Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by a cytokine storm, diffuse alveolar injury, increased pulmonary vascular permeability, and clinical manifestations of acute non-cardiogenic pulmonary edema and refractory hypoxemia (PaO2/FIO2 ≤ 300 mm Hg), which ultimately leads to multi-organ failure. The rapid onset, severity, and lack of effective treatments contribute to its high mortality rate, ranging from 30% to 70%, posing a significant public health threat. ARDS can be triggered by various etiologies, including severe infections (e.g., SARS-CoV, SARS-CoV-2, H5N1) and non-infectious causes. Current treatments are largely non-specific and focus on corticosteroids, traditional Chinese medicine, nutritional support, and mechanical ventilation.
The Berlin criteria (2012) are used for diagnosing ARDS, based on the timing of onset, hypoxemia, pulmonary edema, and associated radiological and physiological disorders. Recent studies suggested that biomarkers could enhance diagnostic sensitivity and specificity. For instance, elevated levels of Angiotensin II (Ang II) have been linked to the severity and prognosis of critical pneumonia, underscoring the importance of the renin-angiotensin system (RAS) in ARDS pathogenesis.
A key factor in the progression of ARDS is the disruption of the local RAS within lung tissues. Research has shown that activation of the Ang II-AT1R axis within the RAS contributes to lung injury. ACE2, a critical negative regulator of RAS, plays an essential role in mitigating lung injury caused by Ang II overproduction. Downregulation of ACE2 in animal models results in an imbalance in the RAS, leading to acute lung injury. Viral infections, including SARS-CoV, SARS-CoV-2, and avian influenza, as well as exposure to certain nanomaterials, can induce ARDS by reducing ACE2 levels, disrupting the RAS balance, particularly through activation of the Ang II-AT1R axis, which leads to an increase in Ang II.
We next discuss the exploration of potential therapeutic strategies involving RAS inhibitors, such as angiotensin receptor blockers (ARBs) and ACE2 supplementation. Studies have demonstrated that ARBs, including losartan, can significantly reduce lung injury and improve survival rates in animal models of ARDS induced by viral infections and other causes. Moreover, recombinant human ACE2 (rhACE2) has shown protective effects by lowering Ang II levels and alleviating pulmonary damage. Additionally, we discuss the therapeutic potential of ARBs in treating Multi-Organ Dysfunction Syndrome (MODS), as RAS dysregulation plays a critical role in organ injury. Clinical trials indicate that ARBs can improve outcomes in COVID-19 patients.
Despite potential adverse effects such as hypotension and electrolyte imbalance, ARBs remain a promising therapeutic option for both ARDS and MODS. Future studies should focus on further elucidating the molecular mechanisms underlying RAS regulation in different etiological contexts and developing personalized treatment strategies to optimize clinical outcomes. Overall, targeting RAS—particularly the Ang II-AT1R axis—represents a novel and promising approach for treating ARDS and MODS, offering a valuable therapeutic avenue for critically ill patients.

In the canonical model of gene transcription, transcription factors regulate the transcription of target genes by binding to double-stranded DNA (dsDNA) containing its specific consensus motifs. In contrast to dsDNA, G-quadruplexes are atypical nucleic acid secondary structures formed by guanine-rich sequences. G-quadruplex structures are involved in regulating various biological processes, including gene transcription, and have emerged as a significant research topic in the field of molecular biology. Recently, many research groups, including us, have revealed that G-quadruplex structures recruit transcription factors to bind to the promoters more efficiently than dsDNA, thereby enhancing target gene expression. However, there is currently a lack of comprehensive summaries and discussions regarding this atypical model of gene transcription regulation. In this review, we first elucidate the characteristics of G-quadruplex structures and the techniques used to identify these structures. G-quadruplexes can be classified into intramolecular and intermolecular types; intramolecular G-quadruplexes are further divided into parallel, antiparallel and hybrid types. The G-quadruplex structures can be determined using techniques such as circular dichroism, nuclear magnetic resonance spectroscopy and gel migration, among others. Then, we discuss the regulatory role of G-quadruplex in gene transcription. G-quadruplexes are mainly highly enriched in gene promoter. Early studies revealed that G-quadruplexes can inhibit gene transcription. However, lots of studies have recently proven that this structure has a new function of recruiting transcription factors to activate gene transcription. Finally, we summarize the classification of transcription factors with G-quadruplex binding activity, including transcription factors with C₂H₂ zinc fingers, forked head/winged helices, and p53 domains. The DNA-binding domain determines the interaction between transcription factors and G-quadruplex. Moreover, we propose future research directions in the field of G-quadruplex and transcription factors in regulating gene transcription. In conclusion, this review can provide important guidance for understanding the concept of G-quadruplex as a cis-acting element for transcriptional activation.

Neuropathic pain (NP) is a type of chronic pain caused by damage or disease of the nervous system. It is mainly characterized by spontaneous pain, hyperalgesia, and allodynia, which seriously affect the quality of life of patients. The pathogenesis of NP is complex, involving abnormal regulation such as peripheral sensitization, central sensitization, ion channel changes, and glial cell activation. In recent years, the role of m6A in NP has attracted extensive attention. However, the research on the role of m⁶A modification in different diseases and pain models is still limited. Therefore, it is particularly important to clarify the role of m6A modification in different diseases and pain models. This article reviews the research progress on the role and mechanism of m⁶A methylation modification in the pathogenesis of NP in recent years, especially the role mechanism of the five classical m⁶A modification factors, METTL3, METTL14, FTO, ALKBH5 and YTHDF1, in mediating the formation of NP in different diseases and pain models, with the expectation of providing new insights and ideas for the drug development and prevention of NP from the perspective of m6A modification.

Gene editing technology has become an important tool for biomedical research because of its high efficiency and precision in target gene localization and cleavage. The technology not only facilitates basic research on gene function, but also provides new strategies for gene therapy of hereditary diseases and genetic improvement of crops. With the integration of artificial intelligence (AI) technology, especially the application of machine learning algorithms, the design and execution of gene editing have become more intelligent. AI technology optimizes the design of sgRNAs through predictive analysis and pattern recognition, improving the specificity and efficiency of editing while reducing the risk of off-target effects. In addition, AI plays a key role in the parsing of large-scale genomic data, providing new perspectives for understanding complex biological processes and disease mechanisms. This paper reviews the research progress of data-driven gene editing technology in target precision, safety enhancement and personalized therapy, aiming to provide reference and inspiration for researchers in the field of gene editing technology and to promote the application and development of AI in gene editing technology.

Alzheimer’s disease (AD) has attracted widespread attention due to its extremely complex pathogenic mechanisms, multiple pathogenic factors, and its heavy burden on patients and the society. In recent years, several studies have revealed various pathogenic mechanisms of AD, and the AD treatments based on these mechanisms become research hotspot in nanomedicine. Nanomaterials with unique physicochemical properties show great potential in AD treatment. Nanomaterials possess good biocompatibility. Moreover, they can regulate and release therapeutic drugs continuously and steadily to ensure the ideal concentrations of drugs reach in the target site. Meanwhile, they can bind with the therapeutic targets precisely to treat AD. Therefore, the development of novel nanodrugs has become an important research area in AD treatment. This article reviews the main pathological features and pathogenic mechanisms of AD, including β-amyloid plaque aggregation, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Additionally, this review mainly discusses the therapeutic strategies of nanomaterials in clearing pathological proteins (such as β-amyloid and Tau proteins), inhibiting oxidative stress, and alleviating neuroinflammation. Finally, this review prospects the risks and challenges faced on current AD treatment strategies by nanomaterials, such as low drug delivery efficiency to the brain and potential side effects after treatment. We also provide suggestions for the future directions in this research field. This review aims to promote the clinical translation of nanomaterials in AD treatment by discussing the research status of this field.

Collagen is a matrix protein essential for maintaining the function of various tissues in animals. There are many types of collagen in vertebrates, and the function of each type of collagen in the body is closely related to its sequence and structure. In addition to the common Gly-X-Y amino acid sequence, there is also a special structure Gly-Gly-Y in the natural collagen. In order to explore its effect on collagen, this study constructed mutants containing Gly-Gly-Y at the levels of collagen polypeptides, long-chain collagen, and collagen polymers. The thermal stability of the mutant before and after mutation was characterized by circular dichroism scanning. At the same time, molecular dynamics simulation was used to calculate the hydrogen bonding probability and bending degree of collagen polypeptides, explaining the molecular mechanism of changes in collagen stability and flexibility. The results showed that the mutant containing the Gly-Gly structure would decrease the Tm value of the sample, but this effect would gradually weaken as the collagen triple helix region lengthened and the degree of protein self-assembly increased, and the reduced Tm values are 5 ℃, 3 ℃, and 1 ℃, respectively. At the same time, the simulation results show that the curvature of the polypeptide containing the Gly-Gly structure also increases to some extent, indicating that the structure near the mutation site has greater flexibility. This provides a new idea for the design of rubber materials with certain flexibility.

The incidence and mortality rate of lung cancer rank among the highest worldwide, severely endangering human health and life. Metformin, an anti-diabetes drug, has been shown to elicit anticancer activities in various tumors. However, its underlying mechanisms remain elusive. In this work, we explore the role of receptor-interacting protein 1 (RIP1) which plays a crucial role in the process of cell death, in metformin-induced anticancer activities in lung cancer. Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death, as evidenced by metformin-induced PARP and caspase cleavage. Furthermore, the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death. Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels (0 vs 80 mmol/L, 100% vs 20%, 100% vs 15%). Additionally, co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner, as metformin promotes Hsp70 degradation, and Hsp70 endogenously interacts with RIP1. Subsequent CCK-8, flow cytometry, and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3β axis. Consistently, results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight. Collectively, these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo, providing novel strategy for lung cancer administration.

Potassium-calcium activates channel subfamily N member 3 (KCNN3/SK3/ KCa2.3) is involved in regulating cellular calcium signaling, muscle contraction and neurotransmitter release. Dysregulation of the KCNN3 channel is associated with the development of various tumors. We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma (STAD) as a prognostic target. By analyzing the Human Protein Atlas (HPA) database and The Cancer Genome Atlas (TCGA) database, we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD, and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD. In addition, we found that high expression of KCNN3 in STAD reduced the IC₅₀ of several drugs in STAD cells, suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD. To investigate the underlying biological mechanism, we identified a potential KCNN3 interaction factor, tumor necrosis factor receptor superfamily member 7 (CD27/TNFRSF7), which is expressed at low levels in STAD. RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels, and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm. Moreover, we confirmed the inhibitory effect of KCNN3 on the proliferation, migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments. Furthermore, GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport. Lastly, we verified through cell co-culture, RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells. Therefore, our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.

Glycoengineering was carried out in the mammalian cell line CHO for the production of protein-based drugs. Firstly, the genome sequence of the Rosa26 locus of CHO cells was determined, the gRNA sequences were designed, and the landing pad was integrated into the Rosa26 locus of CHO cells by CRISPR/Cas9 technology. Three targeting vectors co-expressed by glycosyltransferases, which are β-1,4 galactosyltransferase (B4GALT1), α-2,6-sialyltransferase 1 (ST6GAL1) and N-acetaminoglycosyltransferase III (GnT Ⅲ), were constructed by overlapping PCR and seamless ligation technology, and the three glycosyltransferase genes were integrated into the CHO Rosa26 locus by Cre enzyme-mediated cassette exchange technology. PCR confirmed that three glycosyltransferases had been successfully site-directed integrated into the Rosa26 site. The mRNA expression levels of the three glycosyltransferases were more than 50 000-fold by qRT-PCR, and the protein expression levels of the three glycosyltransferases were more than 4-fold via western blotting (P<0.001). A CHO-engineered cell line with three glycosyltransferases integrated into Rosa26 site was successfully constructed.

To investigate the impact of high salt stress on the metabolic pathways and regulatory mechanisms involved in synthesizing hydroxyectoine (5-HE) in Virgibacillus salexigens, cultures were supplemented with 1.5 and 2.5 mol/L NaCl as control and experimental groups, respectively. High-performance liquid chromatography (HPLC) was used to detect the difference in the amount of 5-HE synthesis. Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations. Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR. Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl. Transcriptomic analysis identified 652 differentially expressed genes across 348 KEGG pathways, with 210 upregulated and 442 downregulated, primarily enriched in pathways such as purine metabolism, amino acid biosynthesis, sulfur metabolism, and biotin metabolism. Validation of 13 genes, including lysC, asd, ectA, ectB, ectC, ectD, thrB, thrC, ilvA, ilvE, AGXT, YckA and GlnQ, showed expression trends consistent with transcriptome data. Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism, lysine degradation, and arginine and proline metabolism. This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway, and provided a basis for the subsequent construction of 5-HE high-yielding strains.

Paclitaxel (PTX) is a first-line chemotherapy drug for breast cancer, but its resistance issues significantly impact clinical treatment efficacy. Fucosylation, especially core fucosylation, is closely related to tumor chemoresistance, resulting in poorchemotherapy responses and poor prognosis in patients. In this study, we investigated the effect and mechanism of the fucosylation inhibitor 2-fluorofucose (2-F-Fuc) on the chemosensitivity of paclitaxel-resistant breast cancer MCF-7/PTX cells. The drug resistanceindex (RI) of MCF-7/PTX cells was 8.49 by MTT assays. Western blotting, real-time PCR, enzyme-linked immunosorbent assay (ELISA) and Lens Culinaris Agglutinin (LCA) lectin imprinting showed that compared with MCF-7 cells, the expression of FUT8, MDR1and core fucosylation in MCF-7/PTX cells was high. Western blotting showed that 2-F-Fuc had a significant inhibitory effect on the growth of MCF-7/PTX cells, and the expression levels of FUT8 and MDR1 were significantly down-regulated after 2-F-Fuc treatment, and the down-regulation was more pronounced in the PTX and 2-F-Fuc combination group (P<0.05). Compared to the control, expression of PCNA in MCF-7/PTX cells in the PTX and the 2-F-Fuc group were down-regulated, and the apoptosis-related proteins, such as cleaved caspase-3 and Bax/Bcl-2 were increased. The level of p-PI3K and p-AKT were down-regulated, and the changes in the combination of 2-F-Fuc and PTX were more robust (P<0.05). The above results showed that the core fucosylation level of MCF-7/PTX cells was significantly increased, and 2-F-Fuc could reduce the core fucosylation level of MCF-7/PTX cells by inhibiting the expression of FUT8, and enhance the sensitivity of drug-resistant cells to PTX, which may correlate with the downregulation of PI3K/AKT signaling pathway proteins.

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow catfish (Pelteobagrus fulvidraco); this study used P. fulvidraco as the research subject. Dual-luciferase reporter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter; coupled with in vivo experiments. The results indicated that the 2 045 bp senp8 promoter sequence contained key transcription factor binding sites such as SP1; TATA-Box; CCAAT-Box; SREBP1; PPARα; and PPARγ. The binding sites of SREBP1 (-901/-910 bp); PPARα (-1 291/-1 308 bp); and PPARγ (-1 292/-1 306 bp) in the senp8 promoter positively regulate its activity; and oleic acid or palmitic acid promote this binding. Furthermore; high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P. fulvidraco; oleic acid or palmitic acid treatment significantly enhanced the activity of the senp8 promoter; and this enhancement could be achieved through the regulatory effects of SREBP1; PPARα; and PPARγ response elements. Additionally; high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P. fulvidraco. This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

Molecular biology experimental skills have become essential for medical and pharmaceutical undergraduates engaged in scientific research practice. To meet the training needs of molecular biology skills in different disciplines and majors, this study establishes a cross-major, cross-disciplinary, and cross-nationality scientific research mutual assistance group. The training of molecular biology experimental skills was combined with a large-scale senior thesis design, where students collectively practiced and mastered a variety of molecular biology skills such as polymerase chain reaction, protein immunoblotting, and enzyme-linked immunosorbent assay in a comprehensive experiment. The implementation of this scientific research mutual assistance group model received positive feedbacks from students, who found that their molecular biology skills had significantly improved. The scores of the ‘Molecular Biology’ exam for the pharmaceutical and biological science major members of the research group were 80.7 and 72.5, respectively, which were significantly higher than the average scores of 74.77 and 67.26 for the same majors. The comprehensive ability of students in molecular biology was enhanced. Multiple members of the research group participated in provincial biopharmaceutical skill competitions and won several second and third prizes. They were successfully funded for six undergraduate innovation and entrepreneurship projects, including one provincial-level and five university-level projects, thus effectively improving students’ scientific research and innovation capabilities. The thesis defense score of the research group members was 86.12, significantly higher than the average score of 83.43 for all members of the same defense group, indicating a significant improvement in students’ senior thesis design level and comprehensive quality. The rate of the research group members to continue their graduate school study was 90%, significantly higher than the average enrollment rate of 38.61% for the same defense group. Taken together, the establishment of a multidisciplinary cross-research mutual assistance group based on senior thesis optimized teaching resources, integrated teaching advantages, and effectively improved undergraduates’ molecular biology experimental skills and scientific research skills.