Direct isolation of small extracellular vesicles from human blood using viscoelastic microfluidics.

Small extracellular vesicles (sEVs; <200 nm) that contain lipids, nucleic acids, and proteins are considered promising biomarkers for a wide variety of diseases. Conventional methods for sEV isolation from blood are incompatible with routine clinical workflows, significantly hampering the utilization of blood-derived sEVs in clinical settings. Here, we present a simple, viscoelastic-based microfluidic platform for label-free isolation of sEVs from human blood. The separation performance of the device is assessed by isolating fluorescent sEVs from whole blood, demonstrating purities and recovery rates of over 97 and 87%, respectively. Significantly, our viscoelastic-based microfluidic method also provides for a remarkable increase in sEV yield compared to gold-standard ultracentrifugation, with proteomic profiles of blood-derived sEVs purified by both methods showing similar protein compositions. To demonstrate the clinical utility of the approach, we isolate sEVs from blood samples of 20 patients with cancer and 20 healthy donors, demonstrating that elevated sEV concentrations can be observed in blood derived from patients with cancer.

Insight into the relationship between metabolite dynamic changes and microorganisms of sea urchin (S. intermedius) gonads during storage.

Sea urchin gonads have high nutritional value and degenerate rapidly during storage. Previous assessment of the freshness of sea urchin gonads was based on experience without valid biochemical indicators. Thus, the current study is to find biochemical indicators representing the freshness of sea urchin gonads. Results showed that the dominant genera of sea urchin gonads were changed from Psychromonas, Ralstonia, and Roseimarinus to Aliivibrio, Psychrilyobacter, and Photobacterium. The differential metabolites of sea urchin gonads were mainly produced through amino acids metabolism. Among them, GC-TOF-MS based differential metabolites had the greatest enrichment in the valine, leucine and isoleucine biosynthesis pathway, while LC-MS based differential metabolites had the greatest enrichment in the alanine, aspartate and glutamate metabolism pathway. The growth of dominant genus (Aliivibrio) had a great influence on the production of differential metabolites. These results will provide valuable information for accurately judging the freshness and shelf life of sea urchin gonads.

Molecular mechanism of thiamine in mitigating drought stress in Chinese wingnut (Pterocarya stenoptera): Insights from transcriptomics.

Urban garden plants are frequently affected by drought, which can hinder their growth, development, and greening effect. Previous studies have indicated that Chinese wingnut (Pterocarya stenoptera) responds to drought stress by increasing the expression of thiamine synthesis genes. In this study, it was found that exogenous thiamine can effectively alleviate the negative effects of drought stress on plants. Forward transcriptome sequencing and physiological tests were further conducted to reveal the molecular mechanism of thiamine in alleviating drought stress. Results showed that exogenous thiamine activated the expression of eight chlorophyll synthesis genes in Chinese wingnut under drought stress. Moreover, physiological indicators proved that chlorophyll content increased in leaves of Chinese wingnut with thiamine treatment under drought stress. Photosynthesis genes were also activated in Chinese wingnut treated with exogenous thiamine under drought stress, as supported by photosynthetic indicators PIabs and PItotal. Additionally, exogenous thiamine stimulated the expression of genes in the auxin-activated signaling pathway, thus attenuating the effects of drought stress. This study demonstrates the molecular mechanism of thiamine in mitigating the effects of drought stress on non-model woody plants lacking transgenic systems. This study also provides an effective method to mitigate the negative impacts of drought stress on plants.

Fusarium-produced vitamin B6 promotes the evasion of soybean resistance by Phytophthora sojae.

Plants can be infected by multiple pathogens concurrently in natural systems. However, pathogen-pathogen interactions have rarely been studied. In addition to the oomycete Phytophthora sojae, fungi such as Fusarium spp. also cause soybean root rot. In a 3-year field investigation, we discovered that P. sojae and Fusarium spp. frequently coexisted in diseased soybean roots. Out of 336 P. sojae-soybean-Fusarium combinations, more than 80% aggravated disease. Different Fusarium species all enhanced P. sojae infection when co-inoculated on soybean. Treatment with Fusarium secreted non-proteinaceous metabolites had an effect equal to the direct pathogen co-inoculation. By screening a Fusarium graminearum mutant library, we identified Fusarium promoting factor of Phytophthora sojae infection 1 (Fpp1), encoding a zinc alcohol dehydrogenase. Fpp1 is functionally conserved in Fusarium and contributes to metabolite-mediated infection promotion, in which vitamin B6 (VB6) produced by Fusarium is key. Transcriptional and functional analyses revealed that Fpp1 regulates two VB6 metabolism genes, and VB6 suppresses expression of soybean disease resistance-related genes. These results reveal that co-infection with Fusarium promotes loss of P. sojae resistance in soybean, information that will inform the sustainable use of disease-resistant crop varieties and provide new strategies to control soybean root rot.

Genome-wide investigation of the WRKY transcription factor gene family in weeping forsythia: expression profile and cold and drought stress responses.

Weeping forsythia is a wide-spread shrub in China with important ornamental, medicinal and ecological values. It is widely distributed in China's warm temperate zone. In plants, WRKY transcription factors play important regulatory roles in seed germination, flower development, fruit ripening and coloring, and biotic and abiotic stress response. To date, WRKY transcription factors have not been systematically studied in weeping forsythia. In this study, we identified 79 WRKY genes in weeping forsythia and classified them according to their naming rules in Arabidopsis thaliana. Phylogenetic tree analysis showed that, except for IIe subfamily, whose clustering was inconsistent with A. thaliana clustering, other subfamily clustering groups were consistent. Cis-element analysis showed that WRKY genes related to pathogen resistance in weeping forsythia might be related to methyl jasmonate and salicylic acid-mediated signaling pathways. Combining cis-element and expression pattern analyses of WRKY genes showed that more than half of WRKY genes were involved in light-dependent development and morphogenesis in different tissues. The gene expression results showed that 13 WRKY genes were involved in drought response, most of which might be related to the abscisic acid signaling pathway, and a few of which might be regulated by MYB transcription factors. The gene expression results under cold stress showed that 17 WRKY genes were involved in low temperature response, and 9 of them had low temperature responsiveness cis-elements. Our study of WRKY family in weeping forsythia provided useful resources for molecular breeding and important clues for their functional verification.

Syndemic Profiles and Sexual Health Risks Among Sexually Exploited Adolescent Girls in Taiwan: A Latent Class Analysis.

Sexually exploited adolescent girls are disproportionately affected by adverse psychosocial conditions, such as intra-familial child physical and sexual abuse, extra-familial violence and sexual assault, alcohol and drug use, and suicide. Syndemic theory suggests that these adverse psychosocial or syndemic conditions are concentrated and co-occurring in socially marginalized populations, including sexually exploited adolescents, and increase their sexual health risks, including pregnancy, abortion, and the acquisition of sexually transmitted diseases (STDs). To examine clusters of syndemic conditions, latent class analysis (LCA) was conducted to classify 335 sexually exploited girls in Taiwan into subgroups based on their probability of experiencing each syndemic condition. We used syndemic class membership to predict their sexual health outcomes, specifically pregnancy, abortion, and the acquisition of STDs. The results of LCA revealed three classes, which were "low-risk syndemic," "moderate-risk syndemic," and "high-risk syndemic." The risk of acquisition of STDs among sexually exploited girls in the "high-risk syndemic class" and "moderate-risk syndemic class" was 239% and 135% higher, respectively, than the risk of acquisition of STDs among sexually exploited girls in the "low-risk syndemic class." Differences between these three classes in pregnancy and abortion were not significant. Our findings support the syndemic theory that a pattern of syndemic conditions is associated with an increased risk of acquiring STDs. Interventions aimed at reducing the acquisition of STDs among sexually exploited girls in Taiwan should adopt a comprehensive approach to address co-occurring conditions.

Metal-Organic Frameworks in Microfluidics Enable Fast Encapsulation/Extraction of DNA for Automated and Integrated Data Storage.

DNA as an exceptional data storage medium offers high information density. However, DNA storage requires specialized equipment and tightly controlled environments for storage. Fast encapsulation within minutes for enhanced DNA stability to do away with specialized equipment and fast DNA extraction remain a challenge. Here, we report a DNA microlibrary that can be encapsulated by metal-organic frameworks (MOFs) within 10 min and extracted (5 min) in a single microfluidic chip for automated and integrated DNA-based data storage. The DNA microlibrary@MOFs enhances the stability of data-encoded DNA against harsh environments. The encoded information can be read out perfectly after accelerated aging, equivalent to being readable after 10 years of storage at 25 °C, 50% relative humidity, and 10 000 lx sunlight radiation. Moreover, the library enables fast retrieval of target data via flow cytometry and can be reproduced after each access.

Evaluation of Guided Respiration Mindfulness Therapy (GRMT) for Reducing Stress in Nurses.

Guided respiration mindfulness therapy (GRMT) is a clinical model of breathwork that has shown promise as a treatment for depression, anxiety, and stress. This study examined the effectiveness of GRMT as a holistically oriented intervention for reducing psychological distress in nurses. Sixty-two nurses were assigned to either five sessions of GRMT or 5 sessions of a mindfulness-based intervention (MBI) comparison condition which were conducted over 5 weeks. A no-treatment control was also included. Session-by-session change in depression, anxiety, and stress, along with change in mindfulness and self-compassion were assessed. Multilevel analysis showed GRMT resulted in statistically significant reductions in overall psychological distress, anxiety, and stress levels, as well as significant increases in mindfulness and self-compassion with large to very large effect sizes. On all measures, GRMT performed better than the comparison MBI intervention which showed no significant effect on stress levels. Results suggest that GRMT can provide nurses with an effective group intervention for reducing stress, and increasing mindfulness and self-compassion which are foundational elements of self-care for the holistic nurse.

Enhanced removal of hexavalent chromium by lignosulfonate modified zero valent iron: Reaction kinetic, performance and mechanism.

The application of lignin derivative as modifier is an economical and efficient approach to improve the reactivity of raw material towards pollutant removal. In this study, lignosulfonate modified zero valent iron (LS-ZVI) was firstly prepared by ball-milling method and utilized for Cr(VI) removal under different conditions. The comparative experiments showed that lignosulfonate modification could significantly enhance the Cr(VI) removal by ZVI from <10 % to 100 % within 90 min reaction. Compared to ZVI, the specific surface area of LS-ZVI increased 3.4 times and surface Fe(0) content increased from 3.4 % to 10.5 % due to the surface erosion, resulting in the high-efficient Cr(VI) removal. Solution and solid-phase analyses indicated that Fe(0) played dominated role and generated Fe(II) involved in Cr(VI) removal process, which mainly included rapid adsorption, reduction and co-precipitation. Batch experiments revealed that lower pH conditions were beneficial for Cr(VI) removal and the effect of co-existing ions (Ca2+, Mg2+, NO3-, Cl-, and SO42-) was negligible except the inhibitory effect of NO3-. Moreover, LS-ZVI also exhibited excellent removal performance for Ni(II), Zn(II), and Cd(II) with removal efficiency beyond 96.6 %. Overall, this work provides a feasible approach for enhancing the reactivity of commercial ZVI in the treatment of heavy metal pollution.

Effect of sulfidation on nitrobenzene removal from groundwater by microscale zero-valent iron: Insights into reactivity, reaction sites and removal pathways.

While it has been recognized that sulfidation can effectively improve the reactivity of microscale zero valent iron (mZVI), there is limited understanding of nitrobenzene (ArNO2) removal by sulfidated mZVI. To understand the reduction capacity and pathway of ArNO2 by sulfidated mZVI, ball-milling sulfidated mZVI (S-mZVIbm) with different S/Fe molar ratios (0-0.2) was used to conduct this experiment. The results showed that sulfidation could efficiently enhance ArNO2 removal under iron-limited and iron excess conditions, which was attributed to the presence of FeSx sites that could provide higher Fe(0) utilization efficiency and stronger passivation resisting for S-mZVIbm. The optimum ArNO2 reduction could be obtained by S-mZVIbm with S/Fe molar ratio at 0.1, which could completely transform ArNO2 to aniline (ArNH2) with a rate constant of 4.36 × 10-2 min-1 during 120-min reaction. FeSx phase could act as electron transfer sites for ArNO2 reduction and it could still be reserved in S-mZVIbm after reduction reaction. The product distribution indicated that sulfidation did not change the types of reduction products, while the removal of ArNO2 by S-mZVIbm was a step-by-step reduction progress along with the adsorption of ArNH2. In addition, a faster reduction of ArNO2 in groundwater/soil system further demonstrated the feasibility of S-mZVIbm in the real field remediation.

Comparative analysis of cold-responsive genes under short-term cold stimulation and cold-adaptive genes under long-term heterogeneous environments reveals a cold adaptation mechanism in weeping forsythia.

Identifying cold-related genes can provide insights into the cold adaptation mechanism of weeping forsythia. In this study, we compared the changes in gene expressions and physiological and biochemical indices under short-term cold stimulation with the changes in gene sequences under a long-term heterogeneous environment to investigate the cold adaptation mechanism in weeping forsythia. The data of adaptive gene sequence changes, e.g., single nucleotide polymorphisms, were obtained from previous landscape genomics studies. The physiological and biochemical indicators and transcriptome results showed that weeping forsythia initiated a series of programs, including increasing cell osmotic pressures, scavenging ROS, activating the defense mechanism that crosses with pathogen infection, and upregulating CBF/DREB1 transcription factor 1, to cope with short-term cold stress. A reanalysis of landscape genomic data suggested that weeping forsythia responded to long-term heterogeneous cold stress by the differentiation of genes related to synthesis of aromatic substances and adenosine triphosphate. Our results supported the hypothesis that the adaptation mechanisms of species to short-term environmental stimulation and long-term stress in heterogeneous environments are different. The differences in cold tolerance among populations are not necessarily obtained by changing cold-responsive gene sequences. This study provides new insights into the cold adaptation mechanisms of plants.

A necroptosis-related prognostic model for predicting prognosis, immune landscape, and drug sensitivity in hepatocellular carcinoma based on single-cell sequencing analysis and weighted co-expression network.

Background: Hepatocellular carcinoma (HCC) is a highly lethal cancer and is the second leading cause of cancer-related deaths worldwide. Unlike apoptosis, necroptosis (NCPS) triggers an immune response by releasing damage-related molecular factors. However, the clinical prognostic features of necroptosis-associated genes in HCC are still not fully explored. Methods: We analyzed the single-cell datasets GSE125449 and GSE151530 from the GEO database and performed weighted co-expression network analysis on the TCGA data to identify the necroptosis genes. A prognostic model was built using COX and Lasso regression. In addition, we performed an analysis of survival, immunity microenvironment, and mutation. Furthermore, the hub genes and pathways associated with HCC were localized within the single-cell atlas. Results: Patients with HCC in the TCGA and ICGC cohorts were classified using a necroptosis-related model with significant differences in survival times between high- and low-NCPS groups (p < 0.05). High-NCPS patients expressed more immune checkpoint-related genes, suggesting immunotherapy and some chemotherapies might prove beneficial to them. In addition, a single-cell sequencing approach was conducted to investigate the expression of hub genes and associated signaling pathways in different cell types. Conclusion: Through the analysis of single-cell and bulk multi-omics sequencing data, we constructed a prognostic model related to necroptosis and explored the relationship between high- and low-NCPS groups and immune cell infiltration in HCC. This provides a new reference for further understanding the role of necroptosis in HCC.

A nomogram for prediction of distant metastasis in patients with hypopharyngeal squamous cell carcinoma: a study based on the SEER database.

BACKGROUND: The prognosis of hypopharyngeal squamous cell carcinoma (HPSCC) is poor due to its high incidence of local invasion and distant metastasis (DM). This study aims to explore the DM risk factors of HPSCC and establish a clinical prediction model. METHODS: We downloaded patient data from the Public Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2018. Univariate and multivariate logistic regression analyses were performed to screen the clinical risk factors for DM of HPSCC. A new nomogram prediction model was then established based on the selected clinical risk factors. We further validated the model's accuracy based on the concordance index (C-index), the area under the receiver operating characteristic (AUC) curve, and the calibration plot. The decision curve analysis (DCA) to test the potential clinical value of the new model was also applied. RESULTS: A total of 3502 patients were enrolled; the patients with HPSCC were randomly assigned to a training set (n=2463) and a validation set (n=1039). Multivariate Logistic model analysis suggested that sex, T stage, N stage, and the total number of tumors were influence factors for DM of HPSCC. We established and validated a novel nomogram prediction model based on the multivariate logistic model with these influence factors. The C-index was 0.943 and 0.849 in the training and validation sets respectively. The AUC of the training set was 0.705 (95% CI: 0.669-0.741), and the validation set was 0.667 (95% CI: 0.609-0.725). The calibration plot shows that the actual observation value was similar to the predicted value, meaning the model has an excellent discrimination ability. DCA of the nomogram in the training and validation sets suggested that our nomogram has potential application value. CONCLUSIONS: We found that sex, T stage, N stage, and the total number of tumors are independent risk factors for DM of HPSCC. We developed a novel prediction model to predict DM in patients with HPSCC. This nomogram can identify patients with a high risk of DM and has a high clinical application value.

Integrated Microfluidic DNA Storage Platform with Automated Sample Handling and Physical Data Partitioning.

Biopolymers are considered a promising alternative for information storage, and the most successful implementation has been using chemically synthesized DNA to represent binary data, which has achieved tremendous progress at multiple fronts bridging biotechnology with digital information. Currently, a majority of these systems are lacking the system integration and process automation expected by users of digital data and overly use tubes/vials for DNA storage. Herein, we present a microfluidic platform for automated storage and retrieval of data-encoding oligonucleotide samples enabled by a microvalve network architecture. Our platform, equipped with individually addressable compartments, offers an orthogonal strategy of data partitioning and file indexing with respect to the molecular-based random access implementation, with each partition amounting to an equivalence of 9.5 TB data within a 4 × 2 mm2 area. We examined the functionality of the presented platform and its compatibility with the DNA storage workflow coupled with nanopore sequencing to fully recover the stored files, demonstrating a significantly enhanced degree of function integration and process automation compared to that of the existing microfluidic approach.

Identification of the KCNQ1OT1/ miR-378a-3p/ RBMS1 Axis as a Novel Prognostic Biomarker Associated With Immune Cell Infiltration in Gastric Cancer.

Background: Gastric cancer (GC) is the second leading cause of cancer-related mortality and the fifth most common cancer worldwide. However, the underlying mechanisms of competitive endogenous RNAs (ceRNAs) in GC are unclear. This study aimed to construct a ceRNA regulation network in correlation with prognosis and explore a prognostic model associated with GC. Methods: In this study, 1,040 cases of GC were obtained from TCGA and GEO datasets. To identify potential prognostic signature associated with GC, Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression were employed. The prognostic value of the signature was validated in the GEO84437 training set, GEO84437 test set, GEO15459 set, and TCGA-STAD. Based on the public databases, TargetScan and starBase, an mRNA-miRNA-lncRNA regulatory network was constructed, and hub genes were identified using the CytoHubba plugin. Furthermore, the clinical outcomes, immune cell infiltration, genetic variants, methylation, and somatic copy number alteration (sCNA) associated with the ceRNA network were derived using bioinformatics methods. Results: A total of 234 prognostic genes were identified. GO and GSEA revealed that the biological pathways and modules related to immune response and fibroblasts were considerably enriched in GC. A nomogram was generated to provide accurate prognostic outcomes and individualized risk estimates, which were validated in the training, test dataset, and two independent validation datasets. Thereafter, an mRNA-miRNA-lncRNA regulatory network containing 4 mRNAs, 22 miRNAs, 201 lncRNAs was constructed. The KCNQ1OT1/hsa-miR-378a-3p/RBMS1 ceRNA network associated with the prognosis was obtained by hub gene analysis and correlation analysis. Importantly, we found that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may play a vital role in the diagnosis and prognosis of GC patients based on Cox regression analyses. Furthermore, our findings demonstrated that mutations and sCNA of the KCNQ1OT1/miR-378a-3p/RBMS1 axis were associated with increased immune infiltration, while the abnormal upregulation of the axis was primarily a result of hypomethylation. Conclusion: Our findings suggest that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may be a potential prognostic biomarker and therapeutic target for GC. Moreover, such findings provide insights into the molecular mechanisms of GC pathogenesis.

Emodin Ameliorates the Efficacy of Carfilzomib in Multiple Myeloma Cells via Apoptosis and Autophagy.

BACKGROUND: Carfilzomib, the proteasome inhibitor, can increase the overall survival rate of multiple myeloma (MM) patients undergoing targeted therapy. However, relapse and toxicity present great challenges for such treatment, so an urgent need for effective combination therapy is necessary. Emodin is a natural chemical compound that inhibits the proliferation of various cancers and can effectively combine with other treatments. In this study, we evaluated the sensitizing effect of emodin combined with carfilzomib on MM cells. METHODS: The cells were treated with emodin, carfilzomib, and a combination of drugs to determine their effects on cell proliferation and viability. The cell cycle distribution and reactive oxygen species (ROS) expression were measured by flow cytometry. The level of RNA and protein were analyzed through real-time qPCR and immunoblotting. RESULTS: Emodin acted synergistically with carfilzomib to reduce the proliferation and viability of MM cell lines in vitro. Furthermore, the combination of emodin and carfilzomib increased ROS production, inducing apoptosis and autophagy pathways via caspase-3, PARP, p62, and LC3B. CONCLUSIONS: These results provide a molecular target for combination therapy in MM patients.

The Diversity of Soil Bacteria and Fungi Under Altered Nitrogen and Rainfall Patterns in a Temperate Steppe.

The response of soil microorganisms to altered nitrogen (N) and rainfall patterns plays an important role in understanding ecosystem carbon and nitrogen cycling processes under global change. Previous studies have separately focused on the effects of N addition and rainfall on soil microbial diversity and community composition. However, the combined and interactive impact of N addition and rainfall on soil microbial diversity and function mediated by plant and soil processes have been poorly investigated for grassland ecosystems. Here, we conducted a field experiment with simulated N addition (N addition: 10 g N m-2yr-1) and altered rainfall pattern [control, rainfall reduction (compared to control -50%); rainfall addition (compared to control + 50%)] to study their interactive effects on soil microbial diversity and function in a temperate steppe of Inner Mongolia. Our results showed that N addition and rainfall addition significantly increased soil bacterial diversity, and the bacterial diversity was positively correlated with soil microbial biomass nitrogen, inorganic nitrogen, and Stipa krylovii root exudate C:N ratio, Allium polyrhizum root exudate C and N, and A. polyrhizum root exudate C:N ratio. N addition and rainfall reduction significantly reduced fungal diversity, which correlated closely with soil microbial biomass carbon and the C:N ratio of A. polyrhizum root exudates. Bacteria were mainly eutrophic r-strategists, and the responses of bacterial function guilds to the interaction between N addition and rainfall pattern were not significant. However, the arbuscular mycorrhizal fungi (AMF), in the functional classification of fungi, were significantly reduced under the condition of N addition and rainfall reduction, and the absolute abundance of the phylum Glomeromycota increased under rainfall addition, suggesting that AMFs are sensitive to altered N and rainfall patterns over short timescales (1 year). Collectively, our results have important implications for understanding the plant-soil-microbe system of grasslands under climate change.

Utilization of hospice and nonhospice care in patients with end-stage renal disease on dialysis.

Objectives: The prevalence of end-stage renal disease (ESRD) and the number of patients undergoing dialysis in Taiwan are high. Since September 2009, the National Health Insurance has started to provide hospice care to patients with renal failure in Taiwan. Therefore, it is necessary to understand the use of hospice and nonhospice care in patients with ESRD on dialysis. We aim to understand trends in patients with ESRD receiving hospice and nonhospice care as well as medical care efforts during the last month of their lives (2009-2013). Materials and Methods: The cohort study was conducted using 1 million randomly selected samples from the Taiwan Health Insurance Research Database for millions of people in Taiwan in 2009-2013. Descriptive statistics were presented to summarize the characteristics of data. To compare differences between cohorts, Chi-square tests and Student's t-tests were used. Mann-Whitney U-tests were performed for nonnormally distributed data. Mantel-Haenszel test was test for trend. Results: We recruited 770 ESRD patients who underwent hemodialysis; among them, 154 patients received hospice care. Patients who received hospice care had a significantly longer survival time after removal of mechanical ventilator (20 vs. 0 days) and after discontinuation of dialysis (2 vs. 0 days) compared with those who did not receive hospice care. Patients who received hospice care had more pain control (61.04% vs. 17.37%, P < 0.0001) and other symptomatic control (55.84% vs. 43.18% with diuretics, P < 0.05; 64.29% and 48.21% with laxatives, P = 0.0004) medications than those who did not. Nevertheless, the overall medical cost in the hospice group was significantly lower (90 USD and 280 USD, P < 0.0001). Conclusion: Our results suggest that the addition of hospice care may permit patients a longer life-support-free survival time. In addition, despite a more frequent symptomatic controlling agent use, hospice care significantly reduced the overall medical expenditure.

Breast-Milk Rubidium and Other Trace Elements are Associated with Neurocognitive Development in Infants at Age of 8 Months.

BACKGROUND: Trace elements may affect neurodevelopment. There is a lack of data on breast-milk rubidium (Rb) in relation to neurodevelopment in infants. The associations of copper (Cu), zinc (Zn) and strontium (Sr) with neurodevelopment in infants remain uncertain. OBJECTIVES: We sought to evaluate the associations of breast-milk Rb (primary exposure), Cu, Zn, and Sr with neurodevelopment in infants at age 8 months. METHODS: The study cohort included 117 breastfed infants. Breast-milk samples were collected at 42 days and 8 months postpartum. Breast-milk Rb, Zn, Cu, and Sr were measured by inductively coupled plasma mass spectrometer. Neurodevelopment was assessed at age 8 months. The primary outcomes were attention and working memory scores, as evaluated by the A-not-B task. Other outcomes included the Mental Development Index (MDI) and Psychomotor Development Index (PDI) as evaluated by the Bayley Scale of Infant Development III. Generalized linear models and restricted cubic spline regression were used to assess the associations between trace elements and neurodevelopment indices. Bonferroni correction was conducted on all data presented. RESULTS: A nonlinear association was observed between breast-milk Rb at 42 days and infant's attention at age 8 months (nonlinearity P = 0.037). Positive associations were observed with infant MDI scores and breast-milk Rb at 42 days (ß = 4.46; P = 0.06) and 8 months (ß = 3.79; P = 0.009) postpartum. Breast-milk Zn at 42 days was positively associated with infant's attention (ß = 0.31; P = 0.039). Sr at 42 days was positively correlated with attention (ß = 0.18; P = 0.043) and MDI scores (ß = 2.18; P = 0.015) at 8 months. Inverted U-shape associations were observed for breast-milk Cu at 42 days with infant attention and PDI scores. All associations were not significant after correction for multiple tests. CONCLUSIONS: Our data suggest that Rb, Zn, Cu, and Sr in breast milk at certain concentrations are associated with neurodevelopment in breastfed infants. Further studies are warranted to validate the findings.

Current and future distribution of the deciduous shrub Hydrangea macrophylla in China estimated by MaxEnt.

Climate change has a significant impact on the growth and distribution of vegetation worldwide. Hydrangea macrophylla is widely distributed and considered a model species for studying the distribution and responses of shrub plants under climate change. These results can inform decision-making regarding shrub plant protection, management, and introduction of germplasm resources, and are of great importance for formulating ecological countermeasures to climate change in the future. We used the maximum entropy model to predict the change, scope expansion/reduction, centroid movement, and dominant climate factors that restrict the growth and distribution of H. macrophylla in China under current and future climate change scenarios. It was found that both precipitation and temperature affect the distribution of suitable habitat for H. macrophylla. Akaike information criterion (AICc) was used to select the feature combination (FC) and the regularization multiplier (RM). After the establishment of the optimal model (FC = QP, RM = 0.5), the complexity and over-fitting degree of the model were low (delta AICc = 0, omission rate = 0.026, difference between training and testing area under the curve values = 0.0009), indicating that it had high accuracy in predicting the potential geographical distribution of H. macrophylla (area under the curve = 0.979). Overall, from the current period to future, the potential suitable habitat of this species in China expanded to the north. The greenhouse effect caused by an increase in CO2 emissions would not only increase the area of high-suitability habitat in Central China, but also expand the area of total suitable habitat in the north. Under the maximum greenhouse gas emission scenario (RCP8.5), the migration distance of the centroid was the longest (e.g., By 2070s, the centroids of total and highly suitable areas have shifted 186.15 km and 89.84 km, respectively).