Editors-in-Chief

Shu-Min DUAN

Zhi-Hong LIU

ISSN 1673-1581

CN 33-1356/Q

Published by

Zhejiang University Press

2022 JIF 4.7

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    Abstract：Cementum, a mineralized connective tissue that covers the tooth root, is crucial in protecting the root from resorption, maintaining occlusal relationships, and supporting tooth function. Cementocytes are embedded within the cementum matrix and extend dendritic processes through the canaliculi. They are thought to be mechanosensitive, responding to changes in mechanical loading, and are physiologically responsive cells associated with the formation of cellular cementum in response to variations in functional demands on the tooth. The wingless and int (Wnt) signaling pathway, which controls cell fate and regulates growth, development, and homeostasis in the body, plays a pivotal regulatory role in normal biological development and disease progression. Currently, the mechanisms by which the Wnt signaling pathway influences cementogenesis and regeneration remain controversial. Research findings on the roles of Wnt/β-catenin signaling in cementoblast differentiation and function have been mixed. Some studies indicate that activating this pathway enhances cementoblast differentiation, while others suggest that Wnt signaling may inhibit it, favoring cell proliferation instead. This paper reviews the structure and physiological roles of cementum, focusing on how Wnt signaling influences the growth and differentiation of cementoblasts. We emphasize the pivotal role of the Wnt pathway in cementum formation and development, as well as in root resorption and repair, and hypothesize that maintaining low Wnt/β-catenin levels is crucial to achieving an optimal balance between cementoblast proliferation and differentiation. Finally, we propose periodontal regeneration treatment strategies based on the Wnt signaling pathway and suggest future research directions.  

    Tiancheng LI, Xinyi ZENG, Shuxian YANG, Lynda Faye BONEWALD, Peipei DUAN

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  • Review

    Abstract：The abnormal accumulation of methylmalonic acid (MMA), the leading cause of methylmalonic acidemia, can cause irreversible damage to the brain, kidney, and cardiovascular system. In addition, the accumulation of MMA in the blood has recently been associated with the occurrence of cancer, restricted bodily movement, and growth retardation. In this review, recent studies on the relationship between the metabolic abnormality of MMA and disease occurrence were summarized, concerning the brain, kidney, cardiovascular system, cancer, and skeletal muscles. It provides a theoretical basis and reference for further research and the treatment of MMA-related pathophysiological changes.  

    Zi’ang WANG, Wenhui CHENG, Teng WANG, Yidi ZHANG, Xin’e SHI, Yuqi LV, Jianjun JIN

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  • Research Article

    Abstract：Excessive ammonia nitrogen has been demonstrated to cause a serious hazard to water environments. Bacteria performing simultaneous nitrification and denitrification (SND) can be effective biological instruments to remove ammonia nitrogen completely from effluents. For the first time, Pseudomonas oleovorans QS-7 with SND function, isolated from the biogas treatment system of a pig farm, was found to efficiently remove ammonia nitrogen. Through the determination of key enzymes and functional genes related to the nitrogen metabolism of strain QS-7, combined with nitrogen balance measurements of the nitrogen metabolic process, it was speculated that the SND pathway of the novel strain is NH4+→NH2OH→NO2-→NO3-→NO2-→NO→N2O→N2. QS-7 exhibited 98.6% ammonia nitrogen removal and a maximum ammonia degradation rate of 9.2 mg/(L·h) at 18 h in 100 mg/L ammonia nitrogen solution. This strain also has a certain capacity to remove nitrate and nitrite nitrogen; the maximum removal efficiencies were 54.22% and 73.93%, respectively, in systems with 100 mg/L of nitrate or nitrite nitrogen as the sole nitrogen source. Nitrogen metabolic balance analysis for QS-7, using ammonia (100 mg/L) as the sole nitrogen source, demonstrated that assimilation (56.1%) is the main mode of nitrogen removal, followed by conversion to N2 (43.6%). Meanwhile, NO2- was not detected, and almost no NOx was produced, which indicates that the nitrogen removal process of QS-7 is environmentally friendly. The optimal environmental conditions for QS-7 were found to be sodium citrate as the carbon source, C/N=10, pH=7.0, 150 r/min, and 30 ℃. The above results indicate that QS-7 may provide a material and conceptual basis for the advancement of SND technology.  

    Hao QIU, Min LIAO, Xiaomei XIE, Xinyue LU, Feng YUAN, Zhe LUO, Chunlin FAN

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  • Research Article

    Abstract：Dietary consumption of eicosapentaenoic acid (EPA) offers diverse health benefits, such as the regulation of blood triglycerides and the prevention of cardiovascular diseases. EPA is naturally synthesized by Schizochytrium sp.; however, its low production level limits its potential for industrial application. The goal of this study was to increase EPA productivity in Schizochytrium sp. by gas‒liquid-phase plasma (GLPP) mutagenesis combined with a high-throughput screening method. First, a diverse array of mutants was generated through GLPP mutagenesis. Next, the mutants with elevated EPA productivity were identified through near-infrared spectroscopy (NIRS). Notably, the M7-25 mutant demonstrated the highest and most consistent EPA production. After the culture medium was optimized, the EPA titer increased from 0.45 to 1.70 g/L. Finally, a cofermentation strategy using ammonia and glucose feeding was employed, and the EPA titer reached 2.08 g/L in a 7-L fermenter. This study reports the highest EPA titer achieved in Schizochytrium sp. via mutagenesis to date, highlighting its great market potential for industrial production.  

    Chao YU, Jialin ZHU, Jinyong WU, Xiangsong CHEN, Shuhuan LU, Xiangyu LI, Sa ZHAO, Weiwei ZHU, Min SHU, Mianbin WU, Jianming YAO

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  • Research Article

    Abstract：Amid the rapid increase of the global population and the quest for sustainable agriculture, the need for enhanced rice breeding strategies has become increasingly pronounced, particularly in Heilongjiang, China’s foremost rice-producing province, renowned for its premium temperate japonica rice. Here, we conducted an extensive genomic investigation of the elite rice cultivars developed in Heilongjiang Province. Using whole-genome re-sequencing of a total of 376 representative cultivars from Heilongjiang, of which 14 were developed by a single research group, we identified 4.9 million single nucleotide polymorphisms (SNPs) and 0.98 million insertions and deletions (InDels), offering a comprehensive perspective on genetic diversity and population structure. We classified the 376 rice cultivars into five subgroups based on their breeding years. Recently bred cultivars, assigned to subgroups HLJ-IV-1 and HLJ-IV-2, showed notable genetic differentiation. Through a selective sweep analysis, significant genomic variation in genes such as OsACBP5, Os4CL5, and GFR1 was pinpointed, reflecting a concerted effort in selecting for broad-spectrum disease resistance and enhanced tillering capacity. Furthermore, to identify the strengths and areas for improvement within those series, we conducted an exhaustive analysis of aromatic compounds and their corresponding genes OsODC and OsBadh2, as well as the advantageous long-grain gene OsGL3.1 haplotype within Hagengdao7. Additionally, strategies for reducing plant height through the introduction of the sd1 gene have been elucidated. With a commitment to expediting the development of superior rice cultivars, our discoveries are poised to raise the sensory attributes and nutritional profile of rice, thereby bolstering the resilience and sustainability of global food systems.  

    Yuhan ZHOU, Naixin LIU, Jiaqi YANG, Baicui CHEN, Chengxin LI, Fanshan BU, Sanling WU, Ziqi ZHOU, Qingtao YU, Qingyao SHU

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  • Research Article

    Abstract：Digestive enzymes of fish are critical to food digestion at the larval stage, but convincing evidence proving the function and necessity of the associated digestive enzymes remains lacking. In this study, we generated the trypsin (try) gene and amylase (amy) gene in the Japanese medaka (Oryzias latipes) using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) for the first time. try deletion significantly decreased the expression of try and digestive capacity in try-/- medaka larvae; after 8.5 h of digestion, incompletely digested brine shrimp was observed in the digestive tract at 4 and 15 d post-hatching (dph) of try-/- medaka larvae. Furthermore, the height of intestinal villi and total body length decreased significantly within 15-dph try-/- medaka larvae. However, amy deletion did not influence the digestion of medaka larvae at 4 dph. Only a small amount of incompletely digested brine shrimp was observed in 15-dph amy-/- medaka larvae. Further analysis of the growth, nitrogen metabolism, and intestinal microbes of try-/- adult medaka showed that the body length and weight of adult medaka decreased significantly, while the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the blood significantly increased. Pathological observation of the liver and intestinal tissues showed that try knockout resulted in vacuolar degeneration of liver cells, thinning of the intestinal wall, sparse arrangement of villi, and lower villi height. High-throughput 16S ribosomal RNA (rRNA) sequencing revealed that try knockout reduced the diversity of intestinal microbes. These findings demonstrated that try was indispensable for medaka larvae because it continuously affects their growth, nitrogen metabolism, and intestinal development.  

    Xiaodan JIA, Shulin TANG, Hexiong FENG, Dimei XU, Chenyuan ZHU, Ke LU, Xufang LIANG

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  • Research Article

    Abstract：Royal jelly (RJ), secreted by the hypopharyngeal and mandibular glands of young worker bees, is rich in proteins, 80%‒90% of which are major royal jelly proteins (MRJPs). While MRJPs from RJ have been shown to exhibit specific biological functions and are also expressed in neuronal cells, their roles in vivo remain poorly understood. The aim of this study was to elucidate the functional roles of individual MRJPs (MRJP1‒9) in vivo by ectopically expressing them in Drosophila neurons in a binary expression system using fluorescent proteins as controls. Transcriptome sequencing revealed that although MRJP1‒9 share similar tertiary structures, their overexpression affects distinct gene sets. MRJP1, MRJP2, MRJP3, MRJP5, and MRJP7 induced more differentially expressed genes (DEGs), while MRJP4, MRJP6, MRJP8, and MRJP9 induced fewer such genes. Weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA) revealed that MRJP1, MRJP2, MRJP3, MRJP5, and MRJP7 regulated overlapping gene sets, including an estradiol-responsive set, and activated cell proliferation pathways. MRJP6 lacked any significant gene set enrichment, while MRJP8 and MRJP9 modulated similar sets. Notably, the neuron-specific overexpression of MRJP1, MRJP2, MRJP3, and MRJP5 in Drosophila showed activated cell proliferation-related pathways and increased body sizes, highlighting their functional diversity and context-dependent effects. These findings expand our understanding of the functional roles of MRJPs and provide a foundation for further exploring their biological significance in honeybees and beyond.  

    Lingqi YU, Danfeng WANG, Xuanhao CHEN, Jiayu XIE, Dongjing WEN, Yi ZHANG, Lirong SHEN, Wenfeng CHEN, Zhenxing LIU, Yufeng YANG

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  • Research Article

    Abstract：Hepatocellular carcinoma (HCC) often requires targeted therapy and immunotherapy due to frequent delayed diagnosis. Sorafenib, the first targeted drug applied to treat HCC, has demonstrated a remarkable therapeutic effect in the clinic. However, its clinical application has been limited by drug resistance and the insufficient understanding of the relevant mechanism. Wilms’ tumor 1-associated protein (WTAP), associated with tumor progression, remains unstated in sorafenib resistance. In this study, WTAP expression patterns in HCC were systematically characterized through integrative analysis of The Cancer Genome Atlas (TCGA) datasets and spatial transcriptomic profiling. To delineate the potential mechanisms of WTAP-mediated sorafenib resistance in HCC, multimodal approaches integrating gene set enrichment analysis (GSEA), predictions from the “oncoPredict” package in vitro experiments, molecular docking simulations, and western blot validation were applied. To further investigate the role of WTAP in drug resistance, hydrodynamic tail vein injection (HTVi) mouse models and immunohistochemistry were utilized. Significant WTAP upregulation was identified in HCC tissues, showing strong associations with tumor progression and adverse clinical outcomes. The knockdown of WTAP sensitized HCC cells to sorafenib in vitro. GSEA, molecular docking analysis, and western blot analysis demonstrated that WTAP induces the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, a critical link in chemoresistance mechanisms. In the HTVi HCC model, the combination of WTAP knockdown with sorafenib markedly suppressed tumor progression and boosted survival rates. These findings highlight that WTAP positively regulates the ERK pathway in HCC, promoting sorafenib resistance; therefore, targeting WTAP may represent a novel strategy to potentiate sorafenib responsiveness in HCC.  

    Yu WU, Guomin JU, Xueyu ZHOU, Jian WU, Shusen ZHENG, Chuanhui PENG

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