This paper investigates the economic and operational trade-offs between continuous manufacturing and batch processing in the context of biopharmaceutical engineering design,through the lens of project management.The s...This paper investigates the economic and operational trade-offs between continuous manufacturing and batch processing in the context of biopharmaceutical engineering design,through the lens of project management.The study explores the fundamental principles of both manufacturing modes,assesses their implications on capital and operational expenditures,and evaluates their performance against key project management metrics such as cost,time,quality,and risk.Drawing on current regulatory guidance,industrial practices,and technological advances,the paper concludes that while continuous manufacturing offers significant benefits in process efficiency and quality control,its implementation requires substantial upfront investment,risk management,and stakeholder alignment.The study aims to support informed decision-making in early-stage biopharmaceutical facility and process design.展开更多
2020年第8期Journal of Pediatric Surgery共发表文章50余篇。本期开篇以特刊形式报道了新冠肺炎疫情对北美多家医院的小儿外科疾病诊疗流程造成的影响;同时介绍了在面对新冠肺炎感染风险下,当地医护人员采取的防控策略[1,2]。本期论著...2020年第8期Journal of Pediatric Surgery共发表文章50余篇。本期开篇以特刊形式报道了新冠肺炎疫情对北美多家医院的小儿外科疾病诊疗流程造成的影响;同时介绍了在面对新冠肺炎感染风险下,当地医护人员采取的防控策略[1,2]。本期论著内容涵盖了胸外科疾病、消化系统疾病、新生儿疾病、儿童创伤及泌尿外科等多领域的研究。本期摘取部分文章进行导读,旨在传播小儿外科领域最新的国际信息。展开更多
Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients...Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients.Exosomes derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane,supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic lesions.For the first time,our study has demonstrated that cluster of differentiation 44(CD44),a transmembrane glycoprotein delivered by exosomes,is involved in the metastatic process of pancreatic cancer.Moreover,CD44 was found to interact with integrin a6b4 to form a complex,thereby remodeling intracellular skeleton proteins,and to promote tumor cell motility through the activation of the Src and Ras signaling cascades.Notably,we also demonstrated that the CD44–a6b4 complex can be delivered to the target region via the paracrine effects of exosomes.The selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines,proinflammatory factors,and growth factors that ultimately support tumor metastasis.Our results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.展开更多
N-methyl-D-aspartate glutamate receptors(NMDARs)play crucial roles in the pathogenesis of neuronal injuries following a stroke insult;therefore,a plethora of preclinical studies focus on better understanding functions...N-methyl-D-aspartate glutamate receptors(NMDARs)play crucial roles in the pathogenesis of neuronal injuries following a stroke insult;therefore,a plethora of preclinical studies focus on better understanding functions of NMDARs and their associated signaling pathways.Over the past decades,NMDARs have been found to exert dual effects in neuronal deaths signaling and neuronal survival signaling during cerebral ischemia.Moreover,many complex intracellular signaling pathways downstream of NMDAR activation have been elucidated,which provide novel targets for developing much-needed neuro-protectants for patients with stroke.In this review,we will discuss the recent progress in understanding the underlying mechanisms of stroke related to NMDAR activation and the potential therapeutic strategies based on these discoveries.展开更多
文摘This paper investigates the economic and operational trade-offs between continuous manufacturing and batch processing in the context of biopharmaceutical engineering design,through the lens of project management.The study explores the fundamental principles of both manufacturing modes,assesses their implications on capital and operational expenditures,and evaluates their performance against key project management metrics such as cost,time,quality,and risk.Drawing on current regulatory guidance,industrial practices,and technological advances,the paper concludes that while continuous manufacturing offers significant benefits in process efficiency and quality control,its implementation requires substantial upfront investment,risk management,and stakeholder alignment.The study aims to support informed decision-making in early-stage biopharmaceutical facility and process design.
文摘2020年第8期Journal of Pediatric Surgery共发表文章50余篇。本期开篇以特刊形式报道了新冠肺炎疫情对北美多家医院的小儿外科疾病诊疗流程造成的影响;同时介绍了在面对新冠肺炎感染风险下,当地医护人员采取的防控策略[1,2]。本期论著内容涵盖了胸外科疾病、消化系统疾病、新生儿疾病、儿童创伤及泌尿外科等多领域的研究。本期摘取部分文章进行导读,旨在传播小儿外科领域最新的国际信息。
基金This work was sponsored by grants from the National Natural Science Foundation of China(81803269 and 81427805)the Science and Technology Commission of Shanghai Municipality(18YF1412100 and 2019Y0150)+2 种基金the National Key Research and Development Program of China(2018YFC2000700)the Key Research Program of the Chinese Academy of Sciences(ZDRW-ZS-2017-1)Shanghai Municipality Health Commission(GWV-10.2-YQ17 and 2019Y0150).
文摘Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients.Exosomes derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane,supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic lesions.For the first time,our study has demonstrated that cluster of differentiation 44(CD44),a transmembrane glycoprotein delivered by exosomes,is involved in the metastatic process of pancreatic cancer.Moreover,CD44 was found to interact with integrin a6b4 to form a complex,thereby remodeling intracellular skeleton proteins,and to promote tumor cell motility through the activation of the Src and Ras signaling cascades.Notably,we also demonstrated that the CD44–a6b4 complex can be delivered to the target region via the paracrine effects of exosomes.The selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines,proinflammatory factors,and growth factors that ultimately support tumor metastasis.Our results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.
文摘N-methyl-D-aspartate glutamate receptors(NMDARs)play crucial roles in the pathogenesis of neuronal injuries following a stroke insult;therefore,a plethora of preclinical studies focus on better understanding functions of NMDARs and their associated signaling pathways.Over the past decades,NMDARs have been found to exert dual effects in neuronal deaths signaling and neuronal survival signaling during cerebral ischemia.Moreover,many complex intracellular signaling pathways downstream of NMDAR activation have been elucidated,which provide novel targets for developing much-needed neuro-protectants for patients with stroke.In this review,we will discuss the recent progress in understanding the underlying mechanisms of stroke related to NMDAR activation and the potential therapeutic strategies based on these discoveries.
