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The huge amount of urea applied has necessitated best-developed practices to slow down the release of nitrogen (N) fertilizer while minimizing nitrate loss. However, the impact of nitrification inhibitors on mineral-N turnover and the associated microbial mechanisms at different stages remains unknown. A 60-day incubation experiment was conducted with four treatments: no fertilizer (CK), urea (U), urea with copper pyrazole (UC), and urea coated with copper pyrazole (SUC), to evaluate the changes about soil ammonia N (NH4+-N) and nitrate N (NO3−-N) levels as well as in soil microbial community throughout the whole incubation period. The results showed that copper pyrazole exhibited significantly higher inhibition rates on urease compared to other metal-pyrazole coordination compounds. The soil NH4+-N content peaked on the 10th day and was significantly greater in UC compared to U, while the NO3−-N content was significantly greater in U compared to UC on the 60th day. Copper pyrazole mainly decreased the expression of nitrifying (AOB-amoA) and denitrifying (nirK) genes, impacting the soil microbial community. Co-occurrence network suggested that Mycobacterium and Cronobacter sakazakii-driven Cluster 4 community potentially affected the nitrification process in the initial phase, converting NH4+-N to NO3−-N. Fusarium-driven Cluster 3 community likely facilitated the denitrification of NO3−-N and caused N loss to the atmosphere in the late stage. The application of copper pyrazole may influence the process of nitrification and denitrification by regulating soil microbial traits (module community and functional genes). Our research indicates that the addition of copper pyrazole alters the community function driven by keystone taxa, altering mineral-N turnover and supporting the use of nitrification inhibitors in sustainable agriculture.

Abstract Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron–astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.

BackgroundObservational research suggests that hypotension is a potential hazard factor of delirium. Nevertheless, previous observational articles are limited in their ability to establish causality between hypotension and delirium. The present study was sought to explore the genetic causal relationship between these two conditions using two-sample Mendelian randomization (MR).MethodsGenome-wide association study (GWAS) summarized data for hypotension and delirium were obtained from the FinnGen Consortium. The researchers utilized several statistical methods, such as inverse-variance weighted (IVW), weighted median, MR Egger, weighted mode, and simple mode in conducting the MR statistical analysis. In order to identify heterogeneity among the MR outcomes, we employed the Cochrane’s Q test. Furthermore, we used the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test to examine horizontal pleiotropy.ResultsThe findings revealed that hypotension was identified as an independent hazard variable for delirium (p = 0.010, odds ratio [OR] [95% confidence interval (CI)] = 1.302 [1.066–1.592]) using the IVW method. The presence of horizontal pleiotropy was found to have minimal impact on establishing causal relationship (p = 0.999), and there was no evidence to suggest heterogeneity between genetic variations (p = 0.379). Additionally, the leave-one-out method demonstrated the stability and robustness of this association.ConclusionWe performed two-sample MR analyses and found evidence of a genetic causal relationship between hypotension and delirium. Our findings suggest that individuals with a genetic predisposition for hypotension may have a higher risk of developing delirium. This suggests that interventions aimed at improving perioperative hypotension could aid in limiting the incidence of delirium.

Abstract Self‐powered pressure detection using smart wearable devices is the subject of intense research attention, which is intended to address the critical need for prolonged and uninterrupted operations. Current piezoelectric and triboelectric sensors well respond to dynamic stimuli while overlooking static stimuli. This study proposes a dual‐response potentiometric pressure sensor that responds to both dynamic and static stimuli. The proposed sensor utilizes interdigital electrodes with MnO2/carbon/polyvinyl alcohol (PVA) as the cathode and conductive silver paste as the anode. The electrolyte layer incorporates a mixed hydrogel of PVA and phosphoric acid. The optimized interdigital electrodes and sandpaper‐like microstructured surface of the hydrogel electrolyte contribute to enhanced performance by facilitating an increased contact area between the electrolyte and electrodes. The sensor features an open‐circuit voltage of 0.927 V, a short‐circuit current of 6 µA, a higher sensitivity of 14 mV/kPa, and outstanding cycling performance (>5000 cycles). It can accurately recognize letter writing and enable capacitor charging and LED lighting. Additionally, a data acquisition and display system employing the proposed sensor, which facilitates the monitoring of athletes’ rehabilitation training, and machine learning algorithms that effectively guide rehabilitation actions are presented. This study offers novel solutions for the future development of smart wearable devices.

Synthetic nitrogen (N) fertilizer has made a great contribution to the improvement of soil fertility and productivity, but excessive application of synthetic N fertilizer may cause agroecosystem risks, such as soil acidification, groundwater contamination and biodiversity reduction. Meanwhile, organic substitution has received increasing attention for its ecologically and environmentally friendly and productivity benefits. However, the linkages between manure substitution, crop yield and the underlying microbial mechanisms remain uncertain. To bridge this gap, a three-year field experiment was conducted with five fertilization regimes: i) Control, non-fertilization; CF, conventional synthetic fertilizer application; CF1/2M1/2, 1/2 N input via synthetic fertilizer and 1/2 N input via manure; CF1/4M3/4, 1/4 N input synthetic fertilizer and 3/4 N input via manure; M, manure application. All fertilization treatments were designed to have equal N input. Our results showed that all manure substituted treatments achieved high soil fertility indexes (SFI) and productivities by increasing the soil organic carbon (SOC), total N (TN) and available phosphorus (AP) concentrations, and by altering the bacterial community diversity and composition compared with CF. SOC, AP, and the soil C:N ratio were mainly responsible for microbial community variations. The co-occurrence network revealed that SOC and AP had strong positive associations with Rhodospirillales and Burkholderiales, while TN and C:N ratio had positive and negative associations with Micromonosporaceae, respectively. These specific taxa are implicated in soil macroelement turnover. Random Forest analysis predicted that both biotic (bacterial composition and Micromonosporaceae) and abiotic (AP, SOC, SFI, and TN) factors had significant effects on crop yield. The present work strengthens our understanding of the effects of manure substitution on crop yield and provides theoretical support for optimizing fertilization strategies.

Abstract Backgrounds The hypoxia-responsive state of cancer is a complex pathophysiological process involving numerous genes playing different roles. Due to the rapid proliferation of cancer cells and chaotic angiogenesis, the clinical features of hypoxia-responsive states are not yet clear in patients with ovarian cancer. Methods Based on the RNA expression levels of 14 hypoxic markers, our study screened out hypoxia-related genes and construct a hypoxic score pattern to quantify the hypoxia-responsive states of a single tumor. Combining clinical prognosis, tumor mutation burden, microsatellite instability, the expression level of the immune checkpoint, IC50, and other indicators to evaluate the impact of different hypoxia-responsive states on clinical prognosis and therapeutic sensitivity. Results Our study identified a subgroup with an active hypoxia-responsive state and they have a worse clinical prognosis but exhibit higher immunogenicity and higher sensitivity to immunotherapy. Conclusions This work revealed that hypoxia-responsive states played an important role in formation of tumor immunogenicity. Evaluating the hypoxia-responsive state will contribute to guiding more effective immunotherapy strategies.

BackgroundBrain lymphatic drainage impairment is a prevalent characteristic in both aging and neurodegeneration. Surgery is more likely to induce excessive neuroinflammation and postoperative neurocognitive disorder (PND) among patients with aging and neurodegeneration. We hypothesized that surgical trauma may aggravate PND through preexisting cerebral lymphatic drainage impairment. However, there remains limited understanding about the role of surgery in changes of neurocognitive function in the populations with preoperative brain lymphatic drainage impairment. This study aims to expand our insight into surgery-induced glymphatic dysfunction, neuroinflammation and PND in middle-aged mice with preoperative brain lymphatic drainage impairment.Materials and methodsDeep cervical lymph nodes ligation (LdcLNs) was performed on middle-aged mice to establish preoperative brain lymphatic drainage impairment. A month later, laparotomy was performed on these mice with or without LdcLNs followed by analysis of brain neuroinflammation, glymphatic function, neuronal damage, and behavioral test.ResultsLdcLNs disrupted meningeal lymphatic drainage. In middle-aged mice with LdcLNs, surgery exacerbated more serious glymphatic dysfunction accompanied by aggravation of A1 astrocytes activation and AQP4 depolarization. Furthermore, surgery caused neuronal damage via reducing expression of neuronal nuclei (NeuN), post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), as well as impairment in exploratory behavior and spatial working memory in middle-aged mice with LdcLNs. Additionally, surgery induced neuroinflammation with elevated microglia activation and increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, as well as activated more expression of HMGB1/TLR-4/NF-κB pathway in middle-aged mice with LdcLNs.ConclusionSurgery exacerbates neuroinflammation and glymphatic dysfunction, ultimately resulting in neuronal damage and neurocognitive disorder in middle-aged mice with preoperative brain lymphatic drainage impairment. These results suggest that brain lymphatic drainage impairment may be a deteriorating factor in the progression of PND, and restoring its function may serve as a potential strategy against PND.

IntroductionArid and semi-arid regions are climate-sensitive areas, which account for about 40% of the world’s land surface area. Future environment change will impact the environment of these area, resulting in a sharp expansion of arid and semi-arid regions. Cotoneaster multiflorus is a multi-functional tree species with extreme cold, drought and barren resistance, as well as ornamental and medicinal functions. It was found to be one of the most important tree species for ecological restoration in arid and semi-arid areas. However, bioclimatic factors play an important role in the growth, development and distribution of plants. Therefore, exploring the response pattern and ecological adaptability of C. multiflorus to future climate change is important for the long-term ecological restoration of C. multiflorus in arid and semi-arid areas.MethodsIn this study, we predicted the potential distribution of C. multiflorus in China under different climate scenarios based on the MaxEnt 2.0 model, and discussed its adaptability and the major factors affecting its geographical distribution.ResultsThe major factors that explained the geographical distribution of C. multiflorus were Annual precipitation (Bio12), Min air temperature of the coldest month (Bio6), and Mean air temperature of the coldest quarter (Bio11). However, C. multiflorus could thrive in environments where Annual precipitation (Bio12) >150 mm, Min air temperature of the coldest month (Bio6) > -42.5°C, and Mean air temperature of the coldest quarter (Bio11) > -20°C, showcasing its characteristics of cold and drought tolerance. Under different future climate scenarios, the total suitable area for C. multiflorus ranged from 411.199×104 km² to 470.191×104 km², which was 0.8~6.14 percentage points higher than the current total suitable area. Additionally, it would further shift towards higher latitude.DiscussionThe MaxEnt 2.0 model predicted the potential distribution pattern of C. multiflorus in the context of future climate change, and identified its ecological adaptability and the main climatic factors affecting its distribution. This study provides an important theoretical basis for natural vegetation restoration in arid and semi-arid areas.

BackgroundThe aim of the present study was to build and internally validate a nomogram model for predicting prolonged length of stay (PLOS) among patients receiving free vascularized flap reconstruction of head and neck cancer (HNC).MethodsA retrospective clinical study was performed at a single center, examining patients receiving free vascularized flap reconstruction of HNC from January 2011 to January 2019. The variables were obtained from the electronic information system. The primary outcome measure was PLOS. Univariate and multivariate analyses were used to find risk factors for predicting PLOS. A model was then built according to multivariate results. Internal validation was implemented via 1000 bootstrap samples.ResultsThe study included 1047 patients, and the median length of stay (LOS) was 13.00 (11.00, 16.00) days. Multivariate analysis showed that flap types ((radial forearm free flap (odds ratio [OR] = 2.238; 95% CI, 1.403-3.569; P = 0.001), free fibula flap (OR = 3.319; 95% CI, 2.019-4.882; P < 0.001)), duration of surgery (OR = 1.002; 95% CI, 1.001-1.003; P = 0.004), postoperative complications (OR = 0.205; 95% CI, 0.129-0.325; P = P < 0.001) and unplanned reoperation (OR = 0.303; 95% CI, 0.140-0.653; P = 0.002) were associated with PLOS. In addition to these variables, blood transfusion was comprised in the model. The AUC of the model was 0.78 (95% CI, 0.711–0.849) and 0.725 (95% CI, 0.605–0.845) in the primary and internal validation cohorts, respectively. The DCA revealed the clinical utility of the current model when making intervention decisions within the PLOS possibility threshold range of 0.2-0.8.ConclusionsOur study developed a nomogram that exhibits a commendable level of accuracy, thereby aiding clinicians in assessing the risk of PLOS among patients receiving free vascularized flap reconstruction for HNC.

miRNA is a type of classic non-coding RNA which is enriched in cancer. Various studies reported that miRNA be involved in the progression and metastasis of TSCC. Exploring pivotal miRNAs and elaborating the mechanisms inducing metastasis are important for improving the prognosis of TSCC patients. Here, Let-7b miRNA was identified as a significant factor contributing to metastasis of TSCC via directly targeting the 3′UTR of MOR mRNA, which leads to abnormally high expression of MOR protein. MOR might bind with SRC and potentially activate p-EGFR through SRC. As a treatment modality, Let-7b miRNA mimics were encapsulated into the endosomal pH-responsive nanoparticles. NPs (Let-7b miRNA mimics) significantly inhibited Cal27 cells in vitro and in vivo metastatic model. Altogether, our data revealed that Let-7b miRNA-MOR-SRC-EGFR axis might be an effective therapeutic target in TSCC metastasis.

A two-dimensional mold model coupled multiphase flow, heat transfer, solidification and mold oscillation was established based on the casting parameters of the mold of plant. The accuracy of the model was verified by comparing the measured by plant and calculated mold powder consumption under the same casting conditions. The mechanism of mold powder consumption and lubrication was analyzed based on the non-sinusoidal oscillation mode, and the effect of non-sinusoidal oscillation parameters on mold powder consumption was discussed. Mold powder consumption was determined by the downward flow velocity of liquid mold powder and the thickness of liquid mold powder film, the liquid mold powder consumption decreased with the decrease of those. When the mold moved downward, the mold powder thickness and downward flow velocity decreased, the minimum mold powder consumption reached at the middle of the negative strip time, and the variation was to opposite when the mold moved upward, the maximum mold powder consumption appeared during the positive strip time. With the decrease of casting speed and modification ratio, and increase of oscillation frequency and oscillation amplitude, the mold powder consumption had the tendency to increase. The nonlinear regression equation was fitted by the Levenberg–Marquardt method combined with the universal global optimization method to evaluate mold powder consumption.

Aqueous zinc-ion batteries (ZIBs) offer numerous advantages, such as high energy density, enhanced safety, and low cost, making them an ideal choice for energy storage and conversion applications in the “postlithium” era. Hydrogel electrolytes, as the key component of flexible ZIBs, combine the ionic conductivity of traditional water electrolytes with the dimensional stability of solid polymer electrolytes. However, it remains a challenge to design comprehensive and appropriate hydrogel electrolytes to provide flexible ZIBs with good reversibility and versatility. This review discusses the engineering design of hydrogel electrolytes required for flexible ZIBs from the viewpoint of an electrolyte designer. The basic properties of the hydrogel electrolytes, zinc anodes, cathodes and electrolyte stabilization effects are described in detail. Furthermore, we explore the various challenges faced by hydrogel electrolytes and propose corresponding strategies. Finally, the review offers insights into the future development of hydrogel-stabilized ZIBs. [ABSTRACT FROM AUTHOR]

With the growing demand for scalable and cost-effective electrochemical energy storage systems, aqueous Zn-ion batteries (ZIBs) have attracted attention as cheap, efficient, and safe energy storage devices. However, practical applications of ZIBs are hampered by some challenges, such as Zn dendrite growth, corrosion, passivation, byproducts, cathodic dissolution, and harmful electrostatic interactions. These problems are directly associated with the electrolytes of ZIBs, which are in contact with both the cathode and anode. Recently, several studies have been conducted to optimize ZIB electrolytes. The electrolyte system includes the electrolyte and solvent. The solvent ensures stable operation of the electrolyte and improves the electrochemical efficiency of the cathode and anode, thus improving the electrochemical performance and stability of ZIBs. However, to date, the effect of solvents on the stability of Zn anodes remains unclear. Therefore, there is a need for detailed studies on solvents for ZIB electrolytes. Herein, we review the research progress in the stabilization of Zn anodes using various solvents, including alcohols, amines, acetonitrile, lipids, ethers, and dimethyl sulfoxide. In addition, we discuss the effects of different solvents on the stabilization mechanism of Zn anodes. Finally, the challenges and prospects of solvents used for stabilizing Zn anodes in electrolytes are analyzed, and future research directions for ZIB electrolyte dissolution are proposed. [ABSTRACT FROM AUTHOR]