Search

This study addressed the challenges of cost and portability in synchronous monitoring water quality and greenhouse gas emissions in paddy-dominated regions by developing a novel Internet of Things (IoT)-based monitoring system (WG-IoT-MS). The system, equipped with low-cost sensors and integrated intelligent algorithms, enabled real-time monitoring of dissolved N 2 O concentrations. Combined with an air-water gas exchange model, the system achieved efficient monitoring and simulation of CO 2 and N 2 O emissions from agricultural water bodies while reducing monitoring costs by approximately 60 %. The proposed method was validated in paddy-dominated regions in Danyang, China. Results indicated the excellence of the dissolved N 2 O concentration model based on support vector regression, demonstrating accurate predictions within a concentration range of 2.003 to 13.247 μg/L. Notably, the model maintained acceptable predictive accuracy (R 2 > 0.70) even when some variables were partially absent (with the number of missing variables < 2 and the missing proportion (MP) ≤ 50 %), making up for the data loss caused by sensor malfunctions. Furthermore, the model performed well (R 2 > 0.80) when testing data sourced from paddy fields and lakes. Finally, CO 2 and N 2 O emissions were successfully monitored, with the results validated using a floating chamber method (R 2 > 0.70). The method provides crucial technical support for quantitative assessment of water quality and greenhouse gas emissions in paddy-dominated regions, laying a foundation for formulating effective emission reduction strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acute myeloid leukemia (AML) is a hematological malignancy with a high recurrence rate. The interaction of chemokine receptor 4/chemokine ligand 12 (CXCR4/CXCL12) mediates homing and adhesion of AML cells in bone marrow, leading to minimal residual disease in patients, which brings a hidden danger for future AML recurrence. Ara-C is a nonselective chemotherapeutic agent against AML. Due to its short half-life and severe side effects, a lipid-like Ara-C derivative (AraN) was synthesized and a dual-function LipoAraN-E5 (135 nm, encapsulation efficiency 99%) was developed, which coloaded AraN and E5, a peptide of the CXCR4 antagonist. LipoAraN-E5 effectively improved the uptake, enhanced the inhibition of leukemia cell proliferation, migration, and adhesion to stromal cells in bone marrow, and mobilized the leukemia cells from bone marrow to peripheral blood via interfering with the CXCR4/CXCL12 axis. LipoAraN-E5 prolonged the plasma half-life of AraN (8.31 vs 0.56 h) and was highly enriched in peripheral blood (3.67 vs 0.05 μmol/g at 8 h) and bone marrow (379 vs 148 μmol/g at 24 h). LipoAraN-E5 effectively prevented the infiltration of leukemia cells in peripheral blood, bone marrow, spleen, and liver, prolonged the mice survival, and showed outstanding antineoplastic efficacy with negligible toxicity, which were attributed to the ingenious design of AraN, the use of a liposomal delivery carrier, and the introduction of E5. Our work revealed that LipoAraN-E5 may be a promising nanocandidate against AML.

The immune system requires a high energy expenditure to resist pathogen invasion. Macrophages undergo metabolic reprogramming to meet these energy requirements and immunologic activity and polarize to M1-type macrophages. Understanding the metabolic pathway switching in large yellow croaker ( Larimichthys crocea ) macrophages in response to lipopolysaccharide (LPS) stimulation and whether this switching affects immunity is helpful in explaining the stronger immunity of hypoxia-tolerant L. crocea . In this study, transcript levels of glycolytic pathway genes ( Glut1 and Pdk1 ), mRNA levels or enzyme activities of glycolytic enzymes [hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase A (LDHA)], aerobic respiratory enzymes [pyruvate dehydrogenase (PDH), isocitrate dehydrogenase (IDH), and succinate dehydrogenase (SDH)], metabolites [lactic acid (LA) and adenosine triphosphate (ATP)], levels of bactericidal products [reactive oxygen species (ROS) and nitric oxide (NO)], and transcripts and level changes of inflammatory factors [IL1β, TNFα, and interferon (IFN) γ] were detected in LPS-stimulated L. crocea head kidney macrophages. We showed that glycolysis was significantly induced, the tricarboxylic acid (TCA) cycle was inhibited, and metabolic reprogramming occurred, showing the Warburg effect when immune cells were activated. To determine the potential regulatory mechanism behind these changes, Lc HIF-1α was detected and found to be significantly induced and transferred to the nucleus after LPS stimulation. LcHif-1α interference led to a significant reduction in glycolytic pathway gene transcript expression, enzyme activity, metabolites, bactericidal substances, and inflammatory factor levels; a significant increase in the aerobic respiration enzymes; and decreased migration, invasion, and phagocytosis. Further ultrastructural observation by electron microscopy showed that fewer microspheres contained phagocytes and that more cells were damaged after LcHif-1α interference. LcHif-1α overexpression L. crocea head kidney macrophages showed the opposite trend, and promoter activities of Ldha and Il1β were significantly enhanced after LcHif-1α overexpression in HEK293T cells. Our data showed that Lc HIF-1α acted as a metabolic switch in L. crocea macrophages and was important in polarization. Hypoxia-tolerant L. crocea head kidney showed a stronger Warburg effect and inhibited the TCA cycle, higher metabolites, and bactericidal substance levels. These results collectively revealed that LcHif-1α may promote the functional activities of head kidney macrophages in protecting hypoxia-tolerant L. crocea from Aeromonas hydrophila infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wang, Gao, Li, Meng, Wu, Ding, Shen and Zhu.)

Dysregulation of deubiquitination contributes to various diseases, including cancer, and aberrant expression of deubiquitinating enzymes is involved in carcinoma progression. As a member of the ovarian tumor (OTU) deubiquitinases, OTUD4 is considered a tumor suppressor in many kinds of malignancies. The biological characteristics and mechanisms of OTUD4 in clear cell renal cell carcinoma (ccRCC) remain unclear. The downregulation of OTUD4 in ccRCC was confirmed based on the TCGA database and a validation cohort of 30-paired ccRCC and para-carcinoma samples. Moreover, OTUD4 expression was detected by immunohistochemistry in 50 cases of ccRCC tissues, and patients with lower levels of OTUD4 showed larger tumor size (p = 0.015). TCGA data revealed that patients with high expression of OTUD4 had a longer overall survival rate. In vitro and in vivo studies revealed that downregulation of OTUD4 was essential for tumor cell growth and metastasis in ccRCC, and OTUD4 overexpression inhibited these malignant phenotypes. We further found that OTUD4 sensitized ccRCC cells to Erastin-induced ferroptosis, and ferrostain-1 inhibited OTUD4-induced ferroptotic cell death. Mechanistic studies indicated that OTUD4 functioned as an anti-proliferative and anti-metastasic factor through the regulation of RNA-binding protein 47 (RBM47)-mediated activating transcription factor 3 (ATF3). OTUD4 directly interacted with RBM47 and promoted its stability via deubiquitination events. RBM47 was critical in ccRCC progression by regulating ATF3 mRNA stability, thereby promoting ATF3-mediated ferroptosis. RBM47 interference abolished the suppressive role of OTUD4 overexpression in ccRCC. Our findings provide mechanistic insight into OTUD4 of ccRCC progression and indicate a novel critical pathway OTUD4/RBM47/ATF3 may serve as a potential therapeutic pathway for ccRCC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The accuracy of atomic sensor is determined by the transverse nuclear spin relaxation time (T 2 ). As the longitudinal nuclear spin relaxation time (T 1 ) is the upper limit of T 2 , it becomes an important metric for evaluating the merits of alkali vapor cells. However, the conventional method for measuring T 1 of pulse delay takes dozens of minutes, which will increase the effect of random errors during the testing process. In order to solve this problem, a method to quickly estimate the value of T 1 is proposed by suppressing the influence of spin exchange relaxation and magnetic field gradient relaxation terms on T 2 . Experimental results indicate that the accuracy is maintained at above 95%, and the testing time is reduced to less than 5%.

Toll-like receptor 2 (TLR2) is a member of TLR family that plays important roles in the innate immune system, such as pathogen recognition and inflammation regulation. In this study, the TLR2 homologue was cloned from razor clam Sinonovacula constricta (denoted as ScTLR2) and its immune function was explored. The full-length cDNA of ScTLR2 comprised 2890 nucleotides with a 5'-UTR of 218 bp, an open reading frame of 2169 bp encoding 722 amino acids and a 3'-UTR of 503 bp. The deduced amino acid of ScTLR2 showed similar structure to TLR2 homologue with a conserved signal peptide, four LRR domains, one LRR-TYP domain, one LRR-CT domain, one transmembrane domain and a conserved TIR domain. ScTLR2 mRNA was detected in all examined tissues with the highest expression in the gill. After Vibrio parahaemolyticus challenge, the mRNA expression of ScTLR2 was significantly induced both in gill and haemocytes. The recombinant ScTLR2-LRR protein could bind all tested PAMPs including LPS, PGN and MAN. Bacterial agglutination assay showed that rScTLR2 could agglutinate the six tested bacteria with a calcium dependent manner. More importantly, ScTLR2 silencing by siRNA transfection could significantly depress the mRNA expression of Myd88, NF-κB, Tollip, IRF1, and IRF8. The survival rate of S. constricta was markedly decreased after V. parahaemolyticus challenge under this condition. Our current study demonstrated that ScTLR2 served as a pattern recognition receptor to induce immune response against invasive pathogen., Competing Interests: Declaration of competing interest We declare that we have no conflict of interest. The Sinonovacula constricta were commercially cultured animals, and all the experiments were conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The study protocol was approved by the Experimental Animal Ethics Committee of Ningbo University, China., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteoarthritis (OA) is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA. These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium. In this study, we found that phosphoglycerate mutase 5 (PGAM5) significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models. To address the role of PGAM5 in macrophages in OA, we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo. Mechanistically, we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways, whereas inhibited M2 polarization via STAT6-PPARγ pathway in murine bone marrow-derived macrophages. Furthermore, we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2 (DVL2) which resulted in the inhibition of β-catenin and repolarization of M2 macrophages into M1 macrophages. Conditional knockout of both PGAM5 and β-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice. Motivated by these findings, we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection, which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis. Collectively, these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA., (© 2024. The Author(s).)

Biofilm-associated infections are one of the most challenging healthcare threats for humans, accounting for 80% of bacterial infections, leading to persistent and chronic infections. The conventional antibiotics still face their dilemma of poor therapeutic effects due to the high tolerance and resistance led by bacterial biofilm barriers. Nanotechnology-based antimicrobials, nanoparticles (NPs), are paid attention extensively and considered as promising alternative. This review focuses on the whole journey of NPs against biofilm-associated infections, and to clarify it clearly, the journey is divided into four processes in sequence as 1) Targeting biofilms, 2) Penetrating biofilm barrier, 3) Attaching to bacterial cells, and 4) Translocating through bacterial cell envelope. Through outlining the compositions and properties of biofilms and bacteria cells, recent advances and present the strategies of each process are comprehensively discussed to combat biofilm-associated infections, as well as the combined strategies against these infections with drug resistance, aiming to guide the rational design and facilitate wide application of NPs in biofilm-associated infections., (© 2024 Wiley-VCH GmbH.)

Background/aim: The natural killer (NK) cell function of patients with malignant tumours may be suppressed by deficiency, and the poor prognosis of renal cell carcinoma (RCC) patients may be due to escape from NK cell cytotoxicity, especially with respect to natural cytotoxicity receptors (NCRs) on the NK cell surface. However, the specific mechanism remains unclear. Therefore, in this study, we sought to explore the role of NCR, especially NCR3 splice variants, in the process of NK cell deficiency in RCC patients., Materials and Methods: We used flow cytometry to analyse the phenotype of NK cells from the peripheral blood and kidney tumour tissue of RCC patients. The NKp30-mediated NK cell killing function was measured by antibody-dependent cell-mediated cytotoxicity (ADCC) in NK and RCC cell coincubation. We extracted RNA from the peripheral blood mononuclear cells (PBMCs) of RCC patients and renal carcinoma tissue and carried out real-time quantitative PCR to detect the mRNA levels of NKp30a, NKp30b and NKp30c. mRNA expression levels of cytokines (IL-6, IL-8, IL-10, IL-18 and TGF-β) based on RNA extracted from renal carcinoma tissue and adjacent normal kidney tissues were also measured by real-time quantitative PCR., Results: Regarding the phenotype of NK cells in RCC patients, the proportion of NK cells in tumour tissue was significantly reduced, with changes in the NK cell proportion being most obvious in NKp30 + NK cells. Furthermore, the results of the ADCC function assay showed limited NKp30 + NK cell-mediated cytotoxicity in RCC patients. Through real-time quantitative PCR, we found lower expression of NKp30a and NKp30b, the immunostimulatory splice variants of NCR3 encoding NKp30, in RCC patients. Moreover, expression of activating cytokines (IL-6 and IL-8) in renal cancer tissue was decreased, though inhibitory cytokine (TGF-β) expression remained unchanged, which may result in an immunosuppressive cytokine microenvironment., Conclusion: Decreased expression of immunostimulatory NCR3 splice variants and the inhibitory cytokine microenvironment in RCC patients may contribute to deficient NK cell cytotoxicity and renal carcinoma cell immune escape from NK cell killing, which may provide a theoretical basis for finding new immunotherapeutic targets for RCC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Gemcitabine (GEM) is a non-selective chemotherapeutic agent used in the treatment of pancreatic cancer. Its antitumor efficacy is limited by a short plasma half-life and severe adverse reactions. To overcome these shortcomings, four novel lipid-like GEM diesters were synthesized and encapsulated into liposomes. Through optimization, dimyristoyl GEM (dmGEM)-loaded liposomes (LipodmGEM) were successfully obtained with an almost complete encapsulation efficiency. Compared to free GEM, LipodmGEM showed enhanced cellular uptake and cell apoptosis, improved inhibition of cell migration on AsPC-1 cells and a greatly extended half-life (7.22 vs. 1.78 h). LipodmGEM succeeded in enriching the drug in the tumor (5.28 vs. 0.03 μmol/g at 8 h), overcoming a major shortcoming of GEM, showed excellent anticancer efficacy in vivo and negligible systemic toxicity, superior to GEM. Attractive as well, suspensions of LipodmGEM remained stable at 2-10 °C away from light for no <2 years. Our results suggest that LipodmGEM might become of high interest for treating pancreatic cancer while the simple strategy we reported might be explored as well for converting other antitumor drugs with high water-solubility and short plasma half-life into attractive nanomedicines., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Arthritis is a group of diseases characterized by joint pain, swelling, stiffness, and limited movement. Osteoarthritis, rheumatoid arthritis, and gouty arthritis are the most common types of arthritis. Arthritis severely affects the quality of life of patients and imposes a heavy financial and medical burden on their families and society at large. As a widely used traditional Chinese medicine, Herba siegesbeckiae has many pharmacological effects such as anti-inflammatory and analgesic, anti-ischemic injury, cardiovascular protection, and hypoglycemic. In addition, it has significant therapeutic effects on arthritis. The rich chemical compositions of H. siegesbeckiae primarily include diterpenoids, sesquiterpenoids, and flavonoids. As one of the main active components of H. siegesbeckiae, kirenol and quercetin play a vital role in reducing arthritis symptoms. In the present study, the research progress in arthritis treatment with the active components of H. siegesbeckiae is reviewed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study aimed to investigate the effects of Bacillus cereus LS2 on the growth performance, innate immunity, intestinal microbiota, and disease resistance of sea cucumber Apostichopus japonicus. After feeding with LS2 for 30 days, results showed that dietary with LS2 had a significant improvement in the growth rate and immune parameters (including total coelomocytes counts, phagocytosis, respiratory burst, and immune-related enzymes) of juvenile sea cucumbers. Subsequently, transcriptome sequencing and qRT-PCR verification were performed to analyze the potential mechanism of LS2 diet and thus improve the immune response of A. japonicus. GO and KEGG pathway analysis indicated that LS2 can primarily activate the "Lectins" and "complement and coagulation cascades" pathways to modulate the innate immunity of the sea cucumbers. Furthermore, 16S rRNA sequencing was used to analyze the intestinal microbial composition of sea cucumbers after dietary with LS2. Results showed that Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were the most prevalent phyla in A. japonicus intestinal microbiota. The abundance of Actinobacteria (46.20%) and Bacteroidetes (12.80%) were significantly higher in the LS2 group, whereas the relative abundance of Proteobacteria (49.98%) and Firmicutes (14.97%) were higher in the control group. The LDA scores of Nocardiaceae and Rhodococcus were also the highest taxa after the dietary administration of LS2, indicating that Actinobacteria phylum played a pivotal role in the intestinal microbial function of A. japonicus. Overall, these results suggested that feeding with Bacillus LS2 may be beneficial for A. japonicus farming., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The inundation process of floodplain wetlands plays a crucial role in maintaining the balance of river ecosystems, which are highly sensitive to hydrological alteration. Nevertheless, the specific mechanisms through which these hydrological changes affect the inundation patterns of floodplain wetlands are still unclear. This study aimed to investigate the impact mechanism of cascade hydropower development on the inundation process of floodplain wetlands. Multitemporal remote sensing datasets and long-term hydrometeorological data series were utilized in this study. By employing the water appearance frequency (WAF) index, wetland hydrological stability assessment, and wavelet analysis, the inundation changes in floodplain wetlands and the underlying hydrological driving mechanisms were examined. The results revealed significant alterations in the inundation frequency of floodplain wetlands due to the construction of upstream dams. Specifically, the construction of the Danjiangkou and Wangfuzhou dams led to an increase in the total inundated area of Part A (16.09 km 2 ) and Part B (76.93 km 2 ), respectively. Conversely, the moderate frequency inundation zone in Part C decreased (26.7 km 2 ) after the construction of the Cuijiaying Dam. The typical floodplain wetland 7 shifted from high to low (8.94 km 2 ) stability after the construction of the Cuijiaying Dam. Furthermore, the cascade hydropower dam construction resulted in increased fluctuations in downstream water discharge. This study provides an effective approach to understanding the impact of cascade hydropower dams on the inundation process of floodplain wetlands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Wetland vegetation biomass is an essential indicator of wetland health, and its estimation has become an active area of research. Zizania latifolia ( Z. latifolia ) is the dominant species of emergent vegetation in Honghu Wetland, and monitoring its aboveground biomass (AGB) can provide a scientific basis for the protection and restoration of this and other wetlands along the Yangtze River. This study aimed to develop a method for the AGB estimation of Z. latifolia in Honghu Wetland using high-resolution RGB imagery acquired from an unoccupied aerial vehicle (UAV). The spatial distribution of Z. latifolia was first extracted through an object-based classification method using the field survey data and UAV RGB imagery. Linear, quadratic, exponential and back propagation neural network (BPNN) models were constructed based on 17 vegetation indices calculated from RGB images to invert the AGB. The results showed that: (1) The visible vegetation indices were significantly correlated with the AGB of Z. latifolia . The absolute value of the correlation coefficient between the AGB and CIVE was 0.87, followed by ExG (0.866) and COM2 (0.837). (2) Among the linear, quadratic, and exponential models, the quadric model based on CIVE had the highest inversion accuracy, with a validation R 2 of 0.37, RMSE and MAE of 853.76 g/m 2 and 671.28 g/m 2 , respectively. (3) The BPNN model constructed with eight factors correlated with the AGB had the best inversion effect, with a validation R 2 of 0.68, RMSE and MAE of 732.88 g/m 2 and 583.18 g/m 2 , respectively. ​Compared to the quadratic model constructed by CIVE, the BPNN model achieved better results, with a reduction of 120.88 g/m 2 in RMSE and 88.10 g/m 2 in MAE. This study indicates that using UAV-based RGB images and the BPNN model provides an effective and accurate technique for the AGB estimation of dominant wetland species, making it possible to efficiently and dynamically monitor wetland vegetation cost-effectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Yang, Li, Cai and Wang.)

The accuracy of inertial measurement performed by the nuclear magnetic resonance gyroscope (NMRG) with two isotopes depends on the duration of transverse relaxation. Extending the relaxation of the xenon isotopes at the same time plays a very important role in the accuracy of gyro. The relaxation time of 129 Xe and 131 Xe can be increased to about 15-20 s by optimizing the buffer gas pressure of N 2 at about 0.57 amg and coating RbH, respectively. According to the results of theoretical analysis and experimentation, the gyro stability reaches 0.6°/h, and the active measurement volume is 3 × 3 × 3 ∼ mm 3 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to explore the mediating role of perceived social support in the association between perceived stress and job burnout in midwives., Design: A descriptive, cross-sectional online survey., Methods: Using the stratified cluster sampling method, 329 midwives in 20 hospitals in China were selected as the participants. They completed self-report assessment measures of job burnout, perceived stress and perceived social support., Results: 63.5% of the participants had job burnout. Perceived stress was negatively associated with social support (r = -.350, p < .01), while it was positively associated with job burnout (r = -.382, p < .01). Social support was negatively correlated with job burnout (r = -.569, p < .01). The total effect of perceived stress on job burnout was 0.474 (95% CI: 0.367 ~ 0.596, p < .01), the direct effect was 0.242 (95% CI: 0.142 ~ 0.355, p < .01), and the indirect effect was 0.232 (95% CI: 0.160 ~ 0.316, p < .01). Social support programmes for midwives should be implemented to control the impact of perceived stress on job burnout., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Microplastic (MP) pollution is a global issue owing to its potential threats to ecosystems and human health. MP pollution in river ecosystems is widely investigated, but the transport process under different hydrological conditions remain unclear. In this study, an approach of particle tracking in conjunction with hydrodynamic modeling was developed to investigate the dispersal and transport processes of microplastic particles in riverine ecosystem. The concentration and dispersal pattern of polyamide (PA), polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET) particles under base flow and flood events with recurrence intervals of 10-year, 20-year and 50-year were identified. Results indicated that rainfall intensity had a significant impact on the microplastic transport in rivers. Higher suspension concentration and lower sedimented concentration were observed in high flow periods, and the sedimented concentration showed a slow increasing trend in the flood recession stage. High water velocity facilitated the microplastic particles to be migrated for a longer distance, and high water flow was conducive to transport more microplastics from source points. Besides, microplastic particles with high density had worse mobility in water and more prone to deposition. PET were likely to be transported for a relatively shorter distance, while PP had higher mobility and took less time to reach the same simulation point. This study put forward an effective approach to understand the transport of MPs in the river. The results obtained are useful to identify pollution hotspots and track pollution paths., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Urban non-point source (NPS) pollution has gradually become one of the important factors affecting the urban water environment. The quantitative evaluation of urban NPS pollution is the priority to identify key control area of urban NPS pollution. Current model applied in China is mainly focused on small-scale area, large-scale spatial continuous simulation is lacking. In this study A spatial continuous evaluation method coupled with high-resolution remote sensing data has been established and the method was applied to Tongzhou, China. With the spatial distribution of land-use type and built-up area which were been obtained by remote sensing technology, the accumulative and wash-off load of urban NPS nitrogen and phosphorus were estimated for the prominent problems of nitrogen and phosphorus nutrient pollution in the rivers in the study area. The main sources of urban NPS Nitrogen and phosphorus pollution are roof and road rainfall runoff respectively. Compared to other urban NPS pollution models, the method developed in this study can quickly realize spatial visualization assessment of urban NPS pollution and provide a means to estimate urban NPS loads in entire city or urban agglomeration, it is applicable for common urban NPS pollutants and also has advantages in areas without data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

5-Fluorouracil (5-FU) is a chemotherapeutic drug against many types of cancers, especially colorectal cancer. However, its short plasma half-life and serious adverse reactions limit its wide clinical applications. To overcome these shortcomings, a novel lipophilic 5-FU carbonate [XL-01, (5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2 H )-yl) methyl tetradecyl carbonate] was designed, synthesized, and encapsulated into liposome (LipoXL-01) by a thin-film dispersion method through formulation screening and optimization. LipoXL-01 was characterized by a particle size of around 100 nm, polydispersity index of 0.200, ζ-potential value of -41 mV, encapsulation efficiency of 93.9%, and drug-loading efficiency of 11.6%. The cellular uptake of LipoXL-01 was increased in a concentration-dependent manner on HCT15 cells. LipoXL-01 could enhance the induction of cell apoptosis and the inhibition of cell migration and arrest the ability of the cell cycle at the S-phase on HCT15 cells better than 5-FU. Additionally, LipoXL-01 exhibited a slow drug release profile with a cumulative release rate of 12% in 8 h. The results of pharmacokinetic and biodistribution studies revealed that LipoXL-01 had a long plasma half-life (7.21 h) and a high tumor accumulation (733 nmol/g at 8 h). The in vivo antitumor effect study also showed that LipoXL-01 had more potent efficacy than 5-FU (65 vs 48% of the tumor-inhibition rate). Simultaneously, negligible systemic toxicity was observed via analyzing the body weight as well as hematological and pathological parameters in the tested mice. The current study suggested that LipoXL-01 might be a promising nanocandidate for chemotherapy of colorectal cancer.

The trade-off between ecological and socioeconomic benefits in the reservoir operation has become a focus issue in the watershed water resource management. However, finding a suitable reservoir ecological operation scheme in the multi-objective cascade reservoir systems remains unclear. At present, most ecological operation models are designed on the basis of water quantity balance, neglecting the dynamic variability of the hydrological process. This study proposed a multi-objective ecological operation system, which coupled a two-dimensional hydrodynamic model with a rainfall-runoff model, and integrated the ecological operation scheme into the hydrodynamic simulation system considering ecological flow. Moreover, the applicability of the operation scheme under climate variability with different hydrological periods was evaluated. Results indicated that multi-reservoir joint operation had the largest effect in normal years; the variation in the monthly hydrological magnitude, extreme events and their duration, temporal change and frequency of streamflow were significantly reduced after reservoir ecological operation. The SAM0-UNICON model performed better than the two other climate models, the ecological deficit (ED) under the Representative Concentration Pathway (RCP) 8.5 climate change scenario was larger than other scenarios with different operation schemes. Future climate change will have a larger impact on discharge change in the wet season than in other hydrological periods. This study emphasises the comprehensive application of the hydrological and hydrodynamic methods, which is of considerable importance for decision-making in basin water resource management and reservoir regulation., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Aims: Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate limiting enzyme of the bile acid biosynthetic pathway to convert cholesterol to bile acids, which is a major output pathway for cholesterol catabolism. In this study, we aimed to assess the potential regulatory mechanisms of microRNA-185 (miR-185) in cholesterol and bile acid homeostasis., Methods: Eight-week-old male ApoE KO mice fed a high-fat diet (HFD) were injected with lentiviruses encoding antisense miR-185 (miR-185-inh). Microarrays were applied to profile miR-185-regulated genes involved in bile acid metabolism. The expression of potential targets of miR-185 was validated using qPCR and Western blotting assay in human hepatoma HepG2 cells., Results: The administration of miR-185-inh correlated with decreased serum total bile acids levels in ApoE KO mice. Microarray gene profiling revealed that inhibition of miR-185 upregulated hepatic CYP7A1 expression in vivo, which was further validated in HepG2 cells and primary hepatic cells in vitro by overexpression or inhibition of miR-185. Furthermore, it was revealed that miR-185 regulated CYP7A1 expression via a FoxO1-involved indirect pathway and that miR-185 directly modulated FoxO1 expression by binding to its mRNA 3'UTR in a traditional post-transcriptional manner. Besides, we also observed that miR-185 regulated CYP7A1 expression by increasing p-AKT/AKT level, which induced the phosphorylation of FoxO1 and promoted FoxO1 degradation at a post-translational level., Conclusions: This study provides convincing evidence on the critical role of miR-185 in FoxO1 modulation at both post-transcriptional and post-translational levels, which accounts for the effects on CYP7A1 gene and its mediated cholesterol-bile acid metabolism. These results suggest an important role of miR-185 as a novel atherosclerosis-protective target for drug discovery., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alkali vapor cells are the core components of atomic sensing instruments such as atomic gyroscopes, atomic magnetometers, atomic clocks, etc. Emerging integrated atomic sensing devices require high-performance miniaturized alkali vapor cells, especially micro-fabricated vapor cells. In this review, bonding methods for vapor cells of this kind are summarized in detail, including anodic bonding, sacrificial micro-channel bonding, and metal thermocompression bonding. Compared with traditional through-lighting schemes, researchers have developed novel methods for micro-fabricated vapor cells under both single- and double-beam schemes. In addition, emerging packaging methods for alkali metals in micro-fabricated vapor cells can be categorized as physical or chemical approaches. Physical methods include liquid transfer and wax pack filling. Chemical methods include the reaction of barium azide with rubidium chloride, ultraviolet light decomposition (of rubidium azide), and the high-temperature electrolysis of rubidium-rich glass. Finally, the application trend of micro-fabricated alkali vapor cells in the field of micro-scale gyroscopes, micro-scale atomic clocks, and especially micro-scale biomagnetometers is reviewed. Currently, the sensing industry has become a major driving force for the miniaturization of atomic sensing devices, and in the near future, the micro-fabricated alkali vapor cell technology of atomic sensing devices may experience extensive developments.

Pancreatic cancer is an aggressive and highly lethal disease with a very poor prognosis. Our previous study found miriplatin can inhibit proliferation of various tumor cells, including pancreatic cancer cells. For the chemotherapy of pancreatic cancer, a novel recombinant human serum albumin (rHSA)-bound miriplatin nanoparticles (rHSA-miPt) were constructed by emulsion-diffusion evaporation method. The optimal formulation was composed of 150 mg of rHSA and 30 mg of miriplatin. The key parameters in rHSA-miPt production were 10 min of high-pressure homogenization in a solution with volume ratio of 10:2 of 5% glucose and chloroform. The rHSA-miPt was characterized with a particle size of 61 ± 10 nm, a zeta potential value of -18 ± 5 mV, encapsulation efficiency of 98.4%, drug loading of 16.4%, T 1/2 of 13.3 h and V d of 0.5 L in Sprague Dawley rats. The concentrations of platinum (Pt) in the tumors were 15 and 22-fold higher than those in the blood at 24 and 72 h in tumor-bearing mice, respectively. The internalization of rHSA-miPt through caveolae-dependent pathway. In vitro, the half-maximal inhibitory concentration (IC 50 ) of rHSA-miPt was 12.7 μM vs more than 100 μM of gemcitabine (Gem). The inhibition rate of tumor growth was 76% of rHSA-miPt and 51% of Gem, respectively. Compared with Gem, rHSA-miPt was identified to be safer and less toxic based on body weight loss in mice (0% vs 20%), the survival rate of mice (100% vs 80%) and hematological and biochemical parameters of the mice including leukocytes, lymphocytes, neutrophils, monocytes, serum alanine aminotransferase and aspartate aminotransferase. The present study revealed that rHSA-miPt might be a promising candidate for pancreatic cancer therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Super-enhancers (SEs) govern macrophage polarization and function. However, the mechanism underlying the signal-dependent latent SEs remodeling in macrophages remains largely undefined. Here we show that the epigenetic reader ZMYND8 forms liquid compartments with NF-κB/p65 to silence latent SEs and restrict macrophage-mediated inflammation. Mechanistically, the fusion of ZMYND8 and p65 liquid condensates is reinforced by signal-induced acetylation of p65. Then acetylated p65 guides the ZMYND8 redistribution onto latent SEs de novo generated in polarized macrophages, and consequently, recruit LSD1 to decommission latent SEs. The liquidity characteristic of ZMYND8 is critical for its regulatory effect since mutations coagulating ZMYND8 into solid compartments disable the translocation of ZMYND8 and its suppressive function. Thereby, ZMYND8 serves as a molecular rheostat to switch off latent SEs and control the magnitude of the immune response. Meanwhile, we propose a phase separation model by which the latent SEs are fine-tuned in a spatiotemporal manner., (© 2021. The Author(s).)

Antibiotics are widely used in humans and animals, but their transformation from surface water to groundwater and the impact of land uses on them remain unclear. In this study, 14 antibiotics were systematically surveyed in a complex agricultural area in Central China. Results indicated that the selected antibiotic concentrations in surface waters were higher in winter (average: 32.7 ng/L) than in summer (average: 17.9 ng/L), while the seasonal variation in groundwaters showed an opposite trend (2.2 ng/L in dry winter vs. 8.0 ng/L in summer). Macrolides were the predominant antibiotics in this area, with a detected frequency of over 90%. A significant correlation between surface water and groundwater antibiotics was only observed in winter (R 2  = 0.58). This study further confirmed the impact of land uses on these contaminants, with optimal buffer radii of 2500 m in winter and 500 m in summer. Risk assessment indicated that clarithromycin posed high risks in this area. Overall, this study identified the spatiotemporal variability of antibiotics in a typical agricultural area in Central China and revealed the impact of land uses on antibiotic pollution in aquatic environments., (Copyright © 2021. Published by Elsevier B.V.)

The large yellow croaker ( Larimichthys crocea ) is an important marine economic fish in China; however, its intolerance to hypoxia causes widespread mortality. To understand the molecular mechanisms underlying hypoxia tolerance in L. crocea , the transcriptome gene expression profiling of three different tissues (blood, gills, and liver) of L. crocea exposed to hypoxia and reoxygenation stress were performed. In parallel, the gene relationships were investigated based on weighted gene co-expression network analysis (WGCNA). Accordingly, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that several pathways (e.g., energy metabolism, signal transduction, oxygen transport, and osmotic regulation) may be involved in the response of L. crocea to hypoxia and reoxygenation stress. In addition, also, four key modules (darkorange, magenta, saddlebrown, and darkolivegreen) that were highly relevant to the samples were identified by WGCNA. Furthermore, some hub genes within the association module, including RPS16, EDRF1, KCNK5, SNAT2, PFKL, GSK-3β, and PIK3CD, were found. This is the first study to report the co-expression patterns of a gene network after hypoxia stress in marine fish. The results provide new clues for further research on the molecular mechanisms underlying hypoxia tolerance in L. crocea .

MicroRNA185 (miR185), an endogenous noncoding RNA with 23 nucleotides, is one of key posttranscriptional modulators of cholesterol metabolism in hepatic cells. The antisense inhibitor of miR185 (miR185i) could decrease cholesterol level in vivo, providing a promising agent for anti-atherosclerosis strategy. In this work, a novel LipomiR185i was constructed by thin film hydration method and post-PEGylation as DOPE: DOTAP: Chol: DSPE-PEG 2000 at the molar ratio of 1:1:1:0.1 with a nitrogen-to-phosphate ratio of 3, through the optimization of three cationic lipids (DOTAP, DODMA and DLin-MC3-DMA), six helper lipids (PC-98T, HSPC, DOPE, DMPC, DPPC and DSPC), different amounts and incorporation approaches of DSPE-PEG 2000 and nitrogen-to-phosphate ratio. LipomiR185i was characterized with a particle size of 174 ± 11 nm, a zeta potential of 7.0 ± 3.3 mV, high encapsulation efficiency and transfection activity. It could protect miR185i from the rapid degradation by nucleases in serum, enhance cellular uptake and promote lysosomal escape in HepG2 cells. LipomiR185i could accumulate in the liver and remain for at least two weeks. More importantly, LipomiR185i significantly down-regulated the hepatic endogenous miR185 level in vitro and in vivo without significant tissue damage at 14 mg⋅kg -1 . The construction of LipomiR185i provides a potential anti-atherosclerotic nanodrug as well as a platform for delivering small RNAs to the liver efficiently and safely., (Copyright © 2021 Elsevier B.V. All rights reserved.)

River delta-front estuaries (DEs) are vital interfaces for fluxes between terrestrial and marine environments. However, deep uncertainty exists in estimating the sedimentary pollutant flux from terrestrial environments in DEs due, in part, to a lack of direct measurements in these dynamic and complicated regions and uncertainty in the calculation method. Due to its high sediment content, the Yellow River (YR) has a strong ability to adsorb phosphorus; therefore, it reliably reflects estuarine sedimentary processes. Here, through the comprehensive analysis of field samples, monitoring data and remote sensing images, we conclude that riverine fine particles control the deltaic estuary pollution status and that particle size is the key factor. Based on the stable relationships between phosphorus and heavy metals, with r 2 values of 0.990, 0.992, and 0.639 for As, Cd, and Cr, respectively, we estimated that the P flux reached 22.68 g/m 2 yr in 2017. Analysis of the YR high-silt sediment load, which has a strong phosphorus adsorption ability and constitutes a substantial fraction of global fluvial sediment transport, revealed a negative correlation between the riverine sediment load and the estuarine phosphorus flux.

This study aims to explore and evaluate the antitumor efficacy of doxorubicin (DOX)-loaded liposomes containing the novel tri-block polymer folate-poly (2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine (F-PEOz-DSPE), compared with folate-polyethylene glycol-distearoyl phosphatidyl ethanolamine (F-PEG-DSPE) to offer an alternative for PEG decorated carriers. PEOz, a pH-sensitive polymer, exhibits similar solubility and segmental flexibility to PEG. In our previous study, PEOz was employed to an F-PEOz-DSPE which was segmentally similar to F-PEG-DSPE and exhibited selective targeting and pH-sensitivity in tumor cells. In this work, DOX-loaded liposomes containing F-PEOz-DSPE (F-PEOz liposome) or F-PEG-DSPE (F-PEG liposome) were prepared. In vivo/vitro antitumor efficacy and biodistribution were compared between the two liposomes. F-PEOz liposome showed higher in vitro antitumor activity and significantly stronger inhibition of tumor growth in HeLa tumor-bearing nude mice (tumor inhibition rate, 81.20 vs 52.99% with the treatment of 9 mg/kg DOX-loaded F-PEOz liposome/F-PEG liposome) and much less toxicity than free DOX. In vivo fluorescence imaging experiment confirmed that F-PEOz liposome accumulated much more than F-PEG liposome in tumor. Based on the above, F-PEOz liposome may be a promising carrier in tumor chemotherapy to achieve better therapeutic efficacy.

Groundwater pollution seriously threatens water resource safety due to high-intensity land use throughout the world. However, the relationship between groundwater pollution characteristics and land use in alluvial plains is still unclear. In this study, the effects of land use on shallow groundwater quality and human health risk were investigated via two sampling campaigns in a typical alluvial plain, namely, Jianghan Plain, China. Results show that the shallow groundwater in this area was polluted by nitrogen (with average concentrations of 5.12 mg/L in the dry season and 4.46 mg/L in the rainy season) and phosphorus (0.29 and 0.13 mg/L in the two seasons, respectively). The nutrient concentrations during the dry season were significantly higher than those during the rainy season (p < 0.05). Correlation analysis indicated that the concentration of nutrients was significantly positively correlated with cultivated land and negatively correlated with water and residence, suggesting that land use patterns can affect the groundwater quality. The best buffer where land use patterns affect the total N concentration was about 1000 m for cultivated land and water, while the optimal ranges for ammonium N were about 1000 and 2500 m for the areas, respectively. For the total phosphorus, a radius of 2000 m leads to the best fitting effect on both areas. Human health risk assessment showed that the total health risk indexes in about 75% of the samples were higher than 1, indicating the potential risk of the shallow groundwater in this area to human health. The results indicate that land use patterns will greatly affect the shallow groundwater quality. Thus, adjusting the land use pattern can improve the water quality and reduce health risks. Identification and selection of appropriate management solutions for the groundwater protection should be based on not only water quality problems but also surface land use patterns.

A novel polymer (PEG 2000 -carborane), self-assembling into spherical vesicles (boron-containing vesicles, BCVs), could be quickly taken up by tumor cells and had an enhance stability in the bloodstream in previous study. To have more comprehensive understanding of BCVs, endocytic mechanism and cytotoxicity assessment were conducted. The results showed that BCVs were taken up in the intact form with cholesterol-dependent pathway during endocytosis, and BCVs exhibited nearly no cytotoxicity. BCVs could accumulate within tumors for at least 24 h. The data would provide reference information and guidance for BCVs' multifunctional application serving as a boron delivery agent for boron neutron capture therapy (BNCT), a hydrophilic and/or hydrophobic drug carrier and a diagnostic imaging fluorescent probe.

Four metal phosphites/phosphates crystal materials C 8 N 4 H 34 Al 2 P 4 O 18 (1), C 3 N 2 H 17 GaP 2 O 8 (2), H 5 In 2 P 3 O 10 (3), and H 9 In 2 P 3 O 13 (4) have been solvothermally synthesized by organic amines in the presence of mixed solvents. Structural analyses indicate that compound 1 and 2 show one-dimensional (1D) chain structures; compound 3 and 4 are three-dimensional (3D) inorganic open-framework indium phosphites. Organic amines show different mechanisms in the four compounds. The 2,2'-bipyridine organic amine acts as a template source and it breaks down small molecules, which enter into the structure of compound 1. For compound 2, 1,2-propanediamine has a role as protonated template and it forms a hydrogen bond with the inorganic skeleton structure. As for compound 3 and 4 without the organic template, the benzylamine and 2,2'-bipyridine mainly serve as structure-directing agent. Especially, compound 3 has an odd seven-ring channel, and compound 4 contains 3D intersecting six-ring, eight-ring, and 10-ring channels. X-ray diffraction (XRD), scanning electron microscopy (SEM), CHN, inductive coupled plasma (ICP), Infrared (IR), and thermal gravimetric (TG) analyze the four compounds.

With the urgent requirement for high-performance rechargeable Li-S batteries, besides various carbon materials and metal compounds, lots of conducting polymers have been developed and used as components in Li-S batteries. In this review, the synthesis of polyaniline (PANI), polypyrrole (PPy) and polythiophene (PTh) is introduced briefly. Then, the application progress of the three conducting polymers is summarized according to the function in Li-S batteries, including coating layers, conductive hosts, sulfur-containing compounds, separator modifier/functional interlayer, binder and current collector. Finally, according to the current problems of conducting polymers, some practical strategies and potential research directions are put forward. We expect that this review will provide novel design ideas to develop conducting polymer-containing high-performance Li-S batteries., Competing Interests: The authors declare no conflict of interest.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that down-regulates hepatic low-density lipoprotein receptor (LDLR) by binding and shuttling LDLR to lysosomes for degradation. The development of therapy that inhibits PCSK9 has attracted considerable attention for the management of cardiovascular disease risk. However, only monoclonal antibodies of PCSK9 have reached the clinic use. Oral administration of small-molecule transcriptional inhibitors has the potential to become a therapeutic option., Methods: Here, we developed a cell-based small molecule screening platform to identify transcriptional inhibitors of PCSK9. Through high-throughput screening and a series of evaluation, we found several active compounds. After detailed investigation on the pharmacological effect and molecular mechanistic characterization, 7030B-C5 was identified as a potential small-molecule PCSK9 inhibitor., Findings: Our data showed that 7030B-C5 down-regulated PCSK9 expression and increased the total cellular LDLR protein and its mediated LDL-C uptake by HepG2 cells. In both C57BL/6 J and ApoE KO mice, oral administration of 7030B-C5 reduced hepatic and plasma PCSK9 level and increased hepatic LDLR expression. Most importantly, 7030B-C5 inhibited lesions in en face aortas and aortic root in ApoE KO mice with a slight amelioration of lipid profiles. We further provide evidences suggesting that transcriptional regulation of PCSK9 by 7030B-C5 mostly depend on the transcriptional factor HNF1α and FoxO3. Furthermore, FoxO1 was found to play an important role in 7030B-C5 mediated integration of hepatic glucose and lipid metabolism., Interpretation: 7030B-C5 with potential suppressive effect of PCSK9 expression may serve as a promising lead compound for drug development of cholesterol/glucose homeostasis and cardiovascular disease therapy. FUND: This work was supported by grants from the National Natural Science Foundation of China (81473214, 81402929, and 81621064), the Drug Innovation Major Project of China (2018ZX09711001-003-006, 2018ZX09711001-007 and 2018ZX09735001-002), CAMS Innovation Fund for Medical Sciences (2016-I2M-2-002, 2016-I2M-1-011 and 2017-I2M-1-008), Beijing Natural Science Foundation (7162129)., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

As the upper section of the Mekong River Basin, the vegetation quality of the Lancang River Basin (LRB) and the related ecological functions are critical for the whole basin. With time-series Moderate Resolution Imaging Spectroradiometer (MODIS) images from 2000 to 2015 and local daily climatic data since 1976, their vertical interaction differences were identified. The results showed that the spatial variation in Normalized difference vegetation index (NDVI) of grassland and forest were sensitive to elevation. The NDVI value in the southern area at elevations less than 3000 m was more than 0.80 and decreased to 0.30-0.60 with elevations higher than 4500 m. The general vegetation quality showed a positive trend under climate change over 16 years. The M-K test of daily precipitation and temperature from 12 local weather stations showed that the basin temperature varied more significantly than precipitation. The temporal correlation between NDVI with precipitation as well as temperature at each pixel indicated that temperature was the dominant factor affecting grassland and forest dynamics in the LRB. The interaction between vegetation and climate was more sensitive at elevations lower than 3000 m. Based on the RCP4.5 scenario, the future temperature distribution was predicted, and its impact on NDVI was simulated at the pixel scale. Under future drier and warmer climate conditions, the responded NDVI in the upper stream with higher elevation may increase soil erosion and decrease streamflow. The NDVI in the downstream area will be improved and be able to adapt to the related climate impacts. Because of the large amount of water and biomass in this basin, higher temperatures will accelerate the decomposition of forest foliar litter. Thus, more organic carbon and forest diffuse pollution will be discharged into the water, potentially affecting the water quality of the whole basin., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Among the popular electrochemical energy storage devices, supercapacitors (SCs) have attracted much attention due to their long cycle life, fast charge and discharge, safety, and reliability. Transition metal oxides are one of the most widely used electrode materials in SCs because of the high specific capacitance. Among various transition metal oxides, Co 3 O 4 and related composites are widely reported in SCs electrodes. In this review, we introduce the synthetic methods of Co 3 O 4 , including the hydrothermal/solvothermal method, sol-gel method, thermal decomposition, chemical precipitation, electrodeposition, chemical bath deposition, and the template method. The recent progress of Co 3 O 4 -containing electrode materials is summarized in detail, involving Co 3 O 4 /carbon, Co 3 O 4 /conducting polymer, and Co 3 O 4 /metal compound composites. Finally, the current challenges and outlook of Co 3 O 4 and Co 3 O 4 -containing composites are put forward., Competing Interests: The authors declare no conflict of interest.

Pathogenic CARD11 mutations cause aberrant nuclear factor κB (NF-κB) activation, which is presumably responsible for multiple immunological disorders. However, whether there is an NF-κB-independent regulatory mechanism contributing to CARD11 mutations related to pathogenesis remains undefined. Using three distinct genetic mouse models, the Card11 knockout (KO) mouse model mimicking primary immunodeficiency, the CARD11 E134G point mutation mouse model representing BENTA (B cell expansion with NF-κB and T cell anergy) disease, and the mouse model bearing oncogenic K215M mutation, we show that CARD11 has a noncanonical function as a negative regulator of the AKT-FOXO1 signal axis, independent of NF-κB activation. Although BENTA disease-related E134G mutant elevates NF-κB activation, we find that E134G mutant mice phenotypically copy Card11 KO mice, in which NF-κB activation is disrupted. Mechanistically, the E134G mutant causes exacerbated AKT activation and reduced FOXO1 protein in B cells similar to that in Card11 KO cells. Moreover, the oncogenic CARD11 mutant K215M reinforces the importance of the noncanonical function of CARD11. In contrast to the E134G mutant, K215M shows a stronger inhibitory effect on AKT activation and more stabilized FOXO1. Likewise, E134G and K215M mutants have converse impacts on B cell development and differentiation. Our results demonstrate that, besides NF-κB, CARD11 also governs the AKT/FOXO1 signaling pathway in B cells. The critical role of CARD11 is further revealed by the effects of pathogenic CARD11 mutants on this noncanonical regulatory function on the AKT-FOXO1 signaling axis., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Nephrolithiasis is a systemic metabolic disease with a worldwide incidence that is increasing yearly, as well as a high recurrence rate; however, this disease's pathogenesis has not been thoroughly elucidated to date. Several epidemiological studies have shown that the risk for developing kidney stones increases in people with dyslipidemia. To explore the mechanism of lipid-induced kidney stones, we established a mouse model for renal urolithiasis based on intraperitoneal injections of glyoxylate (120 mg/kg/d). Lipidomics based on ultra high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-QTOF-MS/MS) was performed to determine the changes in lipid metabolism in serum and kidneys. We screened 179 and 196 different lipid metabolites in the kidneys and serum, respectively, including fatty acyls, glycerophospholipids, sphingolipids, glycerolipids and prenol lipids. We found that polyunsaturated fatty acids, such as arachidonic acid, eicosapentaenoic acid, and docosahexoenoic acid, and ceramides and lysophosphocholines mediated inflammatory responses and that the oxidative stress induced by oleylethanolamine and glycerophosphoethanolamine plasmalogens is closely related to the development of kidney stones. These results provide strong evidence for the relationship between lipid metabolism and the development of kidney stones and suggest a clear direction for future research., (Copyright © 2018. Published by Elsevier B.V.)

The occurrence and temporal-spatial distributions of 13 antibiotics (tetracyclines, sulfonamides, and fluoroquinolones) in the water of a high-intensity aquaculture lake, Honghu Lake, and its associated river network and ponds were investigated. Tetracycline, oxytetracycline, chlortetracycline, and sulfadiazine are the four dominant antibiotics in this region, with maximum and median concentrations of 1454.8 and 304.8ng/L, 2796.6 and 161.9ng/L, 1431.3 and 349.9ng/L, and 499.5 and 106.5ng/L, respectively. The median concentrations of the other nine antibiotics are lower than 57.1ng/L. The highest contaminated sites are located in the Four-lake main canal and its lake inlets. Antibiotic concentrations were higher in November than in May and the concentrations were strongly correlated with water temperature, dissolved oxygen, and nitrates according to redundancy analysis. The source analysis indicated that besides untreated domestic and husbandry sewage, the aquaculture in the lake and ponds is a main source of antibiotics in the study region. The environmental hazards posed by the selected antibiotics were assessed by using the methods of hazard quotient and mixture hazard quotient. The results suggested that tetracycline, oxytetracycline, sulfadiazine, and ciprofloxacin pose medium to high ecological hazard to algae in almost all of the water samples, and the high combination ecological hazards of antibiotics are mainly posed by the high individual hazard quotient of tetracycline in the study area., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Microcystin-LR (MCLR) and copper are commonly found in eutrophic water bodies because of eutrophic run-offs, cyanobacterial blooms, and copper algicide applications. However, the ecotoxicological risk of their combination remains unknown. This study investigated the effect of MCLR, Cu, and their mixture on the growth and physiological responses of Vallisneria natans. Results showed that the combined toxicity of them was concentration dependent. Synergistic effects were elicited at low concentrations of MCLR and Cu exposure (≤0.25+0.64mg/L). Additive or antagonistic effects were induced at higher concentrations. Single and combined exposures could induce oxidative stress, such as increased superoxide anion radical levels. To cope with oxidative stress, V. natans could activate their antioxidant defense systems, such as enhanced superoxide dismutase production and changes in peroxidase activities. Exposure to combined MCLR and Cu (even only with 0.005+0.041mg/L) adversely affected their antioxidant defense systems. As a consequence, malondialdehyde levels significantly increased. The interaction of MCLR and Cu could also significantly increase the bioaccumulations of MCLR and Cu. This increase could be accounted for their synergistic toxic effects on V. natans. Our results suggested that the exacerbated ecological hazard of MCLR and Cu with environmental concentrations may harm aquatic ecosystems., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A two-dimensional (2D) water quality model was established to determine the response of water quality variables and submerged aquatic vegetation biomass to load reduction from watershed inflows and enclosure aquaculture in Honghu Lake in China. Results showed that the total nitrogen (TN) and total phosphorus (TP) loads from upstream discharge were the major external loads in the lake, accounting for 70% and 63% of the total loads, respectively. Scenario simulation results indicated that 93.2% of the lake area in summer (August) and 89.5% in autumn (November) could reach the protective targets (TN<1.0mg/L) under 50% reduction of inflow TN loads. Meanwhile, 58.7% of the lake area in summer and 63.1% in autumn could reach the protective targets (TP<0.05mg/L) under 50% reduction of aquaculture areas. The mass budget results of TN and TP showed that TP immobilisation was larger than TN immobilisation. The immobilisations for TN and TP from July to September were higher than those of other months under the combined impacts of increasing runoff during the wet period, phytoplankton bloom and water residence time. The 2D water quality model provided a relevant example for assessing the effects of runoff and aquaculture activities and served as scientific support for lake management to improve water quality in large shallow macrophytic lakes., (Copyright © 2016. Published by Elsevier B.V.)

An ecological engineering project with confined growth of 1.5 km(2) of Eichhornia crassipes was implemented to remove pollutants in Lake Dianchi. To assess the ecological effects of this project on benthic macroinvertebrate assemblages, a 1-year investigation at the areas inside and outside E. crassipes mats was conducted from May 2013 to May 2014. All the 10 sampling sites in the areas were grouped into two statistically significant clusters mainly corresponding to inside and outside E. crassipes mat areas (EMAs), by clustering analysis. E. crassipes reduced the densities of pollution indicator taxa (e.g., Oligochaeta and Chironomidae larvae); thus, the total densities of benthic macroinvertebrates at the area inside EMAs (mean 328.2 ind./m(2)) were slightly lower than that at the area outside EMAs (mean 505.6 ind./m(2)). Four functional feeding groups including 38 species of benthic macroinvertebrates were collected at the area inside EMAs, while only three functional feeding groups containing 17 species were collected at the area outside EMAs. The biodiversity indices (Shannon-Weiner, Margalef, Simpson, and Peilou indices) and K-dominance curves also showed higher diversity of benthic macroinvertebrates at the area inside EMAs than at the area outside EMAs. These results suggested that a certain scale of engineering application of E. crassipes was beneficial to benthic macroinvertebrate communities in the ultra-eutrophic Lake Dianchi and it could be used as a pioneer species in ultra-eutrophic lake for pollutant removal.

Background: Little is known about the effect of weight loss/gain on kidney function. Analyses are complicated by uncertainty about optimal body surface indexing strategies for measured glomerular filtration rate (mGFR)., Methods: Using data from the African-American Study of Kidney Disease and Hypertension (AASK), we determined the association of change in weight with three different estimates of change in kidney function: (i) unindexed mGFR estimated by renal clearance of iodine-125-iothalamate, (ii) mGFR indexed to concurrently measured BSA and (iii) GFR estimated from serum creatinine (eGFR). All models were adjusted for baseline weight, time, randomization group and time-varying diuretic use. We also examined whether these relationships were consistent across a number of subgroups, including tertiles of baseline 24-h urine sodium excretion., Results: In 1094 participants followed over an average of 3.6 years, a 5-kg weight gain was associated with a 1.10 mL/min/1.73 m(2) (95% CI: 0.87 to 1.33; P < 0.001) increase in unindexed mGFR. There was no association between weight change and mGFR indexed for concurrent BSA (per 5 kg weight gain, 0.21; 95% CI: -0.02 to 0.44; P = 0.1) or between weight change and eGFR (-0.09; 95% CI: -0.32 to 0.14; P = 0.4). The effect of weight change on unindexed mGFR was less pronounced in individuals with higher baseline sodium excretion (P = 0.08 for interaction)., Conclusion: The association between weight change and kidney function varies depending on the method of assessment. Future clinical trials should examine the effect of intentional weight change on measured GFR or filtration markers robust to changes in muscle mass., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Anemia is common in chronic kidney disease (CKD) and associated with poor outcomes. In cross-sectional studies, lower estimated glomerular filtration rate (eGFR) has been associated with increased risk for anemia. The aim of this study was to determine how hematocrit changes as eGFR declines and what factors impact this longitudinal association., Methods: We followed 1094 African-Americans with hypertensive nephropathy who participated in the African-American Study of Kidney Disease and Hypertension. Mixed effects models were used to determine longitudinal change in hematocrit as a function of eGFR. Interaction terms were used to assess for differential effects of age, gender, baseline eGFR, baseline proteinuria, malnutrition and inflammation on eGFR-associated declines in hematocrit. In sensitivity analyses, models were run using iGFR (by renal clearance of I(125) iothalamate) in place of eGFR., Results: At baseline, mean hematocrit was 39% and 441 (40%) individuals had anemia. The longitudinal relationship between eGFR and hematocrit differed by baseline eGFR and was steeper when baseline eGFR was <45 mL/min/1.73 m(2). For example, the absolute decline in hematocrit per 10 mL/min/1.73 m(2) decline in longitudinal eGFR was -3.7, -1.3 and -0.5% for baseline eGFR values of 20, 40 and 60 mL/min/1.73 m(2), respectively (P < 0.001 comparing the longitudinal association between baseline eGFR = 40 or 60 versus baseline eGFR = 20 mL/min/1.73 m(2)). Similarly, male sex, younger age (<65 years) and higher baseline proteinuria (protein-to-creatinine ratio >0.22) were associated with greater hematocrit declines per unit decrease in longitudinal eGFR compared with female sex, older age and low baseline proteinuria, respectively (P-interaction <0.05 for each comparison). The longitudinal eGFR-hematocrit association did not differ by body mass index, serum albumin or C-reactive protein., Conclusions: Men, younger individuals and those with low baseline eGFR (<45 mL/min/1.73 m(2)) or baseline proteinuria are particularly at risk for eGFR-related declines in hematocrit., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The exogenous organic pollutant linear alkylbenzene sulfonate (LAS) pollution and Microcystis bloom are two common phenomena in eutrophic lakes, but the effects of LAS alone on Microcystis remain unclear. In the present study, we investigated the effects of LAS on the growth, photochemical efficiency, and microcystin production of Microcystis aeruginosa in the laboratory. Results showed that low LAS (≤10 mg/L) concentrations improved the growth of M. aeruginosa (12 days of exposure). High LAS (20 mg/L) concentrations inhibited the growth of M. aeruginosa on the first 8 days of exposure; afterward, growth progressed. After 12 days of exposure, the concentrations of chlorophyll a in algal cells were not significantly affected by any of LAS concentrations (0.05 to 20 mg/L) in the present study; by contrast, carotenoid and protein concentrations were significantly inhibited when LAS concentrations reached as high as 20 mg/L. After 6 and 12 days of exposure, low LAS (≤10 mg/L) concentrations enhanced the maximal photochemical efficiency (Fv/Fm) and the maximal electron transport rate (ETRmax) of M. aeruginosa. Furthermore, LAS increased the microcystin production of M. aeruginosa. Extracellular and intracellular microcystin contents were significantly increased after M. aeruginosa was exposed to high LAS concentrations. Our results indicated that LAS in eutrophic lakes may increase the risk of Microcystis bloom and microcystin production.

Background: Prostate cancer is a global health issue. Usually, men with metastatic disease will progress to castration-resistant prostate cancer (CRPC). We aimed to identify the differentially expressed genes (DEGs) in tumor samples from non-castrated and castrated men from LNCaP Orthotopic xenograft models of prostate cancer and to study the mechanisms of CRPC., Material/methods: In this work, GSE46218 containing 4 samples from non-castrated men and 4 samples from castrated men was downloaded from Gene Expression Omnibus. We identified DEGs using limma Geoquery in R, the Robust Multi-array Average (RMA) method in Bioconductor, and Bias methods, followed by constructing an integrated regulatory network involving DEGs, miRNAs, and TFs using Cytoscape. Then, we analyzed network motifs of the integrated gene regulatory network using FANMOD. We selected regulatory modules corresponding to network motifs from the integrated regulatory network by Perl script. We preformed gene ontology (GO) and pathway enrichment analysis of DEGs in the regulatory modules using DAVID., Results: We identified total 443 DEGs. We built an integrated regulatory network, found three motifs (motif 1, motif 2 and motif 3), and got two function modules (module 1 corresponded to motif 1, and module 2 corresponded to motif 2). Several GO terms (such as regulation of cell proliferation, positive regulation of macromolecule metabolic process, phosphorylation, and phosphorus metabolic process) and two pathways (pathway in cancer and Melanoma) were enriched. Furthermore, some significant DEGs (such as CAV1, LYN, FGFR3 and FGFR3) were related to CPRC development., Conclusions: These genes might play important roles in the development and progression of CRPC.

Background: Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT)., Methods and Findings: 450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed. Three immunophenotype categories were compared: i) tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii) sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen); or iii) unexposed (no evidence of maternal infection or CB recall response). Overall, 78.9% of mothers were infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm (33.8%). Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib., Conclusions: There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with malaria and/or helminths during pregnancy. These findings highlight the importance of control and prevention of parasitic infections among pregnant women.

Long-term agricultural development and cultivation conversions affect soil heavy metal balance and the regional environmental safety. In this study, heavy metal parameters were used to identify changes in soil properties in response to land use and cultivation conversions. The integrated soil quality index, which involves seven heavy metal indices, was proposed to assess the environmental risk of long-term human activities in Northeast China. We used the remote sensing and geographical data for the four-term land use distribution from 1979 to 2009 to identify the spatial patterns of regional land use conversions. Then, 41 samples from the top 20 cm of the soil at sites corresponding to these seven types of conversions were collected (permanent dry land, dry land converted from wetland, dry land converted from forest, permanent wetland, permanent forest, paddy land converted from dry land, and paddy land converted from wetland). Based on the local soil properties and tillage practices, the following seven heavy metal parameters were employed: Arsenic (As), Cadmium (Cd), Chromium (Cr), Copper (Cu), Nickel (Ni), Lead (Pb), and Zinc (Zn). The conversion of farmland from wetland resulted in an increase in the concentration of Pb and Cr in the soil. In contrast, the concentrations of Zn, Cu, Ni, and Cd decreased when wetland was converted into farmland because the tillage practices washed these heavy metals away. During the conversion of dry land and paddy land to wetland, the levels of Pb increased by approximately 28.6% and 24.7%, respectively. Under the same conditions, the concentration of As increased by 32.5% and 14.1%, respectively. The integrated index also demonstrated that the farmlands were not contaminated by the heavy metals during long-term agricultural development.

The goal of this study was to identify cancer-associated differentially expressed genes (DEGs), analyze their biological functions and investigate the mechanism(s) of cancer occurrence and development, which may provide a theoretical foundation for bladder cancer (BCa) therapy. We downloaded the mRNA expression profiling dataset GSE13507 from the Gene Expression Omnibus database; the dataset includes 165 BCa and 68 control samples. T‑tests were used to identify DEGs. To further study the biological functions of the identified DEGs, we performed a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Next, we built a network of potentially interacting pathways to study the synergistic relationships among DEGs. A total of 12,105 genes were identified as DEGs, of which 5,239 were upregulated and 6,866 were downregulated in BCa. The DEGs encoding activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT) proteins, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and interleukin (IL)-10 were revealed to participate in the significantly enriched immune pathways that were downregulated in BCa. KEGG enrichment analysis revealed 7 significantly upregulated and 47 significantly downregulated pathways enriched among the DEGs. We found a crosstalk interaction among a total of 44 pathways in the network of BCa-affected pathways. In conclusion, our results show that BCa involves dysfunctions in multiple systems. Our study is expected to pave ways for immune and inflammatory research and provide molecular insights for cancer therapy.