Genome-wide Association Study (GWAS) of mesocotyl elongation based on re-sequencing approach in rice

Annotation of candidate genes anchored by associated SNPs. (XLSX 34 kb

Achieving Responsiveness through Supply Chain Integration: A Moderating Effect of Industry-4.0

This article is aiming to investigate the emerging impact of industry-4.0 on supply chain integration and responsiveness in the electronics industry in China.  Specifically, it is to investigate the moderating effect of industry-4.0 as a strategic factor on the causal relationship from operational integration to supply chain responsiveness. This study develops hypotheses based the on selected literature reviews in the relevant research areas, and tests the hypotheses in the empirical sample data set collected from 76 electronics firms by using hierarchical multiple regression method.  The results of this study shows that industry-4.0 as an emerging strategic factor has not only directly helped the level of market responsiveness of the firms, but also has significantly strengthens the already proven positive causal relationship from operational integration within the supply chain to the overall market responsiveness as part of supply chain performance.  To improve the supply chain responsiveness in the electronics industry, managers can now make more confident and informed decisions to channel their resources towards the initiatives of industry-4.0 by up-grading perhaps their current information systems and business processes, knowing full well the dual benefits offered by the Industry 4.0 initiatives. The study extends the concurrent literature by conceptualising the moderating effect of industry-4.0 on the causal relationship between supply chain integration and business responsiveness.

Vehicle Routing Problem with Soft Time Windows Based on Improved Genetic Algorithm for Fruits and Vegetables Distribution

Fresh fruits and vegetables, perishable by nature, are subject to additional deterioration and bruising in the distribution process due to vibration and shock caused by road irregularities. A nonlinear mathematical model was developed that considered not only the vehicle routing problem with time windows but also the effect of road irregularities on the bruising of fresh fruits and vegetables. The main objective of this work was to obtain the optimal distribution routes for fresh fruits and vegetables considering different road classes with the least amount of logistics costs. An improved genetic algorithm was used to solve the problem. A fruit delivery route among the 13 cities in Jiangsu Province was used as a real analysis case. The simulation results showed that the vehicle routing problem with time windows, considering road irregularities and different classes of toll roads, can significantly influence total delivery costs compared with traditional VRP models. The comparison between four models to predict the total cost and actual total cost in distribution showed that the improved genetic algorithm is superior to the Group-based pattern, CW pattern, and O-X type cross pattern

The protease activity of human ATG4B is regulated by reversible oxidative modification

Macroautophagy/autophagy plays a pivotal role in cytoplasmic material recycling and metabolic turnover, in which ATG4B functions as a "scissor" for processing pro-LC3 and lipidated LC3 to drive the autophagy progress. Mounting evidence has demonstrated the tight connection between ROS and autophagy during various pathological situations. Coincidentally, several studies have shown that ATG4B is potentially regulated by redox modification, but the underlying molecular mechanism and its relationship with autophagy is ambiguous. In this study, we verified that ATG4B activity was definitely regulated in a reversible redox manner. We also determined that Cys292 and Cys361 are essential sites of ATG4B to form reversible intramolecular disulfide bonds that respond to oxidative stress. Interestingly, we unraveled a new phenomenon that ATG4B concurrently formed disulfide-linked oligomers at Cys292 and Cys361, and that both sites underwent redox modifications thereby modulating ATG4B activity. Finally, increased autophagic flux and decreased oxidation sensitivity were observed in Cys292 and Cys361 double site-mutated cells under normal growth conditions. In conclusion, our research reveals a novel molecular mechanism that oxidative modification at Cys292 and Cys361 sites regulates ATG4B function, which modulates autophagy

Prokaryote Distribution Patterns along a Dissolved Oxygen Gradient Section in the Tropical Pacific Ocean

Oceanic oxygen levels are decreasing significantly in response to global climate change; however, the microbial diversity and ecological functional responses to dissolved oxygen (DO) in the open ocean are largely unknown. Here, we present prokaryotic distribution coupled with physical and biogeochemical variables and DO gradients from the surface to near the bottom of a water column along an approximately 12,000-km transect from 13° N to 18° S in the Tropical Pacific Ocean. Nitrate (11.42%), temperature (10.90%), pH (10.91%), silicate (9.34%), phosphate (4.25%), chlorophyll a (3.66%), DO (3.50%), and salinity (3.48%) significantly explained the microbial community variations in the studied area. A distinct microbial community composition broadly corresponding to the water masses formed vertically. Additionally, distinct ecotypes of Thaumarchaeota and Nitrospinae belonging to diverse phylogenetic clades that coincided with specific vertical niches were observed. Moreover, the correlation analysis revealed large-scale natural feedback in which chlorophyll a (organic matter) promoted Thaumarchaeotal biomass at depths that subsequently coupled with Nitrospina, produced and replenished nitrate for phytoplankton productivity at the surface. Low DO also favored Thaumarchaeota growth and fueled nitrate production

Novel CDKs inhibitors for the treatment of solid tumour by simultaneously regulating the cell cycle and transcription control

A novel series of cyclin-dependent kinases (CDKs) inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription, were synthesised. A systematic study of enzymatic and cellular assays led to the identification of compound X22 with a nanomolar potency against CDK4 and CDK9 and potent antiproliferative activities against a panel of tumour cell lines. X22 could induce cell cycle arrest and cell apoptosis in cancer cell lines. X22 dose-dependently inhibits signalling pathways downstream of CDKs in cancer cells. In vivo antitumor activity assays, oral administration of X22 led to significant tumour regression in mouse model without obvious toxicity. Superior anti-cancer efficacy in vitro and in vivo of X22 demonstrated combined depletion of cell cycle and transcriptional CDK all contributed to antitumor activity. Taken together, concomitant inhibition of cell cycle and transcriptional CDK activities provided valuable guide for further structural optimisation

A Novel CDK4/6 and PARP Dual Inhibitor ZC-22 Effectively Suppresses Tumor Growth and Improves the Response to Cisplatin Treatment in Breast and Ovarian Cancer

In recent years, three PARP inhibitors and three CDK4/6 inhibitors have been approved by the FDA for the treatment of recurrent ovarian cancer and advanced ER-positive breast cancer, respectively. However, the clinical benefits of the PARPi or CDK4/6i monotherapy are not as satisfied as expected and benefit only a fraction of patients. Current studies have shown therapeutic synergy for combinations of PARPi and CDK4/6i in breast and ovarian cancers with homologous recombination (HR) proficiency, which represents a new synthetic lethal strategy for treatment of these cancers regardless HR status. Thus, any compounds or strategies that can combine PARP and CDK4/6 inhibition will likely have great potential in improving clinic outcomes and in benefiting more patients. In this study, we developed a novel compound, ZC-22, that effectively inhibited both PARP and CDK4/6. This dual-targeting compound significantly inhibited breast and ovarian cancer cells by inducing cell cycle arrest and severe DNA damage both in vitro and in vivo. Interestingly, the efficacy of ZC-22 is even higher than the combination of PARPi Olaparib and CDK4/6i Abemaciclib in most breast and ovarian cancer cells, suggesting that it may be an effective alternative for the PARPi and CDK4/6i combination therapy. Moreover, ZC-22 sensitized breast and ovarian cancer cells to cisplatin treatment, a widely used chemotherapeutic agent. Altogether, our study has demonstrated the potency of a novel CDK4/6 and PARP dual inhibitor, which can potentially be developed into a monotherapy or combinatorial therapy with cisplatin for breast and ovarian cancer patients with HR proficiency

Niclosamide Triggers Non-Canonical LC3 Lipidation

Autophagy is a highly- evolutionarily-conserved catabolic pathway activated by various cellular stresses. Recently, non-canonical autophagy (NCA), which does not require all of the ATG proteins to form autophagosome or autophagosome-like structures, has been found in various conditions. Moreover, mounting evidence has indicated that non-canonical LC3 lipidation (NCLL) may reflect NCA. We and others have reported that niclosamide (Nic), an anti-helminthic drug approved by the Food and Drug Administration, could induce canonical autophagy via a feedback downregulation of mTOR complex 1. In this study, we found that Nic could also induce NCLL, which is independent of the ULK1 complex and Beclin 1 complex, but dependent on ubiquitin-like conjugation systems. Although bafilomycin A1 and concanamycin A, two known V-ATPase inhibitors, significantly inhibited Nic-induced NCLL, Nic-induced NCLL was demonstrated to be independent of V-ATPase. In addition, the Golgi complex and vimentin were involved in Nic-induced NCLL, which might be a platform or membrane source for Nic-induced LC3-positive structures. These results would be helpful to broaden our understanding of the working mechanisms of Nic and evaluate its pharmacological activities in diseases