Publications

ABSTRACT ‘Manicure Finger’ grape exhibits gradient coloration during veraison, where the lower part of the skin changes color faster and intenser than the upper, giving the same berry a gradient color from green on the top to red on the bottom. This unique characteristic distinguishes it from other table grape varieties and makes it highly commercially valuable. However, because the formation mechanisms of gradient coloration are unclear, ‘Manicure Finger’ lags behind other grapes in the development of breeding, cultivation, and storage technologies, occupying only a small share of the table grape market. Here, based on integrated omics including anthocyanin, flavonoid metabolome, and transcriptome, the substances basis and metabolic mechanisms regulating gradient coloration were thoroughly resolved. In ‘Manicure Finger’, eight anthocyanins including malvidin‐3‐ O ‐glucoside, peonidin‐3‐ O ‐glucoside, and cyanidin‐3‐ O ‐glucoside were identified as color‐presenting substances, while flavones and flavonols, especially kaempferol‐3‐ O ‐rutinoside and quercetin‐3‐ O ‐glucoside, functioned as co‐pigments. Spatial differences in their accumulation were substances basis for gradient coloration. In the lower skin, these substances accumulated faster due to the higher expression levels of structural genes VvF3 ´ 5 ´ H1 , VvF3 ´ 5 ´ H2 , VvANS , VvGT1 , and VvFAOMT , which were further modulated by transcription factors VvMYBA1 , VvMYBA2 , VvMYBA3 , and VvMYBA6 . Novel transcription factors VvbHLH148 , VvMYBA22 , and VvMYBA3 were also most probably involved in this regulatory process. Histone acylation regulated by VvHAC1 and lysine methylation regulated by VvHMT1 might underlie the epigenetic basis of gradient coloration. Overall, the metabolic networks underlying gradient coloration were comprehensively constructed at levels of color‐presenting substances, structural genes and transcription factors, offering valuable insights into the precise regulation of ‘Manicure Finger’ color formation.

A new ultrasound-assisted enzymatic extraction (UAEE) method of starch from kiwifruit was established and optimized using response surface methodology (RSM). Under optimal conditions (the pectinase-to-cellulase-to-papain ratio = 1:2:1 g/kg, solid/liquid ratio = 1:6.68, extraction pH = 5.23, ultrasound power = 300 W, and extraction temperature = 52 °C), the kiwi starch (KS) yield was about 4.25%, and the starch content of KS was 873.23 mg/g. Compared to other extraction methods, UAEE can obtain KS with high yield and purity with a shorter extraction time and less solvent and enzyme. The extracted KS has a low gelatinization enthalpy (8.02 J/g) and a high peak viscosity (7933 cP), with obvious particle properties and low adhesion. In addition, KS is rich in polyphenols, has strong antioxidant activity, and has higher contents of amylose starch (30.74%) and resistant starch (60.18%). This study established a novel and highly efficient method for KS extraction and suggest several possible applications for KS in the food industry.

Scope Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue (BAT) formation and function increases energy expenditure and may protect against obesity. Cyanidin‐3‐glucoside (C3G) is an anthocyanin compound that occurs naturally in many fruits and vegetables. In this study, we investigated the effect and mechanism of C3G on the prevention of obesity. Methods and results Db/db mice received C3G dissolved in drinking water for 16 wk; drinking water served as the vehicle treatment. The total body weight, energy intake, metabolic rate, and physical activity were measured. The lipid droplets, gene expression and protein expression were evaluated by histochemical staining, real‐time PCR, and western blots. We found that C3G increased energy expenditure, limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis, improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also induces brown‐like adipocytes (beige) formation in subcutaneous white adipose tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through increasing mitochondrial number and function. Conclusion Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity.

Abstract IL15, a cytokine of the IL2 family, is pivotal for activating natural killer cells and effector/memory CD8 T cells. Clinical application with various IL15 formulations for cancer therapy, however, has been greatly hindered by its pharmacokinetics and dose-dependent systemic toxicity. A promising approach involves the fusion of IL15 with an anti-TAA antibody or an immune checkpoint antibody, in an attempt to specifically target IL15 to the tumor and its microenvironment while reducing peripheral exposure and toxicity. In this study, we generated a panel of stable IL15 variants (IL15v), utilizing an internally developed AI algorithm, with attenuated binding affinity to IL2Rβ and biological activity. We then engineered a panel of fusion proteins each comprising of a disulfide-bond stabilized IL15v, the IL15Ra sushi domain, and an anti-PD1 antibody IgG. Several lead molecules were produced with good expression level, stability and drugability. These anti-PD1/IL15v fusions not only fully retained their PD1-blocking activity, but also were significantly more potent in promoting the activation of PD1-expressing T cells, comparing to those of PD1-negative cells. In vivo pharmacokinetics and antitumor activity of these anti-PD1/IL15v fusions are currently being investigated. Anti-PD1 targeted delivery of stabilized and attenuated IL15v may provide an effective approach, with an improved safety profile, to reverse the suppressive state of tumor-infiltrating antigen-specific PD1-expressing CD8 T cells. Citation Format: Yun Zhang, Liang Tian, Chenpeng Su, Xiangyu Sun, Ran Hao, Tianhong Li, Dandan Liu, Jiyuan Tian, Xiaoqian Chen, Jian Peng, Zhenping Zhu. AI-guided engineering and preclinical characterization of anti-PD1/IL15 mutein bifunctional fusion proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7264.

3-Alkyl-2-methoxypyrazines (MPs) contribute to the herbaceous flavor characteristics of wine and are generally considered associated with poor-quality wine. To control the MPs in grapes and wine, an accurate understanding of MP metabolism is needed. This review covers factors affecting people in the perception of MPs. Also, the history of O-methyltransferases is revisited, and the present review discusses the MP biosynthesis, degradation, and biochemical regulation. We propose the existence of a cycle between MPs and 3-alkyl-2-hydropyrazines (HPs), which proceeds via O-(de)methylation steps. This cycle governs the MP contents of wines, which make the cycle the key participant in MP regulation by genes, environmental stimuli, and microbes. In conclusion, a comprehensive metabolic pathway on which the HP–MP cycle is centered is proposed after gaining insight into their metabolism and regulation. Some directions for future studies on MPs are also proposed in this paper.