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Abstract Dysnatremia and dyskalemia are common problems in acutely hospitalized elderly patients. These disorders are associated with an increased risk of mortality and functional complications that often occur concomitantly with acute kidney injury in addition to multiple comorbidities. In a single-center prospective observational study, we recruited 401 acute geriatric inpatients. In-hospital outcomes included all-cause mortality, length of stay, and changes in functional status as determined by the Activities of Daily Living (ADL) scale, Eastern Cooperative Oncology Group (ECOG) performance, and Clinical Frailty Scale (CFS). The prevalence of dysnatremia alone, dyskalemia alone, and dysnatremia plus dyskalemia during initial hospitalization were 28.4%, 14.7% and 32.4%, respectively. Patients with electrolyte imbalance exhibited higher mortality rates and longer hospital stays than those without electrolyte imbalance. Those with initial dysnatremia, or dysnatremia plus dyskalemia were associated with worse ADL scores, ECOG performance and CFS scores at discharge. Subgroup analyses showed that resolution of dysnatremia was related to reduced mortality risk and improved CFS score, whereas recovery of renal function was associated with decreased mortality and better ECOG and CFS ratings. Our data suggest that restoration of initial dysnatremia and acute kidney injury during acute geriatric care may benefit in-hospital survival and functional status at discharge.

Variation in resistance of xylem to embolism among flowers, leaves, and stems strongly influences the survival and reproduction of plants. However, little is known about the vulnerability to xylem embolism under drought stress and their relationships to the anatomical traits of pits among reproductive and vegetative organs. In this study, we investigated the variation in xylem vulnerability to embolism in peduncles, petioles, and stems in a woody plant, Magnolia grandiflora. We analyzed the relationships between water potentials that induced 50% embolism (P50) in peduncles, petioles, and stems and the conduit pit traits hypothesized to influence cavitation resistance. We found that peduncles were more vulnerable to cavitation than petioles and stems, supporting the hypothesis of hydraulic vulnerability segmentation that leaves and stems are prioritized over flowers during drought stress. Moreover, P50 was significantly correlated with variation in the dimensions of inter-vessel pit apertures among peduncles, petioles and stems. These findings highlight that measuring xylem vulnerability to embolism in reproductive organs is essential for understanding the effect of drought on plant reproductive success and mortality under drought stress.

Abstract Acute lung injury induced by ischemia–reperfusion (I/R)-associated pulmonary inflammation is associated with high rates of morbidity. Despite advances in the clinical management of lung disease, molecular therapeutic options for I/R-associated lung injury are limited. Zinc finger protein 36 (ZFP36) is an AU-rich element-binding protein that is known to suppress the inflammatory response. A ZFP36 binding site occurs in the 3ʹ UTR of the cAMP‐response element-binding protein (CREB) binding protein (CREBBP) gene, which is known to interact with apoptotic proteins to promote apoptosis. In this study, we investigate the involvement of ZFP36 and CREBBP on I/R-induced lung injury in vivo and in vitro. Intestinal ischemia/reperfusion (I/R) activates inflammatory responses, resulting in injury to different organs including the lung. Lung tissues from ZFP36-knockdown mice and mouse lung epithelial (MLE)-2 cells were subjected to either Intestinal I/R or hypoxia/reperfusion, respectively, and then analyzed by Western blotting, immunohistochemistry, and real-time PCR. Silico analyses, pull down and RIP assays were used to analyze the relationship between ZFP36 and CREBBP. ZFP36 deficiency upregulated CREBBP, enhanced I/R-induced lung injury, apoptosis, and inflammation, and increased I/R-induced lung fibrosis. In silico analyses indicated that ZFP36 was a strong negative regulator of CREBBP mRNA stability. Results of pull down and RIP assays confirmed that ZFP36 direct interacted with CREBBP mRNA. Our results indicated that ZFP36 can mediate the level of inflammation-associated lung damage following I/R via interactions with the CREBBP/p53/p21/Bax pathway. The downregulation of ZFP36 increased the level of fibrosis.

Abstract Among several leading cardiovascular disorders, ischemia–reperfusion (I/R) injury causes severe manifestations including acute heart failure and systemic dysfunction. Recently, there has been increasing evidence suggesting that alterations in mitochondrial morphology and dysfunction also play an important role in the prognosis of cardiac disorders. Long non-coding RNAs (lncRNAs) form major regulatory networks altering gene transcription and translation. While the role of lncRNAs has been extensively studied in cancer and tumor biology, their implications on mitochondrial morphology and functions remain to be elucidated. In this study, the functional roles of Zinc finger protein 36-like 2 (ZFP36L2) and lncRNA PVT1 were determined in cardiomyocytes under hypoxia/reoxygenation (H/R) injury in vitro and myocardial I/R injury in vivo. Western blot and qRT-PCR analysis were used to assess the levels of ZFP36L2, mitochondrial fission and fusion markers in the myocardial tissues and cardiomyocytes. Cardiac function was determined by immunohistochemistry, H&E staining, and echocardiogram. Ultrastructural analysis of mitochondrial fission was performed using transmission electron microscopy. The mechanistic model consisting of PVT1 with ZFP36L2 and microRNA miR-21-5p with E3 ubiquitin ligase MARCH5 was assessed by subcellular fraction, RNA pull down, FISH, and luciferase reporter assays. These results identified a novel regulatory axis involving PVT1, miR-21-5p, and MARCH5 that alters mitochondrial morphology and function during myocardial I/R injury. Using an in vivo I/R injury mouse model and in vitro cardiomyocytes H/R model, we demonstrated that ZFP36L2 directly associates with PVT1 and alters mitochondrial fission and fusion. PVT1 also interactes with miR-21-5p and suppresses its expression and activity. Furthermore, we identified MARCH5 as a modifier of miR-21-5p, and its effect on mitochondrial fission and fusion are directly proportional to PVT1 expression during H/R injury. Our findings show that manipulation of PVT1-miR-21-5p-MARCH5-mediated mitochondrial fission and fusion via ZFP36L2 may be a novel therapeutic approach to regulate myocardial I/R injury.

BackgroundChimeric antigen receptor-engineered T cell (CAR-T) therapy has shown promising potential for anti-cancer treatment. However, for pancreatic ductal adenocarcinoma (PDAC), the lack of infiltrative ability of these CAR-T cells leads to sub-optimal treatment outcome.MethodsChemokine (C-C motif) ligand 19 (CCL19), the expression of which is regulated by the nuclear factor of activated T cell pathway, was transfected into targeting mesothelin CAR-T cells (mesoCAR-N19) using NFAT regulating element. It was expressed in activated CAR-T cells by OKT3 or mesothelin+ tumor cells but not in inactive cells. The migratory ability of these CAR-T cells was then measured. Subsequently, functional identification of these CAR-T cells was performed in vivo. In addition, the tumor lytic activity and proliferation of the CAR-T cells were measured in vitro. The degree of CAR-T cell infiltration and distribution into the PDAC tumors was examined using the immunohistochemical staining of hCD3 and the detection of CAR gene copy number by quantitative PCR. Finally, the functional assessment of chemokine (C-C motif) receptor 7 knock-out was performed in the CAR-T cells.ResultsThrough in vitro Transwell assays, it was demonstrated that mesoCAR-N19 can be specifically expressed in CAR-T cells activated by tumor cells compared with conventional mesothelin CAR-T (mesoCAR) cells. We also observed that upregulating the expression of CCL19 can increase the recruitment of additional T cells. In vivo studies subsequently revealed that this highly specific recruitment of T cell infiltration is associated with enhanced tumor-suppressive activities downstream.ConclusionInduced expression of CCL19 can promote the anti-tumor ability of CAR-T cells by increasing their infiltrative ability. This study potentially uncovered novel method of activating CAR-T cells to enhance their infiltrative capacities, which offers a novel direction for PDAC treatment.

Colorectal cancer is a major health problem, and it is the third most diagnosed cancer in the United States. The current treatment for colorectal cancer includes irinotecan, a topoisomerase I inhibitor, and other targeted drugs, such as bevacizumab and regorafenib. The low response rates and incidence of high toxicity caused by these drugs instigated an evaluation of the anticancer efficacy of a series of 13 thiazolyl hydrazone derivatives of 1-indanone, and four compounds among them show favorable anticancer activity against some of the tested colorectal cancer cell lines with IC50 values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that one of the indanone-based thiazolyl hydrazone (ITH) derivatives, N-Indan-1-ylidene-N’-(4-Biphenyl-4-yl-thiazol-2-yl)-hydrazine (ITH-6), has a better cytotoxicity profile against p53 mutant colorectal cancer cells HT-29, COLO 205, and KM 12 than a p53 wild-type colorectal cancer cell line, such as HCT 116. Mechanistic studies show that ITH-6 arrests these three cancer cell lines in the G2/M phase and induces apoptosis. It also causes a rise in the reactive oxygen species level with a remarkable decrease in the glutathione (GSH) level. Moreover, ITH-6 inhibits the expression of NF-κB p65 and Bcl-2, which proves its cytotoxic action. In addition, ITH-6 significantly decreased tumor size, growth rate, and tumor volume in mice bearing HT-29 and KM 12 tumor xenografts. Moreover, CRISPR/Cas9 was applied to establish an NF-κB p65 gene knockout HT-29 cell line model to validate the target of ITH-6. Overall, the results suggest that ITH-6 could be a potential anticancer drug candidate for p53 mutant colorectal cancers.

Abstract Renal cell cancer (RCC) is the most lethal of all the common urologic cancers and constitutes 2.2% of all malignancy diagnoses. The incidence of RCC has been steadily increasing in recent decades. The classic risk factors of RCC include smoking, hypertension, obesity, genetics, and genetic mutations. Recent studies also revealed that RCC was an immunogenic tumor and affected by host immune status. Among the pan‐cance, RCC presented with the highest degree of immune infiltration, indicating RCC patients might benefit from immunotherapy. A new immune classification of RCC has been developed by Su et al. based on tumor‐infiltrating lymphocytes to guide clinical practice. However, these studies mainly focus on biomarkers derived from tumor microenvironment (TME), the biomarkers based on peripheral blood samples to RCC have rarely been described. We collected peripheral blood samples from RCC patients and their matched healthy controls and detected the number of IL‐2 and IFN‐γ producing cells by implementing an enzyme‐linked immunospot (ELISPOT) assay. This is the first study to report blood‐based immune biomarkers for RCC using an ELISPOT assay. Our results suggested the frequency of IFN‐γ producing cells but not IL‐2 producing cells was associated with RCC risk. These findings warrant further validation in larger prospective studies.

Inflammation is a hallmark of cancers. The purpose of the present study was to evaluate the prognostic potential of hematological inflammatory markers in glioblastoma multiforme (GBM) patients. The clinical data of 99 patients with lower-grade gliomas and 88 patients with GBMs were retrospectively analyzed. The optimal cutoff values for peripheral markers were determined by X-tile. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify markers with prognostic significance. Several scoring systems were constructed by combining these prognostic markers. The predictive accuracies of nomograms incorporating these scoring systems were evaluated by Harrell’s concordance index and receiver operating characteristic curve analysis. GBM patients exhibited higher neutrophil counts (p=0.001), neutrophil-to-lymphocyte ratio (NLR) (p 2.0) (Hazard ratio[HR]=2.519, 95% confidence interval (CI): 1.220-5.204, p=0.013), low LMR (< 2.3) (HR=2.268, 95%CI: 1.172-4.386, p=0.015), or low AGR (< 1.7) (HR=2.924, 95%CI: 1.389-6.135, p=0.005) were associated with poor overall survival in GBM patients. The scoring systems of AGR-NLR, AGR-LMR, and LMR-NLR were associated with GBM survival. The nomogram integrating AGR-NLR score had the best efficacy in predicting GBM survival (c-index=0.874). Pretreatment scores of AGR-NLR, AGR-LMR, and LMR-NLR may serve as prognostic factors for GBM patients, and a nomogram integrating AGR-NLR may provide a reliable tool to facilitate personalized preoperative evaluations.

This article analyzes the application of Chinese speech recognition technology in a non-barrier education system, and studies the construction of bi-modal database for a barrier-free teaching system. Barrier-free teaching is a term used to define systems that are designed to assist deaf students, while bi-modal approaches use both audio and video to assist learning. Based on a case study of a curriculum named "Foundations of Photoshop," the article creates a corpus to make acquisition of experimental data and annotation of corpora. Meanwhile, the authors analyze and design the organization of data and build an essential dictionary and grammar network in the recognition system.

Designing porous carbon materials with metal phosphides as host materials holds promise for enhancing the cyclability and durability of lithium−sulfur (Li−S) batteries by mitigating sulfur poisoning and exhibiting high electrocatalytic activity. Nevertheless, it is urgent to precisely control the size of metal phosphides to further optimize the polysulfide conversion reaction kinetics of Li−S batteries. Herein, a subtlety regulation strategy was proposed to obtain ultra‐small CoP nanoparticles‐decorated hollow carbon nanospheres (CoP@C) by using spherical polyelectrolyte brush (SPB) as the template with stabilizing assistance from polydopamine coating, which also works as carbon source. Leveraging the electrostatic interaction between SPB and Co2+, ultra‐small Co particles with sizes measuring 5.5±2.6 nm were endowed after calcination. Subsequently, through a gas‐solid phosphating process, these Co particles were converted into CoP nanoparticles with significantly finer sizes (7.1±3.1 nm) compared to state‐of‐the‐art approaches. By uniformly distributing the electrocatalyst nanoparticles on hollow carbon nanospheres, CoP@C facilitated the acceleration of Li‐ion diffusion and enhanced the conversion reaction kinetics of polysulfides through adsorption‐diffusion synergy. As a result, Li−S batteries utilizing the CoP@C/S cathode demonstrated an initial specific discharge capacity of 850.0 mAh g−1 at 1.0 C, with a low‐capacity decay rate of 0.03 % per cycle. [ABSTRACT FROM AUTHOR]

As the eLoran signal propagates, its strength gradually diminishes with increasing distance, making subsequent signal capture and terminal development challenging. To address this phenomenon, this paper proposes an improved method based on wavelet hard thresholding. This method applies hierarchical processing to the coefficients obtained after wavelet decomposition, based on the signal's center frequency. It effectively addresses issues like the disappearance of trailing edges and the presence of the noise with large coefficients. Simulation results show that the improved method has the largest output signal-to-noise ratio and effectively improves the problem of tailing vanishing and eliminates the noise with large coefficients. In analog source signal testing, the results show that the method can extract signals of 30 dBμv/m and above well. In actual signal testing, the improved method can extract eLoran signals transmitted over a distance of approximately 1000 km. Based on the results, it can be deduced that the input signal-to-noise ratio is −28.8 dB. Therefore, this method is a suitable and effective solution for extracting weak eLoran signals, providing strong support for signal monitoring in areas at the coverage boundaries of eLoran signals. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery. Early-stage liver metastasis of pancreatic ductal adenocarcinoma (PDAC) makes radical surgery not efficacious. Here, the authors show that MLKL-driven necroptosis contributes to PDAC early-stage metastasis by inducing tumour CD47 upregulation and macrophage extracellular traps formation. [ABSTRACT FROM AUTHOR]

Entity alignment aims to match entities with the same semantics from different knowledge graphs. Most existing studies use neural networks to combine graph-structure information and additional entity information (such as names, descriptions, images, and attributes) to achieve entity alignment. However, due to the heterogeneity of knowledge graphs, aligned entities often do not have the same neighbors, which makes it difficult to utilize the structural information from knowledge graphs and results in a decrease in alignment accuracy. Therefore, in this paper, we propose an interaction model that exploits only the additional information on entities. Our model utilizes names, attributes, and neighbors of entities for interaction and introduces attention interaction to extract features to further evaluate the matching scores between entities. Our model is applicable to Chinese datasets, and experimental results show that it has achieved good results on the Chinese medical datasets denoted MED-BBK-9K. [ABSTRACT FROM AUTHOR]

Alterbutenolide (1), a new butenolide derivative with a long-chain aliphatic acid substitution, together with seven known phenolic compounds i.e. alternariol (2), asperigillol B (3), p-hydroxyphenylacetic acid (4), p-hydroxyphenylethyl alcohol (5), methyl p-hydroxyphenyl acetate (6), 2-(4-hydroxyphenyl)ethyl acetate (7), and 5,6-dihydro-4-methyl-2H-pyran-2-one (8), was isolated from the cultures of a sponge-derived fungus Alternaria alternata I-YLW6-1. The structure of 1 was established on the basis of HR-MS, 1D and 2D NMR, as well as by comparison of the optical rotation data with the literature reported. Compounds 2 and 3 showed significant to moderate inhibitory activities against three harmful microalgae with IC50 values from 3.0 to 36.2 μg/mL, whereas compound 1 only displayed moderate inhibition against Chattonella marina with IC50 value of 34.6 μg/mL. Meanwhile, compounds 3 and 4 showed weak toxicity against brine shrimp larvae with LC50 values >100 μg/mL. [ABSTRACT FROM AUTHOR]

Flash drought (FD) is an onset and intensify rapidly type of drought that can harm the terrestrial ecosystem, and cause economic and agricultural losses. The North China Plain (NCP) is an important agricultural region in China where sustainable development is restricted by the frequent droughts and insufficient water resources. Coping with FD requires an understanding of the FD onset and identification in the NCP. Based on root zone soil moisture (RZSM), standardized evaporative stress ratio (SESR) and multiples of mean evaporative stress ratio (MESR), this study identified the FD events in the NCP from 1981 to 2022, revealed the FD characteristics such as frequency, duration, severity and intensity, explored the temporal and spatial trend, determined the FD hotspots, and demonstrated the impact of FD identification thresholds on the FD identification. The frequency distributions of FD events identified by RZSM, SESR, and MESR are all high in the central and northern NCP and low in the southern, whereas the total duration is high in the southern and eastern NCP and low in the northern. As the FD intensity increases, the onset stage lengthens, the recovery stage shortens, the total duration reduces, and the severity declines. The FD affected areas from various FD identification methods exhibit significant and similar seasonal variations, primarily occurring from May to August. Besides, NCP is prone to extreme and exceptional FDs. The NCP has a decreasing tendency of the FD characteristics, and three hotspots with frequent and serious FD events are identified in the northwestern, eastern and southwestern NCP. The FD frequency is also significantly influenced by the thresholds in the identification methods. This study provides insights into the FD characteristics in the NCP, and clarifies its trend and hotspots, which may be valuable for FD understanding and adaptation. [ABSTRACT FROM AUTHOR]

Environmental sustainability has become an important issue of concern throughout many countries. Among the many sources of concern include air pollution, the effects of which are often capitalized into house prices. In this article, we focus on air pollution in the city of Changsha, China, and the impacts of new pollution regulations on the relationship between pollution exposure and house sales prices. We use the Air Quality Index (Aqi) data from 10 air quality monitoring stations in Changsha to interpolate a previous 12-month average Aqi value for each dwelling unit in the city, based on geographical location. Controlling for important house characteristics such as the living area and the distance to the nearest subway stations, we use the Blue Sky Protection Campaign action plan (BSPC) as the quasi-natural experiment to identify the causal effect of air pollution on house prices. We find dwelling units that were previously in relatively higher-polluted neighborhoods saw their values increase by about 2% after the pollution regulation was implemented, which is statistically significant. This implies China could achieve greater housing wealth for its homeowners by implementing further pollution restrictions, both in Changsha and perhaps also in other parts of the country. Other Asian countries could potentially learn from the results of this analysis. [ABSTRACT FROM AUTHOR]

The objective of this study is to establish controlled-release nitrogen fertilization technology for achieving high yield and reduce carbon emissions. Two late-maturing medium japonica rice varieties, Nanjing 9108 and Taixiangjing 1402, were selected in this study. The controlled-release fertilizer with resin-coated urea (N 43%, the longevity was 100 d) and common urea (46% N) were used as nitrogen fertilizers. Different ratios of basal and panicle nitrogen fertilizers were set for different treatments of 10 : 0 (NM1), 8 : 2 (NM2), 7 : 3 (NM3), and 6 : 4 (NM4). The basal fertilizer was applied using the side-deep fertilization method, with a ratio of 5:5 for resin-coated urea and common urea. The panicle nitrogen fertilizer was common urea. Conventional fertilization (FFT) and no nitrogen fertilizer (0N) control treatments were also included. The effect of different nitrogen fertilizer application methods on rice yield, NH3 volatilization, and greenhouse gas emissions were investigated. The results showed that the side-deep application of controlled-release nitrogen fertilizer delayed the peak of NH3 volatilization, preventing it from occurring at tillering stage compared to the FFT treatment. In addition, the flux of NH3 volatilization and the average flux after topdressing were significantly reduced by the side-deep application of controlled-release nitrogen fertilizer. The NH3 emission accumulation, NH3 emission factor, and NH3 emission intensity were reduced by 25.33%-48.76%, 29.14%-60.81%, and 29.60%-56.01%, respectively. Furthermore, the CH4 emission fluxes were significantly reduced at tillering stage and after heading stage. The N2O emission fluxes were also significantly reduced during the shelving and heading period. The CH4 and N2O emission accumulation were reduced by 20.20%-55.04% and 25.56%-61.56%, respectively. The CH4 emission reduction rate decreased as the proportion of basal and panicle fertilizer decreased. The N2O emission reduction rate followed the order of NM1 > NM3 > NM2 > NM4. The GWP and GHGI were reduced by 20.96%-53.35% and 25.91%-55.40%, respectively. Considering the economic and ecological benefits, NM1 treatment had the best effect on the reduction of NH3 volatilization and greenhouse gas emissions. NM1 treatment reduced the number of fertilization times 1-2 compared with the NM3 and FFT treatments, which was advantageous for achieving green, simple, and large-scale rice production. NM3 treatment exhibited the highest increase in yield, and its impact on reducing NH3 volatilization and greenhouse gas emissions was second only to NM1 treatment. In summary, the present study explored a set of controlled-release nitrogen fertilization method (NM1 and NM3 focused on "light and simple + emission reduction" and "high yield + emission reduction", respectively) suitable for reducing emission and increasing yield of late-maturing medium japonica rice. [ABSTRACT FROM AUTHOR]