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

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

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

Interfacial “Single‐Atom‐in‐Defects” Catalysts Accelerating Li + Desolvation Kinetics for Long‐Lifespan Lithium‐Metal Batteries

The lithium-metal anode is a promising candidate for realizing high-energy-density batteries owing to its high capacity and low potential. However, several rate-limiting kinetic obstacles, such as the desolvation of Li+ solvation structure to liberate Li$^+$, Li$^0$ nucleation, and atom diffusion, cause heterogeneous spatial Li-ion distribution and fractal plating morphology with dendrite formation, leading to low Coulombic efficiency and depressive electrochemical stability. Herein, differing from pore sieving effect or electrolyte engineering, atomic iron anchors to cation vacancy-rich Co$_{1−xS}$ embedded in 3D porous carbon (SAFe/CVRCS@3DPC) is proposed and demonstrated as catalytic kinetic promoters. Numerous free Li ions are electrocatalytically dissociated from the Li$^+$ solvation complex structure for uniform lateral diffusion by reducing desolvation and diffusion barriers via SAFe/CVRCS@3DPC, realizing smooth dendrite-free Li morphologies, as comprehensively understood by combined in situ/ex situ characterizations. Encouraged by SAFe/CVRCS@3DPC catalytic promotor, the modified Li-metal anodes achieve smooth plating with a long lifespan (1600 h) and high Coulombic efficiency without any dendrite formation. Paired with the LiFePO$_4$ cathode, the full cell (10.7 mg cm$^{−2}$) stabilizes a capacity retention of 90.3% after 300 cycles at 0.5 C, signifying the feasibility of using interfacial catalysts for modulating Li behaviors toward practical applications

Construction of a mortality risk prediction model for elderly people at risk of lobectomy for NSCLC

BackgroundAn increasing number of lung cancer patients are opting for lobectomy for oncological treatment. However, due to the unique organismal condition of elderly patients, their short-term postoperative mortality is significantly higher than that of non-elderly patients. Therefore, there is a need to develop a personalised predictive tool to assess the risk of postoperative mortality in elderly patients.MethodsInformation on the diagnosis and survival of 35,411 older patients with confirmed lobectomy NSCLC from 2009 to 2019 was screened from the SEER database. The surgical group was divided into a high-risk mortality population group (≤90 days) and a non-high-risk mortality population group using a 90-day criterion. Survival curves were plotted using the Kaplan-Meier method to compare the differences in overall survival (OS) and lung cancer-specific survival (LCSS) between the two groups. The data set was split into modelling and validation groups in a ratio of 7.5:2.5, and model risk predictors of postoperative death in elderly patients with NSCLC were screened using univariate and multifactorial logistic regression. Columnar plots were constructed for model visualisation, and the area under the subject operating characteristic curve (AUC), DCA decision curve and clinical impact curve were used to assess model predictiveness and clinical utility.ResultsMulti-factor logistic regression results showed that sex, age, race, histology and grade were independent predictors of the risk of postoperative death in elderly patients with NSCLC. The above factors were imported into R software to construct a line graph model for predicting the risk of postoperative death in elderly patients with NSCLC. The AUCs of the modelling and validation groups were 0.711 and 0.713 respectively, indicating that the model performed well in terms of predictive performance. The DCA decision curve and clinical impact curve showed that the model had a high net clinical benefit and was of clinical application.ConclusionThe construction and validation of a predictive model for death within 90 days of lobectomy in elderly patients with lung cancer will help the clinic to identify high-risk groups and give timely intervention or adjust treatment decisions

Polysulfide-mediated solvation shell reorganization for fast Li+ transfer probed by in-situ sum frequency generation spectroscopy

Understanding of interfacial Li$^+$ solvation shell structures and dynamic evolution at the electrode/electrolyte interface is requisite for developing high-energy-density Li batteries. Herein, the reorganization of Li$^+$ solvation shell at the sulfur/electrolyte interface along with the presence of a trace amount of lithium polysulfides is verified by in-situ sum frequency generation (SFG) spectroscopy together with density functional theory (DFT) calculations. Both the spectroelectrochemical and DFT calculation results reveal a strongly competitive anion adsorption of the polysulfide anion additive against the pristine electrolyte anion on the sulfur cathode surface, reorganizing the interfacial local solvation shell structure facilitating rapid Li ion transfer and conduction. Meanwhile, the evolution of the SFG signals along with the discharging/charging cycle exhibits improved reversibility, indicating the transformation of the inner Helmholtz plane layer into a stable molecular-layer polysulfide interphase rather than a dynamic diffusion layer. Consequently, applications in practical Li-S batteries reveal the capacity and cycling stability of the corresponding cells are significantly enhanced. Our work provides a methodology using in-situ SFG for probing solvation reorganization of charge carriers at electrochemical interfaces