Search

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.

Abstract Aversion refers to feelings of strong dislike or avoidance toward particular stimuli or situations. Aversion can be caused by pain stimuli and has a long-term negative impact on physical and mental health. Aversion can also be caused by drug abuse withdrawal, resulting in people with substance use disorder to relapse. However, the mechanisms underlying aversion remain unclear. The ventrolateral periaqueductal gray (vlPAG) is considered to play a key role in aversive behavior. Our study showed that inhibition of vlPAG GABAergic neurons significantly attenuated the conditioned place aversion (CPA) induced by hindpaw pain pinch or naloxone-precipitated morphine withdrawal. However, activating or inhibiting glutamatergic neurons, or activating GABAergic neurons cannot affect or alter CPA response. AKAP150 protein expression and phosphorylated TRPV1 (p-TRPV1) were significantly upregulated in these two CPA models. In AKAP150flox/flox mice and C57/B6J wild-type mice, cell-type-selective inhibition of AKAP150 in GABAergic neurons in the vlPAG attenuated aversion. However, downregulating AKAP150 in glutamatergic neurons did not attenuate aversion. Knockdown of AKAP150 in GABAergic neurons effectively reversed the p-TRPV1 upregulation in these two CPA models utilized in our study. Collectively, inhibition of the AKAP150/p-TRPV1 pathway in GABAergic neurons in the vlPAG may be considered a potential therapeutic target for the CPA response.

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.

Background Lack of tumor-infiltrating T lymphocytes and concurrent T-cell dysfunction have been identified as major contributors to glioblastoma (GBM) immunotherapy resistance. Upregulating CXCL10 in the tumor microenvironment (TME) is a promising immunotherapeutic approach that potentially increases tumor-infiltrating T cells and boosts T-cell activity but is lacking effective delivery methods.Methods In this study, mesenchymal stem cells (MSCs) were transduced with a recombinant lentivirus encoding Cxcl10, Nrf2 (an anti-apoptosis gene), and a ferritin heavy chain (Fth) reporter gene in order to increase their CXCL10 secretion, TME survival, and MRI visibility. Using FTH-MRI guidance, these cells were injected into the tumor periphery of orthotopic GL261 and CT2A GBMs in mice. Combination therapy consisting of CXCL10-Nrf2-FTH-MSC transplantation together with immune checkpoint blockade (ICB) was also performed for CT2A GBMs. Thereafter, in vivo and serial MRI, survival analysis, and histology examinations were conducted to assess the treatments’ efficacy and mechanism.Results CXCL10-Nrf2-FTH-MSCs exhibit enhanced T lymphocyte recruitment, oxidative stress tolerance, and iron accumulation. Under in vivo FTH-MRI guidance and monitoring, peritumoral transplantation of CXCL10-Nrf2-FTH-MSCs remarkably inhibited orthotopic GL261 and CT2A tumor growth in C57BL6 mice and prolonged animal survival. While ICB alone demonstrated no therapeutic impact, CXCL10-Nrf2-FTH-MSC transplantation combined with ICB demonstrated an enhanced anticancer effect for CT2A GBMs compared with transplanting it alone. Histology revealed that peritumorally injected CXCL10-Nrf2-FTH-MSCs survived longer in the TME, increased CXCL10 production, and ultimately remodeled the TME by increasing CD8+ T cells, interferon-γ+ cytotoxic T lymphocytes (CTLs), GzmB+ CTLs, and Th1 cells while reducing regulatory T cells (Tregs), exhausted CD8+ and exhausted CD4+ T cells.Conclusions MRI-guided peritumoral administration of CXCL10 and Nrf2-overexpressed MSCs can significantly limit GBM growth by revitalizing T lymphocytes within TME. The combination application of CXCL10-Nrf2-FTH-MSC transplantation and ICB therapy presents a potentially effective approach to treating GBM.

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.

Abstract Organic field‐effect transistors (OFETs) with low‐voltage‐operating high‐stability are regarded as one of the key components of future electronics. However, it remains a challenge to enhance bias–stress stability, mechanical durability and environmental adaptability while reducing the operating voltage of the flexible OFETs. In this study, a new strategy of introducing high‐dipole‐moment groups into polymer side chains to enhance the intensity of polarization was proposed. This strategy can redirect cyclic carbonate side chains of high‐dipole groups under the action of electric fields and realize stable operation and efficient charge transfer. The experiments showed that high‐performance flexible OFETs were mainly attributed to the synthesized polymers through molecular structure designing which not only have high dielectric constant (k > 5) and high electrical insulating property but also favor the growth of organic semiconductor films. The flexible OFETs still showed excellent mechanical flexibility, high electrical, thermal and humidity stability. In addition, highly OFETs were applied into a floating‐gate memory with fullerene (C60) embedded charge memory layer and an integrated one‐transistor‐one‐transistor memory cell. They exhibited excellent memory performance with a large memory window (8.5 V), current ratio (103), stable retention (2 × 104 s), cyclic endurance (200 cycles), multi‐level memory (over 4 levels) and non‐destructivity.

The initial solidification of the shell and the effect of the negative strip on oscillation marks were studied during the oscillation of the mold. A two-dimensional model was established concerning mold oscillation, which was coupled with fluid flow, heat transfer, and solidification, and the validity of the model was verified. The results show that oscillation marks were formed at the negative strip stage and that the quality of the slabs can be improved by reducing the duration of the negative strip stage. During the negative strip stage, the shell was affected by the strong backflow of liquid slag and the pressure on the surface sharply increased, resulting in the formation of a depression oscillation mark on the shell. The effects of the negative strip stage on the initial solidified shell during each cycle were compared. As the depth of the oscillation mark decreased, the upward shear stress on the shell’s surface increased, without the occurrence of a negative strip stage during one cycle. The results provided a new method for reducing oscillation marks and are of great significance for improving casting slabs’ quality.

Wheat is one of the most important staple crops worldwide. Fusarium head blight severely reduces wheat yield and quality. Cultivation of a novel type of cleistogamous wheat mutant, ZK001, which was created by static magnetic field treatment, is a new strategy for controlling Fusarium head blight. However, little is known about the mechanism of cleistogamy in wheat. The present study demonstrated that anthers of ZK001 were retained on the glumes at all flowering stages, whereas those of YM18 were extruded from the paleae and lemmae. There was a clear difference in the morphological characteristics of lodicules between YM18 and ZK001. Lodicule calcium and potassium contents were significantly higher in YM18 than in ZK001 from white to yellow anther stages. In Fusarium head blight resistance, the diseased kernel rate and deoxynivalenol content of ZK001 were markedly lower than those of YM18 and QM725. Comparative transcriptome analysis of YM18 and ZK001 was performed to identify regulatory mechanisms of cleistogamy. The main differentially expressed genes identified in the spikelets of YM18 and ZK001 at the green anther stage were associated with cell walls, carbohydrates, phytohormones, water channel, and ion binding, transport, and homeostasis. These differentially expressed genes may play an important role in regulating cellular homeostasis, osmotic pressure, and lodicule development. The results indicate that ZK001 lost the ability to push the lemmae and paleae apart during the flowering stage because of the thin lodicules. ZK001 was speculated to provide structural barriers for Fusarium head blight during the flowering stage. The thin lodicule of ZK001 results from low levels of soluble sugar, calcium ions, and potassium ions in the lodicules. These levels are regulated by differentially expressed genes. Keywords: Wheat, Fusarium head blight, Cleistogamy, Lodicule, Transcriptome

In this paper, a new iron-carbon micro-electrolytic filler for wastewater treatment was prepared using the blast furnace dust. The effects of preparation conditions on the performance of the filler during the wastewater treatment were investigated. The optimal preparation conditions of the filler were obtained, which provided an experimental theoretical basis for the use of metallurgical dust sludge in the preparation of micro-electrolytic fillers. From the results of treating methyl orange-simulated wastewater with fillers of different preparation conditions, it could be obtained that the improvement of the filler processing performance requires a suitable iron to carbon ratio, sintering time, and sintering temperature. The optimum preparation conditions were a 1:2 iron-carbon ratio, 30 min sintering time, and 1100 °C sintering temperature. The effect of treatment conditions on the performance of the iron-carbon micro-electrolytic filler was also investigated. The results showed that increasing the filler addition, increasing the treatment temperature, and decreasing the initial pH could effectively improve the treatment efficiency of the filler for methyl orange-simulated wastewater. More than 99% of the methyl orange could be removed in the wastewater under the conditions of 5 g of filler, 40 °C, and pH = 3.

Background: The relationship between urine output (UO) and severe-stage progression in the early phase of acute kidney injury (AKI) remains unclear. This study aimed to investigate the relationship between early-phase UO6−12h [UO within 6 h after diagnosis of stage 1 AKI by Kidney Disease: Improving Global Outcomes (KDIGO) UO criteria] and severe-stage progression of AKI and to identify a reference value of early-phase UO6−12h for guiding initial therapy in critical care.Methods: Adult patients with UO < 0.5 ml/kg/h for the first 6 h after intensive care unit (ICU) admission (meeting stage 1 AKI by UO) and UO6−12h ≥ 0.5 ml/kg/h were identified from the Medical Information Mart for Intensive Care (MIMIC) III database. The primary outcome was progression to stage 2/3 AKI by UO. After other variables were adjusted through multivariate analysis, generalized additive model (GAM) was used to visualize the relationship between early-phase UO6−12h and progression to stage 2/3 AKI by UO. A two-piecewise linear regression model was employed to identify the inflection point of early-phase UO6−12h above which progression risk significantly leveled off. Sensitivity and subgroup analyses were performed to assess the robustness of our findings.Results: Of 2,984 individuals, 1,870 (62.7%) with KDIGO stage 1 UO criteria progressed to stage 2/3 AKI. In the multivariate analysis, early-phase UO6−12h showed a significant association with progression to stage 2/3 AKI by UO (odds ratio, 0.40; 95% confidence interval, 0.34–0.46; p < 0.001). There was a non-linear relationship between early-phase UO6−12h and progression of AKI. Early-phase UO6−12h of 1.1 ml/kg/h was identified as the inflection point, above which progression risk significantly leveled off (p = 0.780). Patients with early-phase UO6−12h ≥ 1.1 ml/kg/h had significantly shorter length of ICU stay (3.82 vs. 4.17 days, p < 0.001) and hospital stay (9.28 vs. 10.43 days, p < 0.001) and lower 30-day mortality (11.05 vs. 18.42%, p < 0.001). The robustness of our findings was confirmed by sensitivity and subgroup analyses.Conclusions: Among early-stage AKI patients in critical care, there was a non-linear relationship between early-phase UO6−12h and progression of AKI. Early-phase UO6−12h of 1.1 ml/kg/h was the inflection point above which progression risk significantly leveled off.

Background Immunotherapy with IFNβ is a promising strategy for treating malignant glioma. However, systemic administration of IFNβ is inadequate because of low intratumoral concentration and major adverse effects. This study aimed to determine whether mesenchymal stem cells (MSCs) can be used as cellular vehicles to locally deliver IFNβ for glioma therapy by using in vivo MRI tracking.Methods A recombinant lentiviral vector encoding IFNβ and ferritin heavy chain (FTH) reporter genes was constructed to transduce MSCs. The effectiveness and safety of transduction were assessed. After the IFNβ and FTH overexpressed MSCs (IFNβ-FTH-MSCs) were transplanted into intracranial orthotopic rat F98 gliomas via peritumoral, intracerebral, intratumoral or intra-arterial injection, MRI was performed to track IFNβ-FTH-MSCs and to evaluate their therapeutic effect on glioma in vivo, as validated by histologic analysis, quantitative PCR and ELISA assays.Results MSCs were efficiently and safely transduced to upregulate their IFNβ secretion and FTH expression by the constructed lentivirus. After peritumoral injection, IFNβ-FTH-MSCs appeared as hypointense signals on MRI, which gradually diminished but remained visible until 11 days. Compared with other administration routes, only peritumoral injection of IFNβ-FTH-MSCs showed a remarkable inhibition on the glioma growth. Nearly 30% of IFNβ-FTH-MSCs survived up to 11 days after peritumoral injection, while most of IFNβ-FTH-MSCs injected via other routes died within 11 days. IFNβ-FTH-MSCs grafted peritumorally secreted IFNβ persistently, leading to pronounced Batf3+ dendritic cells and CD8+ T lymphocyte infiltration within the glioma.Conclusions MSCs can be used as cellular vehicles of IFNβ to treat malignant glioma effectively via peritumoral injection.

Abstract Background Bone is one of the most frequent metastatic sites of advanced breast cancer. Current therapeutic agents aim to inhibit osteoclast-mediated bone resorption but only have palliative effects. During normal bone remodeling, the balance between bone resorption and osteoblast-mediated bone formation is essential for bone homeostasis. One major function of osteoblast during bone formation is to secrete type I procollagen, which will then be processed before being crosslinked and deposited into the bone matrix. Methods Small RNA sequencing and quantitative real-time PCR were used to detect miRNA levels in patient blood samples and in the cell lysates as well as extracellular vesicles of parental and bone-tropic MDA-MB-231 breast cancer cells. The effects of cancer cell-derived extracellular vesicles isolated by ultracentrifugation and carrying varying levels of miR-218 were examined in osteoblasts by quantitative real-time PCR, Western blot analysis, and P1NP bone formation marker analysis. Cancer cells overexpressing miR-218 were examined by transcriptome profiling through RNA sequencing to identify intrinsic genes and pathways influenced by miR-218. Results We show that circulating miR-218 is associated with breast cancer bone metastasis. Cancer-secreted miR-218 directly downregulates type I collagen in osteoblasts, whereas intracellular miR-218 in breast cancer cells regulates the expression of inhibin β subunits. Increased cancer secretion of inhibin βA results in elevated Timp3 expression in osteoblasts and the subsequent repression of procollagen processing during osteoblast differentiation. Conclusions Here we identify a twofold function of cancer-derived miR-218, whose levels in the blood are associated with breast cancer metastasis to the bone, in the regulation of type I collagen deposition by osteoblasts. The adaptation of the bone niche mediated by miR-218 might further tilt the balance towards osteolysis, thereby facilitating other mechanisms to promote bone metastasis.

Abstract Background The response to neoadjuvant chemotherapy (NAC) varies by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) statuses, with responses being lower in ER-positive, HER2-negative tumors as compared with ER-negative, HER2-positive or triple-negative tumors. Neoadjuvant endocrine therapy (NET) is an attractive alternative to NAC for ER-positive, HER2-negative cancer. However, a prior trial comparing NET with standard NAC in ER-positive tumor showed that the difference of response was not significant. Studies demonstrated that the mTOR inhibitor everolimus could sensitize breast tumors to endocrine therapy. A pilot open-label, randomized trial has been designed to evaluate the feasibility, efficacy and tolerability of neoadjuvant everolimus plus letrozole versus NAC in treating postmenopausal women with ER-positive, HER2-negative breast cancer. Methods Forty postmenopausal women with non-metastatic ER-positive, HER2-negative invasive breast cancer with a primary tumor > 2 cm or positive axillary lymph node(s) proved by biopsy will be randomly (1:1) enrolled from Sun Yat-Sen Memorial Hospital to receive neoadjuvant everolimus plus letrozole for 18 weeks or fluorouracil, epirubicin plus cyclophosphamide (FEC) for six cycles before surgery. Primary outcome is the feasibility of the trial. Secondary outcome measures include ultrasound response rate, pathological complete response rate, breast-conserving surgery rate, toxicities, and changes in the percentages of peripheral blood CD4+ T cells, CD8+ T cells, T helper cells, regulatory T cells, and NK cells. Discussion This is the first study to determine the feasibility, efficacy and tolerability of head-to-head neoadjuvant everolimus plus letrozole versus neoadjuvant FEC in treating postmenopausal women with ER-positive, HER2-negative breast cancer. The trial will provide evidence to assess the feasibility of a future multicenter, randomized controlled trial, and will provide valuable clinical data of the immunoregulatory effect of everolimus in breast cancer. Trial registration ClinicalTrials.gov registry, ID: NCT02742051 . Registered on 7 April 2016.

Background Wheat is one of the most important staple crops worldwide. Fusarium head blight (FHB) severely affects wheat yield and quality. A novel bread wheat mutant, ZK001, characterized as cleistogamic was isolated from a non-cleistogamous variety Yumai 18 (YM18) through static magnetic field mutagenesis. Cleistogamy is a promising strategy for controlling FHB. However, little is known about the mechanism of cleistogamy in wheat. Methods We performed a FHB resistance test to identify the FHB infection rate of ZK001. We also measured the agronomic traits of ZK001 and the starch and total soluble sugar contents of lodicules in YM18 and ZK001. Finally, we performed comparative studies at the proteome level between YM18 and ZK001 based on the proteomic technique of isobaric tags for relative and absolute quantification. Results The infection rate of ZK001 was lower than that of its wild-type and Aikang 58. The abnormal lodicules of ZK001 lost the ability to push the lemma and palea apart during the flowering stage. Proteome analysis showed that the main differentially abundant proteins (DAPs) were related to carbohydrate metabolism, protein transport, and calcium ion binding. These DAPs may work together to regulate cellular homeostasis, osmotic pressure and the development of lodicules. This hypothesis is supported by the analysis of starch, soluble sugar content in the lodicules as well as the results of Quantitative reverse transcription polymerase chain reaction. Conclusions Proteomic analysis has provided comprehensive information that should be useful for further research on the lodicule development mechanism in wheat. The ZK001 mutant is optimal for studying flower development in wheat and could be very important for FHB resistant projects via conventional crossing.

Background Oral tongue squamous cell carcinoma (OTSCC) is the most common subtype of oral cancer. A predictive gene signature is necessary for prognosis of OTSCC. Methods Five microarray data sets of OTSCC from the Gene Expression Omnibus (GEO) and one data set from The Cancer Genome Atlas (TCGA) were obtained. Differentially expressed genes (DEGs) of GEO data sets were identified by integrated analysis. The DEGs associated with prognosis were screened in the TCGA data set by univariate survival analysis to obtain a gene signature. A risk score was calculated as the summation of weighted expression levels with coefficients by Cox analysis. The signature was used to distinguish carcinoma, estimated by receiver operator characteristic curves and the area under the curve (AUC). All were validated in the GEO and TCGA data sets. Results Integrated analysis of GEO data sets revealed 300 DEGs. A 16-gene signature and a risk score were developed after survival analysis. The risk score was effective to stratify patients into high-risk and low-risk groups in the TCGA data set (P

Transplantation of neural stem cells (NSCs) is emerging as a new therapeutic approach for stroke. Real-time imaging of transplanted NSCs is essential for successful cell delivery, safety monitoring, tracking cell fate and function, and understanding the interactions of transplanted cells with the host environment. Magnetic resonance imaging (MRI) of magnetic nanoparticle-labeled cells has been the most widely used means to track stem cells in vivo. Nevertheless, it does not allow for the reliable discrimination between live and dead cells. Reporter gene-based MRI was considered as an alternative strategy to overcome this shortcoming. In this work, a class of lentiviral vector-encoding ferritin heavy chain (FTH) and enhanced green fluorescent protein (EGFP) was constructed to deliver reporter genes into NSCs. After these transgenic NSCs were transplanted into the contralateral hemisphere of rats with acute ischemic stroke, MRI and fluorescence imaging (FLI) were performed in vivo for tracking the fate of transplanted cells over a long period of 6 wk. The results demonstrated that the FTH and EGFP can be effectively and safely delivered to NSCs via the designed lentiviral vector. The distribution and migration of grafted stem cells could be monitored by bimodal MRI and FLI. FTH can be used as a robust MRI reporter for reliable reporting of the short-term viability of cell grafts, whereas its capacity for tracking the long-term viability of stem cells remains dependent on several confounding factors such as cell death and the concomitant reactive inflammation.

Pyroelectric composites of triglycine sulfate (TGS)-polyvinylidene difluoride (PVDF) doped with graphene are studied. It is found that the graphene can effectively improve the polling efficiency and thermal property of the composites so that the infrared detective performance can be significantly improved. For example, by adding about 0.83 wt.% of graphene, the infrared detective property can be improved by more than 30%. It is also found that the size of the graphene plays a critical role on the property improvement. For example, the small-sized graphene prepared by ultrasonic exfoliation (UE) method is more effective than the big-sized graphene prepared by electrochemical exfoliation (EE) method.

PKCα (protein kinase C alpha, PRKCA) is an important protein involved in several steps of signaling pathways in lung cancer, and microRNAs (miRNAs) have also been shown to participate in lung carcinogenesis. However, it is not clear how PKCα and miRNAs are correlated in the disease. In this report, we aimed to identify novel miRNAs that target PKCα and to study their biological function. Using bioinformatics analysis, we predicted one novel candidate, miR-203, and found differential expression patterns of miR-203 and PKCα in human lung cancer tissues. Moreover, we experimentally validated miR-203 as a direct regulator of PKCα. Finally, we demonstrated that the targeting of PKCα by miR-203 played a critical role in regulating cell proliferation, apoptosis and migration in lung cancer cells. In summary, this study identifies a novel miRNA that targets PKCα and illustrates that the downregulation of PKCα by miR-203 modulates biological processes in lung cancer cells.

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]