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ABSTRACT: Fatty liver hemorrhagic syndrome (FLHS) has a high incidence rate in laying hens, and lots of FLHS-affected meat products enter the market every year. At the same time, the meat of laying hens is an important component of the human diet. However, the impact of FLHS on meat of laying hens is unknown, which could have a negative impact on consumers. To explore the effects of FLHS on chicken breast meat, a total of 36 twenty-five-wk-old Jingfen laying hens were used in the experiment. The hens were randomly divided into Control group and Model group, with 6 replicates per group and 3 hens per replicate. All chickens were raised in double-story step cages with individual pens. After a 3-wk acclimation period, the formal experiment began at 28 wk of age and lasted for 8 wk. Blood, liver, and breast meat samples were collected for the study of FLHS effects on breast meat. The impact of FLHS on meat quality was assessed by measuring indicators such as water-holding capacity and tenderness of the breast meat. Absolute quantitative lipidomics was employed to reveal the impact of FLHS on the lipid composition of chicken breast meat, and then validated by using RT-qPCR. Moreover, the volatilomics was utilized to detect changes in volatile organic compounds (VOCs) in chicken breast meat and to elucidate the resulting flavor changes. This research results showed that the meat quality of chicken breast meat decreased under FLHS, mainly manifested as reduced water holding capacity and decreased tenderness. The lipid content in the breast meat of FLHS-affected hens was significantly increased (P < 0.05). Among the affected lipids, 38 triglycerides exhibited notable elevation, possibly linked to heightened gene expression, such as lysophosphatidylcholine acyltransferase 3. The breast meat of laying hens with FLHS demonstrated an increased presence of VOCs, with 20 differential VOCs identified. Notably, 14 VOCs, particularly in 2-Undecenal, trans-Geranylacetone and ethyl nonanoate, exhibited substantial increases. These 3 VOCs had been identified as playing an important role in the formation of flavor in the breast meat of FLHS-affected laying hens. Correlation analysis suggested that the increase in these 3 VOCs might be related to the increase in lipid molecules such as phosphatidylethanolamine (38;3e) and acyl carnitine (10:3). In summary, FLHS reduced the breast meat quality of laying hens, altered its lipid profiles, and enhanced its flavor. These findings underscore the profound impact of FLHS on lipid and VOC profiles in chicken breast meat, offering valuable insights for chicken meat quality affected by FLHS.

ABSTRACTPreviously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain–Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016–2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1–34]; adults, 25 years [range, 0–183]) and intensive care unit (children, 16 years [range, 1–30]; adults, 17 years [range, 0–102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Abstract This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This study aims to investigate the chemo-photothermal therapeutic potential of ZIF-8@ICG@Tax nanoparticles (NPs) in the treatment of non-small cell lung cancer (NSCLC). An “all-in-one” theranostic ZIF-8@ICG@Tax NPs was conducted by self-assembly based on electrostatic interaction. First, the photothermal effect, stability, pH responsiveness, drug release, and blood compatibility of ZIF-8@ICG@Tax were evaluated through in vitro testing. Furthermore, the hepatic and renal toxicity of ZIF-8@ICG@Tax were assessed through in vivo testing. Additionally, the anticancer effects of these nanoparticles were investigated both in vitro and in vivo. Uniform and stable chemo-photothermal ZIF-8@ICG@Tax NPs had been successfully synthesized and had outstanding drug releasing capacities. Moreover, ZIF-8@ICG@Tax NPs showed remarkable responsiveness dependent both on pH in the tumor microenvironment and NIR irradiation, allowing for targeted drug delivery and controlled drug release. NIR irradiation can enhance the tumor cell response to ZIF-8@ICG@Tax uptake, thereby promoting the anti-tumor growth in vitro and in vivo. ZIF-8@ICG@Tax and NIR irradiation have demonstrated remarkable synergistic anti-tumor growth properties compared to their individual components. This novel theranostic chemo-photothermal NPs hold great potential as a viable treatment option for NSCLC. Graphical Abstract A novel nano-theranostic platform was developed by encapsulating indocyanine green and paclitaxel within a zeolitie imidazolate framework-8 (ZIF-8). This chemo-phototherapic agent demonstrated accurate tumor targeting and effective suppression effects on both tumor growth in non-small cell lung cancer.

Pharmaceutical wastewater treatment plants (PWWTPs) serve as reservoirs for antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs). In this study, a multiantibiotic-resistant strain of Acinetobacter lwoffii (named N4) was isolated from the dewatered sludge of a PWWTP. N4 exhibited high resistance to both antibiotics and metals, with minimum inhibitory concentrations (MICs) of chloramphenicol and cefazolin reaching 1024 mg·L−1 and MICs of Cu2+ and Zn2+ reaching 512 mg·L−1. Co-sensitization experiments revealed that when antibiotics are co-existing with heavy metal ions (such as TET and Cd2+, AMP and Cu2+) could enhance the resistance of N4 to them. Whole-genome sequencing of N4 revealed a genome size of 0.37 Mb encoding 3359 genes. Among these, 23 ARGs were identified, including dfrA26, bl2beCTXM, catB3, qnrB, rosB, tlrC, smeD, smeE, mexE, ceoB, oprN, acrB, adeF, ykkC, ksgA and sul2, which confer resistance through mechanisms such as efflux pumps, enzyme modification and target bypass. Additionally, the N4 genome contained 187 genes associated with human disease and 249 virulence factors, underscoring its potential pathogenicity. Overall, this study provides valuable insights into ARBs in PWWTPs and highlights the potential risks posed by multidrug-resistant strains such as N4.

Electrochemical ammonia synthesis is being widely investigated to couple with renewable electricity for future sustainable ammonia production. Protonic ceramic electrochemical cells (PCECs) possess superior energy transfer efficiency and remarkable flexibility to produce high-demand chemicals such as H2, CH4, and NH3 from readily available feedstocks (e.g., H2O, CO2, N2). Despite recent advances that have been established, the research for the high-efficiency PCECs for practical ammonia synthesis continues. In this review, we summarized the recent progress of PCECs for ammonia synthesis. First, we briefly introduce the basic mechanisms and protocols of the ammonia synthesis. Then, we systemically introduce the cell configurations, representative electrolytes and electrodes of PCECs for the ammonia synthesis. We highlight the strategies to tune the ion/electron mobility and the catalytic performance, which are related to the defect structures and redox properties of the electrolyte/electrode, and the opportunities for next-generation ammonia synthesis. Finally, perspectives on ammonia synthesis in PCECs are proposed consering the current challenges.

ABSTRACT: In laying hens, fatty liver hemorrhagic syndrome (FLHS) is a common metabolic disorder, which can affect egg production and nutritional value. However, the impact of FLHS on the lipid content in egg yolks was not clear. In this study, FLHS model was induced by using high-energy low-protein diet, and the egg quality was evaluated. Egg yolk lipids were quantitatively analyzed by using ultra-performance liquid chromatography-mass spectrometry combined with multivariate statistical analysis. Gene expressions of the lipoprotein were determined by qRT-PCR and antioxidant capacity of the egg yolk were determined by kits. The elevated blood lipids and extensive lipid droplets observed indicated successful establishment of the FLHS model in laying hens. Measurements of egg quality showed that egg yolk weight was increased in the FLHS group. Lipidomics revealed that 1,401 lipids, comprising 27 lipid subclasses in the egg yolk. According to score plots of principal component analysis and orthogonal partial least squares discriminant analysis, different lipid profile was observed between the control and FLHS groups. A total of 97 different lipid species were screen out. Sphingolipid and glycerophospholipid metabolism were identified as key pathways. Free polyunsaturated fatty acids (PUFA) exhibited an increase in the FLHS group (P < 0.05). Notably, the form of PUFAs was changed that the FLHS group showed an increase in triacylglycerol-docosahexenoic acid and triacylglycerol-arachidonic acid in the egg yolk, while triacylglycerol-α-linolenic acid was decreased (P < 0.05). Total superoxide dismutase was decreased in the egg yolks affected by FLHS. Gene expressions of vitellogenin 2 (VTG2), VTG3, very low-density apolipoprotein II and apolipoprotein B were increased in the liver of laying hens with FLHS (P < 0.05). In conclusion, FLHS promoted the lipid transport from the liver to the yolk by upregulating lipoprotein expression, which altered lipid profile, and reduced antioxidant capacity in the yolk. This study provided a foundation for understanding the changes in lipids, lipid transport and lipid antioxidation capacity in egg yolk from laying hens with FLHS.

A positively charged nanofiltration (NF) membrane is known to have exceptional separation performance for bivalent cations in aqueous solutions. In this study, a new NF activity layer was created using interfacial polymerization (IP) on a polysulfone (PSF) ultrafiltration substrate membrane. The aqueous phase combines the two monomers of polyethyleneimine (PEI) and phthalimide, while successfully producing a highly efficient and accurate NF membrane. The conditions of the NF membrane were studied and further optimized. The aqueous phase crosslinking process enhances the polymer interaction, resulting in an excellent pure water flux of 7.09 L·m−2·h−1·bar−1 under a pressure of 0.4 MPa. Additionally, the NF membrane shows excellent selectivity toward inorganic salts, with a rejection order of MgCl2 > CaCl2 > MgSO4 > Na2SO4 > NaCl. Under optimal conditions, the membrane was able to reject up to 94.33% of 1,000 mg/L of MgCl2 solution at an ambient temperature. Further to assess the antifouling properties of the membrane with bovine serum albumin (BSA), the flux recovery ratio (FRR) was calculated to be 81.64% after 6 h of filtration. This paper presents an efficient and straightforward approach to customize a positively charged NF membrane. We achieve this by introducing phthalimide, which enhances the membrane's stability and rejection performance. HIGHLIGHTS A new positive-charge NF membrane was created for the separation of bivalent cations.; The composite NF membrane demonstrated excellent selectivity and permeability.; The composite NF membrane exhibited steady antifouling properties.;

The converter transformer is one of the core equipment in the high-voltage DC (HVDC) transmission project. The capacity of the converter transformer is much larger than that of an ordinary AC transformer, and its main function is to convert the AC system voltage to the phase change voltage required by the converter. The long-duration induction voltage test is an important technical means to assess the insulation strength of electrical equipment, and the calculation of the inlet capacitance of the converter transformer in the test design is extremely critical. This paper conducts circuit and mathematical modeling based on the structure of a single-phase three-winding converter transformer, calculates the equivalent capacitance between each winding of the converter transformer and each winding to ground by the model, and uses each equivalent capacitance to calculate the voltage added inlet capacitance, then obtains the appropriate compensation inductance. Moreover, the calculated inlet capacitance is verified by using the field test data, and the verification results show the reasonableness of the model. Finally, the calculation results are analyzed for errors and possible sources of errors are pointed out. This inlet capacitance calculation method has some universality and is expected to be promoted and applied in this field.

Background and objectiveSudden unexpected death in epilepsy (SUDEP) has been regarded as a leading cause of premature death in patients with epilepsy (PWE). Although patients, relatives and caregivers have the right to be informed of SUDEP, neurologists prefer not to release the facts for fear of associated anxiety. In the study, a Chinese questionnaire survey was carried out to elucidate effect of SUDEP disclosure on anxiety in PWE and variables determining the anxiety of patients and provided suggestions for SUDEP disclosure.MethodsA survey study in China was conducted. We recruited 305 PWE from 3 tertiary epilepsy centers who attended outpatient clinic from December 2021 to February 2022. Two hundred and thirty-two PWE completed the screening evaluation, survey and Hamilton anxiety rating scale (HAMA) twice with 171 PWE completing third HAMA at follow-up. HAMA scores at baseline, T1, T2 were compared using analysis of variance and dependent samples t-test. The variables related to anxiety were screened out by univariate analysis and used for multivariate logistic regression.ResultWe found 127 (54.7%) among the 232 participants experienced anxiety after SUDEP disclosure. HAMA scores at T1 were significantly higher than at baseline and T2, while there was no statistical difference between baseline and T2. Medical insurance, seizure severity, and whether the PWE supported SUDEP being disclosed to their relatives and caregivers only were associated with the occurrence of anxiety.ConclusionSUDEP disclosures may cause short-term acute anxiety, but have no long-term effects in PWE. Acute anxiety caused by SUDEP disclosure may be more common in PWE with NCMI and severe seizures. Meanwhile, compared with indirect SUDEP disclosure to their relatives and caregivers, direct SUDEP disclosure to PWE reduces the risk of anxiety. Recommendations are provided to avoid anxiety caused by SUDEP disclosure.

Ionic thermoelectric (i-TE) technologies can power Internet of Things (IoT) sensors by harvesting thermal energy from the environment because of their large thermopowers. Present research focuses mostly on using the interactions between ions and matrices to enhance i-TE performance, but i-TE materials can benefit from utilizing different methods to control ion transport. Here, we introduced a new strategy that employs an ion entanglement effect. A giant thermopower of 28 ​mV ​K−1 was obtained in a quasi-solid-state i-TE Gelatin-CF3SO3K–CH3SO3K gel via entanglement between CF3SO3− and CH3SO3− anions. The anionic entanglement effect involves complex interactions between these two anions, slowing anionic thermodiffusion and thus suppressing bipolar effects and boosting p-type thermopower. A Au@Cu | Gelatin-CF3SO3K–CH3SO3K | Au@Cu i-TE device with a generator mode delivers a specific output energy density of 67.2 ​mJ ​m−2 K−2 during 2 ​h of discharging. Long-term operation of the i-TE generator for 10 days shows that the harvested energy density offers an average of 2 ​J ​m−2 per day in a cyclic working-reactivation model at a temperature difference of 6 ​K. The results demonstrate that anionic entanglement is an effective strategy for achieving giant thermopower with i-TE gels, so they have excellent potential for powering IoT sensors.

Fluoride is an essential micronutrient for humans. Nonetheless, when the amount of fluoride ion is greater than required, it will cause skeletal fluorosis and dental fluorosis to threaten human health. In this paper, a series of sodium alginate (SA)-based foam materials are prepared by freeze-drying technique and anchored with the nano-activated alumina (nAl2O3) in the SA to obtain a novel adsorbent of SA-nAl2O3 foam used for fluoride ions removal. The SA-nAl2O3 foam morphology was further explored and confirmed that nAl2O3 existed stably in the SA. The adsorption results showed that the maximal fluoride ion adsorption capacity was 5.09 mg/g with 20 mg/L fluorine solutions at a pH of 3. The adsorption isotherm fitted adequately to the Langmuir isotherm model, which demonstrated that the adsorption process is closer to monolayer adsorption. The adsorption kinetics behavior of SA-nAl2O3 foam was described by a pseudo-second-order model, and the adsorption process occurred by chemisorption. Adsorption thermodynamics analysis emphasized that the adsorption process was spontaneous and endothermic. The main mechanism of the foam is ion exchange. The SA-nAl2O3 foam exhibited excellent regeneration performance and stability after three cycles. HIGHLIGHTS A novel adsorption material of SA-nAl2O3 foam was obtained for fluoride ion removal.; SA-nAl2O3 foam exhibited steady fluoride ion adsorption capacity.; SA-nAl2O3 foam has excellent regenerability after three cycles;

Fluorine is one of the essential trace elements for human life activities, but excessive intake of fluoride poses a great risk to people's health. In this paper, a series of mixed matrix membrane (MMM)-based polysulfone for removing fluoride were prepared by phase inversion, and their properties, adsorption capacity, adsorption isotherms, adsorption kinetics of fluoride ions, and mechanism were all investigated. The results confirmed that the MMM contained a large number of hydroxyl and aluminum functional groups due to resin being added. The MMM exhibited the best fluorine ion adsorption capacity of 2.502 mg/g at a pH of 6 with the initial concentration of 6 mg/L. As well, adsorption kinetics of fluorine ion on MMM followed the pseudo-second-order model, while the adsorption behavior of fluorine ion on MMM was well simulated by the Langmuir isotherm model. The adsorption capacity of MMM remained stable after six cycles and the regeneration efficiency was still above 80%, resulting in a long-term stability adequate for fluorine ion removal. Complexation and ion exchange played a key role in the fluorine ion adsorption of MMM. These results indicated the MMM as novel type of absorbent had an excellent capacity for removing fluoride. HIGHLIGHTS MMM was prepared via phase inversion for removing fluoride.; The addition of resin significantly enhanced fluoride removal via the membrane.; The MMM exhibited the maximum fluoride adsorption capacity of 2.502 mg/g.; Fluoride adsorption by MMM depended on ion-exchange and complexation.; MMM retained stable fluoride adsorption capacity after six cycles.;

Currently, comorbidities of obesity are becoming increasingly frequent. For example, obese women are more susceptible to reproductive diseases; however, the underlying mechanism remains poorly understood. The present study aimed to explore the effect of obesity on female reproduction and discuss changes of the lipid profile in ovarian granulosa cells. Fifty female mice were randomly divided into two groups, one group was fed high-fat diet, the other group was fed standard control diet, food and water freely. After 12 weeks of feeding, the average body weight of the high-fat diet mice (19.027g) was significantly higher than that of the standard control diet mice (36.877g) (P < 0.05). The tissue sections were stained with oil red O, and the online software mage Pro plus 6.0 analyzed the staining results, the lipids in the ovaries and endometria were found to be different between the two groups. Liquid chromatography-electrospray ionization with tandem mass spectrometry (LC-ESI-MS/MS) analysis of ovarian granulosa cells (GCs) was performed, with a total of 228 different lipids being identified, the abundant of 147 were increased and 81 were decreased in the high-fat diet group. Among them, PI (18:1/20:1) was the most different lipid, and high-fat feeding was 85 times higher than standard control group. Among these different lipids, 44% in phospholipid metabolism, 30% in glycerolipid metabolism, and 30% in fat digestion and absorption. The results of this study laid a theoretical foundation of the effects of diet-induced obesity on female reproduction.

Abstract Controlled‐release nitrogen fertilizer (CRNF) is expected to meet the nutrient demands for crop growth with single fertilizer application, so as to achieve high‐yield, high‐efficiency, and labor‐saving cultivation. However, under current CRNF practices, a single application of CRNF in winter wheat (Triticum aestivum L.) usually fails to achieve satisfactory effects due to insufficient nitrogen (N) supply in the later growth stage, contributing to premature leaf senescence and poor grain filling. To determine a reasonable CRNF application strategy for improving the grain weight and yield of winter wheat, the responses of leaf senescence, photosynthetic capacity, grain‐filling characteristics, and grain yield to different CRNF types [polymer‐coated urea (PCU), sulfur‐coated urea (SCU), and urea‐formaldehyde (UF)] and fertilization practices [single fertilization (P1) and twice‐split fertilization (P2)] were investigated. The results showed that, compared with P1, P2 increased the activities of catalase, peroxidase, and superoxide dismutase, alleviated the accumulation of malondialdehyde, delayed flag leaf senescence, and enhanced the net photosynthetic rate (Pn) of the flag leaves, which promoted assimilate accumulation and transport to the grains. These advantages in P2 improved the grain‐filling process of wheat, with the active filling duration (T), average filling rate (G), and maximum filling rate (Gmax) in P2 all being higher than those in P1, which significantly increased the 1000‐grain weight (TGW) and grain yield of wheat. Among the three CRNFs, PCU showed advantages in Pn at the milk‐ripe stage (Zadoks growth stage, GS75), dry matter accumulation post‐anthesis, T, Gmax, and G, which contributed to TGW and grain yield. Overall, our study suggested that the twice‐split application of CRNF could substantially delay leaf senescence post‐anthesis and increase photosynthetic capacity, thus improving grain filling and productivity in winter wheat.

Abstract Li‐ion batteries (LIBs) with excellent cycling stability and high‐energy densities have already occupied the commercial rechargeable battery market. Unfortunately, the high cost and intrinsic insecurity induced by organic electrolyte severely hinder their applications in large‐scale energy storage. In contrast, aqueous Zn‐ion batteries (ZIBs) are being developed as an ideal candidate because of their cheapness and high security. Benefiting from high operating voltage and acceptable specific capacity, recently, manganese‐based oxides with different various crystal structures have been extensively studied as cathode materials for aqueous ZIBs. This review presents research progress of manganese‐based cathodes in aqueous ZIBs, including various manganese‐based oxides and their zinc storage mechanisms. In addition, we also discuss some optimization strategies that aim at improving the electrochemical performance of manganese‐based cathodes, and the design of flexible aqueous ZIBs based on manganese‐based cathodes (MZIBs). Finally, this review summarizes some valuable research directions, which will promote the further development of aqueous MZIBs.

Summary: Flexible thermoelectric generators (f-TEGs) are promising solutions to power supply for wearable devices. However, the high fabrication costs and low output power density of conventional f-TEGs limit their applications. Here, we present a bulk-material-based f-TEG featuring multifunctional copper electrodes for heat concentration and dissipation and fabrics for comfort and heat-leakage reduction. When worn on the forehead, our f-TEG’s maximum output power density (based on the device’s area) reaches 48 μW/cm2 at a wind speed of 2 m/s and an ambient temperature of 15°C. A light-emitting diode (LED) powered by our f-TEG headband with 100 pairs of thermoelectric pillars can illuminate a paper for reading in a dark room at 17.5°C without an external heat sink or forced convection at the cold side. This work provides a general design approach for high-performance f-TEGs at a low cost. The device-level perspectives fill the critical knowledge gap between state-of-the-art material innovations and practical thermoelectric applications.

Cardiac fibrosis, a pathological condition due to excessive extracellular matrix (ECM) deposition in the myocardium, is associated with nearly all forms of heart disease. The processes and mechanisms that regulate cardiac fibrosis are not fully understood. In response to cardiac injury, macrophages undergo marked phenotypic and functional changes and act as crucial regulators of myocardial fibrotic remodeling. Here we show that the mitogen-activated protein kinase (MAPK) phosphatase-5 (MKP-5) in macrophages is involved in pressure overload-induced cardiac fibrosis. Cardiac pressure overload resulting from transverse aortic constriction (TAC) leads to the upregulation of Mkp-5 gene expression in the heart. In mice lacking MKP-5, p38 MAPK and JNK were hyperactivated in the heart, and TAC-induced cardiac hypertrophy and myocardial fibrosis were attenuated. MKP-5 deficiency upregulated the expression of the ECM-degrading matrix metalloproteinase-9 (Mmp-9) in the Ly6Clow (M2-type) cardiac macrophage subset. Consistent with in vivo findings, MKP-5 deficiency promoted MMP-9 expression and activity of pro-fibrotic macrophages in response to IL-4 stimulation. Furthermore, using pharmacological inhibitors against p38 MAPK, JNK, and ERK, we demonstrated that MKP-5 suppresses MMP-9 expression through a combined effect of p38 MAPK/JNK/ERK, which subsequently contributes to the inhibition of ECM-degrading activity. Taken together, our study indicates that pressure overload induces MKP-5 expression and facilitates cardiac hypertrophy and fibrosis. MKP-5 deficiency attenuates cardiac fibrosis through MAPK-mediated regulation of MMP-9 expression in Ly6Clow cardiac macrophages.

Polycyclic aromatic hydrocarbon (PAH) pollution in the soil of industrial legacy sites is a prominent problem when reusing urban land. To estimate the potential risks of PAHs, this study investigated 16 priority PAHs in the soil at different depths in a typical decommissioned industrial site in Tianjin. PAH concentrations were determined via gas chromatography-(tandem) quadrupole mass spectrometry. Incremental lifetime cancer risk (ILCR) assessment was applied to assess the potential risks to the population after land reconstruction. The total concentrations of PAHs in the soil at different depths ranged from 38.3 ng·g−1 to 1782.5 ng·g−1, which were below the risk control standard for soil contamination of development land (GB 36600-2018). Low-ring (two-three ring) PAHs exhibit a dominant component, and the variations in PAH compositions were closely related to the former production units and soil properties. Compared to silty clay layers, PAHs tended to accumulate in the permeable miscellaneous fill layers. Incremental lifetime cancer risk assessment values associated with different exposure pathways for children, adolescents, and adults were calculated. The results showed potential carcinogenic risks for people of varying ages in this area, but they were still acceptable. In general, this legacy site can meet the demands of sustainable land development.

Abstract Background The Hani people in the Honghe Prefecture of Southeastern Yunnan, China, have practiced terraced rice paddy farming for more than 1300 years. These rice fields, combined with the surrounding forests and water systems, form a special agroecosystem that has attracted both tourists and scientists. For centuries, the local people have traditionally collected wild edible plants (WEP) from the agroecosystem, but this unique traditional practice in this area has never been reported. Methods Ethnobotanical fieldwork was conducted in four counties (Yuanyang, Honghe, Jinping, and Lüchun) between 2014 and 2019. Local self-identified Hani people (186) were interviewed, and information concerning local WEP species was obtained, documented, and analyzed. Plant samples and voucher specimens were collected for taxonomic identification. Results A total of 224 WEP species, belonging to 90 families and 170 genera, were recorded as used by the Hani people in Honghe. The most common WEP parts used include fruits, stems, and leaves, and the most common preparation methods include eating as a potherb (wild vegetable) and eating fresh. Some WEPs, like Phyllanthus emblica and Dioscorea subcalva, have unique preparation methods. The use-value (UV) and frequency of utilization index (FUI) of WEP species were analyzed. The 20 WEP species with the highest UV were noted as particularly important to the Hani people’s daily life in Honghe. Conclusion A large majority of these WEP species possess tremendous economic potential for future development. However, the diversity of WEP species, the associated traditional knowledge, and the broader agroecosystem are facing challenges such as biodiversity loss and pollution from chemical pesticides and fertilizers. This study may help local people to recognize the value of local WEP species and associated traditional knowledge, as well as provide ethnobotanical information for the future development of this tourism region.

In this paper, we propose a novel method developed for detecting incomplete ship targets under cloud interference and low-contrast ship targets in thin fog based on superpixel segmentation, and outline its application to optical remote sensing images. The detection of ship targets often requires the target to be complete, and the overall features of the ship are used for detection and recognition. When the ship target is obscured by clouds, or the contrast between the ship target and the sea-clutter background is low, there may be incomplete targets, which reduce the effectiveness of recognition. Here, we propose a new method combining constant false alarm rate (CFAR) and superpixel segmentation with feature points (SFCFAR) to solve the above problems. Our newly developed SFCFAR utilizes superpixel segmentation to divide large scenes into many small regions which include target regions and background regions. In remote sensing images, the target occupies a small proportion of pixels in the entire image. In our method, we use superpixel segmentation to divide remote sensing images into meaningful blocks. The target regions are identified using the characteristics of clusters of ship texture features and the texture differences between the target and background regions. This step not only detects the ship target quickly, but also detects ships with low contrast and under cloud cover. In optical remote sensing, ships at sea under thin clouds are not common in practice, and the sample size generated is relatively small, so this problem is not applicable to deep learning algorithms for training, while the SFCFAR algorithm does not require data training to complete the detection task. Experiments show that the proposed SFCFAR algorithm enhances the detection of obscured ship targets under clouds and low-contrast targets in thin fog, compared with traditional target detection methods and as deep learning algorithms, further complementing existing ship detection methods.

Epigenetic modifications of the genome, including DNA methylation, histone methylation/acetylation, and noncoding RNAs, have been reported to play a fundamental role in regulating immune response during the progression of atherosclerosis. SETDB2 is a member of the KMT1 family of lysine methyltransferases, and members of this family typically methylate histone H3 Lys9 (H3K9), an epigenetic mark associated with gene silencing. Previous studies have shown that SETDB2 is involved in innate and adaptive immunity, the proinflammatory response, and hepatic lipid metabolism. Here, we report that expression of SETDB2 is markedly upregulated in human and murine atherosclerotic lesions. Upregulation of SETDB2 was observed in proinflammatory M1 but not antiinflammatory M2 macrophages. Notably, we found that genetic deletion of SETDB2 in hematopoietic cells promoted vascular inflammation and enhanced the progression of atherosclerosis in BM transfer studies in Ldlr-knockout mice. Single-cell RNA-Seq analysis in isolated CD45+ cells from atherosclerotic plaques from mice transplanted with SETDB2-deficient BM revealed a significant increase in monocyte population and enhanced expression of genes involved in inflammation and myeloid cell recruitment. Additionally, we found that loss of SETDB2 in hematopoietic cells was associated with macrophage accumulation in atherosclerotic lesions and attenuated efferocytosis. Overall, these studies identify SETDB2 as an important inflammatory cell regulator that controls macrophage activation in atherosclerotic plaques.

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.

Optimizing soil properties to match ecological conditions can alleviate stress damage and promote crop growth. However, the suitable soil conditions for wheat growth in an integrated rice–wheat breeding scheme under high rainfall and the mechanisms that affect yield production are not well known. Field experiments were carried out at two sites, which were all located in Jiangsu Province, China, a subtropical monsoon climate zone during two wheat growing seasons, to assess the effects of plow tillage followed by rotary tillage (PR) and no-tillage (NT) on soil physical and chemical properties, wheat seedling growth, grain yield, and spike amounts and quality. The finding indicates that with the reduction in soil mixing, soil bulk density was higher in NT than in PR, which helped to maintain moisture in dry soil. In soils with high water content, in NT, when the wheat field was subjected to waterlogging stress, the drainage decreased to deeper soil possibly due to reduced infiltration and a higher evaporation of surface water. The diurnal variation in soil temperature decreased in NT, and when the soil was cold, NT helped to insulate soils at 0–25 cm. Compared with PR, the contents of available nitrogen and phosphorus increased at 0–20 cm in NT. Root biomass and root activity of wheat seedlings at 0–20 cm were also greater in NT than in PR. Compared with PR, wheat also had more culms at the beginning of the overwintering stage, more spikes, and higher grain yield in NT, but the differences were not significant under excessive soil moisture. Therefore, the soil hydrothermal environment and spatial distributions of nutrients in NT promoted shallow root growth and tiller development in the early phase of wheat growth, which led to higher amounts of spikes per plant that resulted in high-yielding wheat crops.

Environmental conditions (precipitation, temperature and soil properties) differ greatly in different regions and have dual effects on the wheat growth and nutrient release of slow-release fertilizer (SRF). Conventional fertilization methods such as the multiple-split application of urea and the one-time application of SRF may have difficulty achieving a stable and high wheat yield and nitrogen (N) efficiency in various environments. Therefore, the exploration of a rational application strategy of SRF is needed for improving wheat yield and its stability in different regions. A two-year field experiment was conducted in different regions (eight test sites per year) with five patterns: 100% N (270 kg ha−1) SRF applied pre-sowing (M1); 60% N SRF applied pre-sowing and 40% N urea applied at jointing (M2); 60% N SRF applied pre-sowing and 40% N SRF applied at re-greening (M3); M2 reducing the N rate by 15% (M4); M3 reducing the N rate by 15% (M5). The fourth-split application of urea was taken as the control (CK, 270 kg N ha−1). The results suggested that the average yield in M1 decreased by 3.65% of the CK, and the yield stability was poor. Both M2 and M3 significantly increased N efficiency, grain yield and benefit, but the stability of M3 was higher than that of M2 in different environments. Considering further improvements in wheat yield, N efficiency and profit, our results suggested that the twice-split application of SRF, which also improved the adaptability of wheat in different environments, could be recommended for wheat cultivation.

Global warming has changed the suitability of areas traditionally planted with crops, raising concerns about cereal security. To investigate the possibilities and constraints of increasing yields by breaking through traditional area plantings of wheat cultivars, a two-year field experiment was conducted in southern and northern locations in the Yangtze River basin (YRB), China (separated by approximately 180 km), with seven weak-winter types and six semi-winter types, respectively, bred for the two regions. The movement of weak-winter-type cultivars to the north increased or did not change grain yield and their grain yields were not significantly higher than those of local semi-winter-type cultivars. The movement of semi-winter-type cultivars to the south significantly decreased their yields. Thus, breaking through traditional area plantings did not significantly increase grain yields compared with those of local wheat cultivars. Grain yield of wheat planted in the northern YRB was higher by 5 to 20% than that in the southern YRB because of an increase in spikes that resulted from a longer spike formation phase. In addition, the post-anthesis leaf area declined more slowly in the northern YRB because of higher main stem and tiller survival. High-yielding cultivars always had more spikes and larger photosynthetic areas after anthesis than those of low-yielding cultivars regardless of the planting locations, which led to increases in post-anthesis biomass. However, the grain yield of different cultivars was highly variable under different environmental conditions. The coefficient of variation (CV) of grain yield in different cultivars was significantly positively correlated with the CV of spike number and post-anthesis biomass, implying that flexibility spike number and post-anthesis biomass in response to environmental changes can maximize release of yield potential. Therefore, improving main stem and tiller survival can increase spike number and maintain post-anthesis photosynthetic areas and help to establish a large, highly stable, and productive population with a high level of suitability and production through effectively utilizing the resources during the late growth phase. Valuable suggestions for breeding high-yield and -stability cultivars and confirming their planting range in the future are given.

Background/Aims: Abdominal obesity is recognized as the main reason of metabolic syndrome, which is closely related to disordered skeletal and/or abdominal muscle metabolic functions. Metabolomics is a comprehensive assessment system in biological metabolites. The aim of our present study is to investigate the diet-induced metabolic risk factors by metabolic in the abdominal muscles and clarify the relationship between atheroprotective effects of Resveratrol (Rev) and abdominal muscles metabolic components during the development of atherosclerosis. Methods: The mice were randomly divided into three groups including normal group (N), high fat diet (HFD or H) group and high fat diet with Rev treated group (HR). GC-MS combined with pattern recognition approaches were employed to obtain comprehensive metabolic signatures and related differential metabolites after 24 week HFD feeding. Oil Red O staining and Electron microscopy technology (EMT) were employed to detect the size of fatty plaques and intracellular lipid accumulation, respectively. Results: The result indicated that 22 types of metabolites in the abdominal muscles were obviously altered by HFD feeding group. Moreover, Rev treatment obviously increased 11 different kinds of metabolites, most of which were involved in the carbohydrate, amino acid and lipid metabolisms. Importantly, these elevated different metabolites were involved in pathways mainly related to galactose metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism in abdominal muscles. Oil Red O staining and Electron microscopy showed less lipid accumulation in the lesions and decreased intracellular lipid deposition in the foam cells in HR group. Conclusions: We concluded that Rev produced a beneficial effect partially by modulating multiple metabolism pathways and metabolites in the abdominal muscles, which may provide a new protective mechanism of Rev on the progression of atherosclerosis. These notably changed metabolites might be potential biomarkers or therapeutic targets during development of metabolic syndrome and atherosclerosis.

Abiotic stresses, such as heat, salt, waterlogging, and multiple-stress environments have significantly reduced wheat production in recent decades. There is a need to use effective strategies for overcoming crop losses due to these abiotic stresses. Fertilizer-based approaches are readily available and can be managed in all farming communities. This research revealed the effects of sulfur-coated urea (SCU, 130 kg ha−1, release time of 120 days) on wheat crops under heat, salt, waterlogging, and combined-stress climatic conditions. The research was done using a completely randomized design with three replicates. The results revealed that SCU at a rate of 130 kg of N ha−1 showed a significantly (p ≤ 0.05) high SPAD value (55) in the case of waterlogging stress, while it was the lowest (31) in the case of heat stress; the control had a SPAD value of 58. Stress application significantly (p ≤ 0.05) reduced the leaf area and was the highest in control (1898 cm2), followed by salt stress (1509 cm2), waterlogging (1478 cm2), and heat stress (1298 cm2). A significantly (p ≤ 0.05) lowest crop yield was observed in the case of heat stress (3623.47 kg ha−1) among all stresses, while it was 10,270 kg ha−1 in control and was reduced up to 35% after the application of heat stress. Among all stresses, the salt stress showed the highest crop yield of 5473.16 kg ha−1. A significant correlation was observed among growth rate, spike length, yield, and physiological constraints with N content in the soil. The SCU fertilizer was the least effective against heat stress but could tolerate salt stress in wheat plants. The findings suggested the feasibility of adding SCU as an alternative to normal urea to alleviate salt stresses and improve wheat crop growth and yield traits. For heat stress tolerance, the applicability of SCU with a longer release period of ~180 days is recommended as a future prospect for study.

The development of crop cultivars with high nitrogen use efficiency (NUE) under low-N fertilizer inputs is imperative for sustainable agriculture. However, there has been little research on the molecular mechanisms underlying enhanced resilience to low N in high-NUE plants. The comparison of the transcriptional responses of genotypes contrasting for NUE will facilitate an understanding of the key molecular mechanism of wheat resilience to low-N stress. In the current study, the RNA sequencing (RNA-seq) technique was employed to investigate the genotypic difference in response to N deficiency between two wheat NILs (1Y, high-NUE, and 1W, low-NUE). In our research, high- and low-NUE wheat NILs showed different patterns of gene expression under N-deficient conditions, and these N-responsive genes were classified into two major classes, including “frontloaded genes” and “relatively upregulated genes”. In total, 103 and 45 genes were identified as frontloaded genes in high-NUE and low-NUE wheat, respectively. In summary, our study might provide potential directions for further understanding the molecular mechanism of high-NUE genotypes adapting to low-N stress.

Nitrogen (N) is an essential nutrient element for crop productivity. Unfortunately, the nitrogen use efficiency (NUE) of crop plants gradually decreases with the increase of the N application rate. Nevertheless, little has been known about the molecular mechanisms of differences in NUE among genotypes of wheat. In this study, we used RNA-Sequencing (RNA-Seq) to compare the transcriptome profiling of flag leaves at the stage of anthesis in wheat NILs (1Y, high-NUE, and 1W, low-NUE) under normal nitrogen conditions (300 kg N ha−1, corresponding to 1.6 g N pot−1). We identified 7023 DEGs (4738 upregulated and 2285 downregulated) in the comparison between lines 1Y and 1W. The responses of 1Y and 1W to normal N differed in the transcriptional regulatory mechanisms. Several genes belonging to the GS and GOGAT gene families were upregulated in 1Y compared with 1W, and the enhanced carbon metabolism might lead 1Y to produce more C skeletons, metabolic energy, and reductants for nitrogen metabolism. A subset of transcription factors (TFs) family members, such as ERF, WRKY, NAC, and MYB, were also identified. Collectively, these identified candidate genes provided new information for a further understanding of the genotypic difference in NUE.

Summary: As an important regulator of macrophage cholesterol efflux and HDL biogenesis, miR-33 is a promising target for treatment of atherosclerosis, and numerous studies demonstrate that inhibition of miR-33 increases HDL levels and reduces plaque burden. However, important questions remain about how miR-33 impacts atherogenesis, including whether this protection is primarily due to direct effects on plaque macrophages or regulation of lipid metabolism in the liver. We demonstrate that miR-33 deficiency in Ldlr−/− mice promotes obesity, insulin resistance, and hyperlipidemia but does not impact plaque development. We further assess how loss of miR-33 or addition of miR-33b in macrophages and other hematopoietic cells impact atherogenesis. Macrophage-specific loss of miR-33 decreases lipid accumulation and inflammation under hyperlipidemic conditions, leading to reduced plaque burden. Therefore, the pro-atherogenic effects observed in miR-33-deficient mice are likely counterbalanced by protective effects in macrophages, which may be the primary mechanism through which anti-miR-33 therapies reduce atherosclerosis. : miR-33a and miR-33b, the miR-33 family of miRNAs, are important regulators of reverse cholesterol transport and atherosclerosis. Price et al. have developed genetic models to explore the specific roles of miR-33a and miR-33b in atherosclerotic plaque formation. Their findings highlight both the utility and potential issues involved in anti-miR-33 therapies. Keywords: Atherosclerosis, miR-33, HDL-C, metabolism, cholesterol

Abstract Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. Here, we define the contribution of miR‐21 in hematopoietic cells during atherogenesis. Interestingly, we found that miR‐21 is the most abundant miRNA in macrophages and its absence results in accelerated atherosclerosis, plaque necrosis, and vascular inflammation. miR‐21 expression influences foam cell formation, sensitivity to ER‐stress‐induced apoptosis, and phagocytic clearance capacity. Mechanistically, we discovered that the absence of miR‐21 in macrophages increases the expression of the miR‐21 target gene, MKK3, promoting the induction of p38‐CHOP and JNK signaling. Both pathways enhance macrophage apoptosis and promote the post‐translational degradation of ABCG1, a transporter that regulates cholesterol efflux in macrophages. Altogether, these findings reveal a major role for hematopoietic miR‐21 in atherogenesis.

Atherosclerosis is caused by low-density lipoprotein (LDL) buildup in the vessel wall, a process thought to be mediated by LDL receptor alone. Here, the authors show that the endothelium can uptake LDL via ALK1, a TGFβ signalling receptor, suggesting new therapies for blocking LDL accumulation in the vessel wall.

Seminal studies from Nikolai Anichckov identified the accumulation of cholesterol in the arteries as the initial event that lead to the formation of atherosclerotic plaques. Further studies by Gofman and colleagues demonstrated that high levels of circulating low-density lipoprotein cholesterol (LDL-C) was responsible for the accelerated atherosclerosis observed in humans. These findings were confirmed by numerous epidemiological studies which identified elevated LDL-C levels as a major risk factor for cardiovascular disease. LDL infiltrates in the arterial wall and interacts with the proteoglycan matrix promoting the retention and modification of LDL to a toxic form, which results in endothelial cell (EC) activation and vascular inflammation. Despite the relevance of LDL transport across the endothelium during atherogenesis, the molecular mechanism that control this process is still not fully understood. A number of studies have recently demonstrated that low density lipoprotein (LDL) transcytosis across the endothelium is dependent on the function of caveolae, scavenger receptor B1 (SR-B1), activin receptor-like kinase 1 (ALK1), and LDL receptor (LDLR), whereas high-density lipoproteins (HDL) and its major protein component apolipoprotein AI transcytose ECs through SR-B1, ATP-Binding cassette transporter A1 (ABCA1) and ABCG1. In this review article, we briefly summarize the function of the EC barrier in regulating lipoprotein transport, and its relevance during the progression of atherosclerosis. A better understanding of the mechanisms that mediate lipoprotein transcytosis across ECs will help to develop therapies targeting the early events of atherosclerosis and thus exert potential benefits for treating atherosclerotic vascular disease.

In this research contribution, nano-aggregates have been fabricated by introducing lanthanide (Ln3+) ions into solutions of amphiphilic diblock copolymers of polystyrene-b-poly (acrylic acid) (PS-b-PAA). The coordination of acrylic acid segments to lanthanide cations induces diblock copolymer (BCPs) self-assembly in order to design stable white luminescent hybrid nanoparticles with fine uniform particle size. The introduction of Ln3+ ions (Eu3+ and Tb3+) bestows the micelles, precisely white light, upon excitation of 342 nm. Lanthanide coordination cross-linking of poly (acrylic acid) segments, or blocks, endows the micelles higher thermal stability than that of BCPs micelles without cross-linking. As the most important key point of this work, the regular and stable nano-particles with high emission quality can make fully flexible electroluminescent devices with self-formation or uncoordinated into polymer hosts. Instead of inorganic luminescent nanoparticles with hard cores, this method can potentially apply for fully flexible white-light emitting diodes (FFWLEDs).

Maintenance of normal endothelial function is critical to various aspects of blood vessel function, but its regulation is poorly understood. In this study, we show that disruption of baseline fibroblast growth factor (FGF) signaling to the endothelium leads to a dramatic reduction in let-7 miRNA levels that, in turn, increases expression of transforming growth factor (TGF)-β ligands and receptors and activation of TGF-β signaling, leading to endothelial-to-mesenchymal transition (Endo-MT). We also find that Endo-MT is an important driver of neointima formation in a murine transplant arteriopathy model and in rejection of human transplant lesions. The decline in endothelial FGF signaling input is due to the appearance of an FGF resistance state that is characterized by inflammation-dependent reduction in expression and activation of key components of the FGF signaling cascade. These results establish FGF signaling as a critical factor in maintenance of endothelial homeostasis and point to an unexpected role of Endo-MT in vascular pathology.

The previous studies in our laboratory revealed that seven cysteine mutants of apolipoprotein A-I (apoA-I) have different structural features and biological activities in vitro and in vivo. To investigate the potential cardioprotective effects of apolipoprotein A-I(N74C) [apoA-I(N74C)], we examined the anti-inflammatory, antioxidant, and antiatherosclerotic effects of this cysteine mutant in a rapid atherosclerosis model induced by perivascular carotid collar placement in apoE−/− mice. Lipid-free apoA-I(N74C) showed a significant increased antioxidant potency in low density lipoprotein (LDL) oxidation in vitro and reduced intracellular lipid accumulation in THP-1-derived macrophages, relative to wild-type apoA-I (apoA-Iwt). Mice injected with recombinant HDL (rHDL) reconstituted with apoA-I(N74C) (named rHDL74) through tail veins (40 mg/kg of body weight, three injections) had a significant lower level of serum interleukin-6 (IL-6) and enhanced serum antioxidation compared with mice receiving rHDL reconstituted with apoA-Iwt (named rHDLwt). Moreover, compared with rHDLwt, the rHDL74 in vivo injection resulted in a significant decrease in plaque size, ratio of aorta intima to media, arterial remodeling, and macrophage content in lesions. In summary, intravenous injection with rHDL74 reconstituted with apoA-I cysteine mutant apoA-I (N74C) dramatically delays the development of atherosclerosis induced by perivascular carotid collar placement and reduces vascular remodeling in the carotid artery in apoE−/− mice.

Energetic structural material is a kind of materials that are inert under normal conditions but could produce exothermic chemical reaction when subjected to impact. This report shows a kind of energetic structural material of tungsten (W)-polytetrafluoroethylene (PTFE)-aluminum (Al) with density of 4.12 g/cm3, excellent ductility and dynamic compressive strength of 96 MPa. Moreover, 50W-35PTFE-15Al (wt%) can exhibit a high reaction energy value of more than 2 times of TNT per unit mass and 5 times of TNT per unit volume, respectively, but with excellent insensitivity compared with traditional explosives. Under thermal conditions, the W-PTFE-Al composite can keep stable at 773 K. Under impact loading, when the strain rate up to ∼4820 s−1 coupled with the absorbed energy per unit volume of 120 J/cm3, deflagration occurs and combustion lasts for 500 μs. During impact compressive deformation, the PTFE matrix is elongated into nano-fibers, thus significantly increases the reaction activity of W-PTFE-Al composites. The nano-fiber structure is necessary for the reaction of W-PTFE-Al composites. The formation of PTFE nano-fibers must undergo severe plastic deformation, and therefore the W-PTFE-Al composites exhibit excellent insensitivity and safety. Furthermore, the reaction mechanisms of W-PTFE-Al composites in argon and in air are revealed.

Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS) in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/-)) is associated with activation of the platelet derived growth factor (PDGF) signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/-) mice. Moreover, nitric oxide (NO) negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

Bisbenzimides, or Hoechst 33258 (H258), and its derivative Hoechst 33342 (H342) are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects. For example, H342, but not H258, is a potent apoptotic inducer and both H342 and H258 can induce transgene overexpression in in vitro studies. However, the molecular mechanisms by which Hoechst dyes induce apoptosis and enhance transgene overexpression are unclear.To determine the molecular mechanisms underlying different biological effects between H342 and H258, microarray technique coupled with bioinformatics analyses and multiple other techniques has been utilized to detect differential global gene expression profiles, Hoechst dye-specific gene expression signatures, and changes in cell morphology and levels of apoptosis-associated proteins in malignant mesothelioma cells. H342-induced apoptosis occurs in a dose-dependent fashion and is associated with morphological changes, caspase-3 activation, cytochrome c mitochondrial translocation, and cleavage of apoptosis-associated proteins. The antagonistic effect of H258 on H342-induced apoptosis indicates a pharmacokinetic basis for the two dyes' different biological effects. Differential global gene expression profiles induced by H258 and H342 are accompanied by unique gene expression signatures determined by DNA microarray and bioinformatics software, indicating a genetic basis for their different biological effects.A unique gene expression signature associated with H342-induced apoptosis provides a new avenue to predict and classify the therapeutic class of minor groove binders in the drug development process. Further analysis of H258-upregulated genes of transcription regulation may identify the genes that enhance transgene overexpression in gene therapy and promote recombinant protein products in biopharmaceutical companies.The microarray data reported in this article have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no.GSE28616).