Performance of continuous glucose monitoring in patients with acute respiratory failure: a prospective, single-center observational study.

OBJECTIVE: Continuous glucose monitoring (CGM) may have benefits in achieving glycemic control in critically ill patients. The aim of this study was to assess the accuracy of the Freestyle Libre H (professional version of the Libre Pro). in patients with acute respiratory failure (ARF) in the intensive care unit (ICU). METHODS: 52 adult patients with ARF were selected. The performance of CGM was evaluated using arterial blood glucose (aBG) and point-of-care (POC) glucose as reference values. Numerical accuracy was evaluated by the mean absolute relative difference (MARD), Bland-Altman analysis, and %15/15(the percentage of CGM values within 15 mg/dL or 15% of reference values <100 mg/dL or >100mg/dL, respectively), %20/20 and %30/30; Clinical accuracy was assessed by Clarke error grid analysis. RESULTS: 519 and 1504 pairs of aBG/CGM and POC/CGM glucose values were analyzed. The MARD values were 13.8% and 14.7%, respectively. The mean deviation of the Bland‒Altman analysis was 0.82 mmol/L and 0.81 mmol/L. %15/15, %20/20 and %30/30 of aBG values were 62.6%, 75.5%, and 92.4%, respectively; %15/15, %20/20 and %30/30 of POC values were 57.1%, 72.9%, and 88.7%, respectively. The Clarke error grid analysis showed that 97.8% and 99.3% of the values located in the (A+B) zone. Additionally, accuracy of CGM is not affected by general patient factors. CONCLUSION: This study demonstrated that the accuracy of CGM in patients with ARF is lower than that in most outpatients, and it is not affected by general patient factors. Whether CGM is beneficial to glucose management in ICU needs further evaluation.

Development and validation of a model to predict the need for artificial airways for acute trauma patients in the emergency department: a retrospective case-control study.

OBJECTIVE: To develop scores for predicting the need for artificial airway procedures for acute trauma patients in the emergency department (ED). DESIGN: Retrospective case-control. SETTING: A tertiary comprehensive hospital in China. PARTICIPANTS: 8288 trauma patients admitted to the ED within 24 hours of injury and who were admitted from 1 August 2012 to 31 July 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The study outcome was the establishment of an artificial airway within 24 hours of admission to the ED. Based on the different feature compositions, two scores were developed in the development cohort by multivariable logistic regression. The predictive performance was assessed in the validation cohort. RESULTS: The O-SPACER (Oxygen saturation, Systolic blood pressure, Pulse rate, Age, Coma Scale, Eye response, Respiratory rate) score was developed based on the patient's basic information with an area under the curve (AUC) of 0.85 (95% CI 0.80 to 0.89) in the validation group. Based on the basic information and trauma scores, the IO-SPACER (Injury Severity Score, Oxygen saturation, Systolic blood pressure, Pulse rate, Age, Coma Scale, Eye response, Respiratory rate) score was developed, with an AUC of 0.88 (95% CI 0.84 to 0.92). According to the O-SPACER and IO-SPACER scores, the patients were stratified into low, medium and high-risk groups. According to these two scores, the high-risk patients were associated with an increased demand for artificial airways, with an OR of 40.16-40.67 compared with the low-risk patients. CONCLUSIONS: The O-SPACER score provides risk stratification for injured patients requiring urgent airway intervention in the ED and may be useful in guiding initial management. The IO-SPACER score may assist in further determining whether the patient needs planned intubation or tracheotomy early after trauma.

Multiomics Analysis Reveals Leucine Deprivation Promotes Bile Acid Synthesis by Upregulating Hepatic CYP7A1 and Intestinal Turicibacter sanguinis in Mice.

BACKGROUND: Leucine, a branched-chain amino acid, participates in the regulation of lipid metabolism and the composition of the intestinal microbiota. However, the related mechanism remains unclear. OBJECTIVES: Here, we aimed to reveal the potential mechanisms by which hepatic CYP7A1 (a rate-limiting enzyme for bile acid [BA] synthesis) and gut microbiota coregulate BA synthesis under leucine deprivation. METHODS: To this end, 8-wk-old C57BL/6J mice were fed with either regular diets or leucine-free diets for 1 wk. Then, we investigated whether secondary BAs were synthesized by Turicibacter sanguinis in 7-wk-old C57BL/6J germ-free mice gavaged with T. sanguinis for 2 wk by determining BA concentrations in the plasma, liver, and cecum contents using liquid chromatography-tandem mass spectrometry. RESULTS: The results showed that leucine deprivation resulted in a significant increase in total BA concentration in the plasma and an increase in the liver, but no difference in total BA was observed in the cecum contents before and after leucine deprivation. Furthermore, leucine deprivation significantly altered BA profiles such as taurocholic acid and ω-muricholic acid in the plasma, liver, and cecum contents. CYP7A1 expression was significantly upregulated in the liver under leucine deprivation. Leucine deprivation also regulated the composition of the gut microbiota; specifically, it significantly upregulated the relative abundance of T. sanguinis, thus enhancing the conversion of primary BAs into secondary BAs by intestinal T. sanguinis in mice. CONCLUSIONS: Overall, leucine deprivation regulated BA profiles in enterohepatic circulation by upregulating hepatic CYP7A1 expression and increasing intestinal T. sanguinis abundance. Our findings reveal the contribution of gut microbiota to BA metabolism under dietary leucine deprivation.

Dynamic Structures and Fast Transition Kinetics of Oxidized G-Quadruplexes.

8-oxoguanines (8-oxoG) in cells form compromised G-quadruplexes (GQs), which may vary GQ mediated gene regulations. By mimicking molecularly crowded cellular environment using 40% DMSO or sucrose, here it is found that oxidized human telomeric GQs have stabilities close to the wild-type (WT) GQs. Surprisingly, while WT GQs show negative formation cooperativity between a Pt(II) binder and molecularly crowded environment, positive cooperativity is observed for oxidized GQ formation. Single-molecule mechanical unfolding reveals that 8-oxoG sequence formed more diverse and flexible structures with faster folding/unfolding transition kinetics, which facilitates the Pt(II) ligand to bind the best-fit structures with positive cooperativity. These findings offer new understanding on structures and properties of oxidized G-rich species in crowded environments. They also provide insights into the design of better ligands to target oxidized G-rich structures formed under oxidative cell stress.

Dietary Supplementation of Astragalus membranaceus Extract Affects Growth Performance, Antioxidant Capacity, Immune Response, and Energy Metabolism of Largemouth Bass (Micropterus salmoides).

The present study investigated the effects of Astragalus membranaceus extract (AME) on growth performance, immune response, and energy metabolism of juvenile largemouth bass (Micropterus salmoides). Seven diets containing 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, and 0.6% AME (Con, AME0.1, AME0.2, AME0.3, AME0.4, AME0.5, and AME0.6 groups) were formulated and fed to M. salmoides for 8 weeks. Final body weight (FBW), feed intake (FI), weight gain (WG), and specific growth rate (SGR) were all significantly higher in AME0.4 group than in Con group (P < 0.05). Feed conversion rate (FCR) was significantly improved in AME0.5 group compared with Con group (P < 0.05). Whole-body crude protein contents were significantly increased in AME0.2 group (P < 0.05). Whole-body crude lipid contents were significantly lower in AME0.2 and AME0.3 groups, while muscle lipid was upregulated by dietary AME (P < 0.05). Hepatic malondialdehyde (MDA) contents were significantly lowered in AME0.3 and AME0.4 groups, and catalase (CAT) activities were significantly increased in AME0.1 and AME0.2 groups (P < 0.05). Plasma aspartate aminotransferase (AST) level was significantly lowered in AME0.5, and AME0.6 groups, and alanine aminotransferase (ALT) level was lowered in AME0.5 groups (P < 0.05). Plasma triglyceride was declined in AME0.6 group, and glucose was decreased by 0.3%-0.5% AME (P < 0.05). Significantly higher hepatocyte diameter, lamina propria width, and submucosal layer thickness were recorded in AME0.6 groups, while the longest villi height was obtained in AME0.2 and AME0.3 groups (P < 0.05). The mRNA expression levels of insulin-like growth factor 1 (igf1) revealed the growth-promoting effect of AME. The anti-inflammatory and antiapoptotic effects of AME were demonstrated by transcription levels of interleukin 8 (il-8), tumor necrosis factor-alpha (tnf-a), caspase, B-cell lymphoma-xl (Bcl-xl), bcl-2 associated x (Bax), and bcl-2-associated death protein (Bad). The transcription levels of lipid metabolism and gluconeogenesis related genes, including acetyl-CoA carboxylase alpha (acc1), fatty acid synthase (fasn), fatty acid binding protein 1 (fabp1), phosphoenolpyruvate carboxykinase 2 (pepck2), and glucose-6-phosphatase catalytic subunit 1a (g6pc), were reduced by AME treatment, while the levels of glycolysis-related genes, including glucokinase (gck) and pyruvate kinase (pk), were the highest in AME0.2 and AME0.3 groups (P < 0.05). According to polynomial regression analysis of SGR, WG, FCR, whole-body crude lipid, MDA, and ALT, the optimal AME supplementation level was estimated to be 0.320%-0.429% of the diet. These results provided insights into the roles of AME in regulating immunity and metabolism, which highly indicated its potential as immunostimulants and metabolic regulators in diverse aquatic animals.

A Nomogram for Predicting Mortality in Patients with Pneumonia-Associated Acute Respiratory Distress Syndrome (ARDS).

Background: There is no predictive tool developed for pneumonia-associated acute respiratory distress syndrome (ARDS) specifically so far, and the clinical risk classification of these patients is not well defined. Our study aims to construct an early prediction model for hospital mortality in patients with pneumonia-associated ARDS. Methods: In this single-center retrospective study, consecutive patients with pneumonia-associated ARDS admitted into intensive care units (ICUs) in West China Hospital of Sichuan University in China between January 2012 and December 2018 were enrolled. The least absolute shrinkage and selection operator (LASSO) regression and then multivariate logistic regression analysis were used to identify independent predictors which were used to develop a nomogram. We evaluated the performance of differentiation, calibration, and clinical utility of the nomogram. Results: The included patients were divided into the training cohort (442 patients) and the testing cohort (190 patients) with comparable baseline characteristics. The independent predictors for hospital mortality included age (OR: 1.04; 95% CI: 1.02, 1.05), chronic cardiovascular diseases (OR: 2.62; 95% CI: 1.54, 4.45), chronic respiratory diseases (OR: 1.87; 95% CI: 1.02, 3.43), lymphocytes (OR: 0.56; 95% CI: 0.39, 0.81), albumin (OR: 0.94; 95% CI: 0.90, 1.00), creatinine (OR: 1.00; 95% CI: 1.00, 1.01), D-dimer (OR: 1.06; 95% CI: 1.03, 1.09) and procalcitonin (OR: 1.14; 95% CI: 1.07, 1.22). A web-based dynamic nomogram (https://h1234.shinyapps.io/dynnomapp/) was constructed based on these factors. The concordance index (C index) of the nomogram was 0.798 (95% CI: 0.756, 0.840) in the training cohort and 0.808 (95% CI: 0.747, 0.870) in testing cohort. The precision-recall (PR) curves, calibration curves, decision curve analyses (DCA) and clinical impact curves showed that the nomogram has good predictive value and clinical utility. Conclusion: We developed and evaluated a convenient nomogram consisting of 8 clinical characteristics for predicting mortality in patients with pneumonia-associated ARDS.

Development and validation of a prognostic nomogram for predicting in-hospital mortality of patients with acute paraquat poisoning.

This study aimed to develop and validate a predictive model to determine the risk of in-hospital mortality in patients with acute paraquat poisoning. This retrospective observational cohort study included 724 patients with acute paraquat poisoning whose clinical data were collected within 24 h of admission. The primary outcome was in-hospital mortality. Patients were randomly divided into training and validation cohorts (7/3 ratio). In the training cohort, the least absolute shrinkage and selection operator regression models were used for data dimension reduction and feature selection. Multivariate logistic regression was used to generate a predictive nomogram for in-hospital mortality. The prediction model was assessed for both the training and validation cohorts. In the training cohort, decreased level of consciousness (Glasgow Coma Scale score < 15), neutrophil-to-lymphocyte ratio, alanine aminotransferase, creatinine, carbon dioxide combining power, and paraquat plasma concentrations at admission were identified as independent predictors of in-hospital mortality in patients with acute paraquat poisoning. The calibration curves, decision curve analysis, and clinical impact curves indicated that the model had a good predictive performance. It can be used on admission to the emergency department to predict mortality and facilitate early risk stratification and actionable measures in clinical practice after further external validation.

Transferrin-inspired iron delivery across the cell membrane using [(L2Fe)2(µ-O)] (L = chlorquinaldol) to harness anticancer activity of ferroptosis.

Although iron is a bio-essential metal, dysregulated iron acquisition and metabolism result in production of reactive oxygen species (ROS) due to the Fenton catalytic reaction, which activates ferroptotic cell death pathways. The lipophilic Fe(III)-chelator chlorquinaldol (L; i.e., 5,7-dichloro-8-hydroxy-2-methylquinoline) strongly favors the formation of a highly stable binuclear Fe(III) complex [(L2Fe)2(µ-O)] (1) that can mimic the function of the Fe(III)-transferrin complex in terms of the strong binding to Fe(III) and facile release of Fe(II) when the metal center is reduced. It should be noted that the cellular uptake of 1 is not transferrin receptor-mediated but enhanced by the high lipophilicity of chlorquinaldol. Once 1 is transported across the cell membrane, Fe(III) can be reduced by ferric reductase or other cellular antioxidants to be released as Fe(II), which triggers the Fenton catalytic reaction, thus harnessing the anticancer activity of iron. As the result, this transferrin-inspired iron-delivery strategy significantly reduces the cytotoxicity of 1 in normal human embryonic kidney cells (HEK 293) and the hemolytic activity of 1 in human red blood cells (hRBCs), giving rise to the unique tumor-specific anticancer activity of this Fe(III) complex.

Effects of Low-Fish-Meal Diet Supplemented with Coenzyme Q10 on Growth Performance, Antioxidant Capacity, Intestinal Morphology, Immunity and Hypoxic Resistance of Litopenaeus vannamei.

The aim of this study was to evaluate the effects of a low-fish-meal diet supplemented with coenzyme Q10 on the growth, antioxidant capacity, immunity, intestinal health and hypoxic resistance of Litopenaeus vannamei. L.vannamei with an initial weight of 0.66 g were fed with the experimental diets for 56 days. Diets D1 (20% FM level) and D2-D7 (15% FM level), supplemented with 0%, 0.002%, 0.004%, 0.006%, 0.008% and 0.01% coenzyme Q10 were formulated. In terms of growth performance, the weight gain and specific growth rate in the D2 diet were significantly lower than those in the D1 diet (p < 0.05). The final body weight, weight gain and specific growth rate in the D2-D7 diets had an upward trend, and the condition factor in the D2-D7 diets was lower than those in the D1 diet (p < 0.05). There were no significant differences in the crude protein and crude lipid levels in the whole body among all diet treatments (p > 0.05). In terms of hepatopancreas antioxidant parameters, the D5 and D6 diets significantly promoted the total antioxidant capacity and total superoxide dismutase activity, and significantly decreased the malondialdehyde content (p < 0.05). The expression levels of cat, mnsod and gpx in shrimp fed with the D5 and D6 diets were significantly higher than those of shrimp fed with the D2 diet (p < 0.05). In addition, the mRNA level of ProPO was increased in the D4 and D5 diets, and LZM expression was increased in the D6 diet compared with the D1 diet (p < 0.05). The villus height of shrimp fed with diets supplemented with coenzyme Q10 was significantly increased (p < 0.05), and the intestinal thickness and submucosal thickness of shrimp fed with the D6 diet were the highest (p < 0.05). After acute hypoxia stress, lethal dose 50 time in the D3-D7 diets was significantly increased compared with the D1 and D2 diets (p < 0.05), and the highest value was found in the D4 diet (p < 0.05). After stress, the expression levels of TLR pathway-related genes (Toll, Myd88, Pelle, TRAF6 and Dorsal) in the D4 and D6 diets were significantly increased compared with the D2 diet. In general, Litopenaeus vannamei fed with the D6 diet achieved the best growth, antioxidant capacity, immunity, and intestinal morphology among all low FM diets and D4-D6 diets improved hypoxic resistance.

Exploring the Impact of Head Group Modifications on the Anticancer Activities of Fatty-Acid-like Platinum(IV) Prodrugs: A Structure-Activity Relationship Study.

We conducted the first comprehensive investigation on the impact of head group modifications on the anticancer activities of fatty-acid-like Pt(IV) prodrugs (FALPs), which are a class of platinum-based metallodrugs that target mitochondria. We created a small library of FALPs (1-9) with diverse head group modifications. The outcomes of our study demonstrate that hydrophilic modifications exclusively enhance the potency of these metallodrugs, whereas hydrophobic modifications significantly decrease their cytotoxicity. To further understand this interesting structure-activity relationship, we chose two representative FALPs (compounds 2 and 7) as model compounds: one (2) with a hydrophilic polyethylene glycol (PEG) head group, and the other (7) with a hydrophobic hydrocarbon modification of the same molecular weight. Using these FALPs, we conducted a targeted investigation on the mechanism of action. Our study revealed that compound 2, with hydrophilic modifications, exhibited remarkable penetration into cancer cells and mitochondria, leading to subsequent mitochondrial and DNA damage, and effectively eradicating cancer cells. In contrast, compound 7, with hydrophobic modifications, displayed a significantly lower uptake and weaker cellular responses. The collective results present a different perspective, indicating that increased hydrophobicity may not necessarily enhance cellular uptake as is conventionally believed. These findings provide valuable new insights into the fundamental principles of developing metallodrugs.

Photoactive monofunctional platinum(II) anticancer complexes of multidentate phenanthridine-containing ligands: photocytotoxicity and evidence for interaction with DNA.

Pt(II) complexes supported by chelating, multidentate ligands containing π-extended, planar phenanthridine (benzo[c]quinoline) donors (RLPtCl) exhibit a promising in vitro therapeutic index compared with phenanthriplatin, a leading preclinical anticancer complex containing a monodentate phenanthridine ligand. Here, we report evidence for non-specific interactions of CF3LPtCl with DNA through intercalation-mediated turn-on luminescence in O2-saturated aqueous buffer. Brief irradiation with visible light (490 nm) was also found to drastically increase the activity of CF3LPtCl, with photocytotoxicity increased up to 87% against a variety of human cancer cell lines. Mechanistic studies highlight significantly improved cellular uptake of CF3LPtCl compared with cisplatin, with localization in the nucleus and mitochondria triggering effective apoptosis. Photosensitization experiments with 1,3-diphenylisobenzofuran demonstrate that CF3LPtCl efficiently mediates the generation of singlet dioxygen (1O2), highlighting the potential of RLPtCl in photodynamic therapy.

Greenhouse gas emissions from U.S. crude oil pipeline accidents: 1968 to 2020.

Crude oil pipelines are considered as the lifelines of energy industry. However, accidents of the pipelines can lead to severe public health and environmental concerns, in which greenhouse gas (GHG) emissions, primarily methane, are frequently overlooked. While previous studies examined fugitive emissions in normal operation of crude oil pipelines, emissions resulting from accidents were typically managed separately and were therefore not included in the emission account of oil systems. To bridge this knowledge gap, we employed a bottom-up approach to conducted the first-ever inventory of GHG emissions resulting from crude oil pipeline accidents in the United States at the state level from 1968 to 2020, and leveraged Monte Carlo simulation to estimate the associated uncertainties. Our results reveal that GHG emissions from accidents in gathering pipelines (~720,000 tCO2e) exceed those from transmission pipelines (~290,000 tCO2e), although significantly more accidents have occurred in transmission pipelines (6883 cases) than gathering pipelines (773 cases). Texas accounted for over 40% of total accident-related GHG emissions nationwide. Our study contributes to enhanced accuracy of the GHG account associated with crude oil transport and implementing the data-driven climate mitigation strategies.

Lipophilic Fe(III)-Complex with Potent Broad-Spectrum Anticancer Activity and Ability to Overcome Pt Resistance in A2780cis Cancer Cells.

Although iron is essential for all forms of life, it is also potentially toxic to cells as the increased and unregulated iron uptake can catalyze the Fenton reaction to produce reactive oxygen species (ROS), leading to lipid peroxidation of membranes, oxidation of proteins, cleavage of DNA and even activation of apoptotic cell death pathways. We demonstrate that Fe(hinok)3 (hinok = 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), a neutral Fe(III) complex with high lipophilicity is capable of bypassing the regulation of iron trafficking to disrupt cellular iron homeostasis; thus, harnessing remarkable anticancer activity against a panel of five different cell lines, including Pt-sensitive ovarian cancer cells (A2780; IC50 = 2.05 ± 0.90 µM or 1.20 µg/mL), Pt-resistant ovarian cancer cells (A2780cis; IC50 = 0.92 ± 0.73 µM or 0.50 µg/mL), ovarian cancer cells (SKOV-3; IC50 = 1.23 ± 0.01 µM or 0.67 µg/mL), breast cancer cells (MDA-MB-231; IC50 = 3.83 ± 0.12 µM or 2.0 µg/mL) and lung cancer cells (A549; IC50 = 1.50 ± 0.32 µM or 0.82 µg/mL). Of great significance is that Fe(hinok)3 exhibits unusual selectivity toward the normal HEK293 cells and the ability to overcome the Pt resistance in the Pt-resistant mutant ovarian cancer cells of A2780cis.

Visible light-activatable platinum(IV) prodrugs harnessing CD36 for ovarian cancer therapy.

We hereby engineered photoactivatable Pt(IV) metallodrugs that harness CD36 to target ovarian cancer cells. Pt(IV) compounds mimic the structure of fatty acids and take advantage of CD36 as a "Trojan horse" to gain entry into the cells. We confirmed that CD36-dependent entry occurs using graphite furnace atomic absorption spectroscopy with ovarian cancer cells expressing different levels of CD36 and a CD36 inhibitor, SSO. Once the Pt(IV) metallodrugs enter the cancer cells, they can be activated to form Pt(II) with characteristics of cisplatin under visible light (490 nm) irradiation, promoting photoinduced electron transfer from the attached fluorophore to the metal center. This light-induced activation can increase the cytotoxicity of the Pt(IV) metallodrugs by up to 20 times toward ovarian cancer cells, inducing DNA damage and enabling efficient elimination of drug-resistant cancer cells.

Comparison of immune cell profiles associated with heatstroke, sepsis, or cardiopulmonary bypass: Study protocol for an exploratory, case-control study trial.

Introduction: Heatstroke is a life-threatening illness involving extreme hyperthermia and multi-organ failure, and it is associated with high mortality. The immune profiles of heatstroke have not been fully elucidated, and diagnostic and prognostic biomarkers of heatstroke are lacking. This study will analyze immune profiles in heatstroke patients as they differ from profiles in patients with sepsis or aseptic inflammation patients in order to identify diagnostic and prognostic biomarkers. Methods: This exploratory, case-control study will recruit patients with heatstroke, patients with sepsis, patients undergoing cardiopulmonary bypass as well as healthy controls at West China Hospital of Sichuan University from 1 January 2023 to 31 October 2023. The four cohorts will be profiled at one time point in terms of lymphocytes, monocytes, natural killer cells, and granulocytes using flow cytometry, and cell populations will be visualized in two dimensions using t-SNE and UMAP, then clustered using PhenoGraph and FlowSOM. Gene expression in the specific immune cell populations will also be compared across the four cohorts, as will levels of plasma cytokines using enzyme-linked immunosorbent assays. Outcomes in the cohorts will be monitored during 30-day follow-up. Discussion: This trial is, to our knowledge, the first attempt to improve the diagnosis of heatstroke and prediction of prognosis based on immune cell profiles. The study is also likely to generate new insights into immune responses during heatstroke, which may help clarify the disease process and lay the foundation for immunotherapies.

Research on the evolution and the driving forces of land use classification for production, living, and ecological space in China's Qilian Mountains Nature Reserve from 2000 to 2020.

With the rapid development of the economy, problems such as resource depletion, environmental degradation, and increasingly strained human-land relations have become increasingly prominent. The rational layout of the production, living, and ecological spaces is the basis for solving the contradiction between economic development and environmental protection. This paper analyzed the spatial distribution pattern and evolution characteristics of the Qilian Mountains Nature Reserve based on the theory of production, living, and ecological space. The results show that the production and living function indexes are rising. The most advantaged areas are in the northern part of the research area, where the terrain is flat and transportation is convenient. The ecological function index rises, falls, then rises again. The high-value area is located in the south of the study area, and its ecological function is intact. The study area is dominated by ecological space. During the study period, the area of production space increased by 858.5 km2 and the living space area increased by 341.12 km2. The intensification of human activities has separated the continuity of ecological space. The area of ecological space has decreased by 233.68 km2. Among geographical factors, altitude has a significant impact on the evolution of living space. Population density is the main socioeconomic factor in changing the areas of production space and ecological space. This study is expected to provide a reference basis for land use planning and sustainable development of resources and environment in nature reserves.

Supramolecular platinum complexes for cancer therapy.

The rise of supramolecular chemistry offers new tools to design therapeutics and delivery platforms for biomedical applications. This review aims to highlight the recent developments that harness host-guest interactions and self-assembly to design novel supramolecular Pt complexes as anticancer agents and drug delivery systems. These complexes range from small host-guest structures to large metallosupramolecules and nanoparticles. These supramolecular complexes integrate the biological properties of Pt compounds and novel supramolecular structures, which inspires new designs of anticancer approaches that overcome problems in conventional Pt drugs. Based on the differences in Pt cores and supramolecular structures, this review focuses on five different types of supramolecular Pt complexes, and they include host-guest complexes of the FDA-approved Pt(II) drugs, supramolecular complexes of nonclassical Pt(II) metallodrugs, supramolecular complexes of fatty acid-like Pt(IV) prodrugs, self-assembled nanotherapeutics of Pt(IV) prodrugs, and self-assembled Pt-based metallosupramolecules.

Correlation Between Apparent Diffusion Coefficient and the Ki-67 Proliferation Index in Grading Pediatric Glioma.

OBJECTIVE: This study aimed to investigate the correlation between apparent diffusion coefficient (ADC) and the Ki-67 proliferation index with the pathologic grades of pediatric glioma and to compare their diagnostic performance in differentiating grades of pediatric glioma. PATIENTS AND METHODS: Magnetic resonance imaging examinations and histopathologies of 121 surgically treated pediatric gliomas (87 low-grade gliomas [LGGs; grades 1 and 2] and 34 high-grade gliomas [HGGs; grades 3 and 4]) were retrospectively reviewed. The mean tumor ADC (ADCmean), minimum tumor ADC (ADCmin), tumor/normal brain ADC ratio (ADC ratio), and value of the Ki-67 proliferation index of LGGs and HGGs were compared. Correlation coefficients were calculated for ADC parameters and Ki-67 values. The receiver operating characteristic curve was used to determine the diagnostic value of ADCmean, ADCmin, ADC ratio, and Ki-67 proliferation index for differentiating LGGs and HGGs. RESULTS: The ADC values were significantly negatively correlated with glioma grade, and the Ki-67 proliferation index had a significant positive correlation with glioma grade. A significant negative correlation was observed between ADCmean and Ki-67 proliferation index, between ADCmin and Ki-67 proliferation index, and between ADC ratio and Ki-67 proliferation index. The receiver operating characteristic analysis demonstrated moderate to good accuracy for ADCmean in discriminating LGGs from HGGs (area under the curve [AUC], 0.875; sensitivity, 79.3%; specificity, 82.4%; accuracy, 80.2%; positive predictive value [PPV], 92.0%; and negative predictive value [NPV], 60.9% [cutoff value, 1.187] [×10-3 mm2/s]). Minimum tumor ADC showed very good to excellent accuracy with AUC of 0.946, sensitivity of 86.2%, specificity of 94.1%, accuracy of 88.4%, PPV of 97.4%, and NPV of 72.7% (cutoff value, 0.970) (×10-3 mm2/s). The ADC ratio showed moderate to good accuracy with AUC of 0.854, sensitivity of 72.4%, specificity of 88.2%, accuracy of 76.9%, PPV of 94.0%, and NPV of 55.6% (cutoff value, 1.426). For the parameter of the Ki-67 proliferation index, in discriminating LGGs from HGGs, very good to excellent diagnostic accuracy was observed (AUC, 0.962; sensitivity, 94.1%; specificity, 89.7%; accuracy, 90.9%; PPV, 97.5%; and NPV, 78.0% [cutoff value, 7]). CONCLUSIONS: Apparent diffusion coefficient parameters and the Ki-67 proliferation index were significantly correlated with histological grade in pediatric gliomas. Apparent diffusion coefficient was closely correlated with the proliferative potential of pediatric gliomas. In addition, ADCmin showed superior performance compared with ADCmean and ADC ratio in differentiating pediatric glioma grade, with a close diagnostic efficacy to the Ki-67 proliferation index.

Protein Requirements of Oncorhynchus mykiss Cultured in the Convection-Water Cages by Evaluating Growth, Body Composition and Liver Health.

The diet formulation for trout has changed dramatically over the last decade due to changes in the ingredient markets and advances in feed processing technology. The protein requirements of Oncorhynchus mykiss were established at the end of the last century, and it is unclear whether these requirements are applicable to modern dietary formulations. Therefore, an eight-week feeding trial was performed to measure the protein requirements of O. mykiss by evaluating growth, body composition, antioxidation property, innate immune response and liver morphology. The five experimental diets were prepared to contain the same levels of crude lipid (120 g/kg) and graded levels of crude protein (356.3, 383.9, 411.5, 439.2 and 466.8 g/kg). The results suggested that the growth, feed utilization and whole-body crude protein levels were significantly increased when fish were fed diets containing 439.2 and 466.8 g/kg crude protein. Meanwhile, low dietary protein levels (356.3 and 383.9 g/kg) significantly down-regulated the mRNA levels of insulin-like growth factor I, catalase, glutathione peroxidase, superoxide dismutase, complement 3 and lysozyme, and also up-regulated the insulin-like growth factor binding protein 1 as well as proinflammatory cytokine expression in the liver, including interleukin 1ß, interleukin 8 and tumor necrosis factor-α. Moreover, low dietary protein levels (356.3 and 383.9 g/kg) damaged liver structure, suppressed total antioxidative capacity and increased the malondialdehyde content in liver. In conclusion, high dietary protein (439.2 and 466.8 g/kg) promoted fish growth, while low dietary protein (356.3 and 383.9 g/kg) damaged liver structure, induced oxidative stress and inflammatory responses and weakened non-specific immunity. The protein requirement of O. mykiss reared in the convection-water cages is no less than 439.2 g/kg for optimal growth, antioxidant and immune properties.

Association of admission lactate with mortality in adult patients with severe community-acquired pneumonia.

PURPOSE: The present study was conducted to investigate the association of admission lactate with mortality in severe community-acquired pneumonia (SCAP). METHODS: We performed a retrospective, observational, cohort study on adult SCAP patients admitted to intensive care unit (ICU) in West China Hospital of Sichuan University between December 2011 and December 2018. The primary outcome was hospital mortality. Univariate and then multivariate analysis were performed to identify independent risk factors for hospital mortality. The association of admission lactate categories with hospital mortality was examined in three logistic regression models and Kaplan-Meier plots. We also applied restricted cubic splines to estimate the potential non-linear associations. RESULTS: In total, 2275 SCAP patients were included. Admission lactate remained a significant factor for mortality after multivariate regression (OR: 1.085; 95% CI: 1.033,1.141; by continuous variable). After lactate was categorized into quartiles and the confounders were fully adjusted, compared with the quartile 1, ORs (95% CIs) of hospital mortality for quartile 2, quartile 3 and quartile 4 were 1.001 (0.759-1.321), 1.153 (0.877-1.516) and 1.593 (1.202-2.109), respectively (P for trend =0.001). Survival curves indicated that elevated lactate was associated with poor prognosis (P < 0.001). Moreover, this association was non-linear, indicating that increased lactate has the most notable impact on mortality within the range of 1.5 to 4 mmol/L (P non-linear: 0.029 for hospital mortality; 0.004 for ICU mortality). CONCLUSION: Elevated admission lactate has a significant, independent, and potentially non-linear association with increased mortality in SCAP patients.