was also proposed as a crucial component of NSI-based PD imaging. First, a microbubble trace experiment was performed to evaluate the resolution improvement of NSI-based PD over traditional DAS-based PD. Then, both contrast-enhanced and contrast free ultrasound PD images were generated from the scan of a rat brain. The cross-sectional profile of the microbubble traces and microvessels were plotted. FWHM was also estimated to provide a quantitative metric. Furthermore, iso-frequency curves were calculated to provide a resolution evaluation metric over the global field of view. Up to six-fold resolution improvement was demonstrated by the FWHM estimate and four-fold resolution improvement was demonstrated by the iso-frequency curve from the NSI-based PD microvessel images compared to microvessel images generated by traditional DAS-based beamforming. A resolvability of [Formula: see text] was measured from the NSI-based PD microvessel image. The computational cost of NSI-based PD was only increased by 40 percent over the DAS-based PD.

Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease. However, the definitive diagnosis of IPF is impeded by the limited capabilities of current diagnostic methods, which may fail to capture the optimal timing for treatment. The main goal of this study is to determine the feasibility of a nitroreductase (NTR) responsive probe, 18 F-NCRP, for early detection and deterioration monitoring of IPF. 18 F-NCRP was obtained with high radiochemical purity (>95 %). BLM-injured mice were established by intratracheal instillation with bleomycin (BLM) and characterized through histological analysis. Longitudinal PET/CT imaging, biodistribution study and in vitro autoradiography were performed. The correlations between the uptake of 18 F-NCRP and mean lung density (tested by CT), as well as histopathological characteristics were analyzed. In PET imaging study, 18 F-NCRP exhibited promising efficacy in monitoring the progression of IPF, which was earlier than CT. The ratio of uptake in BLM-injured lung to control lung increased from 1.4-fold on D15 to 2.2-fold on D22. Biodistribution data showed a significant lung uptake of 18 F-NCRP in BLM-injured mice. There was a strong positive correlation between the 18 F-NCRP uptake in the BLM-injured lungs and the histopathological characteristics. Given that, 18 F-NCRP PET imaging of NTR, a promising biomarker for investigating the underlying pathogenic mechanism of IPF, is attainable as well as desirable, which might lay the foundation for establishing an NTR-targeted imaging evaluation system of IPF., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The sediment content and transport rate of rivers are crucial indicators reflecting soil erosion, water quality, and water resource management in a region. Studying changes in river sediment transport rates within a basin is essential for evaluating water quality, restoring water ecosystems, and implementing soil and water conservation measures. This study focused on the Shule River Basin and utilized various methods such as moving average, cumulative anomaly, Mann-Kendall mutation test, Mann-Kendall (M-K) trend test, Sen's slope estimation, Correlation analysis, wavelet analysis, R/S analysis, ARCGIS10.7 interpolation, non-uniformity coefficient, and concentration to analyze data from hydrologic stations at Changmapu (CMP), Panjiazhuang (PJZ), and Dangchengwan (DCW). The research examined the temporal and spatial characteristics of sediment transport rates and identified key driving factors. Findings revealed significant increases in annual sediment transport rates at CMP and PJZ by 12.227 and 4.318 kg/s (10a) -1 , respectively, while DCW experienced a decrease of 0.677 kg/s (10a) -1 . The sediment transport rate of the three stations had a sudden change around 1994. The average annual sediment transport rates displayed distinct cycles, with CMP, PJZ, and DCW showing cycles of 51a, 53a, and 29a respectively. Additionally, while CMP and PJZ exhibited a continuous upward trend in sediment transport rates, DCW showed a consistent decline. The annual average sediment transport rates of CMP, PJZ, and DCW were 1305.43 kg/s, 810.06 kg/s, and 247.80 kg/s, respectively. These research findings contribute to enhancing the comprehension of sediment dynamics in the arid region of northwest China and offer a theoretical basis for the restoration and management of ecological environments in similar areas in the future., (© 2024. The Author(s).)

Background: Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are widely used nucleoside reverse transcriptase inhibitors (NRTIs), necessitating a thorough understanding of their safety profiles to ensure optimal patient care and treatment adherence., Methods: We employed statistical methods including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) to compare and evaluate the safety profiles of these NRTIs., Results: TAF was significantly associated with weight increase (ROR: 6.43; 95% CI: 5.93-6.96) and specific psychiatric disorders. TDF showed a notable signal for renal disorders and product-related issues, including product dose omission (ROR: 3.53; 95% CI: 3.22-3.87). Additionally, the study highlighted differences in safety signals related to pregnancy outcomes, with TAF having a higher ROR for maternal exposure (ROR: 7.83; 95% CI: 7.06-8.69) and TDF for fetal exposure (ROR: 4.51; 95% CI: 3.93-5.18), underscoring the need for cautious use in pregnant women. The comparative analysis also identified signals for osteonecrosis (ROR: 108.81; 95% CI: 106.25-111.43) and bone loss (ROR: 714; 95% CI: 685.49-743.68) for TAF and TDF, respectively, highlighting the importance of bone health considerations in treatment plans., Conclusion: These findings underscore the importance of personalized antiviral therapy and patient safety.

Activation of the adenosine 2A receptor (A 2A R) can lead to tumor immunosuppression, which results in poor prognosis of immunotherapy. The aim of this study was to design novel 18 F-labeled probes ([ 18 F]F-PFP 2 and [ 18 F]F-PFP 4 ) to visualize A 2A R in the tumor. The uptake of radioprobes in A 2A R-negative 4T1 breast tumor was lower than that of A 2A R-positive B16F10 melanoma at 1 h p.i. (1.22 ± 0.36% ID/g vs 2.80 ± 0.72% ID/g), 2 h p.i. (1.09 ± 0.20% ID/g vs 2.93 ± 0.76% ID/g) and 3 h p.i. (0.89 ± 0.27% ID/g vs 2.73 ± 0.58% ID/g), respectively. B16F10 lung metastasis models were employed to expand the application scenarios, observing significantly higher uptake of [ 18 F]F-PFP 2 in metastatic lesions compared to normal lung tissue (5.55 ± 2.18% ID/g vs 1.89 ± 0.65% ID/g, tumor/lung ratio ∼3). It is given that [ 18 F]F-PFP 2 might lay the foundation for establishing an A 2A R-targeted imaging evaluation system for tumors, which will provide more precise guidance for personalized treatment.

Introduction: This study systematically evaluates the accuracy of several death risk prediction models for patients with acute coronary syndrome (ACS) through evidence-based methods. We identify the most accurate and effective ACS death risk prediction model and provide an evidence-based basis for clinical healthcare personnel to evaluate their choice of death risk prediction model for ACS patients., Evidence Acquisition: An evidence-based approach was used to study the current death risk prediction model for ACS. First, a literature search was carried out using computer-based and manual searching. The literature databases searched include Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, WanFang Data, CNKI, VPCS, and SinoMed. The search period was limited to 2009 to 2022. Screening, quality evaluation and data extraction were carried out for the included articles. The PROBAST was used to conduct a migration risk assessment. RevMan 5.3 and Meta-DiSc 1.4 were used in combination to determine the model effect sizes. A descriptive analysis was conducted for the data that could not be meta-analyzed., Evidence Synthesis: A total of 8277 articles were initially included in this study. After screening, 25 articles were finally included, involving 11 different risk prediction models. A total of 306,390 patients with ACS were included of which 158,080 (51.6%) were male and 147,793 (48.4%) were female. The patients stemmed from 11 different countries (e.g., China, the USA, Spain, the UK, etc.). The total number of deaths was 23,601. The sensitivity of the GRACE risk prediction model was 0.78, with a specificity of 0.76 and an AUC value of 0.86. The sensitivity of the CAMI risk prediction model was 0.78, with a specificity of 0.70 and an AUC value of 0.85. The sensitivity of the TIMI risk prediction model was 0.51, with a specificity of 0.81, and an AUC value of 0.64. The sensitivity of the REMS risk prediction model was 0.78, with a specificity of 0.46 and an AUC value of 0.41. Eight different risk prediction models (EPICOR, CRUSADE, SAMI, GWTG, LNS, SYNTAX II, APACHE II) that could not be combined with the effect size were also included, with sensitivities ranging from 0.77-0.95, specificities ranging from 0.22-0.99, and AUC values ranging from 0.71-0.92., Conclusions: The GRACE and CAMI risk prediction models demonstrate good accuracy for evaluating the death risk of ACS patients. The accuracy of the TIMI risk prediction model is similar to that of the REMS risk prediction model. The APACHE II, SYNTAX II, EPICOR, and CAMI risk prediction models also show good accuracy for estimating the risk of death in ACS patients, although further validation is needed due to limited evidence. For improved predictive accuracy and to help advance medical interventions, the author recommends that clinical medical staff use the GRACE model to predict the death risk of ACS patients.

Background: Previous studies have reported a close relationship between body mass index (BMI) and bone mineral density (BMD). However, the effects of fat on bone mass remain controversial, particularly for fat tissue distribution. The aim of this study was to evaluate the association between regional fat percentage and BMD using a population-based database., Methods: This study included participants who were referred to the Department of Radio Diagnosis for dual-energy X-ray absorptiometry (DEXA) scan from January 2018 to December 2020. The relationships between BMI and regional fat percentage with BMD were assessed using multiple linear regression and generalized additive models. The risk of low bone mass was determined using logistic regression., Results: There was a negative relationship between the regional fat percentage and femoral neck BMD (FN BMD) or lumbar spine BMD (LS BMD) in both genders ( p < 0.05). In females, an inverted U-shaped relationship was observed between regional fat percentage and BMD at both the femoral neck and lumbar spine. The impact of trunk fat percentage on LS BMD was associated with the highest OR of low bone mass in females (OR 3.1, 95% CI 2.6 to 3.7, p for trend <0.001), while the impact of abdomen fat percentage on FN BMD was associated with the highest OR of low bone mass in males (OR 2.2, 95% CI 1.8 to 2.7, p for trend <0.001)., Conclusion: There was an inverted U-shaped relationship between regional fat percentage and BMD. Excessive regional fat percentage may be harmful to bone health in both genders. To promote bone health, males should restrict their abdomen circumference and avoid abdominal adiposity, while females should control their trunk circumference., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Liu, Wang and Xu.)

Adebrelimab, a novel anti-PD-L1 antibody, has been approved by the National Medical Products Administration of China as an intravenous infusion for use in combination with carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer in 2023. A two-compartment model with empirical time-varying CL for adebrelimab was established based on data from 263 patients receiving body weight-based doses from two clinical studies. Significant covariate effects of baseline body weight, albumin levels, tumor size, neutrophil counts, and presence of anti-drug antibodies were identified on CL of debrelimab, none of which were clinically significant or warranted dose adjustment. The degree of decrease in CL was higher in patients who responded to treatment with adebrelimab than in non-responders. Adebrelimab exposures (AUC, C trough , or C max ) were not identified as a statistically significant factor related to efficacy or safety endpoint in the exposure-response analysis. Distribution of simulated exposure metrics from the flat dose regimen (1200 mg q3w) was similar to the marketed weight-based dosing regimen (20 mg/kg q3w), supporting the alternative flat dose regimen in the clinic., (© 2024 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Ultrasound localization microscopy (ULM) enables deep tissue microvascular imaging by localizing and tracking intravenously injected microbubbles circulating in the bloodstream. However, conventional localization techniques require spatially isolated microbubbles, resulting in prolonged imaging time to obtain detailed microvascular maps. Here, we introduce LOcalization with Context Awareness (LOCA)-ULM, a deep learning-based microbubble simulation and localization pipeline designed to enhance localization performance in high microbubble concentrations. In silico, LOCA-ULM enhanced microbubble detection accuracy to 97.8% and reduced the missing rate to 23.8%, outperforming conventional and deep learning-based localization methods up to 17.4% in accuracy and 37.6% in missing rate reduction. In in vivo rat brain imaging, LOCA-ULM revealed dense cerebrovascular networks and spatially adjacent microvessels undetected by conventional ULM. We further demonstrate the superior localization performance of LOCA-ULM in functional ULM (fULM) where LOCA-ULM significantly increased the functional imaging sensitivity of fULM to hemodynamic responses invoked by whisker stimulations in the rat brain., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO 2 ) microsphere-coated three-dimensional (3D) hierarchical porous chip, named a SiO 2 -chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO 2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non-HCC and HCC subjects are enriched using an SiO 2 -chip and performed RNA sequencing to identify HCC-related long non-coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT-1 and EGFR-AS-1 are two HCC-related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT-PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy-based approach for noninvasive and reliable HCC detection is developed., (© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Acute ST segment elevation myocardial infarction (ASTEMI) is the most common and serious type of AMI, percutaneous coronary intervention (PCI) is currently the most commonly used approach for clinical treatment of ASTEMI. After PCI, patients with ASTEMI are very prone to various complications, which will seriously threaten their health and life safety., Objective: This study aims to analyze the risk factors for complications in patients with acute ST-segment elevation myocardial infarction (ASTEMI) treated with percutaneous coronary intervention (PCI)., Methods: A total of 107 patients with ASTEMI who were subjected to PCI from October 2021 to December 2022 were selected as study subjects. Patients were divided into a safety group (no complications, n = 63) and a risk group (n = 45) based on the presence of postoperative complications. Baseline data (age, sex, etc.), Killip classification, left ventricular ejection fractions (LVEF), and routine blood test results were collected from patients in both groups for Logistic regression analysis to obtain relevant factors affecting the occurrence of post-PCI complications., Results: There were no differences between the safety group and the risk group in terms of sex, age, body mass index (BMI), Killip classification, and infarct site (P > .05). Compared with the safety group, the risk group exhibited a higher proportion of patients with multiple pre-existing diseases, LVEF < 40%, and number of coronary artery lesions ≥ 1, and higher levels of hs-CRP, NT-proBNP, HbA1c and Scr (P < .05). Logistic regression analysis results showed that multiple pre-existing diseases, hs-CRP, NT-proBNP, HbA1c, and Scr were relevant factors affecting the occurrence of post-PCI complications (P < .05)., Conclusion: Multiple pre-existing diseases, hs-CRP, NT-proBNP, HbA1c, and Scr were all independent risk factors for the occurrence of post-PCI complications. Future clinical attention should be paid to these indicators in patients with ASTEMI in order to prevent post-PCI complications.

Organic materials featuring circularly polarized luminescence (CPL) and/or afterglow emission represent an active research frontier with promising applications in various fields, but the achievement of high-performance CPL organic afterglow (CPOA) remains a huge challenge due to the intrinsic contradictions between the luminescent lifetime/dissymmetry factor ( g lum ) and phosphorescent quantum efficiency (PhQY). Herein, we report a simple and universal approach to design efficient CPOA from amorphous copolymers by incorporating chiral chromophores into a nonconjugated clusterization-triggered emissive polymer with plenty of hydron-bonding interactions, followed by aggregation engineering using water dissolution and evaporation. With this chiral copolymerization and aggregation engineering (CCAE) strategy, high-performance CPOA polymers with PhQYs of up to 6.32%, ultralong lifetimes of over 650 ms, g lum values of 3.54 × 10 -3 , and the highest figure-of-merit were achieved at room temperature. Given the impressive CPOA performance of these polymers, the applications in multilevel data anticounterfeiting and reversible displays with high stability were demonstrated. These findings through the CCAE strategy to overcome the inherent restraints of CPOA materials lay the foundation for the development of amorphous polymers with superior CPOA, significantly expanding the understanding of CPL and the design of organic afterglow materials.

High-temperature piezoelectric materials are pivotal to technology applications fields including defense, aerospace, nuclear energy, and oil well logging. However, the acquisition of excellent piezoelectric properties is usually at the cost of temperature stability (reduced Curie temperature and increased high-temperature dielectric loss), which hinders the application of piezoelectric ceramics in harsh environments. In this study, we investigated the effect of Nb 5+ donor and Mn 2+/3+ acceptor doping on the dielectric and piezoelectric properties of BiScO 3 -PbTiO 3 (BS-PT)-based ceramics. In contrast to the acceptor doping, it was found that the donor doping not only enhances the piezoelectric properties but also effectively suppresses the dielectric loss at a high temperature by reducing the oxygen vacancy concentration. Eventually, we simultaneously attained an excellent piezoelectric performance ( d 33 is 553 pC/N at room temperature and 1528 pC/N at 400 °C, respectively) and a low dielectric loss (less than 2% in the temperature range of 150-300 °C) but still with a high Curie temperature ( T C ∼ 445 °C) in Nb 5+ -doped BS-PT ceramics. Furthermore, different in situ measurements were used to demonstrate the remarkable temperature stability up to a high depolarization temperature of ∼400 °C. This work represents significant progress in high-temperature piezoelectric materials and provides a guideline for future efforts on enhancing the piezoelectricity and suppressing the dielectric loss at high temperature.

The riparian zone is an important location of nitrogen removal in the terrestrial and aquatic ecosystems. Many studies have focused on the nitrogen removal efficiency and one or two nitrogen removal processes in the riparian zone, and less attention has been paid to the interaction of different nitrogen transformation processes and the impact of in situ environmental conditions. The molecular biotechnology, microcosm culture experiments and 15 N stable isotope tracing techniques were used in this research at the riparian zone in Weinan section of the Wei River, to reveal the nitrogen removal mechanism of riparian zone with multi-layer lithologic structure. The results showed that the nitrogen removal rate in the riparian zone was 4.14-35.19 μmol·N·kg -1 ·h -1 . Denitrification, dissimilatory reduction to ammonium (DNRA) and anaerobic ammonium oxidation (anammox) jointly achieved the natural attenuation process of nitrogen in the riparian zone, and denitrification was the dominant process (accounting for 59.6%). High dissolved organic nitrogen and nitrate ratio (DOC:NO 3 - ) would promote denitrification, but when the NO 3 - content was less than 0.06 mg/kg, DNRA would occur in preference to denitrification. Furthermore, the abundances of functional genes ( norB, nirS, nrfA ) and anammox bacterial 16S rRNA gene showed similar distribution patterns with the corresponding nitrogen transformation rates. Sedimentary NO X - , Fe(II), dissolved organic carbon (DOC) and the nitrogen transformation functional microbial abundance were the main factors affecting nitrogen removal in the riparian zone. Fe (II) promoted NO 3 - attenuation through nitrate dependent ferrous oxidation process under microbial mediation, and DOC promotes NO 3 - attenuation through enhancing DNRA effect. The results of this study can be used for the management of the riparian zone and the prevention and control of global nitrogen pollution., Competing Interests: FYa, RL, and FG were employed by Power China Northwest Engineering Corporation Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ye, Duan, Sun, Yang, Liu, Gao, Wang and Xu.)

To study the inorganic nitrogen in the process of interaction of river and groundwater and the changes in the microbial community, a vertical simulation device was used to simulate groundwater recharge to river water (upwelling) and river water recharge to groundwater (downwelling). The inorganic nitrogen concentrations in the soil and water solution as well as the characteristics of the microbial community were assessed to determine the inorganic nitrogen transformation and microbial community response in the heterogeneous interaction zone under hydrodynamic action, and the interaction mechanism between nitrogen transformation and the microbial community in the interaction zone was revealed. The removal rates of NO 3 - -N in the simulated solution reached 99.1% and 99.3% under the two fluid-groundwater conversion modes, and the prolonged hydraulic retention time (HRT) of the oxidization-reduction layer in the fine clay area and the high organic matter content made the inorganic nitrogen transformation process dominated by microorganisms more complete. The denitrification during upwelling, dominated by denitrifying bacteria in Sphingomonas, Pseudomonas, Bacillus, and Arthrobacter, was stronger than that during downwelling. Dissimilatory nitrate reduction to ammonium (DNRA), controlled by some aerobic bacteria in Pseudomonas, Bacillus, and Desulfovibrio, was more intense in downflow mode than upflow mode., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study explored the role of MTDH in regulating the sensitivity of breast cancer cell lines to gemcitabine (Gem) and the potential miRNAs targeting MTDH. The expression of MTDH in cancer tissues and cells was detected by immunohistochemical staining or qRT-PCR. The target genes for MTDH were predicted by bioinformatics and further confirmed by dual-luciferase reporter assay and qRT-PCR. Cancer cells were transfected with siMTDH, MTDH, miR-9-3p inhibitor, or mimics and treated by Gem, then CCK-8, colony formation assay, tube formation assay, flow cytometry, wound healing assay, and Transwell were performed to explore the effects of MTDH, miR-9-3p, and Gem on cancer cell growth, apoptosis, migration, and invasion. Expressions of VEGF, p53, cleaved caspase-3, MMP-2, MMP-9, E-Cadherin, N-Cadherin, and Vimentin were determined by Western blot. MTDH was high-expressed in cancer tissues and cells, and the cells with high-expressed MTDH were less sensitive to Gem, while silencing MTDH expression significantly promoted the effect of Gem on inducing apoptosis, inhibiting cell migration, invasion, and growth, and on regulating protein expressions of cancer cells. Moreover, miR-9-3p had a targeted binding relationship with MTDH, and overexpressed miR-9-3p greatly promoted the toxic effects of Gem on cancer cells and expressions of apoptosis-related proteins, whereas overexpressed MTDH partially reversed such effects of overexpressed miR-9-3p. The study proved that miR-9-3p regulates biological functions, drug resistance, and the growth of Gem-treated breast cancer cells through targeting MTDH., (© 2021. The Author(s).)

Background: Klebsiella pneumoniae is a bacterium that can be used as producer for numerous chemicals. Glycerol can be catabolised by K. pneumoniae and dihydroxyacetone is an intermediate of this catabolism pathway. Here dihydroxyacetone and glycerol were produced from glucose by this bacterium based a redirected glycerol catabolism pathway., Results: tpiA, encoding triosephosphate isomerase, was knocked out to block the further catabolism of dihydroxyacetone phosphate in the glycolysis. After overexpression of a Corynebacterium glutamicum dihydroxyacetone phosphate dephosphorylase (hdpA), the engineered strain produced remarkable levels of dihydroxyacetone (7.0 g/L) and glycerol (2.5 g/L) from glucose. Further increase in product formation were obtained by knocking out gapA encoding an iosenzyme of glyceraldehyde 3-phosphate dehydrogenase. There are two dihydroxyacetone kinases in K. pneumoniae. They were both disrupted to prevent an inefficient reaction cycle between dihydroxyacetone phosphate and dihydroxyacetone, and the resulting strains had a distinct improvement in dihydroxyacetone and glycerol production. pH 6.0 and low air supplement were identified as the optimal conditions for dihydroxyacetone and glycerol production by K, pneumoniae ΔtpiA-ΔDHAK-hdpA. In fed batch fermentation 23.9 g/L of dihydroxyacetone and 10.8 g/L of glycerol were produced after 91 h of cultivation, with the total conversion ratio of 0.97 mol/mol glucose., Conclusions: This study provides a novel and highly efficient way of dihydroxyacetone and glycerol production from glucose.

2,3-Dihydroxyisovalerate is an intermediate of valine and leucine biosynthesis pathway; however, no natural microorganism has been found yet that can accumulate this compound. Klebsiella pneumoniae is a useful bacterium that can be used as a workhorse for the production of a range of industrially desirable chemicals. Dihydroxy acid dehydratase, encoded by the ilvD gene, catalyzes the reaction of 2-ketoisovalerate formation from 2,3-dihydroxyisovalerate. In this study, an ilvD disrupted strain was constructed which resulted in the inability to synthesize 2-ketoisovalerate, yet accumulate 2,3-dihydroxyisovalerate in its culture broth. 2,3-Butanediol is the main metabolite of K. pneumoniae and its synthesis pathway and the branched-chain amino acid synthesis pathway share the same step of the α-acetolactate synthesis. By knocking out the budA gene, carbon flow into the branched-chain amino acid synthesis pathway was upregulated, which resulted in a distinct increase in 2,3-dihydroxyisovalerate levels. Lactic acid was identified as a by-product of the process and by blocking the lactic acid synthesis pathway, a further increase in 2,3-dihydroxyisovalerate levels was obtained. The culture parameters of 2,3-dihydroxyisovalerate fermentation were optimized, which include acidic pH and medium level oxygen supplementation to favor 2,3-dihydroxyisovalerate synthesis. At optimal conditions (pH 6.5, 400 rpm), 36.5 g/L of 2,3-dihydroxyisovalerate was produced in fed-batch fermentation over 45 h, with a conversion ratio of 0.49 mol/mol glucose. Thus, a biological route of 2,3-dihydroxyisovalerate production with high conversion ratio and final titer was developed, providing a basis for an industrial process. Key Points • A biological route of 2,3-dihydroxyisovalerate production was setup. • Disruption of budA causes 2,3-dihydroxuisovalerate accumulation in K. pneumoniae. • Disruption of ilvD prevents 2,3-dihydroxyisovalerate reuse by the cell. • 36.5 g/L of 2,3-dihydroxyisovalerate was obtained in fed-batch fermentation.

Background: Biological routes for ethylene glycol production have been developed in recent years by constructing the synthesis pathways in different microorganisms. However, no microorganisms have been reported yet to produce ethylene glycol naturally., Results: Xylonic acid utilizing microorganisms were screened from natural environments, and an Enterobacter cloacae strain was isolated. The major metabolites of this strain were ethylene glycol and glycolic acid. However, the metabolites were switched to 2,3-butanediol, acetoin or acetic acid when this strain was cultured with other carbon sources. The metabolic pathway of ethylene glycol synthesis from xylonic acid in this bacterium was identified. Xylonic acid was converted to 2-dehydro-3-deoxy-D-pentonate catalyzed by D-xylonic acid dehydratase. 2-Dehydro-3-deoxy-D-pentonate was converted to form pyruvate and glycolaldehyde, and this reaction was catalyzed by an aldolase. D-Xylonic acid dehydratase and 2-dehydro-3-deoxy-D-pentonate aldolase were encoded by yjhG and yjhH, respectively. The two genes are part of the same operon and are located adjacent on the chromosome. Besides yjhG and yjhH, this operon contains four other genes. However, individually inactivation of these four genes had no effect on either ethylene glycol or glycolic acid production; both formed from glycolaldehyde. YqhD exhibits ethylene glycol dehydrogenase activity in vitro. However, a low level of ethylene glycol was still synthesized by E. cloacae ΔyqhD. Fermentation parameters for ethylene glycol and glycolic acid production by the E. cloacae strain were optimized, and aerobic cultivation at neutral pH were found to be optimal. In fed batch culture, 34 g/L of ethylene glycol and 13 g/L of glycolic acid were produced in 46 h, with a total conversion ratio of 0.99 mol/mol xylonic acid., Conclusions: A novel route of xylose biorefinery via xylonic acid as an intermediate has been established.

Spexin (SPX) is a novel peptide with pleiotropic functions in adipose tissue including energy balance adjustment, fatty acid uptake, and glucose homeostasis. SPX level is closely associated with cardiovascular risk factors such as age, obesity, hypertension, and diabetes; however, its physiological significance in the cardiovascular system remains mostly undefined. We therefore here investigated the roles of SPX in regulating hypoxia-induced alterations in energy metabolism and mitochondrial function. We firstly confirmed that SPX is expressed in human and mouse cardiac tissue and documented that exposure to hypoxia in vitro reduces SPX level in rat H9C2 cardiomyocytes and primary neonatal rat ventricular myocytes (NRVMs). We then treated primary NRVMs with SPX before exposure to hypoxia, which (1) promoted fatty acid metabolism by enhancing expression of FAT/CD36, CPT1, ACADM, and PPAR-a and PGC1-a; (2) did not improve impaired glucose uptake; and (3) significantly prevented the downregulation of TFAM and mitochondrial electron transport chain complex and restrained UCP2 level and reactive oxygen species (ROS) production, thus enhancing ATP level in cardiomyocytes. In summary, SPX protects energy and mitochondrial homeostasis of cardiomyocytes during hypoxia, thereby highlighting the potential importance of SPX in the treatment of cardiovascular diseases.