Abstract Background Death‐associated protein kinase 1 (DAPK1) is a serine/threonine kinase that plays an important role in regulating neuronal function and is genetically linked to Alzheimer’s disease (AD). We previously showed that DAPK1 expression is markedly increased in 75% of human AD brains. Moreover, we found that DAPK1 promotes tau protein accumulation and its phosphorylation at multiple AD‐related sites. However, it is not known whether and how DAPK1 expression or activity is regulated in AD, including tau hyperphosphorylation and functions. Method We investigated the effects of melatonin on DAPK1 regulation by examining DAPK1 protein stability, and tau hyperphosphorylation and functions using comprehensive approaches in cell culture models, ex vivo mouse models, and human patient tissues. We synthesized biotin‐melatonin to demonstrate direct binding of melatonin and DAPK1. Moreover, we assessed the correlation of melatonin‐regulated DAPK1 expression and Pin1 phosphorylation because DAPK1 increases tau hyperphosphorylation through inhibiting the catalytic activity of Pin1. Result We discovered that melatonin critically regulates DAPK1 by reducing its protein stability, thereby attenuating tau hyperphosphorylation in AD. Melatonin decreases DAPK1 expression in a dose‐ and time‐dependent manner in primary neurons and neuronal cell lines. Moreover, the regulation of DAPK1 by melatonin is not dependent on DAPK1 transcription because DAPK1 mRNA levels are not affected by melatonin. Melatonin promotes the ubiquitination of DAPK1 and decreases its protein stability through a proteasome‐dependent pathway. Furthermore, melatonin directly interacts with the ankyrin repeat domain of DAPK1. Inhibition of DAPK1 by melatonin and a pharmacological DAPK1 inhibitor synergistically reduces tau expression and phosphorylation at multiple AD‐related sites. Melatonin and a DAPK1 inhibitor promote neurite outgrowth and microtubule assembly, which are disrupted by tau hyperphosphorylation. Mechanistically, melatonin‐mediated DAPK1 degradation increases the activity of Pin1, a prolyl isomerase known to play a protective role against tau hyperphosphorylation and AD. Finally, DAPK1 and melatonin levels are inversely correlated in the brains of human AD patients. Conclusion Our study demonstrates a novel role of melatonin in the direct regulation of DAPK1, and that synergistic targeting of DAPK1 by melatonin and DAPK1 inhibitors offers an attractive approach to block tau hyperphosphorylation in AD.
Atmospheric aerosols can alter the direct and diffuse components of global solar radiation, which further influences terrestrial gross primary productivity (GPP) via photosynthesis. To investigate the impact of aerosols on GPP, GPP is modeled using the Boreal Ecosystem Productivity Simulator (BEPS) under two aerosol scenarios (S1& S2) over cropland and grassland ecosystems in the highly polluted North China. In S1, the aerosol-effect is not considered and an original empirical method is used when estimating direct and diffuse solar radiation in BEPS. In S2, BEPS is improved by a new empirical method which incorporates the impact of aerosols using the remote sensing-based aerosol optical depth (AOD). Results suggest that aerosols can reduce GPP of the sunlit leaves by decreasing direct solar radiation, but increase GPP of the shaded leaves by increasing diffuse solar radiation. The impact of aerosols on GPP is more significant over the cropland ecosystem (p < 0.05) with a more complex canopy structure during the peak period of the growing season. Furthermore, an AOD value of 0.3–0.6 with a diffuse fraction (the fraction of diffuse solar radiation in global solar radiation) around 30-40% can largely increase total GPP over the cropland ecosystem. The study improves the accuracy of GPP modeling using BEPS by highlighting the aerosol-effect on GPP via solar radiation over highly polluted regions.Abbreviations: gross primary productivity (GPP); aerosol optical depth (AOD); boreal ecosystem productivity simulator (BEPS)
An ideal situation for conducting change detection is to use multi-temporal images acquired from the same sensor. However, many conditions (such as the discontinuity of sensors, weather conditions) would bring an end to the ideal temporal change detection. Imagery availability issues will force change detection studies in the future to increasingly incorporate multiple sensors. This study conducted change detection between Landsat TM (TM) and Landsat MSS (MSS) images from July 30, 1995 to June 2, 2003. The study area was centered on the Greater Toronto Area (GTA) in south-central Ontario, Canada. Post-classification change detection was used to determine the type of change between the images. Results demonstrated that despite the different spatial resolution of the MSS and TM data, the change detection using both MSS and TM was similar in results to that of TM alone. A change detection where MSS is resampled to 30 meters was most effective in capturing the amount and type of change in the TM change study.
A review on nanosystems as an effective approach against infections of Staphylococcus aureus Kaixiang Zhou,1 Chao Li,1 Dongmei Chen,2 Yuanhu Pan,1 Yanfei Tao,2 Wei Qu,2 Zhenli Liu,2 Xiaofang Wang,3 Shuyu Xie1 1MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, Hubei, China; 3Animal Husbandry and Veterinary Institute of Hebei Province, Baoding, Hebei, China Abstract: Staphylococcus aureus (S. aureus) is an important zoonotic bacteria and hazardous for the health of human beings and livestock globally. The characteristics like biofilm forming, facultative intracellular survival, and growing resistance of S. aureus pose a great challenge to its use in therapy. Nanoparticles are considered as a promising way to overcome the infections’ therapeutic problems caused by S. aureus. In this paper, the present progress and challenges of nanoparticles in the treatment of S. aureus infection are focused on stepwise. First, the survival and infection mechanism of S. aureus are analyzed. Second, the treatment challenges posed by S. aureus are provided, which is followed by the third step including the advantages of nanoparticles in improving the penetration and accumulation ability of their payload antibiotics into cell, inhibiting S. aureus biofilm formation, and enhancing the antibacterial activity against resistant isolates. Finally, the challenges and future perspective of nanoparticles for S. aureus infection therapy are introduced. This review will help the readers to realize that the nanosystems can effectively fight against the S. aureus infection by inhibiting biofilm formation, enhancing intracellular delivery, and improving activity against methicillin-resistant S. aureus and small colony variant phenotypes as well as aim to help researchers looking for more efficient nanosystems to combat the S. aureus infections. Keywords: Staphylococcus aureus, infection mechanism, resistance, antibiotics, nanoparticles
Abstract The quantitative knowledge of global forest litterfall is very important for understanding the global biogeochemical cycle and evaluating of forest ecosystem services. Our aims are to show the spatio‐temporal patterns of forest litterfall and the variation in different forest types and climate zones in the world. We compiled the global forest litterfall dataset of 2347 total litterfall and 1507 leaf litterfall measurements by a survey of literature published. The total litterfall and leaf litterfall were estimated in 2000 and 2009, respectively, through raster and vector calculation based on remote sensing‐based global vegetation cover data. The total litterfall and leaf litterfall were 31.5 Pg and 22 Pg in 2000 and 26 Pg and 18 Pg in 2009, respectively. The spatial pattern of litterfall and leaf litterfall at global scale between 2000 and 2009 was generally similar. The largest fractions of forest litterfall were in evergreen broadleaved forests (37%), followed by needle‐leaved forests (25%), deciduous broadleaved forests (20%), and others (18%) in 2000. The order of the fractions for forest litterfall was the tropical (50%), boreal (24%), temperate (17%), and subtropical forests (9%) in 2000. The ratios of leaf litterfall to litterfall were 70% in 2000 and 72% in 2009. The variability of global litterfall was most explained by the actual evapotranspiration. The reduction in total litterfall and leaf litterfall between 2000 and 2009 was coupled with the decrease in forest areas. The GIS ‐based geostatistics combining with the regression model represents a powerful approach for estimating the global spatial distribution, composition, and magnitude of litterfall.
Detailed land cover change in multitemporal images is an important application for earth science. Many techniques have been proposed to solve this problem in different ways. However, accurately identifying changes still remains a challenge due to the difficulties in describing the characteristics of various change categories by using single-level features. In this article, a multilevel feature representation framework was designed to build robust feature set for complex change detection task. First, four different levels of information from low level to high level, including pixel-level, neighborhood-level, object-level, and scene-level features, were extracted. Through the operation of extracting different level features from multitemporal images, the differences between them can be described comprehensively. Second, multilevel features were fused to reduce the dimension and then used as the input for supervised change detector with initial limited labels. Finally, for reducing the labeling cost and improving the change detection results simultaneously, active learning was conducted to select the most informative samples for labeling, and this step together with the previous steps were iteratively conducted to improve the results in each round. Experimental results of three pairs of real remote sensing datasets demonstrated that the proposed framework outperformed the other state-of-the-art methods in terms of accuracy. Moreover, the influences of scene scale for high-level semantic features in the proposed approach on change detection performance were also analyzed and discussed.
Abstract Purpose To investigate the efficacy and safety of continuous blood purification (CBP) in neonates with septic shock and acute kidney injury (AKI). Methods A retrospective study was conducted in two tertiary care children's hospitals between January 2015 and May 2022. Results In this study, 26 neonates with septic shock and AKI were included with a mortality of 50%. Fourteen neonates (53.8%) received continuous veno-venous hemodiafiltration, while 12 (46.2%) received continuous veno-venous hemofiltration. Compared with the indexes before CBP, urine output increased 12h after CBP initiation ( P = 0.003), and serum creatinine decreased ( P = 0.019). After 24h of CBP, blood urea nitrogen had decreased ( P = 0.006), and mean arterial pressure had increased ( P = 0.007). At the end of CBP, vasoactive inotropic score and blood lactate were decreased ( P = 0.035 and 0.038), and PH was increased ( P = 0.015). The most common complication of CBP was thrombocytopenia, and univariate analysis identified no risk factors for CBP-related death. Conclusion CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. However, the mortality remains high, and whether CBP improves the prognosis of neonates with septic shock and AKI remains unclear.
Abstract Objective : To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge and evaluate the occurrence and risk factors of extrauterine growth retardation (EUGR). Methods : The clinical data of VPI with SGA were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. They were divided into the EUGR group and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < –1.28. Results : This study included 133 eligible VPI with SGA. Following the criterion for the weight at discharge as the 10 th percentile of the Fenton curve, the incidence of EUGR was found to be 98.50% (131/133), and following the criterion of ΔZ value of weight at discharge < –1.28, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-minute Apgar score, and the proportion of male infants in the EUGR group were lower than those in the non-EUGR group ( P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group than those in the non-EUGR group ( P < 0.05). The time to start enteral feeding, the quantity of milk added with human milk fortifier (HMF), the time to reach full fortification, the cumulative fasting time, the time to reach full enteral feeding, the duration of parenteral nutrition (PN), days to reach the target total calorie intake and oral calorie intake (both 110 kcal/kg/d), and the age of recovering birth weight in the EUGR group were significantly higher than that in the non-EUGR group ( P < 0.05). The average weight gain velocity (GV) was significantly lower in the EUGR group than that in the non-EUGR group ( P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) ³ stage 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were significantly higher than that in the non-EUGR group ( P < 0.05). Multivariate logistic regression analysis showed that birth weight, sex (male), and GV were the protective factors for EUGR, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC ³ stage 2 were the independent risk factors. Conclusion : SGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge than using the p-value of weight. Strengthening enteral nutrition support, achieving full breast milk fortification more earlier increasing GV, shortening the recovery time of birth weight, and avoiding NEC can effectively reduce the incidence of EUGR.
196 Background: Cancer survivors often experience substantial psychological distress, such as anxiety and depression, due to cancer diagnosis and treatment. As psychological support is still not a standard part of survivorship care in China, little is known about Chinese oncologists’ attitudes towards referring cancer survivors to this service. Methods: We conducted a cross-sectional survey among oncologists who were attending the 18 th annual meeting of Chinese Society of Clinical Oncology (CSCO, September 16 th - 20 th 2015) in Xiamen, China. Participants voluntarily completed a questionnaire measuring their demographics and occupational information. The outcome variable was willingness to refer cancer survivors to psychological support. We used a multivariate logistic regression model to evaluate the factors associated with such willingness. Results: Among 351 responders, 53% were male, with a mean age of 38±9 years. Half of the oncologists were senior attendings, 34% were junior attendings, and 17% were residents. More than half of the physicians (58%) had an additional Masters or PhD degree. The majority of oncologists (263, 79%) were willing to refer their patients to psychological support as part of survivorship care. Physicians over 40 years old were more likely to recommend psychological support than their younger colleagues (85% versus 76%, p = 0.048). In multi-variable logistic regression model, controlled by gender and education level, physicians > 40 years were associated with more willingness to refer their patients to psychological support than physicians ≤ 40 years (odds ratio [OR] 2.9, 95% confidential interval [C.I.]1.4-6.1, p= 0.01); compared to residents, junior attendings were more likely to recommend psychological support (OR 2.8, 95% C.I. 1.1-7.1, p= 0.03). Conclusions: The majority of Chinese oncologists were willing to refer cancer survivors for psychological support; age and position appeared to impact such willingness. By further educating young Chinese oncologists about the importance of psychological care during survivorship, we can help develop a health care delivery system that better meets Chinese cancer survivors’ psychosocial needs.
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