Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Breast cancer is one of the most common cancers of females and is a leading cause of tumor-related death in women.Negative emotion frequently presents in patients like anxiety and depression and chronic stress which may lead to depression is a major risk factor of the cancer development.Stress leads to dysfunctions of cells,molecules and neural circuits,thus promoting depression.Chronic stress promotes the occurrence and development of breast cancer through related neurotransmitters and also affects the prognosis of breast cancer patients.

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Dopaminergic neurons in the ventral tegmental area (VTA) play an important role in cognition, emergence from anesthesia, reward, and aversion, and their projection to the cortex is a crucial part of the "bottom-up" ascending activating system. The prelimbic cortex (PrL) is one of the important projection regions of the VTA. However, the roles of dopaminergic neurons in the VTA and the VTA^DA-PrL pathway under sevoflurane anesthesia in rats remain unclear. In this study, we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist (Chloro-APB) into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats, while injection of a dopamine D1 receptor antagonist (SCH23390) deepened anesthesia. The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTA^DA-PrL pathway prolonged the induction time and shortened the emergence time of anesthesia. These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTA^DA-PrL pathway facilitates emergence from sevoflurane anesthesia.
Anesthesia ; Animals ; Dopaminergic Neurons/metabolism* ; Rats ; Receptors, Dopamine D1/metabolism* ; Sevoflurane/pharmacology* ; Ventral Tegmental Area/metabolism*

ObjectiveTo determine the situation and challenges of innovation platforms in China， and to explore the construction strategy of Shanghai Nutrition Innovation Platform， which is suitable for Shanghai and may achieve the research and transformation of nutrition innovation and population health， so as to coordinate， unite and gather the superior resources of all parties and promote nutrition innovation. MethodsConstruction scheme and operational mechanism of Shanghai Nutrition Innovation Platform were explored by literature review， expert consultation and questionnaire. ResultsThere were various forms of innovation platforms in China. However， challenges were identified， such as decentralizing force， resource rearrangement and insufficient sharing effect. Shanghai Nutrition Innovation Platform adopted a modular organizational structure， which was divided into central group， node group， and subject group. Shanghai Center for Disease Control and Prevention， as the central organization， is responsible for the platform operation management. The expert database as an academic committee selected key organizations from nutrition-related universities， research institutes， academic associations， centers for disease control and prevention， hospitals and the industry. Based on the opening of its own innovation resources， the platform made effective use of external innovation resources and formed a closely integrated nutrition innovation network of multiple disciplines. ConclusionThis study promotes the construction of innovation platform model of cooperation， co-construction and resource sharing， and provides reference for the construction of innovation platform in China.

Allografts ; COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Kidney Transplantation/adverse effects* ; SARS-CoV-2

Metabolic engineering has been developed for nearly 30 years since the early 1990s, and it has given a great impetus to microbial strain breeding and improvement. Aromatic chemicals are a variety of important chemicals that can be produced by microbial fermentation and are widely used in the pharmaceutical, food, feed, and material industry. Microbial cells can be engineered to accumulate a variety of useful aromatic chemicals in a targeted manner through rational engineering of the biosynthetic pathways of shikimate and the derived aromatic amino acids. This review summarizes the metabolic engineering strategies and biosynthetic pathways for the production of aromatic chemicals developed in the past 30 years, with the aim to provide a valuable reference and promote the research in this field.
Biosynthetic Pathways ; Fermentation ; Metabolic Engineering ; Shikimic Acid

Objective : To investigate the clinicopathological features and survival rate of oral squamous cell carcinoma patients in China. Methods: The clinicopathological characteristics, stage, treatment modality, and 5-year disease-specific survival (DSS) rate of 1 915 OCSCC patients who received initial treatment at the Sun Yat-sen University Cancer Center from 1990 to 2013 were collected and analyzed. The clinicopathological characteristics, stage, treatment modality, and 5-year disease-specific survival (DSS) rate of OCSCC patients treated during the successive decades of 1990-1999, 2000-2009, and 2010-2013 were analyzed retrospectively to show the trends over time. Results : The average age of all OCSCC patients who received initial treatment at this cancer center from 1990 to 2013 was 54.8 years (SD, 12.6 years). The sex ratio was approximately 2:1. The oral tongue was the site most prone for OCSCC, accounting for 63.6% of all cases. The proportions of early-stage (Ⅰ-Ⅱ) and advanced-stage (Ⅲ-Ⅳ) cases were approximate. Regarding the treatment modality, surgery-based treatment accounted for 80.4%. Survival analysis showed that the 5-year DSS rate of all cases was 57%. Survival decreased with age. The survival of females, nonsmokers, and nondrinkers was higher than that of males, smokers, and drinkers. The 5-year DSS rates of patients with squamous cell carcinoma of the lips, oral tongue, and other sites of the oral cavity were 81%, 63%, and 42%, respectively. The 5-year DSS rates of patients who received surgery-based treatment and nonsurgical treatment were 66% and 19%, respectively. The analysis of trends over time showed that in the period of 1990-1999 and 2010-2013, the age and sex ratio were relatively stable. The proportion of patients with squamous cell carcinoma of the lips and oral tongue gradually decreased, while the proportion of those with squamous cell carcinoma of the other sites of the oral cavity gradually increased. The proportion of surgery-based treatment increased from 77.7% to 91.3%. The 5-year DSS rate gradually increased from 53% in 1990-1999 to 64% in 2010-2013. The 5-year DSS rate of female patients increased significantly from 55% to 78%. However, the 5-year DSS rate of male patients was relatively stable. The 5-year DSS rate of patients who received surgery-based treatment gradually increased from 62% to 69%. Conclusion The 5-year DSS rate has steadily improved for OCSCC patients at this cancer center from 1990-2013, especially in female patients. The 5-year DSS rate of patients with squamous cell carcinoma of the oral tongue has reached the rate in developed countries worldwide. The proportion and survival rate of patients who received surgery-based treatment gradually increased. The survival rate of patients with squamous cell carcinoma of the other sites of the oral cavity was significantly lower than that of patients with squamous cell carcinoma of the lips and oral tongue, suggesting that more effort should be put into the treatment of patients with squamous cell carcinoma of the other sites of the oral cavity to improve the survival rate in the future.

Objective To investigate the epidemiological characteristics of renal transplantation recipients, effective prevention and control measures. Methods A total of 456 renal transplant recipients were monitored from January 2014 to December 2017. Postoperative infection including baseline data, infection site and infectious pathogen type was analyzed. Results Among 456 renal transplant recipients, 78 cases (17.1%) developed nosocomial infection. Postoperative infection time was 9(3-21) d. Infection sites mainly included the lower respiratory tract, urinary system and blood infection. Infection pathogens consisted of Staphylococci (n=13), Enterococcus faecium (n=6), fungi (n=6), Stenotrophomonas maltophilia (n=4), Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=4), Staphylococcus epidermidis (n=4), Klebsiella pneumoniae (n=1), Escherichia coli (n=1) and other negative bacteria (n=9). Among them, 11 cases (14%) were infected with multi-drug resistant bacteria, and 4 cases died. Conclusions In renal transplant recipients, the incidence of nosocomial infection is relatively high, with early postoperative onset, common multiple drug-resistant bacterial infection and high mortality. Preoperative preparations should be fully implemented, postoperative lower respiratory tract infection should be actively prevented and prevention and treatment measures for multidrug-resistant bacteria should be standardized.

Objective Investigate the effect of neonatal hyperbilirubinemia on the detection of HBsAg by chemiluminescence and its elimination methods.Methods Case control study.The HBsAg in human serum was detected in 200 cases of hyperbilirubinemia neonates who were hospitalized in Beijing Children's Hospital,Capital Medical University from July 2015 to May 2016 and whose serum total bilirubin level exceeded 200 μmol/L.The positive serum was further detected by 16 200×g high-spoed centrifugation or blue light irradiation for 8 hours,and the results of re-assay of HBsAg were recorded.The retest positive serum wastested for HBV DNA load and checked the results of their mother's examination in HBV.136 adult serum samples with total bilirubin levels exceeding 200 μmol/L in the Peking University First Hospital,were taken as reference to compare the influence of hyperbilirubinemia between adults and newborns on the determination of HBsAg.Results The median level of serum total bilirubin in neonates was 259.0 μ mol/L (226.5,312.5);median level of indirect bilirubin 244.1 μmol / L(212.5,295.8).Median level of serum total bilirubin in adults 356.4 μmol/L(295.9,435.1);median level ofindirect bilirubin 137.1 μmol/L (107.8,172.7).The HBsAg test was negative in adults,11 cases (5.5％) were positive in newborns,their" HBV DNA load was less than＜100 IU/ml.Among them,9 have inoculated hepatitis B vaccine and 2 were unknown.10 of 11 mothers of infants were healthy and 1 was positive for HBsAg,HBeAb,HBcAb.2 of the 11 positive specimens turned negative of HBsAg after high-speed centrifugation.In addition to high speed centrifugation,4 cases turned negative after blue light irradiation.5 cases remained positive after high speed centrifugation and blue light irradiation.Conclusions Neonatal hyperbilirubinemia,which is different from that of adults,is mainly caused by indirectly bilirubin increased,which is one of the main reasons for false positive detection of HBsAg by chemiluminescence in neonates.High-speed centrifugation and blue light irradiation can eliminate the influence of serum indirect bilirubin on the detection of HBsAg to the greatest extent.