Provenance variation of root C, N, P, and K stoichiometric characteristics under different diameter classes of Larix gmelinii.

For exploring the difference of root stoichiometric characteristics among diameter classes and provenances, we examined the contents and stoichiometric ratios of carbon (C), nitrogen (N), phosphorus (P), and potassium (K) in three diameter classes of roots (0-1, 1-2 and 2-5 mm, respectively) of 39-year-old Larix gmelinii grown in a common garden. The results showed that root element contents and their stoichiometric ratios had significant difference among three diameter classes of roots. C content, C:N, C:P, C:K were the lowest, and N, P, K contents, N:P, and N:K were the highest in 0-1 mm diameter class roots. Compared with the 1-2 and 2-5 mm diameter class roots, 0-1 mm diameter class roots had different seasonal dynamics, which might be caused by the fact that 0-1 mm diameter class roots are absorptive roots and the other diameter class roots are transport roots. There was no provenance difference in C content among all diameter class roots, while significant provenance differences were found in N, K contents, C:N, and C:K in 0-1 mm diameter class roots, and great provenance differences for in P content, C:P, N:P, and N:K in 0-1 and 1-2 mm diameter class roots. N content, K content, C:P, N:P, and N:K in 0-1 mm diameter class roots had positive correlation with the aridity index of seed-source sites, while the P content, C:N and C:K had negative correlations. The stoichiometric characteristics were related with the diameter (or function) of roots, and had significant provenance differences in 0-1 mm (absorptive root) and 1-2 mm diameter class roots, which might be attributed to their genotypic adaptation to the environment of seed-source sites.

Visualization of porosity and pore size gradients in electrospun scaffolds using laser metrology.

We applied a recently developed method, laser metrology, to characterize the influence of collector rotation on porosity gradients of electrospun polycaprolactone (PCL) widely investigated for use in tissue engineering. The prior- and post-sintering dimensions of PCL scaffolds were compared to derive quantitative, spatially-resolved porosity 'maps' from net shrinkage. Deposited on a rotating mandrel (200 RPM), the central region of deposition reaches the highest porosity, ~92%, surrounded by approximately symmetrical decreases to ~89% at the edges. At 1100 RPM, a uniform porosity of ~88-89% is observed. At 2000 RPM, the lowest porosity, ~87%, is found in the middle of the deposition, rebounding to ~89% at the edges. Using a statistical model of random fiber network, we demonstrated that these relatively small changes in porosity values produce disproportionately large variations in pore size. The model predicts an exponential dependence of pore size on porosity when the scaffold is highly porous (e.g., >80%) and, accordingly, the observed porosity variation is associated with dramatic changes in pore size and ability to accommodate cell infiltration. Within the thickest regions most likely to 'bottleneck' cell infiltration, pore size decreases from ~37 to 23 µm (38%) when rotational speeds increased from 200 to 2000 RPM. This trend is corroborated by electron microscopy. While faster rotational speeds ultimately overcome axial alignment induced by cylindrical electric fields associated with the collector geometry, it does so at the cost of eliminating larger pores favoring cell infiltration. This puts the bio-mechanical advantages associated with collector rotation-induced alignment at odds with biological goals. A more significant decrease in pore size from ~54 to ~19 µm (65%), well below the minimum associated with cellular infiltration, is observed from enhanced collector biases. Finally, similar predictions show that sacrificial fiber approaches are inefficient in achieving cell-permissive pore sizes.

1,25(OH)2D3 mitigate cancer-related fatigue in tumor-bearing mice: Integrating network pharmacological analysis.

Cancer-related fatigue (CRF) is one of the most common and serious complications in cancer patients, which greatly reduces the quality of life. The mechanism induced fatigue may be diverse. In this study, we tried to investigate the effect of 1,25(OH)2D3, the active metabolite of vitamin D on CRF in Lewis lung cancer-bearing mice. Network pharmacological analysis, behavioral testing, western blotting, ELISA and flow cytometry were used. We found that there was an interaction between proteins related to the role of 1,25(OH)2D3 and CRF-related proteins. The results of animal model experiments showed that 1,25(OH)2D3 could mitigate the CRF behavior of tumor-bearing mice, and the treatment of 1,25(OH)2D3 reduced the levels of inflammatory factors, changed the tryptophan metabolism direction, and caused changes in immune cells. Collectively, 1,25(OH)2D3 might improve CRF in tumor-bearing mice by changing the direction of tryptophan metabolism and inflammatory factor levels. This study provided a possible solution for patients with clinical CRF.

Dissecting cell diversity and connectivity in skeletal muscle for myogenesis.

Characterized by their slow adhering property, skeletal muscle myogenic progenitor cells (MPCs) have been widely utilized in skeletal muscle tissue engineering for muscle regeneration, but with limited efficacy. Skeletal muscle regeneration is regulated by various cell types, including a large number of rapidly adhering cells (RACs) where their functions and mechanisms are still unclear. In this study, we explored the function of RACs by co-culturing them with MPCs in a biomimetic skeletal muscle organoid system. Results showed that RACs promoted the myogenic potential of MPCs in the organoid. Single-cell RNA-Seq was also performed, classifying RACs into 7 cell subtypes, including one newly described cell subtype: teno-muscular cells (TMCs). Connectivity map of RACs and MPCs subpopulations revealed potential growth factors (VEGFA and HBEGF) and extracellular matrix (ECM) proteins involvement in the promotion of myogenesis of MPCs during muscle organoid formation. Finally, trans-well experiments and small molecular inhibitors blocking experiments confirmed the role of RACs in the promotion of myogenic differentiation of MPCs. The RACs reported here revealed complex cell diversity and connectivity with MPCs in the biomimetic skeletal muscle organoid system, which not only offers an attractive alternative for disease modeling and in vitro drug screening but also provides clues for in vivo muscle regeneration.

Low-intensity walking as mild medication for pressure control in prehypertensive and hypertensive subjects: how far shall we wander?

Successful prevention and treatment of hypertension depend on the appropriate combination of antihypertensive drug therapy and nondrug lifestyle modification. While most hypertension guidelines recommend moderate- to high-intensity exercise, we decided to explore a mild yet effective type of exercise to add to hypertension management, especially in populations with complications or frailty. After comparing the short-term cardiovascular effects of low-speed walking versus high-speed walking for 3 kilometers (km) (3 km/h versus 6 km/h) in young, healthy volunteers, we delivered low-speed walking (low-intensity walking, 2.5 metabolic equivalents of task, METs) as exercise therapy in 42 prehypertensive and 43 hypertensive subjects. We found that one session of 3 km low-intensity walking exerted a transient pressure-lowering effect as well as a mild negative chronotropic effect on heart rate in both the prehypertensive and hypertensive subjects; these short-term benefits on blood pressure and heart rate were accompanied by a brief increase in urine ß-endorphin output. Then we prescribed regular low-intensity walking with a target exercise dose (exercise volume) of 500-1000 METs·min/week (50-60 min/day and 5-7 times/week) in hypertensive subjects in addition to their daily activities. Regular low-intensity walking also showed mild but significant blood pressure-lowering and heart rate-reducing effects in 7 hypertensive subjects within two months. It is hypothesized that regular low-intensity exercise of the necessary dose could be taken as a pragmatic and supplementary medication for hypertension management.

Two new species of Nazeris Fauvel in the Luoxiao Mountain Range, China(Coleoptera, Staphylinidae, Paederinae).

Six species of the genus Nazeris Fauvel, 1873 are recorded in the Luoxiao Mountain Range, China. Two of them are described: N. yipingae sp. n. and N. jiaweii sp. n. Nazeris xiaobini Hu Li, 2015 and N. rufus Hu Li, 2015 are newly recorded from Hubei Province. An identification key to the Nazeris species in this area and a map showing their distribution are given.

Metformin decreases IL-22 secretion to suppress tumor growth in an orthotopic mouse model of hepatocellular carcinoma.

Epidemiological, preclinical and cellular studies in the last 5 years have shown that metformin exerts anti-tumoral properties, but its mode of action in cancer remains unclear. Here, we investigated the effects of metformin on a mouse hepatocellular carcinoma (HCC) model and tumor-associated T cell immune responses. Oral metformin administration led to a significant reduction of tumor growth, which was accompanied by decreased interleukin-22 (IL-22). Meanwhile, IL-22-induced STAT3 phosphorylation and upregulation of downstream genes Bcl-2 and cyclin D1 were inhibited by metformin. At the cellular level, metformin attenuated Th1- and Th17-derived IL-22 production. Furthermore, metformin inhibited de novo generation of Th1 and Th17 cells from naive CD4(+) cells. These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-γ and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-γt [Th17], respectively). The effects of metformin on T cell differentiation were mediated by downregulated STAT3 and STAT4 phosphorylation via the AMP-activated kinase-mammalian target of rapamycin complex 1 pathway. Notably, metformin led to a reduction in glucose transporter Glut1 expression, resulting in less glucose uptake, which is critical to regulate CD4(+) T cell fate. Taken together, these findings provide evidence for the growth-inhibitory and immune-modulatory effects of metformin in HCC and thus, broaden our understanding about the action of metformin in liver cancer treatment.

MicroRNA-24 modulates aflatoxin B1-related hepatocellular carcinoma prognosis and tumorigenesis.

MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66-8.47) and overall survival (HR = 3.58, 95% CI = 2.34-5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis.