Loss of β‐cell number and function is a hallmark of diabetes. β‐cell preservation is emerging as a promising strategy to treat and reverse diabetes. Here, we first found that Pdia4 was primarily expressed in β‐cells. This expression was up‐regulated in β‐cells and blood of mice in response to excess nutrients. Ablation of Pdia4 alleviated diabetes as shown by reduced islet destruction, blood glucose and HbA1c, reactive oxygen species (ROS), and increased insulin secretion in diabetic mice. Strikingly, this ablation alone or in combination with food reduction could fully reverse diabetes. Conversely, overexpression of Pdia4 had the opposite pathophysiological outcomes in the mice. In addition, Pdia4 positively regulated β‐cell death, dysfunction, and ROS production. Mechanistic studies demonstrated that Pdia4 increased ROS content in β‐cells via its action on the pathway of Ndufs3 and p22phox. Finally, we found that 2‐β‐D‐glucopyranosyloxy1‐hydroxytrideca 5,7,9,11‐tetrayne (GHTT), a Pdia4 inhibitor, suppressed diabetic development in diabetic mice. These findings characterize Pdia4 as a crucial regulator of β‐cell pathogenesis and diabetes, suggesting Pdia4 is a novel therapeutic and diagnostic target of diabetes.

Background Protein disulfide isomerases a4 (Pdia4) is known to be involved in cancer development. Our previous publication showed that Pdia4 positively promotes cancer development via its inhibition of procaspase‐dependent apoptosis in cancer cells. However, nothing is known about its role in the cancer microenvironment. Results Here, we first found that Pdia4 expression in lung cancer was negatively correlated with patient survival. Next, we investigated the impact of host Pdia4 in stromal cells during cancer development. We showed that Pdia4 was expressed at a low level in stromal cells, and this expression was up‐regulated akin to its expression in cancer cells. This up‐regulation was stimulated by tumour cell‐derived stimuli. Genetics studies in tumour‐bearing wild‐type and Pdia4–/– mice showed that host Pdia4 promoted lung cancer development in the mice via cancer stroma. This promotion was abolished in Rag1–/– mice which lacked T and B cells. This promotion could be restored once T and B cells were added back to Rag1–/– mice. In addition, host Pdia4 positively regulated the number and immunosuppressive function of stromal cells. Mechanistic studies showed that host Pdia4 positively controlled the Stat3/Vegf pathway in T and B lymphocytes via its stabilization of activated Stat3 in a Thioredoxin‐like domain (CGHC)‐dependent manner. Conclusions These findings identify Pdia4 as a possible target for intervention in cancer stroma, suggesting that targeting Pdia4 in cancer stroma is a promising anti‐cancer approach.

Arabidopsis CHLOROPLAST IMPORT APPARATUS 2 (CIA2) and its paralogous protein CIA2-LIKE (CIL) are nuclear transcription factors containing a C-terminal CCT motif. CIA2 promotes the expression of nuclear genes encoding chloroplast-localized translocons and ribosomal proteins, thereby increasing the efficiency of protein import and synthesis in chloroplasts. We have previously reported that CIA2 and CIL form a homodimer or heterodimer through their C-terminal sequences and interact with other nuclear proteins, such as CONSTANS (CO), via their N-terminal sequences, but the function of CIL had remained unclear. In this study, we verified through transgenic cia2 mutant plants expressing the CIL coding sequence that CIL is partially functionally redundant to CIA2 during vegetative growth. We also compared phenotypes and gene expression profiles of wildtype Col-0, cia2, cil, and cia2/cil mutants. Our results indicate that CIA2 and CIL coordinate chloroplast biogenesis and function mainly by upregulating the expression of the nuclear factor GOLDEN2-LIKE 1 (GLK1) and chloroplast transcription-, translation-, protein import-, and photosynthesis-related genes, with CIA2 playing a more crucial role. Furthermore, we compared flowering phenotypes in single, double, and triple mutant plants of co, cia2, and cil. We found that CIA2 and CIL participate in modulating long-day floral development. Notably, CIA2 increases flower number and height of the inflorescence main axis, whereas CIL promotes flowering.

Abstract-Fluctuations in the output power of large-scale wind farms can have a considerable influence on power quality and stability, leading to the risk of grid frequency deviation, particularly in isolated power system. Fluctuations in wind power can be smoothing through the inclusion of wind-storage system. In this system, wind turbines are connected with battery energy storage system (BESS). This paper proposes a novel operation control strategy, referred to as prediction-based control (PBC). The proposed strategy (which utilizes predicted changes in wind power generation) can effectively smooth the fluctuation in the output power of wind farms (WFs), based on the concept of confidence intervals. Furthermore, the rolling-wave planning and dynamic control of the BESS enhances its capacity. Finally, the proposed control strategy provides an avenue by which to examine the characteristics of large-scale WFs and BESS for better planning, design, and operations. Index Terms-Grid-level battery energy storage system, wind farm, real-time control, prediction-based control, wind turbines, wind power fluctuation. I. INTRODUCTIONGrowing demand for energy and alternative sources of electricity prompted the establishment of large-scale WFs in Taiwan, which are connected to and operate in parallel with the public grid. However, wind power is characterized by random fluctuations [1]-[3], and the fluctuation in output power from WFs brings enormous challenges to grid security, such as peak power and frequency deviation, stability, and power quality [4], [5]. Therefore, smoothing the fluctuation in output power of a WF is a critical issue.A number of schemes have been developed with the aim of smoothing the fluctuations inherent in wind power generation, most of which employ energy storage systems with real-time control [6]-[8]. Unfortunately, most existing methods consider only present fluctuations in the power output of wind-storage systems, and not future fluctuations. Thus, in [9], it was indicated that BESS devices can be used to adjust the output active-and reactive-power and enable rapid response in compensating for power imbalances associated with fluctuations in wind power. This paper proposes a novel operation control strategy, referred to as prediction-based control, for use in BESS systems to smooth the fluctuations in output power of WFs. The proposed prediction-based control system takes into account anticipated fluctuations in the power generated by the WF (via forecasting) as well as the charging and discharging capability of BESS based on simple control strategy. In other words, prediction-based control method be able to facilitate dynamic operations in BESS systems. The efficacy of the proposed PBC method was demonstrated in a number of practical case studies. Fig. 1 illustrates a sample wind-storage system comprising a WF and BESS. The proposed prediction-based control is used to control the charging and discharging of the BESS system and coordinate the time-varying fluctuations in power output of the WF. T...