Chinese hamster ovary (CHO) cells are the most established and versatile mammalian expression system for the large-scale production of recombinant therapeutic proteins, owing to their genetic stability, adaptability to serum-free suspension culture, and ability to perform human-like post-translational modifications. More than 70% of biologics approved by the U.S. Food and Drug Administration rely on CHO-based production platforms, underscoring their central role in modern biopharmaceutical manufacturing. Despite these advantages, CHO systems continue to face three persistent bottlenecks that limit their potential for high-yield, reproducible, and cost-efficient production: excessive metabolic burden during high-density culture, heterogeneity of glycosylation patterns, and progressive loss of long-term expression stability. This review provides an integrated analysis of recent advances addressing these challenges and proposes a forward-looking framework for constructing intelligent and sustainable CHO cell factories. In terms of metabolic regulation, excessive lactate and ammonia accumulation disrupts energy balance and reduces recombinant protein synthesis efficiency. Optimization of culture parameters such as temperature, pH, dissolved oxygen, osmolarity, and glucose feeding can effectively alleviate metabolic stress, while supplementation with modulators including sodium butyrate, baicalein, and S-adenosylmethionine promotes specific productivity (qP) by modulating apoptosis and chromatin structure. Furthermore, genetic engineering strategies—such as overexpression of MPC1/2, HSP27, and SIRT6 or knockout of Bax, Apaf1, and IGF-1R—have demonstrated significant improvements in cell viability and product yield. The combination of multi-omics metabolic modeling with artificial intelligence (AI)-based prediction offers new opportunities for building self-regulating CHO systems capable of dynamic adaptation to environmental stress. Regarding glycosylation uniformity, which determines therapeutic efficacy and immunogenicity, gene editing-based glycoengineering (e.g., FUT8 knockdown or ST6Gal1 overexpression) has enabled the humanization of CHO glycan profiles, minimizing non-human sugar residues and enhancing drug stability. Process-level strategies such as galactose or manganese co-feeding and fine control of temperature or osmolarity further allow rational regulation of glycosyltransferase activity. Additionally, in vitro chemoenzymatic remodeling provides a complementary route to construct human-type glycans with defined structures, though industrial applications remain constrained by cost and scalability. The integration of model-driven process design and AI feedback control is expected to enable real-time prediction and correction of glycosylation deviations, ensuring batch-to-batch consistency in continuous biomanufacturing. Long-term expression stability, another critical challenge, is often impaired by promoter silencing, chromatin condensation, and random genomic integration. Molecular optimization—such as the use of improved promoters (CMV, EF-1α, or CHO endogenous promoters), Kozak and signal peptide refinement, and incorporation of chromatin-opening elements (UCOE, MAR, STAR)—helps maintain durable transcriptional activity, while site-specific integration systems including Cre/loxP, Flp/FRT, φC31, and CRISPR/Cas9 can enable single-copy, position-independent gene insertion at genomic safe-harbor loci, ensuring stable, predictable expression. Collectively, this review highlights a paradigm shift in CHO system optimization driven by the convergence of genome editing, synthetic biology, and artificial intelligence. The transition from empirical optimization to rational, data-driven design will facilitate the development of programmable CHO platforms capable of autonomous regulation of metabolic flux, glycosylation fidelity, and transcriptional activity. Such intelligent cell factories are expected to accelerate the transformation from laboratory-scale research to industrial-scale, high-consistency, and economically sustainable biopharmaceutical manufacturing, thereby supporting the next generation of efficient and customizable biologics manufacturing.

Chinese hamster ovary (CHO) cells are the most established and versatile mammalian expression system for the large-scale production of recombinant therapeutic proteins, owing to their genetic stability, adaptability to serum-free suspension culture, and ability to perform human-like post-translational modifications. More than 70% of biologics approved by the U.S. Food and Drug Administration rely on CHO-based production platforms, underscoring their central role in modern biopharmaceutical manufacturing. Despite these advantages, CHO systems continue to face three persistent bottlenecks that limit their potential for high-yield, reproducible, and cost-efficient production: excessive metabolic burden during high-density culture, heterogeneity of glycosylation patterns, and progressive loss of long-term expression stability. This review provides an integrated analysis of recent advances addressing these challenges and proposes a forward-looking framework for constructing intelligent and sustainable CHO cell factories. In terms of metabolic regulation, excessive lactate and ammonia accumulation disrupts energy balance and reduces recombinant protein synthesis efficiency. Optimization of culture parameters such as temperature, pH, dissolved oxygen, osmolarity, and glucose feeding can effectively alleviate metabolic stress, while supplementation with modulators including sodium butyrate, baicalein, and S-adenosylmethionine promotes specific productivity (qP) by modulating apoptosis and chromatin structure. Furthermore, genetic engineering strategies—such as overexpression of MPC1/2, HSP27, and SIRT6 or knockout of Bax, Apaf1, and IGF-1R—have demonstrated significant improvements in cell viability and product yield. The combination of multi-omics metabolic modeling with artificial intelligence (AI)-based prediction offers new opportunities for building self-regulating CHO systems capable of dynamic adaptation to environmental stress. Regarding glycosylation uniformity, which determines therapeutic efficacy and immunogenicity, gene editing-based glycoengineering (e.g., FUT8 knockdown or ST6Gal1 overexpression) has enabled the humanization of CHO glycan profiles, minimizing non-human sugar residues and enhancing drug stability. Process-level strategies such as galactose or manganese co-feeding and fine control of temperature or osmolarity further allow rational regulation of glycosyltransferase activity. Additionally, in vitro chemoenzymatic remodeling provides a complementary route to construct human-type glycans with defined structures, though industrial applications remain constrained by cost and scalability. The integration of model-driven process design and AI feedback control is expected to enable real-time prediction and correction of glycosylation deviations, ensuring batch-to-batch consistency in continuous biomanufacturing. Long-term expression stability, another critical challenge, is often impaired by promoter silencing, chromatin condensation, and random genomic integration. Molecular optimization—such as the use of improved promoters (CMV, EF-1α, or CHO endogenous promoters), Kozak and signal peptide refinement, and incorporation of chromatin-opening elements (UCOE, MAR, STAR)—helps maintain durable transcriptional activity, while site-specific integration systems including Cre/loxP, Flp/FRT, φC31, and CRISPR/Cas9 can enable single-copy, position-independent gene insertion at genomic safe-harbor loci, ensuring stable, predictable expression. Collectively, this review highlights a paradigm shift in CHO system optimization driven by the convergence of genome editing, synthetic biology, and artificial intelligence. The transition from empirical optimization to rational, data-driven design will facilitate the development of programmable CHO platforms capable of autonomous regulation of metabolic flux, glycosylation fidelity, and transcriptional activity. Such intelligent cell factories are expected to accelerate the transformation from laboratory-scale research to industrial-scale, high-consistency, and economically sustainable biopharmaceutical manufacturing, thereby supporting the next generation of efficient and customizable biologics manufacturing.

The child, male,11 years old, Han nationality, student of Qiandongnan Miao Autonomous Prefecture, Guizhou Province, visited the General Hospital of Hunan Medical University on October 1,2024 due to“cough, chest tightness for 10 days and pericardial effusion was found for 8 days.”The child has a history of eating raw crabs. Admission examination: shortness of breath, slightly cyanotic lips, mild trifoveal symptoms, low heart sound, and routine blood showed significant eosinophil elevation. Serological examination showed that pulmonary fluke antibody IgG was positive, chest and abdomen CT and cardiac ultrasound showed a large amount of pericardial effusion, medium pleural effusion on the right side with lower right lung insufficiency, small pleural effusion on the left side, small effusion on the abdominal cavity, three-point Slight reflux of the valve. Considering that it is a clinical diagnosis case of complication flukesomyces disease, the child was given a praziquantel tablet,25 mg/kg,3 times a day, for 3 consecutive days. The treatment was treated at the above dose for 1 week interval for 1 course of treatment, and 3 courses were given. After three months, the child recovered well after the follow-up visit. The child did not complain of special discomfort, and the CT showed a small amount of effusion.

Objective To explore the relationship between triglyceride-glucose index(TyG)and acute ischemic stroke with large vessel occlusion(AIS-LVO)of anterior circulation.Methods A retrospective study was conducted on patients with anterior circulation AIS-LVO who underwent emergency endovascular thrombectomy at Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2019.According to modified Rankin scale(mRS)score 90 d after operation,the patients were assigned to favorable outcome group(mRS score 0-2)or unfavorable outcome group(mRS score 3-6),and the TyG was compared.According to the median of TyG,the patients were assigned to low-TyG group(TyG＜8.57)or high-TyG group(TyG ≥8.57),and the clinical data,laboratory indexes,and imaging characteristics were compared.Receiver operating characteristic curve was used to evaluate the predictive value of TyG for poor prognosis.Results A total of 135 patients were enrolled,with 72 in the favorable outcome group and 63 in the unfavorable outcome group.The TyG of the unfavorable outcome group was significantly higher than that of the favorable outcome group(8.82+0.63 vs 8.43+0.60,P＜0.001).There were 67 patients in the low-TyG group and 68 in the high-TyG group.Compared with the low-TyG group,the proportion of patients with hyperlipidemia history(P=0.003),systolic blood pressure at admission(P=0.018),fasting blood glucose level(P＜0.001),and triglyceride level(P＜0.001)were significantly higher in the high-TyG group,the infarct core volume was significantly larger(P=0.025),the high density lipoprotein-cholesterol level was significantly lower(P=0.013),and the mRS score 90 d after operation was significantly higher(3[1,5]vs 1[0,5],P=0.049).The TyG had certain predictive value for poor prognosis in anterior circulation AIS-LVO patients(area under curve value=0.662,95％confidence interval 0.571-0.753).Conclusion TyG is elevated in anterior circulation AIS-LVO patients with poor prognosis,and may be a potential prognostic indicator for anterior circulation AIS-LVO patients.

Nitrofurantoin(NFT)is a nitrofuran antibiotic commonly used as a veterinary drug to treat bacterial infections in animals.However,due to the low solubility and bioaccumulation properties,NFT is prone to leave excessive residues in animal-derived foods and water systems,posing serious threats to human health and ecosystems.Therefore,there is an urgent need to develop an efficient and rapid detection method for NFT.In this work,nitrogen-doped carbon nanomaterials with unique bowl-like structures(N-CNBs)were synthesized via a hydrothermal-carbonization method.The morphology,surface structure,and specific surface area of N-CNBs were characterized using transmission electron microscopy(TEM),scanning electron microscopy(SEM),and X-ray photoelectron spectroscopy(XPS).The N-CNB modified glassy carbon electrode(N-CNB/GCE)was prepared,and the electrochemical test revealed that the N-CNB/GCE exhibited higher conductivity and larger electrochemical active surface area compared to bare GCE and nitrogen-doped hollow carbon nanosphere-modified electrode(N-HCNS/GCE).Additionally,the N-CNB/GCE demonstrated superior electrocatalytic activity toward NFT.An NFT electrochemical sensor was constructed based on N-CNB/GCE.The detection conditions of the sensor were optimized,and differential pulse voltammetry(DPV)was employed for NFT detection under optimal experimental conditions.The established NFT electrochemical sensor had a wide linear range of 0.4-500 μmol/L,a low detection limit(S/N=3)of 0.015 μmol/L and high selectivity,with excellent stability and reproducibility.The practical feasibility of this sensor was confirmed by analysis of NFT in milk and tap water samples,with spiked recoveries ranging from 94.2%to 108.9%.

With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Stroke is one of the leading causes of death and disability worldwide， ranking as the second leading cause of mortality globally and the primary cause of adult disability. Its pathological process involves complex cascade mechanisms， with high incidence and disability rates， posing a major threat to human health. According to statistics from the World Health Organization， more than 13 million new cases of stroke occur globally each year， resulting in direct medical costs and socioeconomic burdens amounting to hundreds of billions of dollars. In recent years， breakthroughs in the study of programmed cell death mechanisms have provided new insights into stroke treatment. Among them， ferroptosis， a novel form of cell death driven by iron-dependent lipid peroxidation， has attracted widespread attention in the pathological process of stroke. Ferroptosis is closely associated with iron metabolism disorders， oxidative stress， and lipid peroxidation， and exhibits unique regulatory effects in key pathological processes of stroke， such as ischemia-reperfusion injury， disruption of the blood-brain barrier， and neuronal apoptosis. It plays an important role in post-stroke neurological damage. Chinese medicine， as an essential component of traditional Chinese medicine （TCM）， has demonstrated advantages in modulating ferroptosis and exerting neuroprotective effects. This review systematically summarizes current research on the neuroprotective mechanisms of Chinese medicine compound formulas and monomers through the regulation of ferroptosis pathways in post-stroke conditions， aiming to provide a basis for optimizing clinical treatment strategies and exploring new therapeutic approaches， and to offer new strategies and approaches for stroke treatment.

Stroke is one of the leading causes of death and disability worldwide， ranking as the second leading cause of mortality globally and the primary cause of adult disability. Its pathological process involves complex cascade mechanisms， with high incidence and disability rates， posing a major threat to human health. According to statistics from the World Health Organization， more than 13 million new cases of stroke occur globally each year， resulting in direct medical costs and socioeconomic burdens amounting to hundreds of billions of dollars. In recent years， breakthroughs in the study of programmed cell death mechanisms have provided new insights into stroke treatment. Among them， ferroptosis， a novel form of cell death driven by iron-dependent lipid peroxidation， has attracted widespread attention in the pathological process of stroke. Ferroptosis is closely associated with iron metabolism disorders， oxidative stress， and lipid peroxidation， and exhibits unique regulatory effects in key pathological processes of stroke， such as ischemia-reperfusion injury， disruption of the blood-brain barrier， and neuronal apoptosis. It plays an important role in post-stroke neurological damage. Chinese medicine， as an essential component of traditional Chinese medicine （TCM）， has demonstrated advantages in modulating ferroptosis and exerting neuroprotective effects. This review systematically summarizes current research on the neuroprotective mechanisms of Chinese medicine compound formulas and monomers through the regulation of ferroptosis pathways in post-stroke conditions， aiming to provide a basis for optimizing clinical treatment strategies and exploring new therapeutic approaches， and to offer new strategies and approaches for stroke treatment.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.