TBK1 is paradoxical in tumor development: a focus on the pathway mediating IFN-I expression.

TANK-binding kinase 1 (TBK1) is a member of the IKK family and plays a crucial role in the activation of non-canonical NF-κB signaling and type I interferon responses. The aberrant activation of TBK1 contributes to the proliferation and survival of various types of tumor cells, particularly in specific mutational or tumorous contexts. Inhibitors targeting TBK1 are under development and application in both in vivo and in vitro settings, yet their clinical efficacy remains limited. Numerous literatures have shown that TBK1 can exhibit both tumor promoting and tumor inhibiting effects. TBK1 acts as a pivotal node within the innate immune pathway, mediating anti-tumor immunity through the activation of innate immune responses. Facilitating interferon-I (IFN-I) production represents a critical mechanism through which TBK1 bridges these processes. IFN has been shown to exert both beneficial and detrimental effects on tumor progression. Hence, the paradoxical role of TBK1 in tumor development may necessitate acknowledgment in light of its downstream IFN-I signaling cascade. In this paper, we review the signaling pathways mediated by TBK1 in various tumor contexts and summarize the dual roles of TBK1 and the TBK1-IFN pathways in both promoting and inhibiting tumor progression. Additionally, we highlight the significance of the TBK1-IFN pathway in clinical therapy, particularly in the context of immune response. We anticipate further advancements in the development of TBK1 inhibitors as part of novel cancer treatment strategies.

Identification of macrophage differentiation related genes and subtypes linking atherosclerosis plaque processing and metabolic syndrome via integrated bulk and single-cell sequence analysis.

Metabolic syndrome(MS) is a separate risk factor for the advancement of atherosclerosis(AS) plaque but mechanism behind this remains unclear. There may be a significant role for the immune system in this process. This study aims to identify potential diagnostic genes in MS patients at a higher risk of developing and progressing to AS. Datasets were retrevied from gene expression omnibus(GEO) database and differentially expressed genes were identified. Hub genes, immune cell dysregulation and AS subtypes were identified using a conbination of muliple bioinformatic analysis, machine learning and consensus clustering. Diagnostic value of hub genes was estimated using a nomogram and ROC analysis. Finally, enrichment analysis, competing endogenous RNA(ceRNA) network, single-cell RNA(scRNA) sequencing analysis and drug-protein interaction prediction was constructed to identify the functional roles, potential regulators and distribution for hub genes. Four hub genes and two macrophage-related subtypes were identified. Their strong diagnostic value was validated and functional process were identified. ScRNA analysis identified the macrophage differentiation regulation function of F13A1. CeRNA network and drug-protein binding modes revealed the potential therapeutic method. Four immune-correlated hub genes(F13A1, MMRN1, SLCO2A1 and ZNF521) were identified with their diagnostic value being assesed, which F13A1 was found strong correlated with macrophage differentiation and could be potential diagnostic and therapeutic marker for AS progression in MS patients.

Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation.

BACKGROUND: Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM: To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS: Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS: Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P < 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION: AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.

Retraction Notice to: Circular RNA Cdr1as Upregulates SCAI to Suppress Cisplatin Resistance in Ovarian Cancer via miR-1270 Suppression.

[This retracts the article DOI: 10.1016/j.omtn.2019.07.012.].

Characterization of an agmatine N-acetyltransferase from Bactrocera dorsalis that modulates ovary development.

Agmatine N-acetyltransferase (AgmNAT), which catalyzes the formation of N-acetylagmatine from acetyl-CoA and agmatine, is a member of the GCN5-related N-acetyltransferase family. So far, knowledge of the physiological roles of AgmNAT in insects is limited. Here, we identified one gene encoding protein homologous to that of Drosophila AgmNAT using sequence information from an activity-verified Drosophila AgmNAT in a BLAST search of the Bactrocera dorsalis genome. We expressed and purified B. dorsalis AgmNAT in Escherichia coli and used the purified enzyme to define the substrate specificity for acyl-CoA and amine substrates. Our application of the screening strategy to BdorAgmNAT led to the identification of agmatine as the best amine substrate for this enzyme, with the highest kcat/Km value. We successfully obtained a BdorAgmNAT knockout strain based on a wild-type strain (WT) using the CRISPR/Cas9 technique. The ovary development of the BdorAgmNAT knockout mutants was delayed for 10 days compared with the WT specimens. Moreover, mutants had a much smaller mature ovary size and laid far fewer eggs than WT. Loss of function of BdorAgmNAT caused by RNAi with mature WT females did not affect their fecundity. These findings indicate that BdorAgmNAT is critical for oogenesis. Our data provide the first evidence for AgmNAT in regulating ovary development.

Role of STING in the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a prevalent form of lung cancer. Patients with advanced NSCLC are currently being treated with various therapies, including traditional radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. However, a considerable proportion of advance patients who cannot benefit from them. Consequently, it is essential to identify a novel research target that offers an encouraging perspective. The stimulator of interferon genes (STING) has emerged as such a target. At present, it is confirmed that activating STING in NSCLC tumor cells can impede the proliferation and metastasis of dormant tumor cells. This review focuses on the role of STING in NSCLC treatment and the factors influencing its activation. Additionally, it explores the correlation between STING activation and diverse therapy modalities for NSCLC, such as radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. Furthermore, it proposes the prospect of innovative therapy methods involving nanoparticles, with the aim of using the features of STING to develop more strategies for NSCLC therapy.

Identification and validation of an endoplasmic-reticulum-stress-related gene signature as an effective diagnostic marker of endometriosis.

Background: Endometriosis is one of the most common benign gynecological diseases and is characterized by chronic pain and infertility. Endoplasmic reticulum (ER) stress is a cellular adaptive response that plays a pivotal role in many cellular processes, including malignant transformation. However, whether ER stress is involved in endometriosis remains largely unknown. Here, we aimed to explore the potential role of ER stress in endometriosis, as well as its diagnostic value. Methods: We retrieved data from the Gene Expression Omnibus (GEO) database. Data from the GSE7305 and GSE23339 datasets were integrated into a merged dataset as the training cohort. Differentially expressed ER stress-related genes (DEG-ERs) were identified by integrating ER stress-related gene profiles downloaded from the GeneCards database with differentially expressed genes (DEGs) in the training cohort. Next, an ER stress-related gene signature was identified using LASSO regression analysis. The receiver operating characteristic curve was used to evaluate the discriminatory ability of the constructed model, which was further validated in the GSE51981 and GSE105764 datasets. Online databases were used to explore the possible regulatory mechanisms of the genes in the signature. Meanwhile, the CIBERSORT algorithm and Pearson correlation test were applied to analyze the association between the gene signature and immune infiltration. Finally, expression levels of the signature genes were further detected in clinical specimens using qRT-PCR and validated in the Turku endometriosis database. Results: In total, 48 DEG-ERs were identified in the training cohort. Based on LASSO regression analysis, an eight-gene-based ER stress-related gene signature was constructed. This signature exhibited excellent diagnostic value in predicting endometriosis. Further analysis indicated that this signature was associated with a compromised ER stress state. In total, 12 miRNAs and 23 lncRNAs were identified that potentially regulate the expression of ESR1, PTGIS, HMOX1, and RSAD2. In addition, the ER stress-related gene signature indicated an immunosuppressive state in endometriosis. Finally, all eight genes showed consistent expression trends in both clinical samples and the Turku database compared with the training dataset. Conclusions: Our work not only provides new insights into the impact of ER stress in endometriosis but also provides a novel biomarker with high clinical value.

The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

Intraoperative frozen section pathology of vaginal margin in radical hysterectomy on the prognosis and quality of life for patients with IB2-IIA2 cervical cancer: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Several risk factors have been identified that compromise the treatment outcome in patients with early-to-mid-stage cervical cancer (CC) who are primarily treated with radical surgery. However, there is no report on the impact of intraoperative frozen pathology examination of vaginal margins on the prognosis of patients with CC. This study aimed to conduct a randomized controlled trial (RCT) to determine whether selective vaginal resection can reduce the incidence of operative complications and the risk of postoperative radiotherapy. The impact of the length of the vagina removed in radical hysterectomy (RH) on prognosis and quality of life (QoL) for IB2-IIA2 CC patients will be investigated. METHODS: A multicenter, non-inferiority, RCT at 7 institutions in China is designed to investigate the effect of intraoperative frozen pathology exam of vaginal margin in RH on the survival outcomes for patients with IB2-IIA2 CC. Eligible patients aged 18-70 years will be randomly assigned online by one-to-one random allocation to receive intraoperative frozen pathology exam of vaginal margin or not. If frozen pathology indicates positive margin, continue resection of 1 centimeter of vaginal tissue until negative margin is achieved. The primary end point is 2-year disease-free survival (DFS). Adverse events (AEs) caused by further vagina resection, 5-year DFS, 2-year overall survival (OS), 5-year OS and AEs caused by radiotherapy and QoL are secondary end points. A total of 310 patients will be enrolled from 7 tertiary hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2000035668.

Identification and validation of KIF23 as a hypoxia-regulated lactate metabolism-related oncogene in uterine corpus endometrial carcinoma.

AIMS: The "Warburg effect" has been developed from the discovery that hypoxia-inducible factor 1α (HIF-1α) could promote the conversion of pyruvate to lactate. However, no studies have linked hypoxia and lactate metabolism to uterine corpus endometrial carcinoma (UCEC). MAIN METHODS: Sequencing and clinical data of patients with UCEC were extracted from The Cancer Genome Atlas (TCGA) database. Hypoxia-related lactate metabolism genes (HRLGs) were screened using Spearman's correlation analysis. A prognostic signature based on HRLGs was developed using the least absolute shrinkage and selection operator (LASSO) algorithm. A comprehensive analysis was conducted on the molecular features, immune environment, mutation patterns, and response to drugs between different risk groups. In vitro and in vivo experiments were performed to verify the function of KIF23. KEY FINDINGS: A five HRLG-based prognostic signature was identified. The prognostic outcome was unfavorable for the high-risk subgroup. Observation of increased pathway activities associated with cell proliferation and DNA damage repair was noted in the high-risk subgroup. Additionally, notable correlations were observed between risk score and immune microenvironment, mutational features, and drug responsiveness. Further, we confirmed KIF23 as a novel oncogene in UCEC, whose silencing decreased proliferation and promoted apoptosis of cancer cells. KIF23 knockdown reduced tumor growth in nude mice. We demonstrated that KIF23 was upregulated under hypoxic stress in a HIF-1α dependent manner. Moreover, KIF23 regulated lactate dehydrogenase A expression. SIGNIFICANCE: The developed HRLG-related signature was associated with prognosis, immune microenvironment, and drug sensitivity in UCEC. We also revealed KIF23 as a hypoxia-regulated lactate metabolism-related oncogene.

The quest for nanoparticle-powered vaccines in cancer immunotherapy.

Despite recent advancements in cancer treatment, this disease still poses a serious threat to public health. Vaccines play an important role in preventing illness by preparing the body's adaptive and innate immune responses to combat diseases. As our understanding of malignancies and their connection to the immune system improves, there has been a growing interest in priming the immune system to fight malignancies more effectively and comprehensively. One promising approach involves utilizing nanoparticle systems for antigen delivery, which has been shown to potentiate immune responses as vaccines and/or adjuvants. In this review, we comprehensively summarized the immunological mechanisms of cancer vaccines while focusing specifically on the recent applications of various types of nanoparticles in the field of cancer immunotherapy. By exploring these recent breakthroughs, we hope to identify significant challenges and obstacles in making nanoparticle-based vaccines and adjuvants feasible for clinical application. This review serves to assess recent breakthroughs in nanoparticle-based cancer vaccinations and shed light on their prospects and potential barriers. By doing so, we aim to inspire future immunotherapies for cancer that harness the potential of nanotechnology to deliver more effective and targeted treatments.

A publicly available newborn ear shape dataset for medical diagnosis of auricular deformities.

Early and accurate diagnosis of ear deformities in newborns is crucial for an effective non-surgical correction treatment, since this commonly seen ear anomalies would affect aesthetics and cause mental problems if untreated. It is not easy even for experienced physicians to diagnose the auricular deformities of newborns and the classification of the sub-types, because of the rich bio-metric features embedded in the ear shape. Machine learning has already been introduced to analyze the auricular shape. However, there is little publicly available datasets of ear images from newborns. We released a dataset that contains quality-controlled photos of 3,852 ears from 1,926 newborns. The dataset also contains medical diagnosis of the ear shape, and the health data of each newborn and its mother. Our aim is to provide a freely accessible dataset, which would facilitate researches related with ear anatomies, such as the AI-aided detection and classification of auricular deformities and medical risk analysis.

Mutual regulation of PD-L1 immunosuppression between tumor-associated macrophages and tumor cells: a critical role for exosomes.

Tumor cells primarily employ the PD-1/PD-L1 pathway to thwart the anti-tumor capabilities of T lymphocytes, inducing immunosuppression. This occurs through the direct interaction of PD-L1 with PD-1 on T lymphocyte surfaces. Recent research focusing on the tumor microenvironment has illuminated the pivotal role of immune cells, particularly tumor-associated macrophages (TAMs), in facilitating PD-L1-mediated immunosuppression. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. In addition to receiving signals from tumor-derived exosomes that promote PD-L1 expression, TAMs also exert control over PD-L1 expression in tumor cells through the release of exosomes. This paper aims to summarize the mechanisms by which exosomes participate in this process, identify crucial factors that influence these mechanisms, and explore innovative strategies for inhibiting or reversing the tumor-promoting effects of TAMs by targeting exosomes.

Exploring the catalytic diversity of two short-chain dehydrogenases/reductases from Stachybotrys chartarum.

Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from Stachybotrys chartarum 3.5365. Substrate scope investigation revealed that both of the enzymes possessed the ability to oxidize ß-OH to ketone specifically, and exhibited substrate promiscuity and high stereo-selectivity for efficiently catalyzing the structurally different prochiral ketones to chiral alcohols. These findings not only suggest that ScSDR1 and ScSDR2 might be potent synthetic tools in drug research and development, but also provide good examples for further engineered enzymes with higher efficiency and stereo-selectivity.

Fontan-associated liver disease current status and transplantation consideration / 中华肝脏病杂志

Fontan-associated liver disease (FALD) is one of the main complications after the Fontan procedure, manifesting mostly as liver fibrosis and even cirrhosis, with a high incidence rate and a lack of typical clinical symptoms that seriously affect patient prognosis. The specific cause is unknown, although it is considered to be associated with long-term elevated central venous pressure, impaired hepatic artery blood flow, and other relevant factors. The absence of association between laboratory tests, imaging data, and the severity of liver fibrosis makes clinical diagnosis and monitoring difficult. A liver biopsy is the gold standard for diagnosing and staging liver fibrosis. The most important risk factor for FALD is time following the Fontan procedure; therefore, it is recommended to do a liver biopsy 10 years after the Fontan procedure and to be cautious for the presence of hepatocellular carcinoma. Combined heart-liver transplantation is a recommended choice with favorable outcomes for patients with Fontan circulatory failure and severe hepatic fibrosis.

Perinatal risk factors for the occurrence of singleton apparently stillborn infants / 中国当代儿科杂志

OBJECTIVES@#To identify the perinatal risk factors for the occurrence of singleton apparently stillborn infants.@*METHODS@#This was a case-control study. A total of 154 singleton neonates with gestational age ≥28 weeks and Apgar score of 0-1 who were subsequently successfully resuscitated in the Obstetrics and Gynecology Hospital of Fudan University from January 2006 to December 2015 were enrolled as the case group (apparently stillborn group). A total of 616 singleton infants born from January 2006 to December 2015 (1-minute Apgar score >1) were randomly selected in a 1:4 ratio as the control group. Univariate analysis and multivariate logistic regression were used to analyze the perinatal risk factors for the occurrence of apparently stillborn infants.@*RESULTS@#The gestational age and birth weight in the apparently stillborn group were significantly lower than those in the control group (P<0.05). The incidences of fetal hydrops, cord prolapse, grade III meconium-stained amniotic fluid, placental abruption, breech presentation, severe pre-eclampsia, maternal general anesthesia at delivery, abnormal antenatal fetal heart monitoring and decreased fetal movement were significantly higher in the apparently stillborn group than those in the control group (P<0.05). The multivariate logistic analysis showed that the mother had general anesthesia at delivery (OR=34.520), decreased antenatal fetal movement (OR=28.168),placental abruption (OR=15.641), grade III meconium-stained amniotic fluid (OR=6.365), abnormal antenatal fetal heart monitoring (OR=5.739), and breech presentation (OR=2.614) were risk factors for the occurrence of apparently stillborn infants (P<0.05), while higher gestational age was a protective factor (OR=0.686, P<0.05).@*CONCLUSIONS@#Attention needs to be paid to mothers with abnormal prenatal fetal heart monitoring, decreased fetal movement, preterm labor, placental abruption, breech presentation, grade III meconium-stained amniotic fluid, and general anesthesia. Preparations for resuscitation should be done to rescue apparently stillborn infants.

Responses of blood parameters and hemoglobin subtypes in plateau zokors and plateau pikas to different altitude habitats / 生理学报

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α2β2 and fetal α2ε2 hemoglobins were identified, while erythrocytes of plateau zokors only had adult α2β2 hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.

Cloning and prokaryotic expression analysis of AlCMK from Atractylodes lancea / 药学学报

4-(Cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase (CMK) was one of the key enzymes in the methylerythritol-4-phosphate (MEP) pathway to generate terpenoids. In this study, based on the transcriptome data of Atractylodes lancea, the sequence of the CMK gene was cloned, named AlCMK (GenBank accession number OM283293). The results showed that AlCMK contains a 1 230 bp open reading frame (ORF) encoding 409 amino acids. The deduced protein had a theoretical molecular weight of 44 752.53 and an isoelectric point of 6.67. Transmembrane structure analysis showed that there was no transmembrane structure, and the secondary structure of AlCMK was predicted to be mainly composed of random coil. Homologous alignment revealed that AlCMK shared high sequence identity with the CMK proteins of Tanacetum cinerariifolium, Osmanthus fragrans, Eucommia ulmoides, Lonicera japonica and Salvia miltiorrhiza. Phylogenetic analysis indicated that AlCMK protein had the higher homology with CMK protein of Compositae. The pET-32a-AlCMK prokaryotic expression vector was constructed and a fusion protein with molecular mass of about 65 kDa was expressed in the E. coli BL21 (DE3). The qRT-PCR was used to analyze the expression pattern of AlCMK gene in different tissues and after MeJA treatment. Meanwhile, the enzyme activity was determined by ELISA kit. The results showed that AlCMK gene was tissue-expressed in different origins and its expression was induced by MeJA, and the results of the enzyme activity assay showed that the AlCMK enzyme activity in different regions was higher in the leaves. The subcellular localization showed that AlCMK was located in the chloroplast. This study provides a reference for further elucidating the biological function of AlCMK gene in terpenoid synthesis pathway in Atractylodes lancea.

Construction and application of recombinant human UDP-glucuronosyltransferases expression systems / 药学学报

In the research and development of new drugs, it is very important to investigate the in vitro metabolism of candidate drugs. Traditional models such as liver microsomes have many limitations, while the in vitro model of recombinant human drug metabolizing enzymes is considered as an important and useful approach because of its convenient access, stable activity and low cost. In this study, six major human UDP-glucuronosyltransferases (UGTs) genes (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) were cloned from human liver cDNA and heterologously expressed in Saccharomyces cerevisiae and baculovirus-infected insect cell. UGT1A1, 1A3, 1A6 and 1A9 were successfully expressed in yeast and showed glucuronidation activity against a variety of different structural types of substrates, but their activities were low. All six UGTs were successfully expressed and exhibited significantly improved glucuronidation activity when Trichopolusia ni cells BTI-TN5B1-4 (High Five) were used as the host. The recombinant human UGTs expressed in insect cells can catalyze the glucuronidation of their specific substrates, and the glucuronidation products were synthesized at milligram-scale with yields of 13%-66% for the first time, of which the structures were identified via MS, 1H NMR, and 13C NMR spectroscopic analysis. Above all, the recombinant human UGTs yeast and insect cell expression systems constructed in this study can be used for in vitro metabolism evaluation in the early stage of new drugs research and development, and also provide a new tool for the synthesis of glucuronide metabolites.

Treatment and prognosis of 826 infants with critical congenital heart disease: a single center retrospective study / 中华心血管病杂志

Objective: To analyze the current status of clinical treatment and factors influencing postoperative mortality in infants with critical congenital heart disease (CCHD) in China, optimize the perioperative management of CCHD, and provide a new scientific basis for clinical decision-making for the optimal management of these patients. Methods: This is a retrospective single-center study. Infants diagnosed with CCHD in Guangdong Provincial People's Hospital from January 2017 to December 2019 (aged 0-1 years at admission) were enrolled. General clinical information, inpatient treatment information, prognosis and complications were collected and analyzed. Multivariate logistic regression analysis was used to explore the independent risk factors of postoperative death in infants with CCHD. Results: A total of 826 infants with CCHD were included, including 556 males (67.3%) and the age at first admission was 51.0 (5.0,178.3) days. 264 (32.0%) cases were tetralogy of Fallot and 137 (16.6%) cases were total anomalous pulmonary venous return. 195 cases (23.6%) were diagnosed prenatally. 196 cases (23.7%) were treated with prostaglandin. The preoperative invasive ventilation time was 0 (0, 0) hour, and the postoperative invasive ventilation time was 95.0 (26.0, 151.8) hours. A total of 668 cases (80.9%) underwent surgical treatment. The age was 100.5 (20.0, 218.0) days during operation and the operation time was 190.0 (155.0, 240.0) hours. Sixty-two cases (7.5%) received medical treatment, and 96 cases (11.6%) gave up treatment. A total of 675 cases (81.7%) were discharged with improvement, 96 cases (11.6%) were discharged after giving up treatment, 55 cases (6.7%) died and 109 cases (13.2%) were readmitted within one year. Complications occurred in 565 (68.6%) cases, including pneumonia in 334 cases (40.4%) and cardiac arrhythmias in 182 cases (22.0%). Multifactorial analysis showed that delayed chest closure (OR=49.775, 95%CI 3.291-752.922, P=0.005), prolonged post-operative invasive ventilator ventilation (OR=1.003, 95%CI 1.000-1.005, P=0.038) and cardiac hypoplasia syndrome (OR=272.658, 95%CI 37.861-1 963.589, P<0.001) were the independent risk factors for mortality in CCHD infants post-operation. Conclusions: Tetralogy of Fallot and total anomalous pulmonary venous return account for the majority of infants with CCHD. The proportion of infants diagnosed prenatally was less than 1/4. The majority CCHD infants received surgical treatment. The main complications are pneumonia and arrhythmia. Delayed chest closure, prolonged postoperative invasive ventilator ventilation and low cardiac output syndrome are the independent risk factors for postoperative death in infants with CCHD.