Brefeldin A increases the quantal size and alters the kinetics of catecholamine release from rat adrenal chromaffin cells.

The fungal metabolite, brefeldin A (BFA), is known to inhibit guanine nucleotide exchange on the ADP-ribosylating factors that are involved in vesicle membrane trafficking. Here, we investigated the action of BFA on Ca2+-regulated exocytosis in single rat adrenal chromaffin cells. Incubation of chromaffin cells with BFA (1 or 10 microM) for 2 h effectively disrupted the Golgi membranes but did not affect the pattern of catecholamine release triggered by high extracellular K+, which was monitored with carbon fiber amperometry along with cytosolic Ca2+ measurement. The BFA treatment, however, increased the mean quantal size of catecholamine-containing vesicles and the occurrence of amperometric events with a "foot" or "stand alone" signal (which reflects sluggish or incomplete dilation of the fusion pore). To examine whether BFA altered the Ca2+-dependence of exocytosis, we employed the whole-cell recording technique in conjunction with the capacitance measurement to measure exocytosis evoked from the entire cell during voltage-gated Ca2+ entry. Our results suggested that BFA treatment did not alter either the initial rate of capacitance increase or the total amount of capacitance increase. Therefore, in chromaffin cells, BFA treatment affects Ca2+-regulated exocytosis predominantly by increasing the quantal size and by slowing the fusion kinetics of some vesicles.     

Constructing China's greenways naturally

Roads are a prominent feature of many landscapes, and high road densities create correspondingly high ecological impacts by altering landscape patterns, interrupting ecological flows, increasing erosion, fragmenting habitat, and facilitating the spread of invasive species. Here, we describe the construction of “near-natural greenways” that produce environmentally and socially harmonious road systems that meet the needs of both the environment and the socioeconomic development in China and that satisfy environmental, ecological, educational, traffic safety, economic, and sustainable developmental goals. In the last decade, China has embarked upon the implementation of a network of near-natural greenways with the vision of linking economic development with nature conservation by means of improved rehabilitation of existing road systems and improved construction of new roads. Ecological science, and especially landscape ecology, will play an important role in the planning and implementation of future near-natural greenways in China and around the world.     

炭疽芽胞杆菌(Bacillus anthracis)检测质粒的构建及其应用

根据炭疽芽胞杆菌(Bacillus anthracis)毒性质粒pX01和pX02上的2个毒力相关基因cya和capA的序列特点,以pIJ2925为出发载体,采用一步重叠延伸PCR技术(One-step Overlap Extension PCR,简称OOE-PCR)构建了包含cya基因和capA基因保守区DNA片段的炭疽检测质粒pBIB2006。采用复合PCR对模拟炭疽危险品进行分析,结果表明pBIB2006可以为炭疽芽胞杆菌的检测提供准确、安全和方便的阳性参照品,从而为检测炭疽芽胞杆菌和炭疽芽胞杆菌灭活疫苗提供了便利。     

Efficiency Boost in All-Small-Molecule Organic Solar Cells: Insights from the Re-Ordering Kinetics

Achieving high-performance in all-small-molecule organic solar cells (ASM-OSCs) significantly relies on precise nanoscale phase separation through domain size manipulation in the active layer. Nonetheless, for ASM-OSC systems, forging a clear connection between the tuning of domain size and the intricacies of phase separation proves to be a formidable challenge. This study investigates the intricate interplay between domain size adjustment and the creation of optimal phase separation morphology, crucial for ASM-OSCs’ performance. It is demonstrated that exceptional phase separation in ASM-OSCs’ active layer is achieved by meticulously controlling the continuity and uniformity of domains via re-packing process. A series of halogen-substituted solvents (Fluorobenzene, Chlorobenzene, Bromobenzene, and Iodobenzene) is adopted to tune the re-packing kinetics, the ASM-OSCs treated with CB exhibited an impressive 16.2% power conversion efficiency (PCE). The PCE enhancement can be attributed to the gradual crystallization process, promoting a smoothly interconnected and uniformly distributed domain size. This, in turn, leads to a favorable phase separation morphology, enhanced charge transfer, extended carrier lifetime, and consequently, reduced recombination of free charges. The findings emphasize the pivotal role of re-packing kinetics in achieving optimal phase separation in ASM-OSCs, offering valuable insights for designing high-performance ASM-OSCs fabrication strategies.     

Oxygen‐Deficient Blue TiO2 for Ultrastable and Fast Lithium Storage

Developing a titanium dioxide (TiO₂)‐based anode with superior high‐rate capability and long‐term cycling stability is important for efficient energy storage. Herein, a simple one‐step approach for fabricating blue TiO₂ nanoparticles with oxygen vacancies is reported. Oxygen vacancies can enlarge lattice spaces, lower charge transfer resistance, and provide more active sites in TiO₂ lattices. As a result, this blue TiO₂ electrode exhibits a highly reversible capacity of 50 mAh g^?1 at 100 C (16 800 mA g^?1) even after 10 000 cycles, which is attributable to the combination of surface capacitive process and remarkable diffusion‐controlled insertion revealed by the kinetic analysis. The strategy of employing oxygen‐deficient nanoparticles may be extended to the design of other robust semiconductor materials as electrodes for energy storage.     

Developability studies before initiation of process development

Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2−8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples. We present here three case studies reflecting three typical outcomes: (1) no major or unexpected degradation is found and the study results are used to inform early identification of degradation pathways and potential critical quality attributes within the Quality by Design framework defined by US Food and Drug Administration guidance documents; (2) identification of specific degradation pathway(s) that do not affect potency of the molecule, with subsequent definition of proper process control and formulation strategies; and (3) identification of degradation that affects potency, resulting in program termination and reallocation of resources.     

20(S)-Protopanaxadiol Inhibition of Progression and Growth of Castration-Resistant Prostate Cancer

Castration-resistant progression of prostate cancer after androgen deprivation therapies remains the most critical challenge in the clinical management of prostate cancer. Resurgent androgen receptor (AR) activity is an established driver of castration-resistant progression, and upregulation of the full-length AR (AR-FL) and constitutively-active AR splice variants (AR-Vs) has been implicated to contribute to the resurgent AR activity. We reported previously that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) can reduce the abundance of both AR-FL and AR-Vs. In the present study, we further showed that the effect of PPD on AR expression and target genes was independent of androgen. PPD treatment resulted in a suppression of ligand-independent AR transactivation. Moreover, PPD delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen deprivation and inhibited the growth of castration-resistant 22Rv1 xenograft tumors with endogenous expression of AR-FL and AR-Vs. This was accompanied by a decline in serum prostate-specific antigen levels as well as a decrease in AR levels and mitoses in the tumors. Notably, the 22Rv1 xenograft tumors were resistant to growth inhibition by the next-generation anti-androgen enzalutamide. The present study represents the first to show the preclinical efficacy of PPD in inhibiting castration-resistant progression and growth of prostate cancer. The findings provide a rationale for further developing PPD or its analogues for prostate cancer therapy.     

Association of Common Variants in LOX with Keratoconus: A Meta-Analysis

Background

Several case-control studies have been performed to examine the association of genetic variants in lysyl oxidase (LOX) with keratoconus. However, the results remained inconclusive and great heterogeneity might exist across populations.

Method

A comprehensive literature search for studies that published up to June 25, 2015 was performed. Summary odds ratios (OR) and 95% confidence intervals (CI) of each single nucleotide polymorphism (SNP) were estimated with fixed effects model when I ²<50% in the test for heterogeneity or random effects model when I ²>50%. Publication bias was evaluated using funnel plots and Egger’s test.

Results

A total of four studies including 1,467 keratoconus cases and 4,490 controls were involved in this meta-analysis. SNPs rs2956540 and rs10519694 showed significant association with keratoconus, with ORs of 0.71 (95% CI: 0.63–0.80, P = 1.43E-08) and 0.77 (95% CI: 0.61–0.97, P = 0.026), respectively. In contrast, our study lacked sufficient evidences to support the association of rs1800449/rs2288393 with keratoconus across populations.

Conclusion

This meta-analysis suggested that two LOX variants, rs2956540 and rs10519694, may affect individual susceptibility to keratoconus, while distinct heterogeneity existed within this locus. Larger-scale and multi-ethnic genetic studies on keratoconus are required to further validate the results.