Carbon, Nitrogen and Phosphorus Stoichiometry in Natural and Plantation Forests in China

Ecological stoichiometry is essential for understanding the biogeochemical cycle in forest ecosystems. However, previous studies of ecological stoichiometry have rarely considered the impacts of forest origins, which could help explain why to date so much uncertainty has been reported on this subject. In this study, we tried to reduce this uncertainty by examining carbon (C), nitrogen (N) and phosphorus (P) in roots, litter and soil in both natural and plantation forests throughout China. The sampled forest sites were divided into three groups according to the identified succession stages: early (ES), middle (MS) and late (LS) stages. Our results show that soil C, N and P concentrations were significantly higher in natural (NF) than in plantation (PL) forests. As succession/growth proceeded, P concentrations significantly increased in litter, roots and soil in NF, while the opposite occurred in PL. These results indicate that NF are able to use P more efficiently than PL, especially in the LS. Furthermore, the higher root N:P ratio indicates that the growth of PL was limited by P in both MS and LS. Our results also suggest that geographical and climatic factors are not the dominant factors in the differences in P between NF and PL, and, even more clearly and importantly, that native forests with native species are more capable of conserving P than planted forests, which are frequently less diverse and dominated by fast-growing non-site native species. These results will help improve biogeochemical models and forest management throughout the world

Trajectories of Haemoglobin and incident stroke risk: a longitudinal cohort study.

BACKGROUND: Studies have demonstrated that high or low haemoglobin increases the risk of stroke. Previous studies, however, performed only a limited number of haemoglobin measurements, while there are dynamic haemoglobin changes over the course of a lifetime. This longitudinal cohort study aimed to classify the long-term trajectory of haemoglobin and examine its association with stroke incidence. METHODS: The cohort consisted of 11,431 participants (6549 men) aged 20 to 50 years whose haemoglobin was repeatedly measured 3-9 times during 2004-2015. A latent class growth mixture model (LCGMM) was used to classify the long-term trajectory of haemoglobin concentrations, and hazard ratios (HRs) and 95% confidence intervals (95% CI) according to the Cox proportional hazard model were used to investigate the association of haemoglobin trajectory types with the risk of stroke. RESULTS: Three distinct trajectory types, high-stable (n = 5395), normal-stable (n = 5310), and decreasing (n = 726), were identified, with stroke incidence rates of 2.7, 1.9 and 3.2 per 1000 person-years, respectively. Compared to the normal-stable group, after adjusting for the baseline covariates, the decreasing group had a 2.94-fold (95% CI 1.22 to 7.06) increased risk of developing stroke. Strong evidence was observed in men, with an HR (95% CI) of 4.12 (1.50, 11.28), but not in women (HR = 1.66, 95% CI 0.34, 8.19). Individuals in the high-stable group had increased values of baseline covariates, but the adjusted HR (95% CI), at 1.23 (0.77, 1.97), was not significant for the study cohort or for men and women separately. CONCLUSIONS: This study revealed that a decreasing haemoglobin trajectory was associated with an increased risk of stroke in men. These findings suggest that long-term decreasing haemoglobin levels might increase the risk of stroke

Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes

The perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature-on-a-chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single-cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions

Topical capsaicin in PLGA NPs decreases acute itch and heat pain

Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent

Conformational changes in HL60 cells during differentiation and apoptosis induced by genistein

Genistein can induce not only differentiation but also apoptosis in HL60 human leukemia cells. During the differentiation and apoptosis, the HL60 cells undergo some conformational changes. Fourier transform infrared (FT-IR) was employed to detect those changes. The results showed that the contents of DNA/protein and glycoprotein/protein increased. The α-helix of the membrane protein also increased. In addition, the JG(CZJYOJG) (H) stretching mode of serine, threonine and tyrosine residues of the cell proteins also changed. Those conformational changes suggest some mechanisms for how genistein affects the HL60 cells

Effects of dioscin extracted from Polygonatum Zanlanscianense Pamp on several human tumor cell lines

Dioscin was extracted and isolated from Polygonatum Zanlanscianense   Pamp. The effects of dioscin on HL60, HeLa, H14, and MDA-MB-435 cell lines were studied with the results showing that dioscin dramatically inhibited the growth of the MDA-MB-435, H14, HL60, and HeLa cell lines. The IC50 of dioscin on these cell lines were 2.6, 0.8, 7.5, and 4.5 μmol/L respectivel

Preclinical Models of Brain Metastases in Breast Cancer

Breast cancer remains a leading cause of mortality among women worldwide. Brain metastases confer extremely poor prognosis due to a lack of understanding of their specific biology, unique physiologic and anatomic features of the brain, and limited treatment strategies. A major roadblock in advancing the treatment of breast cancer brain metastases (BCBM) is the scarcity of representative experimental preclinical models. Current models are predominantly based on the use of animal xenograft models with immortalized breast cancer cell lines that poorly capture the disease’s heterogeneity. Recent years have witnessed the development of patient-derived in vitro and in vivo breast cancer culturing systems that more closely recapitulate the biology from individual patients. These advances led to the development of modern patient-tissue-based experimental models for BCBM. The success of preclinical models is also based on the imaging technologies used to detect metastases. Advances in animal brain imaging, including cellular MRI and multimodality imaging, allow sensitive and specific detection of brain metastases and monitoring treatment responses. These imaging technologies, together with novel translational breast cancer models based on patient-derived cancer tissues, represent a unique opportunity to advance our understanding of brain metastases biology and develop novel treatment approaches. This review discusses the state-of-the-art knowledge in preclinical models of this disease