Professor Zheng Ji (1900-2010) was one of the outstanding pioneers in the field of biochemistry in China, who continued to achieve fruitful research results in basic scientific fields such as nutrition and aging in his later years, laying a solid foundation for the development of biochemistry in China. Professor Zheng Ji not only participated in the establishment of the Chinese Society of Biochemistry and the development of the "Chinese Journal of Biochemistry and Molecular Biology," but also initiated the"Zheng Ji-Zhang Changying Outstanding Paper Award" in the journal. The textbook "General Biochemistry", which he personally authored, was highly praised, reprinted multiple times, and has become a classic textbook in the field within the country, winning the national second prize for excellent teaching materials. He also vigorously promoted the popularization of biochemistry and health knowledge. His academic achievements and dedication have profoundly influenced several generations of biochemistry researchers.

In 1952, China carried out departmental adjustments among universities to strengthen its higher education. In 1953, a specialized program on Biochemistry was established within theSpecialty of Human and Animal Physiology at Peking University, and a Biochemistry Teaching and Research Division was then set up. In 1956, the first biochemistry major was established in Peking University among all the comprehensive universities in China. The biochemistry teaching emphasized its foundation in both biology and chemistry, and tried to educate students with sound foundations, sufficient practices, and great inspiration. The research work focused on three key areas: protein structures and functions, neurobiology, and nucleic acid functions. Dr. Zhang Longxiang’s protein research group was the first to chemically synthesize an octapeptide in China and to determine the changes in chemical structure and properties of trypsin after its autocleavage. They also determined the amino acid sequence of the lactate dehydrogenase M-chain of giant panda for the purpose of proposing a new classification system on these animals. Later, research on protein molecular design was conducted, on the basis of which the State Key Laboratory of Protein Engineering was established at Peking University. Xu Changfa and Ru Binggen constructed a new type of guided thrombolytic agent through protein engineering. Shen Tong and Wang Jingyan studied the metabolism of animal brains under low temperature and hypoxia conditions, and Dr. Wang Jingyan also studied neuropeptides. Drs. Shen Tong and Zhu Shenggeng developed various methods for isolating and purifying nucleic acids. Via the integration of genetic information through retrotransposons, Zhu Shenggeng isolated multiple specific antigens and antibodies by utilizing the phage display technique. Dr. Chen Tongdu investigated the changes in chemical structure and properties during protein denaturation, nutriology as well as the redox reactions in biology. Dr. Wang Zhimei assisted Dr. Chen Tongdu in continuing Dr. Hsien Wu’s research on protein denaturation. The Biochemistry Teaching and Research Division also attached great importance in serving the society, including its great efforts in training teachers for other universities and organizing the China-United States Biochemistry Examination and application (CUSBEA) program, as well as publishing a biochemistry textbook widely used in China since 1980. During the reform and opening up period of China, a large number of young faculty members joined the biochemistry department of Peking University, and the role of research groups has been fully appreciated, resulting in a series of new achievements in biochemistry teaching and research. However, biochemistry is facing significant conceptual changes and needs new ideas and methodologies. Therefore, it remains important to organize the faculty members into teaching and research unit for more effective teaching and research.

The β-barrel outer membrane protein is a kind of membrane integration protein widely existing in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts. The biogenesis of β-barrel outer membrane proteins in living bacterial cells is an extremely complex process, including the synthesis of nascent polypeptide chains in the cytoplasm, the translocation across the inner membrane, the transportation through the hydrophilic periplasmic space and finally the folding, assembly and insertion to the outer membrane to complete the whole process. During the biogenesis of β-barrel outer membrane proteins, it is critical to unveil how the periplasmic quality control factors such as SurA, Skp and DegP assist the folding and transportation of the nascent β-barrel outer membrane proteins through the hydrophilic periplasmic space, and how the SecYEG-SecDF-Yidc complex on the inner membrane and the BAM complex on the outer membrane act during the biogenesis of β-barrel outer membrane proteins. This review delves into the research progress of the mechanism of β-barrel outer membrane protein biogenesis in Gram-negative bacteria and also the application of various new technologies such as in vivo protein photo-crosslinking analysis and high through-put protein electrophoresis (SDS-PAGE) for exploring such dynamic cellular processes as protein biogenesis.

The success of “New Medical Sciences” in higher education requires effective tools in evaluating students’ performance in courses. Previously, we reported a teamwork (T), critique (C) and appreciation (A) (TCA) ideological and political model, a teaching model widely applied in Basic Medical courses. TCA is an abbreviation derived from Tricarboxylic Acid Cycle in Biochemistry as an analogy for nurturing the abilities of thinking and teamwork (T), critique (C) and appreciation (A), which hopefully could provide students with moral norms for cognition, science and life. This paper further explores the tools to assess the educational outcomes of the TCA model, by which teachers can collect feedback and reflect on teaching quality and effectiveness. Addressing the challenges of individual differences in large classes, fragmented learning feedback, and the difficulty of measuring meta-cognition in educational evaluation, this study employs strategies of value-added assessment, matrix assessment and norm-transferable assessment to evaluate the TCA abilities from the aspects of thinking quality, thinking creativity, cooperation ability, iterative thinking, dialectical thinking and job responsibility. By modifying/using 18 evaluation tools in Education and Psychology, we have established a rubric system composed of 30 primary indicators (with 11 newly designed, 10 partly modified and 9 directly adopted), along with 49 secondary indicators and 98 tertiary indicators to enhance the feasibility of the evaluation process. This rubric system was applied to Biochemistry teaching among the five-year-program undergraduates at Air Force Medical University. Specifically, thinking and teamwork are evaluated by creative works from “the magic biochemical-circle”, while critiques are assessed in large classes under the guidance of basic and clinical teachers, coupled with appreciation measured by job responsibility in a task-driven virtual reality (VR) project. The results indicate that Biochemistry teaching not only accumulates knowledge in students, but also achieves the goals in nurturing values and cognition. The inclusion of creative performance evaluation, cooperative learning and clinical case studies, can enhance students’ interpersonal skills, cooperation, quality of thinking, creative thinking, iterative thinking and dialectical thinking to varying degrees. TCA-based Biochemistry teaching has a long-lasting impact on character education, and is capable of inducing positive long-term changes in students’ cognition and lifestyle. Taken together, with the help of this rubric system, teachers can promptly acknowledge the effectiveness of their teaching, thereby facilitating their teaching strategies.

Extrachromosomal circular DNA (eccDNA) is a special kind of circular DNA molecules in nucleus of eukaryotes. These molecules are derived from chromosome genomes, and can independently participate in a variety of cell physiological or pathological processes, which are closely associated with the occurrence and development of tumors. The discovery of eccDNA can be traced back to the 1970s, and with the development of molecular biology technology, researchers have gradually revealed its important function in cancer. The formation of eccDNA is a complex process involving multiple mechanisms, including breakage-fusion-bridge cycle, chromothripsis, translocation-deletion-amplification, episome model and fork stalling and template switching, etc. eccDNA, especially large molecular weight eccDNA (>1 Mb, also known as ecDNA), plays an important role in promoting the amplification and activation of oncogenes, driving tumor heterogeneity and drug resistance, and has shown broad application potential as a molecular marker for tumor liquid biopsy. This review summarizes the exploration history, biogenesis, functions in tumor biology and detection, specificity in different types of tumors and analysis methods of eccDNA, and also discusses its application value in clinical diagnosis and treatment of tumors, so as to provide reference for further exploration of eccDNA in basic research and clinical practice of tumors.

Ubiquitination represents a critical post-translational modification of proteins, capable of inducing alterations in the stability, cellular localisation and activity of substrate proteins. Consequently, it plays a pivotal role in a multitude of essential cellular processes. The intracellular parasite Legionella pneumophila releases in excess of 300 effector proteins into its host cell via its distinctive type IVB secretion system. These effector proteins regulate the physiological activity of host cells, thereby facilitating the growth and reproduction of Legionella and ultimately resulting in Legionella infection in humans. In the context of host infection, a number of effector proteins have been identified as regulators of the host cell ubiquitination system. Together with SidJ, SdjA, DupA/DupB, LnaB, and MavL, SidEs precisely and dynamically modulate the ubiquitination pathway of host cells, thereby providing a suitable environment for L. pneumophila to survive. The clarification of the biological functions of LnaB and MavL has led to the elucidation of this complex non-canonical ubiquitination regulatory cycle in L. pneumophila. This review presents a summary of the structural and enzymatic basis of non-classical ubiquitination mediated by SidEs, along with an examination of its biological significance in regulating endoplasmic reticulum rearrangement and promoting Legionella-containing vacuole formation in host cells; the mechanism by which SidJ/SdjA regulates the phosphoribosylation activity of SidEs; and DupA/DupB, LnaB and MavL reverse the ubiquitination of host substrate proteins by SidEs through a multi-step catalytic reaction. In conclusion, this study will provide a reference for further understanding the detailed mechanism and biological significance of this type of non-classical ubiquitination modification, as well as offering insights into the pathogenic mechanism of L. pneumophila.

Alpha-enolase 1 (ENO1) is a multifunctional protein that serves as a glycolysis enzyme, a plasminogen receptor, and a DNA-binding protein, playing a critical role in tumorigenesis and progression. Long non-coding RNAs (lncRNAs) are crucial regulators of chromatin structure and gene expression. Accumulated data have unveiled that lncRNAs regulate ENO1 through multiple pathways. In the nucleus, lncRNAs act on the ENO1 promoter to regulate its transcription. In the cytoplasm, lncRNAs affect ENO1 translation by acting directly or indirectly with ENO1 mRNA and by adsorbing small ribonucleic acids as sponges. Additionally, in the cytoplasm, lncRNAs influence the stability, enzyme activity, and other functions of ENO1 by directly binding to the ENO1 protein and acting as scaffold molecules to form a polymer with ENO1. In tumors, the abnormal expression of lncRNA regulates the overexpression and function of ENO1, promoting the proliferation and metastasis of tumor cells. There is currently some knowledge on the interaction between lncRNA and ENO1, and further investigation is needed to reveal the specific molecular mechanisms and biological functions, as well as the potential applications of lncRNA in clinical treatment. Here, we review the regulatory role of lncRNAs on ENO1, focusing on 16 identified lncRNAs that regulate ENO1. Understanding the regulatory effects of lncRNAs on ENO1 will enhance our knowledge of the regulatory network involving ENO1 in tumor cells and may reveal new targets for cancer treatment.

The pathogenesis of central precocious puberty (CPP) is due to the early initiation of the function of the hypothalamic-pituitary-gonadal axis, which is driven by the gonadotrophin-releasing hormone (GnRH) from the hypothalamus. The increase of GnRH secretion will promote the secretion of gonadotropin by the pituitary gland, which leads to the development of reproductive organs and the secretion of sex hormones. The timing of puberty onset is influenced by the interaction between nutritional, environmental, and socioeconomic factors. In the study of pathogenic genes, loss-of-function mutations of MKRN3, LIN28 and DLK1 genes can lead to early onset of puberty, among which loss-of-function mutations of MKRN3 are one of the most common single-gene causes of familial CPP. Since 2013, when the MKRN3 mutation was first identified in five CPP families, the role of MKRN3 in adolescence has gradually been discovered. MKRN3 is a member of the E3 ubiquitin ligase family and is expressed in the central nervous system of many eukaryotes. MKRN3 may act as an E3 ubiquitin ligase to inhibit GnRH activity. Recently, more and more studies have explored the molecular mechanism of MKRN3 in CPP, revealing a variety of genes and proteins that interact with MKRN3. For example, MKRN3 can inhibit KISS1 and TAC3 activities, thereby affecting the expression of kisspeptin and neurokinin B to regulate GnRH secretion. MKRN3 also inhibited GNRH1 mRNA translation through PABPC1 ubiquitination. In addition, there are other targets such as MBD3, IGF2BP1 and NPTX1, all of which are involved in GnRH regulation downstream of MKRN3. Upstream of MKRN3, miR-30 can bind to three sites in the 3 '-untranslated region of the MKRN3 gene to block MKRN3 transcription. Here we review the role of MKRN3 in the pathogenesis of CPP and the research progress of its molecular mechanism, which will help to better understand the pathogenesis of CPP, provide new ideas and treatment methods for CPP-related fields in the future, and lay a theoretical foundation for further exploration of the molecular mechanism of MKRN3.

Sesamol is a fat-soluble natural polyphenol compound found in sesame seeds and sesame oil, which is widely used in food. Sesamol can effectively scavenge free radicals in the body, reduce oxidative stress, and protect cells from damage, therefore it plays an important role in the prevention of cardiovascular disease, cancer and neurodegenerative diseases. It has been widely studied for its various pharmacological functions such as antioxidant, antibacterial, anti-inflammatory, neuroprotective, cardioprotective, immunomodulatory and antitumor. In recent years, sesamol, as a safe and non-toxic chemical substance, has received extensive attention in the field of tumor research and is expected to be used as a clinical drug for tumor therapy in the future. In this paper, through the collection and analysis of relevant literature on sesamol at home and abroad, we reviewed the biological functions of sesamol in antioxidant, anti-inflammatory, antibacterial, regulating energy metabolism, cardiovascular protection, and neuroprotection, etc. as well as its mechanism of action. Furthermore, this review also focused on the role of sesamol in regulating cellular energy metabolism, inducing apoptosis, blocking the cell cycle, modifying epigenetic modifications, promoting cellular autophagy, inhibiting angiogenesis, reducing the tolerance of chemotherapeutic drugs, and so on. In addition, this paper also focused on the anti-tumor effects of sesamol by regulating cell energy metabolism, inducing cell apoptosis, modulating epigenetic modification, promoting cell autophagy, inhibiting angiogenesis, and reducing the tolerance of chemotherapeutic drugs, etc. This review aims to provide a new theoretical basis for the development of tumor therapeutic drugs.

Hilar cholangiocarcinoma is insidious in onset and often causes obstructive jaundice due to bile stasis, leading to impaired liver function. For tumors with malignant obstructive jaundice, biliary drainage is often performed before surgery in clinical practice. Currently, the commonly used drainage methods are percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde biliary drainage (ERBD), but there are controversies over the advantages and disadvantages of the two drainage methods. PTBD drainage can often lead to tumor implantation metastasis, but the underlying mechanism remains unclear. We detected tumor cells in PTBD and ERBD bile samples from hilar cholangiocarcinoma patients, subsequently explored their tumorigenicity and mechanisms through tumorsphere assay in vitro and xenograft tumor models in vivo. The experiments included benign gallstones group (30 cases) as a negative control, PTBD group (14 cases) and ERBD group (13 cases). Tumorsphere formation was identified in 3 cases (23%) among the 13 cases of ERBD group, in 6 cases (42%) among the 14 cases of PTBD group, but there were no tumor cells or formed tumorspheres in the 30 cases of benign gallstone group. The tumor sphere formation ability of cells in the PTBD group was significantly higher than that in ERBD group. Subcutaneous xenograft tumor assays showed that tumor growth in the PTBD group was significantly higher than that in the ERBD group. Tumor cells in PTBD bile possessed stronger tumorigenicity compared with the ERBD group. Mechanically, stem cell transcription factor Nanog mRNA levels were significantly higher in the PTBD group compared to the ERBD group. Both tumorsphere formation and xenograft tumor growth were reduced by Nanog knockdown in three cases of the PTBD group, indicating the important roles of Nanog in tumorigenicity of PTBD group tumor cells. The half-life of Nanog mRNA was longer in PTBD group cells than in ERBD group cells, suggesting potential post-transcriptional regulation on Nanog mRNA. The Nanog m⁶A level was higher in PTBD group tumor cells compared to the ERBD group. Analysis of methyltransferases and demethylases, ALKBH5 (α-ketoglutarate dependent dioxygenase alkb family homolog 5) mRNA levels were lower in the PTBD group than in the ERBD group and significantly correlated with the m⁶A level of Nanog. ALKBH5 knockdown led to an increase in the m⁶A level of Nanog, while ALKBH5 overexpression decreased the m⁶A level of Nanog. Dual-luciferase activity assays demonstrated that ALKBH5 knockdown significantly enhanced luciferase activity, whereas ALKBH5 overexpression reduced it. Further studies confirmed that ALKBH5 knockdown upregulated both the mRNA and protein levels of Nanog, whereas overexpressing ALKBH5 downregulated them. ALKBH5 mediated the demethylation modification of Nanog mRNA, and the lower levels of ALKBH5 expression in the PTBD group promoted Nanog’s m⁶A modification. Overexpressing ALKBH5 decreased tumorsphere growth, while ALKBH5 knockdown increased it, which was subsequently reduced by the simultaneous Nanog knockdown again. In sum, tumor cells in PTBD and ERBD drainage bile from hilar cholangiocarcinoma patients exhibited tumorigenicity. Compared to the ERBD group, tumor cells in PTBD bile with lower ALKBH5 expression levels enhanced Nanog’s m⁶A modification to upregulate Nanog expression levels, resulting in stronger tumorigenicity. These findings are significant for elucidating propensity to tumor implantation metastasis from PTBD drainage.

Mitochondrial transcription factor B1 (TFB1M) is mainly involved in mitochondrial DNA transcription and related to the development of hepatocellular carcinoma and breast cancer. However, its role in colon cancer is unclear. In this study, the expression level of TFB1M in colon cancer and its prognosis were analyzed based on TCGA and other databases and IHC assays. Differentially expressed genes (DEGs) were screened and subjected to the analysis of functional enrichment, mutation analysis, immune cell infiltration, and drug sensitivity analysis. CCK-8 and flow cytometry were used to detect the effects of overexpression of TFB1M on the viability, apoptosis and cell cycle distribution of colon cancer cells. Our results showed that the expression level of TFB1M was significantly up-regulated in colon cancer, and its expression level was correlated with the N stage and TNM stage (P<0.05). The prognosis of colorectal cancer patients in the high TFB1M expression group was worse. Functional enrichment results showed that TFB1M was related to leukocyte-mediated immunity, immunoglobulin production and other signaling pathways. Mutation results showed that high-frequency mutated genes, such as ZFHX4, RYR2, PIK3CA and FAT4, had significantly higher mutation frequencies in the TFB1M high-expression group (all P<0.05). In addition, the expression level of TFB1M was significantly higher in the PIK3CA and FAT4 mutation groups (all P<0.05). Immune infiltration results showed that the percentage of CD4⁺ memory activated T cells was increased in the TFB1M high expression group, while the percentage of Treg cells was reduced. The drug sensitivity results showed that patients in the TFB1M high expression group might be more sensitive to Tozasertib, cytarabine, vincristine, etc., while patients in the TFB1M low expression group might be more sensitive to Dasatinib, JQ1, ERK_2440, etc. The results of cellular experiments showed that over-expression of TFB1M enhanced viability, reduced apoptosis and increased the percentage of S-phase and G2/M-phase cells in colon cancer cells. Altogether, the results indicated that TFB1M might play a key role in the growth of colon cancer cells by regulating immune cell infiltration and function.

This study aims to investigate whether resistance exercise can effectively alleviate disuse skeletal muscle atrophy by activating the skeletal muscle Piezo1/AMPK/PGC-1α signaling pathway, improving mitochondrial function and promoting myogenesis. 8-week-old male C57BL/6J mice were used. Disuse muscle atrophy was simulated by hind limb plaster fixation, and the mice were divided into the control group, the disuse muscle atrophy group, the disuse muscle atrophy + resistance exercise group, and the disuse muscle atrophy + resistance exercise + Piezo1 inhibitor group. The resistance exercise group underwent an 8-week resistance training program. Methods such as Western Blotting, immunofluorescence staining, and mitochondrial mass and function detection were employed to evaluate skeletal muscle mass, function, mitochondrial status, and myogenesis. Resistance exercise significantly increased the cross-sectional area of skeletal muscle in mice with disuse muscle atrophy by 23% (P < 0.01) and the relative mass of skeletal muscle by 11% (P < 0.01). Resistance exercise led to an average increase of 206 m in the longest running distance of mice (P < 0.01), an average increase of 36.7 g in the maximum bearing capacity (P < 0.01), and an average reduction of 1.5 s in the balance beam crawling time (P < 0.01). Meanwhile, it upregulated the expression of the protein levels of Piezo1, AMPK, and PGC-1α (P < 0.01). In addition, resistance exercise increased the activity or protein expression levels of MMP, TFAM, COXⅠ, CS, ATPB, ATPase, ATP, p-mTOR/mTOR, p-P70S6K/P70S6K, Pax7, and MyoD in skeletal muscle (P < 0.05, P < 0.01). However, inhibiting Piezo1 decreased the expression of the above enzyme activities and protein levels (P < 0.05, P < 0.01). Resistance exercise alleviates disuse skeletal muscle atrophy effectively by activating the Piezo1/AMPK/PGC-1α pathway, improving skeletal muscle mitochondrial quality and function, and promoting protein synthesis and myogenesis.

This research aims to construct a stable epithelial cell senescence model for screening and evaluation of senolytics. We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A, including the optimal induction concentration, the optimal intervention time, and the optimal senescence duration, and confirmed the feasibility of MCF 10A as an epithelial senescence model by multiple ways. The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day. Under the optimal induction conditions, the positive rate of senescence-associated β-galactosidase (SA-β-gal) staining in the treated group reached 97%. At the same time, biochemical results of detecting the expression of mRNA, proteins, and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype (SASP), p16, p21 and p53 in the treated group were significantly higher than those in the control cells, and Lamin B1 was significantly decreased (P<0.001), which were consistent with the specific characteristics of senescence. In summary, an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study, which will promote the screening of senolytics for senescent epithelial cells.

The long non-coding RNA KCNQ1OT1 plays an important role in promoting the occurrence and development of various cancers. However, there is currently no systematic analysis of KCNQ1OT1 in pan cancer. To elucidate the value of KCNQ1OT1 in tumor diagnosis and prognosis, this study analyzed its expression levels in pan-cancer tissues and its impact on patient prognosis. By analyzing the regulatory mechanism of KCNQ1OT1 in gastric cancer, new molecular targets may be found for the diagnosis and treatment of gastric cancer. Using Sangerbox 3.0, ACLBI and UALCAN databases, we found the expression levels of KCNQ1OT1 were increased in 7 tumor tissues types (P<0.05). We found KCNQ1OT1 expression was correlated with poor prognosis in many tumor types using Sangerbox 3.0 database. We used R software to analyze the differential genes between the high and low expression groups of KCNQ1OT1 in gastric cancer patients (P<0.05, log2FoldChange>1). The GO and KEGG enrichment analysis showed that KCNQ1OT1 was involved in the glutamine metabolism of gastric cancer. The cell counting and Western blot detection showed that knocking down KCNQ1OT1 significantly reduced the gastric cancer cell activity, SLC1A5 expression level and SLC1A5-mediated glutamine transport process (P<0.01). Bioinformatics, RNA immunoprecipitation and dual luciferase analysis confirmed that KCNQ1OT1 competitively bind to miR-138-5p to promote the expression of SLC1A5. Finally, ChIP-seq data was used to detect the high H3K27ac signaling at the gene locus of KCNQ1OT1, and ChIP-qPCR was used to verify that P300-mediated enhancer activity regulated the high expression of KCNQ1OT1 in gastric cancer. KCNQ1OT1 can serve as an independent diagnostic biomarker and prognostic predictor in various tumors. Targeting the KCNQ1OT1/miR-138-5p/SLC1A5 signaling axis to regulate glutamine metabolism may provide new strategies and molecular targets for the treatment of gastric cancer.