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Background: To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion. Method: This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization. Results: A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days–6.0 days vs. median=5.0 days, IQR: 3.0 days–8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3–2.0 mmol/L vs. median=0.0 mmol/L, IQR: −0.2 to 0.8 mmol/L, respectively; P

Long historical records and free accessibility have made Landsat data valuable for time-series analysis. However, Landsat time-series analysis is restricted for coastal areas due to the lack of sufficient numbers of clear images. The generation of synthetic Landsat images using model-fitting methods is accepted as an effective means of overcoming this problem. But for coastal areas, available observations are typically sparse and irregular, leading to ill-fitted models that distort synthetic Landsat images. In this study, we propose a linear harmonic model with different orders and implement it on an annual basis to generate synthetic Landsat images based on the Google Earth Engine (GEE) platform. First, we incorporated the available observations from adjacent years and filtered them by season to address the problems of data sparsity and irregularity. Then, we combined the threshold segmentation and ridge regression approaches to address the fake cloud problem, which sometimes contaminates synthetic Landsat images in summer. All cloud-free real Landsat images from five typical sites along China’s coasts during 1986–2020 were used to evaluate the accuracy and robustness of the synthetic Landsat images generated using our proposed methods. The principal results are as follows: (1) the R2 value of the linear harmonic model averaged across different Landsat bands and land cover types was 0.640, and the model was especially successful in simulating the surface reflectance in near NIR bands in forest and grassland areas; (2) 81.1% of the synthetic Landsat images covered by fake clouds were effectively restored, and there was the particular need to remove fake clouds for the synthetic Landsat images at low latitudes; (3) The mean absolute error for our synthetic Landsat images was 0.015, with the rate of 0.124; this was achieved under the clear-sky probability of only 36% and the average number of annual observations below 9, indicating a good performance. Compared with the continuous change detection and classification (CCDC) and seasonal median composite (SMC) methods, our proposed method offers advantages in both the accuracy and integrity of synthetic Landsat images. Our proposed method for synthesizing images also has potential for application to global coastal areas and other satellite datasets.

Abstract Prior research has identified associations between immune cells and aplastic anaemia (AA); however, the causal relationships between them have not been conclusively established. A two-sample Mendelian randomisation analysis was conducted to investigate the causal link between 731 immune cell signatures and AA risk using publicly available genetic data. Four types of immune signatures, including relative cell, absolute cell (AC), median fluorescence intensities and morphological parameters, were considered sensitivity analyses were also performed to verify the robustness of the results and assess potential issues such as heterogeneity and horizontal pleiotropy. Following multiple test adjustments using the False Discovery Rate (FDR) method, no statistically significant impact of any immunophenotype on AA was observed. However, twelve immunophenotypes exhibited a significant correlation with AA without FDR correction (p of IVW

Abstract Solar-driven atmospheric water extraction (SAWE) is a sustainable technology for decentralized freshwater supply. However, most SAWE systems produce water intermittently due to the cyclic nature, with adoption hindered by complex design requirements or periodic manual operations. Herein, a fully passive SAWE system that can continuously produce freshwater under sunlight is presented. By optimizing the three-dimensional architecture to facilitate spontaneous mass transport and efficient energy utilization, this system can consistently produce 0.65 L m−2 h−1 of freshwater under 1-sun illumination at 90% relative humidity (RH) and functions in arid environments with an RH as low as 40%. We test the practical performance of a scaled-up system in Thuwal, Saudi Arabia over 35 days across two seasons. The system produces 2.0–3.0 L m−2 per day of freshwater during the summer and 1.0–2.8 L m−2 per day of freshwater during the fall, without requiring additional maintenance. Intriguingly, we demonstrate the system’s potential for off-grid irrigation by successfully growing cabbage plants using atmospheric water. This passive SAWE system, harnessing solar energy to continuously extract moisture from air for drinking and irrigation, offers a promising solution to address the intertwined challenges of energy, water, and food supply, particularly for remote and water-scarce regions.

BackgroundThe prevalence of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has an upward trend in sepsis patients and can be associated with poor outcomes. Thyroid hormones are expected to be correlated with inflammation, immunity, and metabolism. Thus, the purpose of this study was to evaluate the effect of thyroid hormones on the occurrence of PICS and then further explore the optimal level of them in sepsis.MethodsThis retrospective observational study used the online database Medical Information Mart for Intensive Care (MIMIC)-IV. Univariate and multivariate logistic regression analyses were employed to determine correlations between thyroid hormone levels and PICS. A combination of independent PICS development factors was established with accuracy assessed using the area under the receiver operating characteristic curve (AUC-ROC).ResultsPatients were divided into PICS (n=205) and non-PICS (n=671) groups. The third quartiles of triiodothyronine (T3) (60-80ng/dl) and thyroxine (T4) (5.5-6.8ug/dl) had the lowest PICS incidence and the adjusted odds ratio (OR) was 0.33 (T3, p=0.009) and 0.39 (T4, p=0.006), respectively, compared with the first quartiles of T3 and T4. For patients with a pre-existing T3 deficiency, severe deficiency (T3

BackgroundIn recent years, septic shock remains a common fatal disease in the intensive care unit (ICU). After sufficient fluid resuscitation, some patients still experience tachycardia, which may lead to adverse effects on cardiac function. However, the use of β-blockers in the treatment of septic shock remains controversial. Thus, the purpose of this study is to evaluate the efficacy of β-blockers in the treatment of patients with septic shock and explore the most appropriate patient subgroups for this treatment.MethodsThis retrospective observational study enrolled septic shock patients from the Medical Information Mart for Intensive Care (MIMIC)-IV and used propensity score matching (PSM) to balance some baseline differences between patients with and without β-blockers treatment. The primary outcome was the 28-day mortality. Length of stay (LOS) in the ICU and hospital, and the degree of support for organs such as circulatory, respiratory and renal systems were also assessed. Subgroup analysis and multivariate logistic regression were performed to determine the relationship between β-blockers therapy and 28-day mortality in different patient groups.ResultsA total of 4,860 septic shock patients were enrolled in this study and 619 pairs were finally matched after PSM. Our analysis revealed that β-blocker therapy was associated with a significant improvement in 28-day mortality (21.5% vs. 27.1%; P = 0.020) and led to a prolonged LOS in both the ICU and hospital. Subgroup analysis indicated that there was an interaction between cardiovascular diseases and β-blocker therapy in patients with septic shock. Patients with pre-existing heart disease or atrial arrhythmias were more likely to derive benefits from β-blocker treatment.ConclusionWe found β-blockers therapy was effective to improve 28-day mortality in patients with septic shock. Patients in the subgroup with cardiovascular diseases were more likely to benefit from β-blockers in mortality.

The effects of soybean soaking time (6, 8, 10, 12, 14, 16 h) on the physicochemical properties and sensory quality of soymilk were studied, which provided theoretical support for the selection of soybean soaking time. Soybean moisture content and distribution, soluble protein content, solid content, particle size, viscosity, stability and sensory score were used as indicators to analyze the influence of soaking time on the quality of soymilk and determine the optimal soaking time of soybean. The relationships between soaking time, soybean moisture composition and soymilk quality were analyzed by using the Pearson's correlation method. The results of low-field NMR showed that with the increase of soaking time, the signal values of T21, T22 and T23 increased, and the proportion of adsorbed water increased. The soybean moisture reached saturation after 12 h soaking. The results of the quality study showed that with the increase of soaking time, the protein transfer rate, the average particle size at volume and viscosity of soymilk had a trend of increasing first and then decreasing. The total solids content decreased significantly (P

Polymyxins are the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. However, this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resistance gene-1 (mcr-1). Given the high concentration of matrix metalloproteinase 3 (MMP-3) in bacterial pneumonia, limited plasma accumulation of colistin (CST) in the lung, and potential toxicity of ionic silver (Ag+), we designed a feasible clinical transformation platform, an MMP-3 high-performance lung-targeted bio-responsive delivery system, which we named “CST&Ag@CNMS”. This system exhibited excellent lung-targeting ability (>80% in lungs), MMP-3 bio-responsive release property (95% release on demand), and synergistic bactericidal activity in vitro (2–4-fold minimum inhibitory concentration reduction). In the mcr-1+ CST-resistant murine pneumonia model, treatment with CST&Ag@CNMS improved survival rates (70% vs. 20%), reduced bacteria burden (2–3 log colony-forming unit [CFU]/g tissue), and considerably mitigated inflammatory response. In this study, CST&Ag@CNMS performed better than the combination of free CST and AgNO3. We also demonstrated the superior biosafety and biodegradability of CST&Ag@CNMS both in vitro and in vivo. These findings indicate the clinical translational potential of CST&Ag@CNMS for the treatment of lung infections caused by CST-resistant bacteria carrying mcr-1.

Abstract Efficiently capturing radioactive methyl iodide (CH3I), present at low concentrations in the high-temperature off-gas of nuclear facilities, poses a significant challenge. Here we present two strategies for CH3I adsorption at elevated temperatures using a unified azolate-based metal-organic framework, MFU-4l. The primary strategy leverages counter anions in MFU-4l as nucleophiles, engaging in metathesis reactions with CH3I. The results uncover a direct positive correlation between CH3I breakthrough uptakes and the nucleophilicity of the counter anions. Notably, the optimal variant featuring SCN- as the counter anion achieves a CH3I capacity of 0.41 g g−1 at 150 °C under 0.01 bar, surpassing all previously reported adsorbents evaluated under identical conditions. Moreover, this capacity can be easily restored through ion exchange. The secondary strategy incorporates coordinatively unsaturated Cu(I) sites into MFU-4l, enabling non-dissociative chemisorption for CH3I at 150 °C. This modified adsorbent outperforms traditional materials and can be regenerated with polar organic solvents. Beyond achieving a high CH3I adsorption capacity, our study offers profound insights into CH3I capture strategies viable for practically relevant high-temperature scenarios.

Ciliated microeukaryotes (ciliates) are distinguished by their cilia, which are rich in tubulin. We developed a method for tubulin staining in ciliate cells that involves using live-cell tubulin-staining dyes instead of antibodies thereby streamlining the staining process, which is effective across diverse ciliate lineages. Moreover, our method allows integration with immunofluorescence staining using antibodies when needed. The potential applications of this technique extend to cell biology and ciliate morphological and ecological studies.

In order to explore the effects of different rice drying methods on physicochemical properties and taste quality of rice before and after soaking, the same variety of japonica rice after natural drying and hot air drying was used as the main raw material to explore the effects of different rice drying methods on water content, water distribution, microstructure, crystal structure, gelatinization characteristics, iodine blue value, taste value and texture characteristics of rice before and after soaking. The results showed that there were more cracks in the hot-air drying group, and the relative crystallinity, recovery value and gelatinization temperature were significantly lower than those in the natural drying group (P

Accurate high-resolution maps of oil palm plantations underpin effective management of environmental and socio-economic impacts at global, regional, and national levels. However, young industrial and highly irregular small-holder plantations are mostly unmapped and not included in official FAO statistics. This issue is addressed here by discriminating global oil palm plantation in 2020 into four subclasses: Industrial Mature Oil Palm (IMOP); Industrial Young Oil Palm (IYOP); Smallholder Mature Oil Palm (SMOP); and Smallholder Young Oil Palm (SYOP). Data, resolved to 4.77 m, from Planet & NICFI, Sentinel-1/2, were combined with other layers using the image-oriented classification and regression tree (CART) algorithm which performed best in classification tests. Results show that SMOP dominates distributional extent, but it was also the most accurately mapped subclass typically found at 500–1000 m altitude. IMOP had the most extensive altitude range of 500–1300 m, while IYOP and SYOP were found at similar altitudes of 500–800 m and 500–900 m respectively. Recent developments in South East Asia show oil palm plantations expanding into new areas with a slope of 24 degrees. Results provide data to support Sustainable Development Goal by assisting future oil palm-related development planning and monitoring in the world's major oil palm-growing countries.

Abstract Enteral nutrition (EN) is important for critically ill patients. This study investigated the current situation of EN treatment in SHANGHAI intensive care units (ICUs). We hypothesized that improving EN practice in SHANGHAI may benefit the prognosis of ICU patients. Clinical information on EN use was collected using clinic information forms in 2019. The collected data included the patient’s general clinical information, EN prescription status, EN tolerance status, and clinical outcomes. The observation time points were days 1, 3, and 7 after starting EN. A total of 491 patients were included. The proportion of EN intolerance (defined as 0.5 g/kg/day on day 3 or day 7 might affect the 28-day mortality. Risk factors with EN tolerance on day 7 by logistic regression showed that the AGI grade on day 1 was a major factor against EN tolerance. The proportion of EN tolerance in SHANGHAI ICU patients was low. Achieving tolerance on day 7 after the start of EN is a protective factor for 28-day survival. Improving EN tolerance and protein intake maybe beneficial for ICU patients.

Effectively and rationally allocating land resources, while coordinating urban expansion with internal renewal strategies, is crucial for achieving high-quality regional development in coastal urban agglomerations. Land-use suitability assessment (LSA) is a key method for coastal land-use planning, but it is primarily used to delineate ecological redlines or areas for urban expansion, often overlooking the spatial analysis needed for urban renewal. This is particularly critical in coastal urban agglomerations facing land scarcity and ecological fragility. Here, we combined land use and the Analytical Hierarchical Process (to consider stakeholder priorities) in a Minimum cumulative resistance model (MCRM) to determine suitable coastal urban growth and renewal based on a suite of 12 indicators relevant to development intensity and stock space. Application to the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) indicates a dominance of the Ecological Buffer Zone (70.5%), and the available stock space in the GBA comprises only 9.2% of the total area. Our modeling framework tailored different development strategies for different cities: Huizhou and Zhaoqing had space for urban expansion to varying degrees, while other cities were found to be suitable for urban renewal due to low stock space and high development intensity. Our modeling approach, incorporating stakeholder input and objective evaluation of geographic land-use information, can assist planners in improving ecological security while promoting high-quality developments in coastal areas.

Abstract The role of host genetic factors in COVID-19 outcomes remains unclear despite various genome-wide association studies (GWAS). We annotate all significant variants and those variants in high LD (R2 > 0.8) from the COVID-19 host genetics initiative (HGI) and identify risk genes by recognizing genes intolerant nonsynonymous mutations in coding regions and genes associated with cis-expression quantitative trait loci (cis-eQTL) in non-coding regions. These genes are enriched in the immune response pathway and viral life cycle. It has been found that host RNA binding proteins (RBPs) participate in different phases of the SARS-CoV-2 life cycle. We collect 503 RBPs that interact with SARS-CoV-2 RNA concluded from in vitro studies. Combining risk genes from the HGI with RBPs, we identify two COVID-19 risk loci that regulate the expression levels of FUBP1 and RAB2A in the lung. Due to the risk allele, COVID-19 patients show downregulation of FUBP1 and upregulation of RAB2A. Using single-cell RNA sequencing data, we show that FUBP1 and RAB2A are expressed in SARS-CoV-2-infected upper respiratory tract epithelial cells. We further identify NC_000001.11:g.77984833C>A and NC_000008.11:g.60559280T>C as functional variants by surveying allele-specific transcription factor sites and cis-regulatory elements and performing motif analysis. To sum up, our research, which associates human genetics with expression levels of RBPs, identifies FUBP1 and RAB2A as two risk genes for COVID-19 and reveals the anti-viral role of FUBP1 and the pro-viral role of RAB2A in the infection of SARS-CoV-2.

To balance the nutrition and improve quality of sausages. This research investigated quality improvements of Sichuan sausages by 41.5% poultry, rabbit meat and fish addition. The moisture, crude fat, crude protein contents, pH, Aw, colour, texture, TBARS, protein carbonyl, free thiol groups, fatty acids composition and sensory attributes of pork, poultry, rabbit meat and fish mixture group sausages were evaluated. The results showed that the hardness of pork and rabbit meat mixture group sausages (76.37, 68.01 kg) was significant (P

Abstract Background With the widespread spread of carbapenem-resistant gram-negative bacteria (CR-GNB) in medical facilities, the carriage of CR-GNB among critically ill patients has become a significant concern in intensive care units (ICU). This study aimed to develop a scoring system to identify CR-GNB carriers upon ICU admission. Methods Consecutive critically ill patients admitted to the ICU of Shanghai Ruijin Hospital between January 2017 and December 2020 were included. The patients were then divided into training and testing datasets at a 7:3 ratio. Parameters associated with CR-GNB carriage were identified using least absolute shrinkage and selection operator regression analysis. Each parameter was assigned a numerical score ranging from 0 to 100 using logistic regression analysis. Subsequently, a four-tier risk-level system was developed based on the cumulative scores, and assessed using the area under the receiver operating characteristic curve (AUC). Results Of the 1736 patients included in this study, the prevalence of CR-GNB carriage was 10.60%. The clinical scoring system including seven variables (neurological disease, high-risk department history, length of stay ≥ 14 days, ICU history, invasive mechanical ventilation, gastrointestinal tube placement, and carbapenem usage) exhibited promising predictive capabilities. Patients were then stratified using the scoring system, resulting in CR-GNB carriage rates of 2.4%, 12.0%, 36.1%, and 57.9% at the respective risk levels (P

Alzheimer’s disease (AD) is a neurodegenerative disease that seriously affects human health, and current treatment strategies are far from meeting clinical needs. Inspired by multi-target drug design strategies, a series of novel natural products-based melatonin–hydroxyquinoline hybrids were designed and synthesized, targeting anti-oxidation and metal-chelating at the same time. Most of the compounds showed significant oxygen radical absorbance capacity and Aβ1–42 aggregation inhibition. Moreover, the compounds possess good blood-brain barrier permeability. 6b and 6c have a good ability to alleviate oxidative stress induced by hydrogen peroxide. 6b and 6c possess metal-chelating properties with the chelation ratio being 2:1. Furthermore, 6b can significantly mitigate metal-induced Aβ aggregation. This work may provide a new multi-target treatment strategy for Alzheimer’s disease.

Abstract Macrophages are immune cells with high plasticity that are widely distributed in all tissues and organs of the body. Under the influence of the immune microenvironment of breast tumors, macrophages differentiate into various germline lineages. They exert pro-tumor or tumor-suppressive effects by secreting various cytokines. Pyroptosis is mediated by Gasdermin family proteins, which form holes in cell membranes and cause a violent inflammatory response and cell death. This is an important way for the body to fight off infections. Tumor cell pyroptosis can activate anti-tumor immunity and inhibit tumor growth. At the same time, it releases inflammatory mediators and recruits tumor-associated macrophages (TAMs) for accumulation. Macrophages act as “mediators” of cytokine interactions and indirectly influence the pyroptosis pathway. This paper describes the mechanism of action on the part of TAM in affecting the pyroptosis process of breast tumor cells, as well as its key role in the tumor microenvironment. Additionally, it provides the basis for in-depth research on how to use immune cells to affect breast tumors and guide anti-tumor trends, with important implications for the prevention and treatment of breast tumors. Video Abstract

Abstract Sepsis involves endothelial cell (EC) dysfunction, which contributes to multiple organ failure. To improve therapeutic prospects, elucidating molecular mechanisms of vascular dysfunction is of the essence. ATP-citrate lyase (ACLY) directs glucose metabolic fluxes to de novo lipogenesis by generating acetyl-Co-enzyme A (acetyl-CoA), which facilitates transcriptional priming via protein acetylation. It is well illustrated that ACLY participates in promoting cancer metastasis and fatty liver diseases. Its biological functions in ECs during sepsis remain unclear. We found that plasma levels of ACLY were increased in septic patients and were positively correlated with interleukin (IL)-6, soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule 1 (sVCAM-1), and lactate levels. ACLY inhibition significantly ameliorated lipopolysaccharide challenge-induced EC proinflammatory response in vitro and organ injury in vivo. The metabolomic analysis revealed that ACLY blockade fostered ECs a quiescent status by reducing the levels of glycolytic and lipogenic metabolites. Mechanistically, ACLY promoted forkhead box O1 (FoxO1) and histone H3 acetylation, thereby increasing the transcription of c-Myc (MYC) to facilitate the expression of proinflammatory and gluco-lipogenic genes. Our findings revealed that ACLY promoted EC gluco-lipogenic metabolism and proinflammatory response through acetylation-mediated MYC transcription, suggesting ACLY as the potential therapeutic target for treating sepsis-associated EC dysfunction and organ injury.

Abstract Background Delayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored. Methods Peripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry. Results PD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1−/− mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis. Conclusion In this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets.

Background: The changes in hormones, diet, and hygiene associated with pregnancy are associated with oral diseases. There is insufficient awareness of the importance of oral health during pregnancy. This study investigated the oral health status and knowledge amongst pregnant women in Shanghai. Methods: This cross-sectional study enrolled pregnant women at the Shanghai Red House Obstetrics & Gynecology Hospital in December 2020. The Fourth National Oral Health Questionnaire was used to evaluate the oral health status. Decayed/missing/filled teeth (DMFT) were the sum of the number of decayed, missing due to caries, and filled teeth. The chi-square test and Kruskal–Wallis test were used to compare the groups. Results: A total of 224 pregnant women were enrolled. The rates of dental caries were 69.8%, periodontal health was 1.8%, calculus detection was 95.6%, shallow periodontal pocket was 51.1%, deep periodontal pocket was 4.9%, regular oral examination was 22.8%, correct brushing was 49.6%, and prepregnancy oral examination was 20.1%. DMFT was 2.27, and the caries filling ratio was 45.4%. The number of missing teeth increased with age (P < .001). Only 26.3% used dental floss more than once a day, 47.3% rinsed the mouth more than twice a day, and 46.9% cleaned their tongue coating every week. In addition, 99% of the pregnant women agreed that “oral health was vital to their lives” and 97.7% agreed that “regular oral examination was necessary.” Conclusions: The oral health status amongst pregnant women in Shanghai was poor, but oral health awareness and attitudes were relatively high.

Abstract Background DNA methylation is a form of epigenetic modification that regulates gene expression. However, there are limited data on the comprehensive analysis of DNA methylation regulated gene mutations (DMRGM) in acute myeloid leukemia (AML) mainly referring to DNA methyltransferase 3α (DNMT3A), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), and Tet methylcytidine dioxygenase 2 (TET2). Results A retrospective study of the clinical characteristics and gene mutations in 843 newly diagnosed non-M3 AML patients was conducted between January 2016 and August 2019. 29.7% (250/843) of patients presented with DMRGM. It was characterized by older age, higher white blood cell count, and higher platelet count (P

Abstract Background Diabetic patients with community-acquired pneumonia (CAP) have an increased risk of progressing to severe CAP. It is essential to develop predictive tools at the onset of the disease for early identification and intervention. This study aimed to develop and validate a clinical feature-based nomogram to identify diabetic patients with CAP at risk of developing severe CAP. Method A retrospective cohort study was conducted between January 2019 to December 2020. 1026 patients with CAP admitted in 48 hospitals in Shanghai were enrolled. All included patients were randomly divided into the training and validation samples with a ratio of 7:3. The nomogram for the prediction of severe CAP development was established based on the results of the multivariate logistic regression analysis and other predictors with clinical relevance. The nomogram was then assessed using receiver operating characteristic curves (ROC), calibration curve, and decision curve analysis (DCA). Results Multivariate analysis showed that chronic kidney dysfunction, malignant tumor, abnormal neutrophil count, abnormal lymphocyte count, decreased serum albumin level, and increased HbA1c level at admission was independently associated with progression to severe CAP in diabetic patients. A nomogram was established based on these above risk factors and other predictors with clinical relevance. The area under the curve (AUC) of the nomogram was 0.87 (95% CI 0.83–0.90) in the training set and 0.84 (95% CI 0.78–0.90). The calibration curve showed excellent agreement between the predicted possibility by the nomogram and the actual observation. The decision curve analysis indicated that the nomogram was applicable with a wide range of threshold probabilities due to the net benefit. Conclusion Our nomogram can be applied to estimate early the probabilities of severe CAP development in diabetic patients with CAP, which has good prediction accuracy and discrimination abilities. Since included biomarkers are common, our findings may be performed well in clinical practice and improve the early management of diabetic patients with CAP.

Conventional salt-rejection evaporators typically exhibit low evaporation rate due to large heat loss. Here, authors demonstrate a solar evaporator featuring vertically aligned mass transfer bridges that takes advantage of the conductive heat to enable optimized water transport and salt backflow.

Abstract Acute myeloid leukemia (AML) is a complex, heterogeneous malignant hematologic disease. Although multiple prognostic-related genes gave been explored in previous studies, there are still many genes whose prognostic value remains unclear. In this study, a total of 1532 AML patients from three GEO databases were included, five genes with potential prognostic value (DLC1, NF1B, DENND5B, TANC2 and ELAVL4) were screened by weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE). Based on this, we conducted survival analysis of the above five genes through the TCGA database and found that low level of DLC1 was detrimental to the long-term prognosis of AML patients. We also performed external validation in 48 AML patients from our medical center to analyze the impact of DLC1 level on prognosis. In conclusion, DLC1 may be a potential marker affecting the prognosis of AML, and its deficiency is associated with poor prognosis.

Radioactive molecular iodine (I2) and methyl iodide (CH3I) coexist in the off-gas stream of nuclear power plants at low concentrations and only few adsorbents can effectively adsorb low-concentration I2 and CH3I simultaneously. Here, the authors demonstrate simultaneous capture of I2 and CH3I at low concentrations by exploiting different adsorptive sites in a covalent organic framework.

ObjectiveSarcopenia is a typical age-related disorder characterized by loss of muscle mass, strength, and physical function. Resistance training has a noticeable effect on sarcopenia, but there is no consensus on whether nutritional supplements can boost this effect. We conducted a meta-analysis of relevant literature to investigate the therapeutic effect of resistance training combined with nutrition intervention on sarcopenia compared with resistance training alone.MethodsCochrane Library, PubMed, Web of Science, Embase, Sinomed, CNKI, VIP, and Wanfang Data were searched for relevant studies on resistance training combined with nutritional intervention for aging adults with sarcopenia. The retrieval period ranged from the inception of the databases to May 24, 2022. Literature screening and information extraction were performed by two researchers. The Physiotherapy Evidence Database (PEDro) scale was adopted for literature quality evaluation and Stata 15.0 software for analysis.ResultsTwelve clinical trials were included, involving 713 older adults diagnosed with sarcopenia, of whom 361 were assigned to the experimental group and 352 to the control group. Compared with the control group, grip strength of the experimental group was substantially elevated [WMD = 1.87, 95% CI (0.01, 3.74), P = 0.049]. Subgroup analysis demonstrated that vitamin D and protein increased grip strength and gait speed. There were no significant improvement in grip strength and gait speed in the protein and vitamin D free subgroup.ConclusionsThis meta-analysis demonstrated that resistance training combined with additional nutritional supplementation, especially compound nutritional supplements that included protein and vitamin D, might further enhance grip strength rather than muscle mass in older adults with sarcopenia.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022346734.

Abstract Background Effective removal of pathogenic bacteria is key to improving the prognosis of sepsis. Polymorphonuclear neutrophils (PMNs) are the most important components of innate cellular immunity and play vital roles in clearing pathogenic bacteria. However, the metabolic characteristics and immunomodulatory pathways of PMNs during sepsis have not been investigated. In the present study, we explored the immune metabolism characteristics of PMNs and the mechanism by which neutrophilic glycolysis is regulated during sepsis. Methods Metabolomics analysis was performed on PMNs isolated from 14 septic patients, 26 patients with acute appendicitis, and 19 healthy volunteers. Transcriptome analysis was performed on the PMNs isolated from the healthy volunteers and the patients with sepsis to assess glycolysis and investigate its mechanism. Lipopolysaccharide (LPS) was used to stimulate the neutrophils isolated from the healthy volunteers at different time intervals to build an LPS-tolerant model. Chemotaxis, phagocytosis, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were evaluated. Results Transcriptomics showed significant changes in glycolysis and the mTOR/HIF-1α signaling pathway during sepsis. Metabolomics revealed that the Warburg effect was significantly altered in the patients with sepsis. We discovered that glycolysis regulated PMNs’ chemotaxis and phagocytosis functions during sepsis. Lactate dehydrogenase A (LDHA) downregulation was a key factor in the inhibition of glycolysis in PMNs. This study confirmed that the PI3K/Akt-HIF-1α pathway was involved in the LDHA expression level and also influenced PMNs’ chemotaxis and phagocytosis functions. Conclusions The inhibition of glycolysis contributed to neutrophil immunosuppression during sepsis and might be controlled by PI3K/Akt-HIF-1α pathway-mediated LDHA downregulation. Our study provides a scientific theoretical basis for the management and treatment of patients with sepsis and promotes to identify therapeutic target for the improvement of immune function in sepsis.

IntroductionMcCune-Albright syndrome (MAS) is a low-incidence syndrome consisting of the clinical triad of fibrous structural dysplasia of bone, endocrine disease, and skin pigmentation. Thyroid dysfunction is the second most common endocrine dysregulation in MAS. However, there are no treatment guidelines for MAS complicated with hyperthyroidism. Notably, no case of MAS complicated with retrosternal goiter and hyperthyroidism has been reported to our knowledge.Case presentationWe report a 27-year-old man with MAS who developed the typical triad of bone fibrous dysplasia, skin pigmentation and hyperthyroidism, complaining of recent fast-growing neck mass and difficulty in breathing. Hyperthyrodism was under control by Thiamazole, and computed tomography showed an enlarged thyroid extending retrosternally. We performed a total thyroidectomy on the patient. At the 1-year follow-up, the patient's dyspnea, hyperthyroidism, and bone pain were all significantly alleviated.ReviewWe searched the literature for previous case reports concerning MAS patients complicated with thyroid dysregulation. A total of 17 articles and 22 patients were identified to form our database. Among them, 9 studies clearly mentioned surgical intervention in 11 patients, and prognoses were also reported. Surgery was the most common intervention chosen and indicated a satisfactory prognosis.ConclusionWe report a rare case of MAS patient complicated with retrosternal goiter and hyperthyroidism. Our review provides an overview of MAS cases requiring interventions on thyroid function, and total thyroidectomy should be a proper treatment for these patients.

IntroductionHumans have the ability to efficiently extract summary statistics (i.e., mean) from a group of similar objects, referred to as ensemble coding. Recent studies have demonstrated that ensemble perception of simple objects is modulated by the visual working memory (VWM) task through matching features in VWM. However, few studies have examined the extending scope of such a matching feature effect and the influence of the organization mode (i.e., the way of combining memory matching features with ensemble properties) on this effect. Two experiments were done to explore these questions.MethodsWe used a dual-task paradigm for both experiments, which included a VWM task and a mean estimation task. Participants were required to adjust a test face to the mean identity face and report whether the irregular objects in a memory probe were identical or different to the studied objects. In Experiment 1, using identity faces as ensemble stimuli, we compared participants’ performances in trials where a subset color matched that of the studied objects to those of trials without color-matching subsets. In Experiment 2, we combined memory matching colors with ensemble properties in common region cues and compared the effect with that of Experiment 1.ResultsResults of Experiments 1 and 2 showed an effect of the VWM task on high-level ensemble perception that was similar to previous studies using a low-level averaging task. However, the combined analysis of Experiments 1 and 2 revealed that memory matching features had less influence on mean estimations when matching features and ensemble properties combined in the common region than when combined as parts of a complete unit.ConclusionThese findings suggest that the impact of memory matching features is not limited by the level of stimulus feature, but can be impacted by the organization between matching features and ensemble target properties.

Abstract Background Histone deacetylases (HDACs) engage in the regulation of various cellular processes by controlling global gene expression. The dysregulation of HDACs leads to carcinogenesis, making HDACs ideal targets for cancer therapy. However, the use of HDAC inhibitors (HDACi) as single agents has been shown to have limited success in treating solid tumors in clinical studies. This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy. Methods Transcriptome sequencing and bioinformatics analysis were performed to screen for genes responsive to HDACi in breast cancer cells. The effects of HDACi on cell viability were detected using the MTT assay. The mRNA and protein levels of genes were determined by quantitative reverse transcription‐PCR (qRT‐PCR) and Western blotting. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The binding of CREB1 (cAMP‐response element binding protein 1) to the promoter of the KDELR (The KDEL (Lys‐Asp‐Glu‐Leu) receptor) gene was validated by the ChIP (chromatin immunoprecipitation assay). The association between KDELR2 and protein of centriole 5 (POC5) was detected by immunoprecipitation. A breast cancer‐bearing mouse model was employed to analyze the effect of the HDAC3‐KDELR2 axis on tumor growth. Results KDELR2 was identified as a novel target of HDAC3, and its aberrant expression indicated the poor prognosis of breast cancer patients. We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients. The results of the ChIP assay and qRT‐PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1. The HDAC3‐KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation. Moreover, the HDAC3‐KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo. Conclusion Our results uncovered a previously unappreciated function of KDELR2 in tumorigenesis, linking a critical Golgi‐the endoplasmic reticulum traffic transport protein to HDAC‐controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer.

ABSTRACT Klebsiella pneumoniae poses a critical challenge to clinical and public health. Along with conjugative plasmids, nonconjugative resistance or virulence plasmids associated with carbapenem-resistant K. pneumoniae (CRKP), hypervirulent K. pneumoniae (hvKP), and even carbapenem-resistant and hypervirulent K. pneumoniae (CR-hvKP) strains have been spreading globally. In this study, a clinical CRKP strain KP2648 was isolated, and the transferability of its plasmids was assessed using conjugation experiments. The transconjugants were characterized by polymerase chain reaction (PCR) detection, XbaI and S1-pulsed-field gel electrophoresis (PFGE), and/or whole-genome sequencing. Genetically modified IncN3 plasmids were employed to elucidate the self-transferability and the mobilization mechanisms. KP2648 has three natural plasmids: a nonconjugative IncFIB/IncHI3B virulence plasmid, a nonconjugative IncFII/IncR carbapenem-resistant plasmid, and a self-transferable IncN3 plasmid with a high conjugation frequency (7.54 ± 1.06) × 10−1. The IncN3 plasmid could mobilize the coexisting nonconjugative virulence/resistance plasmids either directly or by employing intermediate E. coli with two forms: a hybrid plasmid fused with IncN3 or a cotransfer with the helper plasmid, IncN3. Various mobile genetic elements, including ISKpn74, ISKpn14, IS26, ISShes11, ISAba11, and Tn3, are involved in the genetic transposition of diverse hybrid plasmids and the cotransfer process during the intra/interspecies transmission. IMPORTANCE Nowadays, the underlying mobilization mechanism and evolutionary processes of nonconjugative virulence or resistance plasmids in Klebsiella pneumoniae remain poorly understood. Our study revealed the high conjugation ability of IncN3 plasmid isolated from carbapenem-resistant K. pneumoniae and confirmed its capability to mobilize the nonconjugative virulence or resistance plasmids. The self-transferable IncN3 plasmid could facilitate the transmission of pathogenicity and genetic evolution of carbapenem-resistant and hypervirulent K. pneumoniae, including hv-CRKP (virulence plasmid obtained by carbapenem-resistant K. pneumoniae) and CR-hvKP (resistance plasmid obtained by hypervirulent K. pneumoniae), warranting further monitoring.

AimsTo construct an automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain with high accuracy, which could preserve the inherent voxel intensity and Regions of interest (ROI) morphological characteristics simultaneously.Methods and resultsThe transformation relationship from standardized space to individual space was obtained by firstly normalizing individual image to the Paxinos space and then inversely transformed. On the other hand, all the regions defined in the atlas image were separated and resaved as binary mask images. Then, transforming the mask images into individual space via the inverse transformations and reslicing using the 4th B-spline interpolation algorithm. The boundary of these transformed regions was further refined by image erosion and expansion operator, and finally combined together to generate the individual parcellations. Moreover, two groups of MEMRI images were used for evaluation. We found that the individual parcellations were satisfied, and the inherent image intensity was preserved. The statistical significance of case-control comparisons was further optimized.ConclusionsWe have constructed a new automatic method for individual parcellation of rat brain MEMRI images, which could preserve the inherent voxel intensity and further be beneficial in case-control statistical analyses. This method could also be extended to other imaging modalities, even other experiments species. It would facilitate the accuracy and significance of ROI-based imaging analyses.

BackgroundAcute myeloid leukemia (AML) is a malignant and molecularly heterogeneous disease. It is essential to clarify the molecular mechanisms of AML and develop targeted treatment strategies to improve patient prognosis.MethodsAML mRNA expression data and survival status were extracted from TCGA and GEO databases (GSE37642, GSE76009, GSE16432, GSE12417, GSE71014). Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were performed. Functional enrichment analysis and protein-protein interaction (PPI) network were used to screen out hub genes. In addition, we validated the expression levels of hub genes as well as the prognostic value and externally validated TRIM32 with clinical data from our center. AML cell lines transfected with TRIM32 shRNA were also established to detect the proliferation in vitro.ResultsA total of 2192 AML patients from TCGA and GEO datasets were included in this study and 20 differentially co-expressed genes were screened by WGCNA and differential gene expression analysis methods. These genes were mainly enriched in phospholipid metabolic processes (biological processes, BP), secretory granule membranes (cellular components, CC), and protein serine/threonine kinase activity (molecular functions, MF). In addition, the protein-protein interaction (PPI) network contains 15 nodes and 15 edges and 10 hub genes (TLE1, GLI2, HDAC9, MICALL2, DOCK1, PDPN, RAB27B, SIX3, TRIM32 and TBX1) were identified. The expression of 10 central genes, except TLE1, was associated with survival status in AML patients (p

Abstract Background Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia–reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. Methods Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), and Qubin (GB7) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. Results Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. Conclusions Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.

Abstract Background There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such “functional metabolites” in ARDS using metabolomics and in vivo experiments in a mouse model. Methods Metabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for “functional metabolites”, which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of “functional metabolites” in the lung injury and mortality caused by the respiratory disorder. Results The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS. Conclusion Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine. Trial registration Chinese Clinical Trial Registry, ChiCTR1800015930 . Registered 29 April 2018, http://www.chictr.org.cn/edit.aspx?pid=25609&htm=4

Drug resistance, including adriamycin (ADR)-based therapeutic resistance, is a crucial cause of chemotherapy failure in breast cancer treatment. Acquired chemoresistance has been identified to be closely associated with the overexpression of P-glycoprotein (P-gp/ABCB1). Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) can be involved in carcinogenesis; however, its roles in ABCB1-mediated ADR resistance are poorly understood. In this study, we identified a panel of differentially expressed lncRNAs, mRNAs, and microRNAs (miRNAs) in MCF-7 and MCF-7/ADR cell lines through RNA sequencing (RNA-seq) technologies. GAS5 level was downregulated whereas ABCB1 level was upregulated in the resistant breast cancer tissues and cells. Overexpression of GAS5 significantly enhanced the ADR sensitivity and apoptosis, and it inhibited the efflux function and expression of ABCB1 in vitro, while knockdown of GAS5 had the opposite effects. Further mechanism-related investigations indicated that GAS5 acted as an endogenous “sponge” by competing for miR-221-3p binding to regulate its target dickkopf 2 (DKK2), and then it inhibited the activation of the Wnt/β-catenin pathway. Functionally, GAS5 enhanced the anti-tumor effect of ADR in vivo. Collectively, our findings reveal that GAS5 exerted regulatory function in ADR resistance possibly through the miR-221-3p/DKK2 axis, providing a novel approach to develop promising therapeutic strategy for overcoming chemoresistance in breast cancer patients. Keywords: lncRNA GAS5, miR-221-3p, ABCB1, drug resistance, breast cancer

N6-methyladenosine (m6A) RNA methylation has been considered the most prevalent, abundant, and conserved internal transcriptional modification throughout the eukaryotic mRNAs. Typically, m6A RNA methylation is catalyzed by the RNA methyltransferases (writers), is removed by its demethylases (erasers), and interacts with m6A-binding proteins (readers). Accumulating evidence shows that abnormal changes in the m6A levels of these regulators are increasingly associated with human tumorigenesis and drug resistance. However, the molecular mechanisms underlying m6A RNA methylation in tumor occurrence and development have not been comprehensively clarified. We reviewed the recent findings on biological regulation of m6A RNA methylation and summarized its potential therapeutic strategies in various human cancers.

Urban land optimization in urban agglomerations plays an important role in promoting territorial spatial planning to achieve high-quality development, land ecological suitability (LES) is one of the important variables influencing its urbanization and needs to be considered in urban growth simulation and modeling. This research proposed a multi-objective urban land optimization (MULO) model based on the non-dominated sorting genetic algorithm II (NSGA-II) which integrates the LES assessment. MULO starts with LES analysis based on a fuzzy analytical hierarchy process (AHP) and a minimum cumulative resistance (MCR) model. Then, two-step linear regression is used to optimize the quantity structure of built-up land. Finally, suitability and compactness are assigned to NSGA-II as objectives to obtain optimal spatial patterns. Taking the example of the Guangdong–Hong Kong–Macao Greater Bay Area, we found that all the newly added built-up land in 2030 is distributed in peri-urban areas around the original settlements, with approximate clustering in the northern part of Guangzhou and the southern part of Foshan under a balanced development scenario. This study highlights the importance of LES in urban growth modeling, and MULO can provide effective support for the spatial planning of urban agglomerations.

Objectives: Neuropsychological tests are an important basis for the memory impairment diagnosis in Alzheimer’s disease (AD). However, multiple memory tests might be conflicting within-subjects and lead to uncertain diagnoses in some cases. This study proposed a framework to diagnose the uncertain cases of memory impairment.Methods: We collected 2,386 samples including AD, mild cognitive impairment (MCI), and cognitive normal (CN) using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and three different neuropsychological tests (Mini-Mental State Examination, Alzheimer’s Disease Assessment Scale-Cognitive Subscale, and Clinical Dementia Rating) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A deep learning (DL) framework using FDG-PET was proposed to diagnose uncertain memory impairment cases that were conflicting between tests. Subsequent ANOVA, chi-squared, and t-test were used to explain the potential causes of uncertain cases.Results: For certain cases in the testing set, the proposed DL framework outperformed other methods with 95.65% accuracy. For the uncertain cases, its positive diagnoses had a significant (p < 0.001) worse decline in memory function than negative diagnoses in a longitudinal study of 40 months on average. In the memory-impaired group, uncertain cases were mainly explained by an AD metabolism pattern but mild in extent (p < 0.05). In the healthy group, uncertain cases were mainly explained by a non-energetic mental state (p < 0.001) measured using a global deterioration scale (GDS), with a significant depression-related metabolism pattern detected (p < 0.05).Conclusion: A DL framework for diagnosing uncertain cases of memory impairment is proposed. Proved by longitudinal tracing of its diagnoses, it showed clinical validity and had application potential. Its valid diagnoses also provided evidence and explanation of uncertain cases based on the neurodegeneration and depression mental state.

Abstract Background The poultry red mite (PRM), Dermanyssus gallinae, is one of the most economically deleterious threats to laying-hen industry worldwide. Macrocyclic lactones (MLs) have been widely used in control of mites in mammals, but the effects of MLs on PRMs are not well studied. The main objective of the present study was to systematically evaluate the effects of three MLs, i.e. eprinomectin (EPR), moxidectin (MOX) or ivermectin (IVM), on PRMs fed on chicks following oral administration. Methods Chicks in treatment groups were orally administrated with EPR, MOX or IVM at a dose of 5.0 mg/kg bodyweight. Chicks in the control group received the carrier solvent without drug. Chicks in each cage were then infested with 200 starved adult D. gallinae. After infestation and feeding for 12 h, engorged mites were collected to evaluate the acaricidal efficacy of the MLs, and its impacts on the reproduction and blood-meal digestion of D. gallinae. Results MOX, IVM and EPR demonstrated higher acaricidal efficacies post-treatment compared with the control, i.e. 45.60% for MOX, 71.32% for IVM and 100% for EPR on Day 10. MLs did not have significant effects on the blood-meal ingestion of PRMs, but significantly slowed down blood digestion (P < 0.0001). The oviposition rate, egg hatching rate and fecundity of PRMs in treatment groups were remarkably reduced. Among the three MLs, EPR exhibited the highest performance against PRMs, with an oviposition rate of 1.04%, fecundity of 0.33 eggs per mite and a zero egg hatching rate in EPR treated groups. Conclusions EPR, MOX or IVM administrated orally to chicks increased the mortality of D. gallinae, significantly slowed down their blood-meal digestion and significantly reduced their reproductive capability which included the oviposition rate, fecundity and egg hatching rate. The present study highlights the potential of MLs in the control of PRMs.

Glioma is the most common primary craniocerebral malignant tumor, arising from the canceration of glial cells in the brain and spinal cord. The quality of life and prognosis of patients with this disease are still poor. Doxorubicin (DOX) is one of the most traditional and economical chemotherapeutic drugs for the treatment of glioma, but its toxic effect on normal cells and the resistance of tumor cells to DOX make the application of DOX in the treatment of glioma gradually less effective. To solve this problem, we co-encapsulated DOX and endogenous tumor suppressor miR-125b into nanoparticles (NPs) by nanoprecipitation methods, and passively targeted them into glioma cells. In vitro experiments show that miR-125b and DOX can be effectively encapsulated into nanoparticles with different ratios, and by targeting YES proto-oncogene 1 (YES1), they can affect the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/p53 pathway and induce brain glioma cell apoptosis. They can also affect the DNA damage repair process and inhibit cell proliferation. The obtained data suggest that co-delivery of DOX and miR-125b could achieve synergistic effects on tumor suppression. Nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy.

A band selection model was described for efficient and accurate remotely-sensed vegetation mapping in cloudy mixed-vegetation areas, demonstrated with an application on mapping mangroves in Southeast Asia (SE Asia). We show how to use multi-source satellite imagery and Cloud Computing Platforms to improve mapping and computational efficiency in complex environments. A key element of the method relies upon field surveys to establish a detailed sample database that includes easily-confused land cover. The Maximal Separability and Information (MSI) model was developed to select key bands for target land cover classification from multiple satellite imagery based on two principles: 1. maximize separability of the target cover from other land cover; and 2. maximize and prioritize information from band combinations. Application of the MSI model to map mangroves in SE Asia using three optical and SAR data systems (Landsat OLI, Sentinel-2 and Sentinel-1) showed: 1. Sentinel-2 is better at classifying mangrove than Landsat and Sentinel-1; and 2. SWIR, NIR and Red bands (with SWIR in particular) are effective in separating mangrove from other vegetation. The MSI-mapped mangroves showed lower computation cost compared to using all bands from individual satellites, and higher accuracy (above 90%) when applied to SE Asia. It was robust in tolerating smaller sample sizes, thereby demonstrating computational feasibility and substantial improvements with the MSI model for large-scale land cover mapping in complex environments.

The present study aimed to elucidate the mechanism of dietary betaine, as a lipid-lowering substance, on the regulation of lipid metabolism and inflammation in juvenile black seabream (Acanthopagrus schlegelii) fed a high fat diet. An 8-week feeding trial was conducted in black seabream with an initial weight of 8.39 ± 0.01g fed four isonitrogenous diets including Control, medium-fat diet (11%); HFD, high-fat diet (17%); and HFD supplemented with two levels (10 and 20 g/kg) of betaine, HFD+B1 and HFD+B2, respectively. SGR and FE in fish fed HFD+B2 were significantly higher than in fish fed HFD. Liver histology revealed that vacuolar fat droplets were smaller and fewer in bream fed HFD supplemented with betaine compared to fish fed HFD. Betaine promoted the mRNA and protein expression levels of silent information regulator 1 (Sirt1), up-regulated mRNA expression and protein content of lipid peroxisome proliferator-activated receptor alpha (pparα), and down-regulated mRNA expression and protein content of sterol regulatory element-binding protein-1(srebp-1). Furthermore, the mRNA expression levels of anti-inflammatory cytokines in liver and intestine were up-regulated, while nuclear factor kB (nf-kb) and pro-inflammatory cytokines were down-regulated by dietary betaine supplementation. Likewise, in fish that received lipopolysaccharide (LPS) to stimulate inflammatory responses, the expression levels of mRNAs of anti-inflammatory cytokines in liver, intestine and kidney were up-regulated in fish fed HFD supplemented with betaine compared with fish fed HFD, while nf-kb and pro-inflammatory cytokines were down-regulated. This is the first report to suggest that dietary betaine could be an effective feed additive to alleviate hepatic steatosis and attenuate inflammatory responses in black seabream fed a high fat diet by modulating the Sirt1/Srebp-1/Pparɑ pathway.

BackgroundWe previously found that microbial disruption in Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) patients are long-lasting. Long-term microbial dysbiosis may lead to changes in metabolites. Short-chain fatty acids (SCFAs) are microbial fermentation products and show beneficial effects in patients with pneumonia. In this study, we aimed to explore the association between circulating SCFA levels and clinical outcomes in patients with PA-VAP.MethodsIn this study, we analyzed SCFAs in the serum of 49 patients with PA-VAP by gas chromatography-mass spectrometry analysis. Twenty of these patients died, and 29 survived. The correlation between serum SCFAs and patient survival and immune parameters was analyzed.ResultsWe developed a partial least squares discriminant analysis (PLS-DA) model to examine differential SCFAs in 49 patients with PA-VAP. Among the seven SCFAs, only acetic acid was increased in non-survivors (P = 0.031, VIP > 1). Furthermore, high levels of acetic acid (>1.96ug/ml) showed increased 90-day mortality compared to low levels of acetic acid (

Urban agglomerations (UA) are attracting increasing research attention as a global emergent phenomenon, whereby regional collaborative linkages between cities attracts and agglomerates development. However, these studies also acknowledge that ecological values may be negatively impacted by re-development, ecological fragmentation, and proximity or downstream impacts. Sustainable development, therefore, requires balancing forces from economic attraction and ecological repulsion. Forces similar to economic ones may also operate in attracting ecological enhancement towards higher-valued ecological regions; however, research regarding the role of the self-collaborative gravity-like forces shaping UA is limited in land use optimization. To assist planners, this study developed a new multi-objective land use optimization of UA that explored the intensity of economic ties and ecological gradients using the multi-objective NSGA-II algorithm. In this model, economic linkage intensity (ELI) and accessibility were used to calculate a modified GDP (gross domestic product), while the NDVI (normalized difference vegetation index) was used for the modified ESV (ecosystem services value). Spatial allocation with implicit economic accessibility relationships was enhanced through a two-step mutation operator, including a “gravity flip” spatial orientation factor. Compared to the standard NSGA-II algorithm, models of future land use of the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) in 2030 have shown that the modified GDP value in our model increased by 7.41%, while the conversion rate of high-density vegetation reduced by 7.92%. The results highlighted the importance of linkage and accessibility factors in enhancing the clustering of cities. In tandem, the modified ESV also enhances ecosystem services contributions of higher value vegetated land through decentralized built-up developments. The proposed model provides managers with a comprehensive and efficient land use solution model that accounts for intrinsic linkage factors shaping the development of compact urban agglomerations.

A novel surface plasmon resonance (SPR) sensor system using a smartphone based on the metal nanoshell array sensing method is proposed and developed. The micro-flow injection method was used to prepare two-dimensional colloidal microsphere template, the metal nanoshell array was fabricated by combining the microsphere template and the magnetron sputtering technology. A smartphone and a diffraction grating are employed as interrogation system, in which a fiber with a 45° polished tip connect the flashlight and the camera on the smartphone. The diffraction grating spreads the transmission spectrum over the camera's pixels to allow for repeatable measurements of wavelength shifts of the sensor. The reflection intensity of sensor can be measured by smartphone and the surrounding refractive index is monitored by the shift of the reflection spectrum. The experimental results show that the sensitivity of the SPR refractive index sensor based on the metal nanoshell array is about 927 nm/RIU for a refractive index (RI) range from 1.352 to 1.363, and the quality factor of that is about 18.5. The results show that this technique can provide a low-cost, portable and intelligent diagnostic platform for the measurement of the SPR refractive index sensor.

Abstract Background Acute pancreatitis (AP) is a life-threatening disease that requires early identification of patients at risk of developing infectious complications. Immunosuppression is an initial event that is key to AP pathogenesis. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system is reported to mediate evasion of host immune surveillance in many diseases; however, the relationship between PD-1/PD-L1 expression and these parameters or infectious complications in AP has not been elucidated. This study was conducted to determine whether PD-1 and PD-L1 are upregulated and to reveal the relationship between PD-1/PD-L1 expression and the development of infectious complications in AP. Methods Sixty-three patients with AP and 32 sex- and age-matched healthy control subjects were prospectively enrolled. On days 1 and 3 after the onset of AP, we measured PD-1 expression in peripheral CD4+ T cells and PD-L1 and human leukocyte antigen-DR (HLA-DR) expression in CD14+ monocytes using flow cytometry. Plasma interleukin (IL)-10 levels were measured by enzyme-linked immunosorbent assay. Results Compared with healthy volunteers, the percentages of PD-1-expressing CD4+ lymphocytes and PD-L1-expressing CD14+ monocytes were increased in patients with AP on days 1 and 3 after onset, especially those with infectious complications. Moreover, increased PD-1/PD-L1 expression was associated with increased occurrence of infectious complications, decreased circulating lymphocytes, and increased plasma IL-10 concentration. Multivariate regression analysis indicated that the increased percentage of PD-L1-expressing CD14+ monocytes was an independent risk factor for infectious complications in AP. Area under the ROC curve analysis showed the combination of Acute Physiology and Chronic Health Evaluation II score and PD-L1 and HLA-DR expression in CD14+ monocytes had high accuracy in predicting infectious complications in patients with AP. Conclusions The PD-1/PD-L1 system plays an essential role in the early immunosuppression of AP. PD-L1 expression in CD14+ monocytes may be a new marker for predicting risk of infectious complications in patients with AP.