Multiple myeloma (MM) is the second most common hematological malignancy, predominantly affecting the elderly. With the development of an aging society in China, the incidence of MM has been steadily increasing, becoming a significant concern for public health and a considerable socioeconomic burden. Over the past two decades, breakthroughs have been achieved in both clinical management and basic research on MM. However, the field now stands at a crossroads for the next phase, facing numerous developmental directions and challenges.

Multiple myeloma (MM) is a hematologic malignancy characterized by the malignant proliferation of plasma cells. Currently, proteasome inhibitors (PIs),immunomodulatory drugs (IMiDs), and autologous hematopoietic stem cell transplantation (ASCT) are the primary approaches used to improve the survival outcomes of MM patients. However, as treatment advances, most patients still face refractory and relapsed diseases, and the path to a cure remains challenging. In recent years, monoclonal antibodies (mAbs), chimeric antigen receptor T cells (CAR-T),antibody-drug conjugates (ADCs), and bispecific antibodies (BsAbs) have all demonstrated promising efficacy in clinical studies and applications. These antibody and cell-based immunotherapies have brought new hope to patients with refractory and relapsed MM (RRMM). Each type of immunotherapy offers unique advantages in activating immune cells, targeting tumors, and improving patient outcomes, yet they also encounter challenges related to safety and resistance. In the future, with continuous advancements in molecular biology and antibody engineering, novel immunotherapeutic products are expected to achieve synergistic effects through combination strategies, thereby providing longer survival benefits and improved life quality for RRMM patients. This article aims to review the latest progress in immunotherapy for MM, systematically discussing the mechanisms of action, current clinical applications, and future development trends of mAbs, CAR-T, ADCs, and BsAbs. It is intended to serve as a comprehensive reference for researchers and clinicians and promote advancing precision immunotherapy for MM.

UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size (1 292 residues) and dual E2/E3 enzymatic activities, enabling diverse ubiquitylation types. Unlike typical E2 enzymes (150~200 residues), UBE2O’s multifunctionality allows it to regulate substrate degradation, subcellular localization, and functional modulation. Emerging studies highlight its critical roles in protein quality control, erythroid differentiation, metabolic regulation, and maintenance of circadian rhythm. Dysregulation of UBE2O is implicated in various diseases, including cancers, neurodegenerative disorders, and metabolic diseases. This review extensively discusses the unique structural features, diverse biological functions, and pathological roles of UBE2O, as well as its therapeutic potential for associated diseases.

Acquired resistance to the proteasome inhibitor bortezomib (BTZ) poses a significant challenge in the treatment of multiple myeloma (MM). During the acquisition of BTZ resistance, metabolic reprogramming is actively engaged in MM cells. However, the key regulatory genes and molecular mechanisms mediating bortezomib resistance through this metabolic rewiring have not been fully elucidated. This study aims to investigate the regulatory role of pyrimidine metabolites in drug resistance of MM and their underlying molecular mechanisms. Screening via CCK-8 assays demonstrated that the pyrimidine metabolite uridine is associated with BTZ resistance in MM (P<0.05). In vitro experiments, including CCK-8 assays, Western blotting, and flow cytometry, demonstrated that uridine partially suppresses bortezomib-induced apoptosis in MM cells (P<0.05). In vivo, experiments utilizing Vk*MYC mouse models, subcutaneous tumor models, and intramedullary bone marrow transplantation models showed that the combination of BTZ and uridine significantly accelerated tumor growth, exacerbated bone destruction, and increased tumor cell infiltration in tumor-bearing mice (P<0.05). RNA sequencing analysis revealed that uridine primarily affects mitochondrial translation in MM at the transcriptional level. Seahorse energy metabolism assays demonstrated that uridine enhances mitochondrial oxidative phosphorylation without significantly altering glycolysis. Transcriptomic analysis further identified a significant upregulation of cytochrome c oxidase subunit 5B (COX5B) transcription in uridine-treated groups (P<0.05). Functional studies confirmed that COX5B is a key molecule mediating uridine’s effects on mitochondrial function in MM cells. In conclusion, uridine promotes BTZ resistance in MM by upregulating COX5B transcription and protein expression, thereby enhancing cytochrome c oxidase activity and regulating mitochondrial oxidative phosphorylation. This study delineates the role of uridine in the development of bortezomib resistance in MM and elucidates its COX5B-mediated metabolic reprogramming mechanism, providing a theoretical foundation for developing targeted therapies against relapsed/refractory MM.

A subset of patients with multiple myeloma (MM) present with reduced serum vitamin B12 levels at initial diagnosis; however, its clinical significance and underlying mechanisms remain unclear. Vitamin B12 plays a crucial role in hematopoiesis and immune regulation. This study aims to elucidate its association with extramedullary diseases, immune function, and prognosis in MM patients. A retrospective analysis was conducted of 92 newly diagnosed MM patients, who received treatment at the Second Affiliated Hospital of Soochow University between January 2020 and December 2023. Patients were classified into a low vitamin B12 group (n=37) and a normal vitamin B12 group (n=55) based on their serum vitamin B12 levels. The findings revealed that the incidence of extramedullary infiltration was significantly higher in the low vitamin B12 group than in the normal group (26.5% vs. 17.0%, P=0.031). Survival analysis demonstrated that patients with low vitamin B12 levels had significantly shorter overall survival (OS) and progression-free survival (PFS) (OS: P=0.0123; PFS: P=0.0136). Additionally, these patients showed a decreasing trend in peripheral blood total T cell, CD4⁺ T cell, and CD8⁺ T cell counts, with serum vitamin B12 levels showing a significant positive correlation with the total T cell count (R=0.2717, P=0.0135) and CD4⁺ T cell count (R=0.2175, P=0.0497). In conclusion, reduced serum vitamin B12 levels at initial diagnosis are significantly associated with poor prognosis in MM patients and may serve as a potential prognostic biomarker. Furthermore, vitamin B12 deficiency may contribute to immune dysfunction, particularly impaired T cell immunity, and a higher incidence of extramedullary diseases.

Although teniposide (VM26) is widely used in the treatment of lymphoma, its poor water solubility, low bioavailability and systemic toxicities still limit its clinical application. Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26, but there is an urgent need to overcome the problem of its non-specific targeting. Therefore, in this paper, we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system (VM26-TNDS), and characterised its drug encapsulation rate, particle size and zeta potential. We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor, in terms of cellular targeting, inhibitory effect of proliferation, and induction of apoptosis and necrosis. The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85%, and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation. Based on CD44 receptor expression, Granta-519 (high expression), Raji (medium-low expression) and SU-DHL-4 (almost no expression) were screened for cellular experiments. Compared with VM26-NDS, the targeted modification could effectively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells. The inhibitory proliferative effect and apoptotic necrosis-inducing ability of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells, whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells, reflecting the targeting advantage for VM26-TNDS, as expected. However, its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations (0.25 μmol/L and 0.5 μmol/L), which met the expectation. The above results indicate that a teniposide-targeted nano-delivery system, VM26-TNDS, has been successfully prepared in this study. VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor, thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect. Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo experimental evidence.

The rise of nanomedicine has opened up new avenues for drug delivery and tumor treatment. Nanocarriers, in particular, have become core tools in the field of drug delivery. Anti-cancer peptides (ACPs) can achieve anti-tumor effects by inducing tumor cell apoptosis, inhibiting angiogenesis, and regulating the immune microenvironment. Their low toxic side effects and drug resistance make them important in the field of cancer treatment. However, ACPs face limitations such as poor stability, short in vivo half-life, and low targeted delivery efficiency, which seriously limit their therapeutic effects and further development. Nanocarriers provide an efficient, flexible and precise solution for the delivery of ACPs due to their advantages of increasing drug solubility, changing drug distribution in the body and improving drug targeting. This review systematically summarizes the structural characteristics and biological properties of four types of nanocarriers, including liposome nanocarriers, polymer nanocarriers, inorganic nanocarriers, and self-assembled peptides, and focuses on analyzing the application examples of nanocarriers in enhancing the stability of ACPs, improving targeted delivery efficiency, improving bioavailability, and overcoming drug-resistant tumor treatment. We also summarize in detail the structural pros and cons of these four carriers. Finally, we look forward to the development direction of research on the combination of nanocarriers and ACPs, in order to provide a theoretical basis for the clinical application of ACPs.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly serious chronic liver disease worldwide, with complex pathogenesis and many challenges in diagnosis and treatment. In recent years, genome-wide studies have revealed the important roles of epigenetic modifications in the development of NAFLD, especially the involvement of imprinted genes. The parental origin effect of NAFLD suggests that imprinted genes play a key role in its pathogenesis. The Dlk1-Dio3 gene cluster, as one of the largest clusters of imprinted genes, has become a focus of research because of its central role in embryonic development and metabolic regulation. This review explores the structure and function of the Dlk1-Dio3 gene cluster and its potential role in NAFLD pathogenesis. This gene cluster plays a key role in the “second strike” of NAFLD through a complex regulatory network that affects biological processes such as lipid metabolism, glucose metabolism, inflammatory response and oxidative stress in the liver. Specifically, DLK1 acts as a negative regulator, inhibiting adipocyte differentiation and thus reducing hepatic lipid accumulation, while DIO3 promotes adipocyte differentiation and increases hepatic lipid accumulation by regulating thyroid hormone conversion. In addition, the Dlk1-Dio3 gene cluster regulates lipid metabolism by modulating multiple microRNAs (e.g. miR-370, miR-122, etc.). miR-370 exacerbates lipid accumulation by inhibiting CPT1α; miR-122 up-regulates SREBP-1c and promotes fatty acid synthesis; and miR-379/410 clusters increase lipid scavenging capacity by decreasing lipid accumulation. Long non-coding RNA MEG3 also plays an important role in NAFLD. meg3 promotes fatty acid oxidation and reduces lipid droplet accumulation by up-regulating SIRT6, and attenuates lipid synthesis by inhibiting the Wnt/mTOR signaling pathway through binding to miR-21. In terms of insulin resistance, DLK1 inhibits gluconeogenesis and promotes fatty acid oxidation by activating the PI3K/Akt/mTOR pathway, thereby reducing hepatic lipid burden. DIO3, on the other hand, affects insulin sensitivity by regulating thyroid hormones and promotes the development of NAFLD. Meanwhile, the Dlk1-Dio3 gene cluster also plays an important role in regulating oxidative stress and inflammatory responses, and DLK1 attenuates hepatic oxidative stress injury by inhibiting inflammatory factor expression and activating antioxidant signaling. Taken together, the Dlk1-Dio3 gene cluster plays a multidimensional role in the occurrence and development of NAFLD, providing potential biomarkers and therapeutic targets.

The incidence of gastrointestinal tumors is increasing year by year and it has become a worldwide health problem with high incidence and poor prognosis. Ferroptosis, a new type of cell death, is mainly caused by abnormal intracellular iron metabolism leading to excess iron, which results in high production of intracellular reactive oxygen species (ROS) and accumulation of lipid peroxides. With the gradual deepening of the study of ferroptosis, it is found that ferroptosis can sensitize gastrointestinal tumor cells to drug therapy, so as to achieve a better therapeutic effect. Therefore, ferroptosis has attracted widespread attention in the field of treatment of gastrointestinal tumors in recent years. Traditional Chinese medicines have a long history and have been widely utilized in the treatment of cancer due to its low cost and fewer adverse effects. More and more studies have found that traditional Chinese medicine can induce ferroptosis in gastrointestinal tumors and thus inhibit tumor cell growth and metastasis. Here we first introduce the theory of ferroptosis, then further present traditional Chinese medicine monomers that induce ferroptosis in gastrointestinal tumor cells through modulating iron metabolism, inhibiting ferroptosis related antioxidant system and regulating nuclear factor erythroid 2-related factor 2 (NRF2), thereby inhibiting gastrointestinal tumorigenesis and progression. Moreover, we expound the research of anti-gastrointestinal tumor using traditional Chinese medicine and traditional Chinese medicine monomer combined with chemotherapy drugs to provide a new way of thinking for the treatment of digestive tract tumors.

Mesenchymal stem cells (MSCs) induces fusion of multiple monocyte macrophages by secreting key cytokines such as receptor activator for nuclear factor-κB ligand (RANKL) and macrophage CSF (M-CSF) to form multinucleated macrophages thereby SUMO-specific protease 3 (SENP3) modifies proteins by de-SUMOylation, which in turn affects the stability, localization and activity of substrate proteins. Based on the previous work in our laboratory, we found that the number of osteoclasts increased in mice with SENP3 knockdown in MSC (^***P<0.001). To further explore the mechanism, using immunofluorescence as well as Western blotting assay, we found that knockdown of the Hedgehog (Hh) signaling pathway by SENP3 increased the transcription factor glioma-associated oncogene homolog 2 (Gli2), which is the most important transcription factor for the production of osteoclasts. CHIP-qPCR results showed that Gli2 promoted COX2 transcription by binding to cyclooxygenase-2 (COX2) promoter regions -1 235~-1 249 and -1 158~-1 172 (^*P<0.05); meanwhile, the main secretion product of COX2, peptide, was detected by ELISA (^*P<0.05). The level of prostaglandin E2 (PGE2), the main secretory product of COX2, was increased in the supernatant of the culture medium of MSC with knockdown of SENP3 by ELISA (^***P<0.001). PGE2 is known to mediate cell migration and osteoclastogenesis through E-type prostanoid receptor 2 (EP2) and E-type prostanoid receptor 4 (EP4). In the study, the expression of EP4 receptor was found to be elevated in differentiated osteoclasts (^**P<0.01). The inhibitors of the EP4 receptor significantly reduced the expression of nuclear factor-activated T cell 1 (NFATc1), Cathepsin K (Ctsk), and tartrate resistant acid phosphatase (TRAP) genes (^*P<0.05) and decreased osteoclastogenesis (^***P<0.001), suggesting that EP4 receptors play a critical role in PGE2-mediated osteoclast differentiation. In conclusion, SENP3 deletion in mouse MSCs promotes COX2 transcription and PGE2 secretion through activation of the Hh signaling pathway thereby promoting osteoclast formation.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PIEZO2 in osteoarthritis (OA), we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line. By mapping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA, we employed the CRISPR/Cas9 synergistic activation mediator (SAM) system to precisely integrate transcriptional activation elements into the PIEZO2 promoter region. Lentiviral-mediated targeted genomic integration ensured endogenous PIEZO2 overexpression, confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting, which revealed membrane-specific localization of PIEZO2 protein (localization efficiency: 78.49%). Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA, while Western blotting validated enhanced membrane-localized protein expression. Strikingly, PIEZO2-overexpressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls: type II collagen mRNA expression decreased to 50% of baseline levels, whereas matrix metalloproteinase 13 (MMP13) mRNA surged by 20-fold. These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress (10% strain, 0.5 Hz, 8 h/day for 2 consecutive days). Collectively, we successfully generated a human chondrocyte model with stable PIEZO2 overexpression, which faithfully mirrors mechanotransduction-driven OA progression. This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosignaling networks and advancing targeted therapeutic discovery.

The engineering application of microbially induced carbonate precipitation (MICP) is limited by pH-dependent conformational dynamics of urease. Focusing on the α-subunit urease from Sporosarcina pasteurii, this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11. Results showed that under neutral conditions (pH 7-8), key histidine residues (HIS139/HIS249) exhibited minimal displacement (<0.5 Å), the longest hydrogen bond lifetime (>8 ps), highest conformational stability (root mean square deviation, RMSD: 0.15-0.18 nm), and optimal catalytic activity (conductivity change rate: 0.03 mS/cm·min^-1, CaCO₃ precipitation: 3.84 g). Extreme pH (pH 3/11) induced structural collapse (displacement up to 1.8 Å) and complete activity loss. Simulations revealed that neutral pH stabilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume (~120 ų) and moderate conformational coherence (correlation coefficient ~0.8). This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states, providing theoretical support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

Copy number variation encompassing SNP plays an important role in IVD and precision medicine. As the most commonly used method, FISH could not overcome the probe cross-reactivity which is common when to detect SNP. Here we developed a quantitative and qualitative method on copy number variation encompassing SNP. In this study, the rs76711854 was used as an example to establish a quantitative method by advantage of probe cross-reactivity. The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR. The allelic genotypes were verified by Sanger sequencing. Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digital PCR. The different clusters (2D) and fluorescence intensity layers (1D) exist by adding probe with cross-reactivity. The A/G ratio measured by digital PCR is 2:1, which is verified by probe targeting to the SNP. The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa. The data suggest that there is a multi-copy variation at this locus in DU145 cells. The method applied here is based on one single cross-reactivity probe via digital PCR.

Biochemistry, as a fundamental course for science and engineering majors related to biology and chemistry, holds a significant position in the curriculum. The course team at Dalian Minzu University is committed to teaching innovation, adopting the outcome-based education (OBE) concept for teaching design and incorporating ideological and political elements, in order to achieve the dual goals of knowledge transmission and value guidance. The team has established a three-dimensional teaching goal of "knowledge, morality, and ability", covering "consolidating core knowledge, cultivating moral sentiment, and enhancing innovation ability". Through a multi-dimensional integrated teaching method of "three integrations and five combinations", multiple rounds of teaching practice have been carried out in the applied chemistry major using "classification and specificity of enzyme" as an example. The output of teaching results and survey questionnaires show that students highly recognize the teaching design and its "process-based learning" evaluation method, fully reflecting the student-centered teaching idea. Research has shown that OBE design combined with ideological and political elements can effectively promote students’ knowledge acquisition, moral growth, and innovation ability improvement in the course of Biochemistry. This teaching design not only helps students construct correct worldviews, outlooks on life, and values, but also significantly enhances their innovative thinking and practical abilities. This teaching design can not only effectively improve the teaching quality of the course, but also provide new perspectives and ideas for the teaching design of Biochemistry, realizing the organic integration of professional knowledge imparting and ideological and political education, and has certain innovation and practical significance.

The aim of this study is to explore a new path of empowering ideological and political education in courses with digital intelligence technology, therefore to improve the teaching quality of biology courses in universities, promote the comprehensive implementation of the fundamental task of cultivating morality and talents, and continuously improve the level of "three pronged education". By using the biology course "Immunology" as a practical carrier, we have constructed a dual-driven framework of "ideological and political guidance+digital intelligence empowerment" utilizing digital tools to further highlight pedagogical feature enhancement, curricular optimization, innovative teaching models, multidimensional assessment, and enhanced teaching refinement. The empowerment of digital intelligence in the ideological and political construction of the course "Immunology" has achieved notable progress. Students’ professional abilities and ideological and political literacy have significantly improved, and the proportion of students with excellent grades has been increasing year by year (81.93% of students with good grades or above in 2024), demonstrating outstanding performance in various social practice activities; The course exhibits excellent demonstration and radiation effects on campus, and the teaching results have been supported by the Ministry of Education and provincial-level education reform projects. This study serves as a practical example for the digital transformation of ideological and political education in higher education courses, providing reference and innovative insights for implementing ideological and political elements in other courses of biology majors.