Enhancing and stabilizing monoclonal antibody production by Chinese hamster ovary (CHO) cells with optimized perfusion culture strategies

The perfusion medium is critical in maintaining high cell concentration in cultures for the production of monoclonal antibody by Chinese hamster ovary cells. In this study, the effects of perfusion culture strategies when using different media on the process stability, product titer, and product quality were investigated in 3-L bioreactor. The results indicated that continuous perfusion could maintain higher levels of cell density, product titer, and quality in comparison with those of the intermittent perfusion culture. Next, the perfusion culture conditions with different perfusion rates and temperature reduction methods were further optimized. When combining the high perfusion rates and delayed reduction of culture temperature at day 6, the product titer reached a higher level of 16.19 g/L with the monomer relative abundant of 97.6%. In this case, the main peak of the product reached 56.3% and the total N-glycans ratio was 95.2%. To verify the effectiveness of the optimized perfusion culture in a larger scale, a 200-L bioreactor was used to perform and the final product titer reached the highest level of 16.79 g/L at day 16. Meanwhile, the product quality (monomer abundant of 97.6%, main peak of 56.3%, and N-glycans ratio of 96.5%) could also be well maintained. This study provided some guidance for the high-efficient production of monoclonal antibody by CHO cells via optimized perfusion culture strategy

Prospects of single atom catalysts for dendrite-free alkali metal batteries

High-energy-density alkali metal batteries (AMBs) offer a potentially promising and sustainable option for energy storage. However, notorious dendrite growth and uncontrollable plating behaviors resulting from random spatial ion/atom distribution and related high barriers restrict the development of AMBs. Different from interphase engineering and architecture construction, the emerging catalysis modulation is proposed to overcome above-related barriers, achieving uniform alkali metal nucleation and atom diffusion. Among the various catalysts, single atom catalysts (SACs) exhibit an atomic exposure of nearly 100%, displaying high atomic catalytic capability and efficiency. Although it is still at an early stage, the adoption of SACs for modulating alkali metal ion/atom desolvation or diffusion has shown great promise in both fundamental research and practical applications. In this review, the fabrications and characterizations of SACs are briefly summarized, and the principal mechanisms of SAC-incorporated alkali metal anode systems are highlighted in terms of electrochemical analysis, microscopic/spectroscopic characterizations, and theoretical simulations. In addition, sustainable paths for future critical battery chemistry and material selections based on SACs are highlighted. The associated opportunities and challenges are further prospected to achieve a high-performance alkali metal anode

Gene-MOE: A sparsely gated prognosis and classification framework exploiting pan-cancer genomic information

Benefiting from the advancements in deep learning, various genomic analytical techniques, such as survival analysis, classification of tumors and their subtypes, and exploration of specific pathways, have significantly enhanced our understanding of the biological mechanisms driving cancer. However, the overfitting issue, arising from the limited number of patient samples, poses a challenge in improving the accuracy of genome analysis by deepening the neural network. Furthermore, it remains uncertain whether novel approaches such as the sparsely gated mixture of expert (MOE) and self-attention mechanisms can improve the accuracy of genomic analysis. In this paper, we introduce a novel sparsely gated RNA-seq analysis framework called Gene-MOE. This framework exploits the potential of the MOE layers and the proposed mixture of attention expert (MOAE) layers to enhance the analysis accuracy. Additionally, it addresses overfitting challenges by integrating pan-cancer information from 33 distinct cancer types through pre-training.We pre-trained Gene-MOE on TCGA pan-cancer RNA-seq dataset with 33 cancer types. Subsequently, we conducted experiments involving cancer classification and survival analysis based on the pre-trained Gene-MOE. According to the survival analysis results on 14 cancer types, Gene-MOE outperformed state-of-the-art models on 12 cancer types. Through detailed feature analysis, we found that the Gene-MOE model could learn rich feature representations of high-dimensional genes. According to the classification results, the total accuracy of the classification model for 33 cancer classifications reached 95.8%, representing the best performance compared to state-of-the-art models. These results indicate that Gene-MOE holds strong potential for use in cancer classification and survival analysis

Toward Low‐Temperature Zinc‐Ion Batteries: Strategy, Progress, and Prospect in Vanadium‐Based Cathodes

Low-temperature vanadium-based zinc ion batteries (LT-VZIBs) have attracted much attention in recent years due to their excellent theoretical specific capacities, low cost, and electrochemical structural stability. However, low working temperature surrounding often results in retarded ion transport not only in the frozen aqueous electrolyte, but also at/across the cathode/electrolyte interface and inside cathode interior, significantly limiting the performance of LT-VZIBs for practical applications. In this review, a variety of strategies to solve these issues, mainly including cathode interface/bulk structure engineering and electrolyte optimizations, are categorially discussed and systematically summarized from the design principles to in-depth characterizations and mechanisms. In the end, several issues about future research directions and advancements in characterization tools are prospected, aiming to facilitate the scientific and commercial development of LT-VZIBs

Antibiotics influence the risk of anti-drug antibody formation during anti-TNF therapy in Chinese inflammatory bowel disease patients

Aims: The formation of anti-drug antibodies (ADAs) during anti-tumor necrosis factor (anti-TNF) therapy is reported to lead to reducing serum drug levels, which may bring about a loss of response to treatment. Previous research has suggested an association between specific antibiotic classes and ADA formation during anti-TNF therapy. However, there are few studies specifically examining this association in Chinese inflammatory bowel disease (IBD) patients. Therefore, our study aimed to evaluate the possible effect of antibiotic use on ADA formation to anti-TNF therapy in Chinese patients with IBD.Methods: A total of 166 patients with IBD, including 149 with Crohn’s disease (CD) and 17 with ulcerative colitis (UC), were included in this retrospective analysis. These patients were initially treated with anti-TNF therapy (infliximab or adalimumab) after January 2018 and reviewed with available ADA levels before October 2023. After univariable analysis of all the variables, a multivariate Cox proportional hazards model was used to assess the association between antibiotic use and ADA development.Results: Among 166 IBD patients treated with infliximab (108/166, 65.1%) or adalimumab (58/166, 34.9%), 31 patients (18.7%) were measured as positive ADA levels. Cox proportional hazard model demonstrated an increased risk of ADA formation in IBD patients who used β-lactam-β-lactamase inhibitor combinations (BL-BLIs) (HR = 5.143, 95%CI 1.136–23.270, p = 0.033), or nitroimidazoles (HR = 4.635, 95%CI 1.641–13.089, p = 0.004) during 12 months before the ADA test. On the contrary, a reduced risk was noted in patients treated with fluoroquinolones (HR = 0.258, 95% CI 0.072–0.924, p = 0.037). Moreover, the median serum infliximab or adalimumab concentration in patients with positive ADA levels was significantly lower than that in patients with negative ADA levels (infliximab: 0.30 vs. 1.85 μg/mL, p < 0.0001; adalimumab: 0.45 vs. 7.55 μg/mL, p = 0.0121).Conclusion: ADA development is associated with various antibiotic classes. BL-BLIs and nitroimidazoles might increase the risk of ADA formation during anti-TNF therapy in Chinese IBD patients, while the treatment with fluoroquinolones could probably reduce such risk. There were certain limitations in the retrospective analysis of the study, therefore, the results are just for reference, and other studies are needed to further confirm our findings

Accelerated Li⁺ Desolvation for Diffusion Booster Enabling Low‐Temperature Sulfur Redox Kinetics via Electrocatalytic Carbon‐Grazfted‐CoP Porous Nanosheets

Lithium–sulfur (Li–S) batteries are famous for their high energy density and low cost, but prevented by sluggish redox kinetics of sulfur species due to depressive Li ion diffusion kinetics, especially under low-temperature environment. Herein, a combined strategy of electrocatalysis and pore sieving effect is put forward to dissociate the Li+ solvation structure to stimulate the free Li+ diffusion, further improving sulfur redox reaction kinetics. As a protocol, an electrocatalytic porous diffusion-boosted nitrogen-doped carbon-grafted-CoP nanosheet is designed via forming the NCoP active structure to release more free Li+ to react with sulfur species, as fully investigated by electrochemical tests, theoretical simulations and in situ/ex situ characterizations. As a result, the cells with diffusion booster achieve desirable lifespan of 800 cycles at 2 C and excellent rate capability (775 mAh g−1 at 3 C). Impressively, in a condition of high mass loading or low-temperature environment, the cell with 5.7 mg cm−2 stabilizes an areal capacity of 3.2 mAh cm−2 and the charming capacity of 647 mAh g−1 is obtained under 0 °C after 80 cycles, demonstrating a promising route of providing more free Li ions toward practical high-energy Li–S batteries

Autocrine prolactin promotes prostate cancer cell growth via Janus kinase-2-signal transducer and activator of transcription-5a/b signaling pathway.

The molecular mechanisms that promote progression of localized prostate cancer to hormone-refractory and disseminated disease are poorly understood. Prolactin (Prl) is a local growth factor produced in high-grade prostate cancer, and exogenously added Prl in tissue or explant cultures of normal and malignant prostate is a strong mitogen and survival factor for prostate epithelium. The key signaling proteins that mediate the biological effects of Prl in prostate cancer are Signal Transducer and Activator of Transcription (Stat)-5a/5b via activation of Janus kinase-2. Importantly, inhibition of Stat5a/b in prostate cancer cells induces apoptotic death. Using a specific Prl receptor antagonist (Delta1-9G129R-hPRL), we demonstrate here for the first time that autocrine Prl in androgen-independent human prostate cancer cells promotes cell viability via Stat5 signaling pathway. Furthermore, we examined a unique clinical material of human hormone refractory prostate cancers and metastases and show that autocrine Prl is expressed in 54% of hormone-refractory clinical human prostate cancers and 62% prostate cancer metastases. Finally, we demonstrate that autocrine Prl is expressed from both the proximal and distal promoters of the Prl gene in clinical human prostate cancers and in vivo and in vitro human prostate cancer models, independently of pituitary transcription factor-1 (Pit-1). Collectively, the data provide novel evidence for the concept that autocrine Prl signaling pathway is involved in growth of hormone-refractory and metastatic prostate cancer. The study also provides support for the use of Prl receptor antagonists or other therapeutic strategies to block the Prl-Janus kinase-2-Stat5 signaling pathway in advanced prostate cancer