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Abstract Objective This study aims to compare the perioperative outcomes and disease-free survival (DFS) between pneumonectomy after immunochemotherapy and chemotherapy. Methods We retrospectively identified patients who received neoadjuvant immunotherapy (n = 15) or chemotherapy alone (n = 12) in our single center between 2021 and 2023. The primary end point was 30-day major complications. The secondary end point was major pathologic response. Results There was no significant difference in operation time, blood loss and postoperative stay time between ICI (Received immune checkpoint inhibitor treatment including PD-1 and PD-L1 inhibitors) and Chemo cohort. There were also no difference in postoperative complications including complications > grade III, 90-day death and bronchial fistula. The pCR rate was 40.0% (6/15) in the ICI cohort versus 0.0% (0/12) in the chemo cohort (p = 0.020). The MPR or pCR rate was 60.0% (9/15) in the ICI cohort versus 8.3% (1/12) in the chemo cohort (p = 0.014). ICI cohort was associated with an improved overall 1, 2, and 3-year disease-free survival(DFS)compared with chemo cohort. At the same time, both patients received ICI and Chemo were grouped according to whether pCR occurred or not, and it was found that DFS in the pCR group was better than DFS in the non-pCR group. Conclusions Based on our results, we argue that compared with pneumonectomy after isolated chemotherapy, pneumonectomy after immunochemotherapy not added 90-day mortality, postoperative, morbidity, but improved DFS; thus, it should be the induction therapy choice for anatomically eligible centrally located lung cancers.

Summary: Dopaminergic neurons derived from human induced pluripotent stem cells recapitulate key pathogenic phenotypes observed in Parkinson’s disease (PD). Here, we present a protocol to analyze oxidized dopamine and the recruitment of parkin onto synaptic vesicles in neurons derived from patients with mutations in parkin that cause autosomal recessive PD. We describe steps for neuronal differentiation, live-cell microscopy, detection of oxidized dopamine, and labeling of synaptic vesicles. These protocols can be applied to studies of other forms of genetic and sporadic forms of PD.For complete details on the use and execution of this protocol, please refer to Song et al.1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background The problem-based learning (PBL) model has been widely carried out in many fields of medical colleges and universities. Immunochemistry as a cross-disciplinary science plays a vital role in preventing the occurrence of diseases and bridging the development of Life Science and Medicine. But now the Immunochemistry course still lacks the teaching practice in PBL. To explore the significance of PBL applied in the Immunochemistry course, the effect of the PBL model on the learning of undergraduates majoring in Chemicobiology was systematically evaluated. Methods The teaching objects were the undergraduates majoring in Chemicobiology from Guizhou Medical University. The PBL model was applied in the Immunochemistry course. 62 undergraduates in Grade 2018 were set as the control group and adopted the traditional expository model. 93 undergraduates in Grades 2019–2020 were separately set as the experimental groups, which adopted the PBL model based on traditional lecture-based learning. In the PBL model, six cases related to course contents were designed for the students to complete. The final exams of the undergraduates in Grades 2018–2020 were analyzed by the score ranges (

BackgroundMetagenomic next-generation sequencing (mNGS) of plasma cell-free DNA (cfDNA) shows promising application for complicated infections that cannot be resolved by conventional microbiological tests (CMTs). The criteria for cfDNA sequencing are currently in need of agreement and standardization.MethodsWe performed a retrospective cohort observation of 653 patients who underwent plasma cfDNA mNGS, including 431 with suspected bloodstream infections (BSI) and 222 with other suspected systemic infections. Plasma mNGS and CMTs were performed simultaneously in clinical practice. The diagnostic efficacy of plasma mNGS and CMTs in the diagnosis of blood-borne and other systemic infections was evaluated using receiver operating characteristic (ROC) curves. The sensitivity and specificity of the two methods were analyzed based on the final clinical outcome as the gold standard.ResultsThe mNGS test showed an overall positive rate of 72.3% (472/653) for detecting microorganisms in plasma cfDNA, with a range of 2 to 6 different microorganisms detected in 171 patient specimens. Patients with positive mNGS results were more immunocompromised and had a higher incidence of severe disease (P

Based on the lung adenocarcinoma (LUAD) gene expression data from the cancer genome atlas (TCGA) database, the Stromal score, Immune score and Estimate score in tumor microenvironment (TME) were computed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm. And gene modules significantly related to the three scores were identified by weighted gene co-expression network analysis (WGCNA). Based on the correlation coefficients and P values, 899 key genes affecting tumor microenvironment were obtained by selecting the two most correlated modules. It was suggested through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis that these key genes were significantly involved in immune-related or cancer-related terms. Through univariate cox regression and elastic network analysis, genes associated with prognosis of the LUAD patients were screened out and their prognostic values were further verified by the survival analysis and the University of ALabama at Birmingham CANcer (UALCAN) database. The results indicated that eight genes were significantly related to the overall survival of LUAD. Among them, six genes were found differentially expressed between tumor and control samples. And immune infiltration analysis further verified that all the six genes were significantly related to tumor purity and immune cells. Therefore, these genes were used eventually for constructing a Naive Bayes projection model of LUAD. The model was verified by the receiver operating characteristic (ROC) curve where the area under curve (AUC) reached 92.03%, which suggested that the model could discriminate the tumor samples from the normal accurately. Our study provided an effective model for LUAD projection which improved the clinical diagnosis and cure of LUAD. The result also confirmed that the six genes in the model construction could be the potential prognostic biomarkers of LUAD.

The promotion of industrial-mode production of Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (C. pilosula) has expanded the demand for the postharvest storage of fresh roots. Further research is needed to establish comprehensive methods to evaluate the impact of storage conditions. This study simulated the storage process of roots at near-freezing temperature [NFT (−1 °C)] and traditional low temperatures (−6 °C, 4 °C and 9 °C) for 40 days. At different storage stages, correlation analysis was conducted using quantitative data on 20 parameters, including sensory quality, active components, antioxidant capacity and physiological changes. Appearance and principal component analysis could distinguish between fresh and stored samples, while NFT samples on the 40th day of storage were similar to fresh ones. Correlation analysis indicated that NFT storage could maintain the sensory quality by increasing the antioxidant enzyme activity and active components, reducing the accumulation of reactive oxygen species and malondialdehyde and reducing the activity of browning-related enzymes and cell-wall-degrading enzymes. These findings highlight the importance of the overall quality evaluation of fresh roots and emphasize the potential to improve fresh root and dried medicinal material quality by regulating storage conditions such as temperature.

Abstract Previous studies have revealed that miRNAs participate in the pathogenesis of ovarian cancer; however, whether miR-600 is also involved remains unclear. In this study, we aimed to investigated the role of miR-600 in ovarian cancer progression. Here, miR-600 expression was significantly upregulated in ovarian cancer tissues and stem cells. Functional studies showed that miR-600 promoted ovarian cancer cell stemness, proliferation and metastasis. Mechanistic studies revealed that Kruppel like factor 9 (KLF9) was indicated as the target of miR-600. The luciferase reporter assay suggested that miR-600 directly bound to the 3′-untranslated region of KLF9. Additionally, miR-600 expression was negatively associated with KLF9 expression in human ovarian cancer tissues. Si-KLF9 partially abolished the discrepancy of self-renewal, growth and metastasis capacity between miR-600 knockdown ovarian cancer cells and control cells. In conclusion, our results suggest that miR-600 promotes ovarian cancer cell stemness, proliferation and metastasis via directly downregulating KLF9, and impairing miR-600 levels may be a new treatment strategy for ovarian cancer in the future.

Background Acanthopanacis Cortex (AC) is a valuable Chinese medicine, which exerts beneficial effects on anti-fatigue, anti-stress, and inflammatory modulation in the periphery. However, the central nervous system (CNS) function of AC has not been clearly illustrated. As communication between the peripheral immune system and the CNS converges, it promotes a heightened neuroinflammatory environment that contributes to depression. We investigated the effect of AC against depression through neuroinflammatory modulation. Methods Network pharmacology was used to screen for target compounds and pathways. Mice with CMS-induced depression were used to evaluate the efficacy of AC against depression. Behavioral studies and detection of neurotransmitters, neurotrophic factors, and pro-inflammatory cytokines were performed. The IL-17 signaling cascade was involved to further investigate the underlying mechanism of AC against depression. Results Twenty-five components were screened by network pharmacology and the IL-17 mediated signaling pathway was associated with the antidepressant action of AC. This herb had a beneficial effect on CMS-induced depressive mice, including improvements in depressive behavior, modulation of neurotransmitter levels, neurotrophic factors, and pro-inflammatory cytokines. Conclusions Our results revealed that AC exhibits effects on anti-depression and one of the mechanisms was mediated by neuroinflammatory modulation.

Rhizosphere microorganisms are the main factors affecting the formation of high quality medicinal materials and promoting the accumulation of secondary metabolites. However, the composition, diversity, and function of rhizosphere microbial communities in endangered wild and cultivated Rhizoma Atractylodis Macrocephalae (RAM) and their relationships with active component accumulation have remained unclear. In this study, high-throughput sequencing and correlation analysis were used to study the rhizosphere microbial community diversity (bacteria and fungi) of three RAM species and its correlation with the accumulation of polysaccharides, atractylone, and lactones (I, II, and III). A total of 24 phyla, 46 classes, and 110 genera were detected. The dominant taxa were Proteobacteria, Ascomycota, and Basidiomycota. The microbial communities in both wild and artificially cultivated soil samples were extremely species-rich, but there were some differences in their structure and the relative abundances of microorganism taxa. Meanwhile, the contents of effective components in wild RAM were significantly higher than those in cultivated RAM. Correlation analysis showed that 16 bacterial and 10 fungal genera were positively or negatively correlated with active ingredient accumulation. These results showed that rhizosphere microorganisms could play an important role in component accumulation and might lay a foundation for future research on endangered materials.

Absrtact: Hawthorn, the sliced and dried ripe fruits of Crataegus pinnatifida Bge. Var. Major N. E. Br. (Rosaceae), is an edible and medicinal substance with a variety of health-promoting benefits. Hawthorn needs to be stored in warehouses after harvesting to meet people's perennial demand. However, it is easily infested by insects of Plodia interpunctella and Tribolium castaneum during storage, which inevitably leads to poor quality and causes adverse effects on people's health. So far, there has been no report on insect-infested hawthorn. In this study, we analyzed the changes of metabolites in hawthorn before and after insect infestation and screened out potential biomarkers to effectively and quickly detect the occurrence of insect infestation. A combination analysis of 1H nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to identify the primary and secondary metabolites. By the comparison of hawthorn and insect-infested hawthorn samples, it was found that the differences were mainly manifested in the content of metabolites. The metabolites of 32 and 1463 were identified by 1H NMR and UPLC-MS analysis, respectively. According to the parameters of VIP >1 and P 1.0, P 1 or

Summary: In this study, allyl isothiocyanate (AITC) was prepared as the dry powder inhalation by loading cyclodextrin metal-organic framework (CD-MOF) to enhance pulmonary delivery. β-CD-MOF and γ-CD-MOF both could be used to carry AITC with the optimal loading conditions (50˚C, nCD: nAITC = 1:7, 7 h). Compared with β-CD-MOF, γ-CD-MOF had more advantages in AITC loading due to its high drug loading and stable crystal morphology. The particle size and the mass median aerodynamic diameter of γ-CD-MOF-AITC were accorded with the aerodynamic characteristics of lung inhalation. γ-CD-MOF-AITC might be deposited effectively in the deep lung, and the release rate of AITC reached over 90% within 5 min. Meanwhile, it had good pulmonary local tolerance, permeability, and no significant toxicity. Such results indicated that γ-CD-MOF could be used as a dry powder inhaler carrier to deliver safely AITC to lung and increase its pulmonary absorption.

Early researches have revealed that circular RNA (circRNA) had the potential of biomarkers and could affect tumor progression through regulatory networks. However, few research focused on the function of circRNA in lung adenocarcinoma and the regulation mechanism of competitive endogenous RNA. In present study, through differential expression analysis, 10 circRNAs, 98 miRNAs(microRNA) and 2497 mRNAs were screened. Based on the 10 circRNAs and related databases, a competitive endogenous RNA regulatory network (ceRNA network) containing 7 circRNAs, 13 miRNAs and 147 mRNAs was constructed. KEGG and GO analysis suggested that 147 mRNAs were obviously enriched in biological pathway related to LUAD. By constructing a PPI network, 12 hub genes were identified by MCODE. The result of survival analysis showed that 10 hub genes (BIRC5, MKI67, CENPF, RRM2, BUB1, MELK, CEP55, CDK1, NEK2, TOP2A) were significantly related to the survival of LUAD. We randomly divided 483 clinical data into two parts: train set and validation set. The train set was used for Cox regression analysis, 3 prognostic factors (stage, T, CDK1) were screened. The nomogram model was constructed based on stage, T and CDK1. The model was evaluated by ROC curve, calibration chart, Kaplan-Meier (KM) curve and validation set data. The results indicated that the model has good accuracy. Our study elucidated the regulatory mechanism of circRNA in lung adenocarcinoma, and the nomogram model also provided insight for the clinical analysis of lung adenocarcinoma.

BackgroundMetagenomic next-generation sequencing (mNGS) is increasingly being used to detect pathogens directly from clinical specimens. However, the optimal application of mNGS and subsequent result interpretation can be challenging. In addition, studies reporting the use of mNGS for the diagnosis of invasive fungal infections (IFIs) are rare.ObjectiveWe critically evaluated the performance of mNGS in the diagnosis of pulmonary IFIs, by conducting a multicenter retrospective analysis. The methodological strengths of mNGS were recognized, and diagnostic cutoffs were determined.MethodsA total of 310 patients with suspected pulmonary IFIs were included in this study. Conventional microbiological tests (CMTs) and mNGS were performed in parallel on the same set of samples. Receiver operating characteristic (ROC) curves were used to evaluate the performance of the logarithm of reads per kilobase per million mapped reads [lg(RPKM)], and read counts were used to predict true-positive pathogens.ResultThe majority of the selected patients (86.5%) were immunocompromised. Twenty species of fungi were detected by mNGS, which was more than was achieved with standard culture methods. Peripheral blood lymphocyte and monocyte counts, as well as serum albumin levels, were significantly negatively correlated with fungal infection. In contrast, C-reactive protein and procalcitonin levels showed a significant positive correlation with fungal infection. ROC curves showed that mNGS [and especially lg(RPKM)] was superior to CMTs in its diagnostic performance. The area under the ROC curve value obtained for lg(RPKM) in the bronchoalveolar lavage fluid of patients with suspected pulmonary IFIs, used to predict true-positive pathogens, was 0.967, and the cutoff value calculated from the Youden index was −5.44.ConclusionsIn this study, we have evaluated the performance of mNGS-specific indicators that can identify pathogens in patients with IFIs more accurately and rapidly than CMTs, which will have important clinical implications.

BackgroundDeafness-dystonia-optic neuronopathy (DDON) syndrome, a condition that predominantly affects males, is caused by mutations in translocase of mitochondrial inner membrane 8A (TIMM8A)/deafness dystonia protein 1 (DDP1) gene and characterized by progressive deafness coupled with other neurological abnormalities. In a previous study, we demonstrated the phenotype of male mice carrying the hemizygous mutation of Timm8a1-I23fs49X. In a follow-up to that study, this study aimed to observe the behavioral changes in the female mutant (MUT) mice with homologous mutation of Timm8a1 and to elucidate the underlying mechanism for the behavioral changes.Materials and methodsHistological analysis, transmission electron microscopy (EM), Western blotting, hearing measurement by auditory brainstem response (ABR), and behavioral observation were compared between the MUT mice and wild-type (WT) littermates.ResultsThe weight of the female MUT mice was less than that of the WT mice. Among MUT mice, both male and female mice showed hearing impairment, anxiety-like behavior by the elevated plus maze test, and cognitive deficit by the Morris water maze test. Furthermore, the female MUT mice exhibited coordination problems in the balance beam test. Although the general neuronal loss was not found in the hippocampus of the MUT genotype, EM assessment indicated that the mitochondrial size showing as aspect ratio and form factor in the hippocampus of the MUT strain was significantly reduced compared to that in the WT genotype. More importantly, this phenomenon was correlated with the upregulation of translation of mitochondrial fission process protein 1(Mtfp1)/mitochondrial 18 kDa protein (Mtp18), a key fission factor that is a positive regulator of mitochondrial fission and mitochondrial size. Interestingly, significant reductions in the size of the uterus and ovaries were noted in the female MUT mice, which contributed to significantly lower fertility in the MUT mice.ConclusionTogether, a homologous mutation in the Timm8a1 gene caused the hearing impairment and psychiatric behavioral changes in the MUT mice; the latter phenotype might be related to a reduction in mitochondrial size regulated by MTP18.

ObjectiveHilar and lung lymph node metastases (N1) are defined as ipsilateral bronchial and intrapulmonary lymph nodes. However, the cleaning standards for ipsilateral bronchial lymph nodes in different lobes and segments within the same lobe in segmentectomy are not clearly defined.Materials and methodsSixty-six patients undergoing pulmonary resection for the treatment of lung cancer were evaluated. Intraoperatively visible non-tumor-bearing lobe (NTBL) and post-operatively non-tumor-bearing segment (NTBS) lymph nodes were removed and analyzed. The associations between the NTBL LNs and clinicopathological characteristics were analyzed.ResultsNon-tumor-bearing lobe LNs metastases were found in 8 (12.1%) of the 66 patients, NTBS LNs metastasis were not found (0/13). The presence of NTBL metastases was significantly associated with age (

Abstract Gastric cancer (GC) is one of the most common types of malignancy. Its potential molecular mechanism has not been clarified. In this study, we aimed to explore potential biomarkers and prognosis-related hub genes associated with GC. The gene chip dataset GSE79973 was downloaded from the GEO datasets and limma package was used to identify the differentially expressed genes (DEGs). A total of 1269 up-regulated and 330 down-regulated genes were identified. The protein-protein interactions (PPI) network of DEGs was constructed by STRING V11 database, and 11 hub genes were selected through intersection of 11 topological analysis methods of CytoHubba in Cytoscape plug-in. All the 11 selected hub genes were found in the module with the highest score from PPI network of all DEGs by the molecular complex detection (MCODE) clustering algorithm. In order to explore the role of the 11 hub genes, we performed GO function and KEGG pathway analysis for them and found that the genes were enriched in a variety of functions and pathways among which cellular senescence, cell cycle, viral carcinogenesis and p53 signaling pathway were the most associated with GC. Kaplan-Meier analysis revealed that 10 out of the 11 hub genes were related to the overall survival of GC patients. Further, seven of the 11 selected hub genes were verified significantly correlated with GC by uni- or multivariable Cox model and LASSO regression analysis including C3, CDK1, FN1, CCNB1, CDC20, BUB1B and MAD2L1. C3, CDK1, FN1, CCNB1, CDC20, BUB1B and MAD2L1 may serve as potential prognostic biomarkers and therapeutic targets for GC.

Abstract Background Acori Tatarinowii Rhizome (ATR) is a well-recognized Chinese herbal medicine prescribed to treat neurological disorders. The essential oil (ATEO) is considered as the active fraction of ATR and the content of ATEO is used as the only indicator for ATR content determination. The quality of ATEO varies widely due to region difference; however, little is known about how to study ATEO quality chemically and biologically in response to region difference. Thus, it is of great importance to identify volatile active components in ATEO to conduct quality study. In this study, we analyzed ATEO from different regions in China using chemical component analysis combined with biological activity evaluation. Methods GC-MS was used to obtain different volatile component profiles of ATEO and significantly changed volatile components were screened out. The neuroprotective activities of ATEO, including anti-oxidation, anti-inflammation and neurotrophic functions, were revealed in C6 glioma cells. The correlation study between the bioactivities and the components was performed. Results 57 volatile components, including terpenoids, phenylpropanoids, aromatic compounds, and other aliphatic compounds, were identified. 8 volatile components (β-asarone, cis-methyl isoeugenol, γ-asarone, methyleugenol, calarene, longifolene, β-caryophyllene and caryophyllene oxide) from ATEO were significantly changed due to region difference and 2 of them (β-asarone and γ-asarone) showed strong correlation with neuroprotective activities. Conclusions Our results reveal that ATEO from different regions in China show great changes in chemical composition and biological activity. Moreover, phenylpropanoids (β-asarone and γ-asarone) present strong correlation with the bioactivities, which are considered as volatile active components in ATEO. The findings will be useful for the development of quality study of ATEO.

Abstract Docosahexaenoic acid (DHA) enriched in brain can yield many important degradation products after the attack of hydroxyl radicals, which is known to serve as a nutraceutical and neuroprotective effects. Oxidative stress is a commonly observed feature of Alzheimer’s disease (AD). Therefore, uniformly radiolabeled DHA plays an important role in studying the oxidative fate of DHA in vivo and vitro. However, carbon isotope labeled DHA isn’t commercially available now. The heterotrophic microalgae Crypthecodinium cohnii (C. cohnii) has been identified as a prolific producer of DHA. In this study, the growth rate and DHA production in C. cohnii were optimized in a new defined media, and the biosynthesis of U-13C-DHA from U-13C-glucose and U-14C-DHA from U-14C-glucose were analyzed by HPLC–MS/MS. Approximately 40 nmoles of U-13C-DHA with higher isotopic purity of 96.8% was produced in a 300 μL batch, and ~ 0.23 μCi of U-14C-DHA with significant specific activity of 5–6 Ci/mol was produced in a 300 μL batch. It was found that C. cohnii had the optimal growth and DHA accumulation at 25 °C in this defined media (C/N = 10). An efficient protocol for the biosynthesis of U-13C-DHA and U-14C-DHA were set up firstly, which provides the basic support for the analysis of oxidative degradation products of DHA in AD.

A high performance liquid chromatography-diode array detector (HPLC-DAD) was used to establish the HPLC fingerprint. Chemometrics methods were used to discriminate against the gender of flower buds of Populus tomentosa based on areas of common peaks calibrated with the HPLC fingerprint. The score plot of principal component analysis (PCA) showed a clear grouping trend (R2X, 0.753; Q2, 0.564) between female and male samples. Two groups were also well discriminated with orthogonal partial least squares-discriminant analysis (OPLS-DA) (R2X, 0.741; R2Y, 0.980; Q2, 0.970). As the hierarchical clustering analysis (HCA) heatmap showed, all samples were separated into two groups. Four compounds were screened out by S-plot and variable importance in projection (VIP > 1.0). Two of them were identified as siebolside B and tremulacin. This study demonstrated that HPLC fingerprints combined with chemometrics can be applied to discriminate against dioecious plants and screen differences, providing a reference for identifying the gender of dioecious plants.

Ischemic stroke (IS) is a multifactorial disease caused by the interaction of multiple environmental and genetic risk factors, and it is the most common cause of disability. The immune microenvironment and inflammatory response participate in the whole process of IS occurrence and development. Therefore, the rational use of relevant markers or characteristic pathways in the immune microenvironment will become one of the important therapeutic strategies for the treatment of IS. We collected peripheral blood samples from 10 patients diagnosed with IS at the First Affiliated Hospital of Gannan Medical University and First Affiliated Hospital, Jinan" University, and from 10 normal people. The GSE16561 dataset was downloaded from the Gene Expression Omnibus (GEO) database. xCell, gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA) and immune-related gene analysis were used to evaluate the differences in the immune microenvironment and characteristic pathways between the IS and control groups of the two datasets. xCell analysis showed that the IS-24h group had significantly reduced central memory CD8+ T cell, effector memory CD8+ T cell, B cell and Th1 cell scores and significantly increased M1 macrophage and macrophage scores. GSEA showed that the IS-24h group had significantly increased inflammation-related pathway activity(myeloid leukocyte activation, positive regulation of tumor necrosis factor biosynthetic process, myeloid leukocyte migration and leukocyte chemotaxis), platelet-related pathway activity(platelet activation, signaling and aggregation; protein polymerization; platelet degranulation; cell-cell contact zone) and pathology-related pathway activity (ERBB signaling pathway, positive regulation of ERK1 and ERK2 cascade, vascular endothelial growth factor receptor signaling pathway, and regulation of MAP kinase activity). Immune-related signature analysis showed that the macrophage signature, antigen presentation-related signature, cytotoxicity-related signature, B cell-related signature and inflammation-related signature were significantly lower in the IS-24h group than in the control group. In this study, we found that there were significant differences in the immune microenvironment between the peripheral blood of IS patients and control patients, as shown by the IS group having significantly reduced CD8+ Tcm, CD8+ Tem, B cell and Th1 cell scores and significantly increased macrophage and M1 macrophage scores. Additionally, inflammation-related, pathological, and platelet-related pathway activities were significantly higher in the IS group than in the control group.

Qingpi, the dried immature pericarp of Citrus reticulata Blanco, is a commonly used medicinal food with some health-promoting benefits. In general, it is essential that Qingpi be stored for a period of time, but there are no reports about the number of storage years needed to obtain the best quality of Qingpi. Our aim was to determine the best storage time of Qingpi by studying the physicochemical properties and metabolite changes in product stored from 1 to 5 years. As a result, the color of Qingpi became darker during storage. Both the levels of three flavonoids (hesperidin, nobiletin, and tangeretin) and total flavonoids (TFs) and the antioxidant activity decreased during storage and the total phenolics (TPs) content fluctuated during storage. Cluster analysis was performed on the color parameters measured using a color difference meter, revealing that the color of Qingpi differed before and after 3 years of storage. A total of 9 special differential metabolites were identified that could be used to distinguish the storage years of Qingpi. This is the first study to report the quality changes of Qingpi during storage. The optimized results of the quality evaluation indicated that Qingpi should be stored for no more than 3 years.

Leishmania belongs to a genus of the protozoan parasites that causes leishmaniasis, and includes cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). In this case, Leishmania amastigotes were found on cytomorphology examination of the bone marrow specimen, followed by 1,076 Leishmania donovani reads using metagenomic next generation sequencing (mNGS). Since being definitely diagnosed with VL/HIV coinfection, the patient was treated with liposomal amphotericin B as the parasite-resistant therapy and was discharged after clinical cure. But nearly a year later, on the mNGS follow-up, L. donovani was detected in the patient’s blood plasma specimen with 941 reads, suggesting that a relapse of leishmaniasis had occurred. These results indicate that leishmaniasis still exists in China and may represent a public health concern. This case could be helpful in the differential diagnosis of leishmaniasis, and for determining disease progression, prevention, and control of vectors and reservoir hosts.

ObjectivesMultiple primary lung cancers (MPLCs) are an increasingly well-known clinical phenomenon, but there is a lack of high-level evidence for their optimal clinical diagnosis and therapeutic approaches. Thus, we analysed genetic variation to determine the intertumoural heterogeneity and branch evolution of synchronous multiple primary lung adenocarcinomas.MethodsWe performed multiplex mutational sequencing on 93 synchronous multiple primary lung adenocarcinoma lesions from 42 patients who underwent surgical resection.ResultsThe high discordance rate of mutation was 92.9% (n=39) between tumours in individual patients. EGFR, TP53 and KRAS mutations were detected in 57 (61.3%), 19 (20.4%) and 11 (11.8%) of the 93 tumours, respectively. 16 cases of multiple primary lung adenocarcinomas simultaneously harboured EGFR mutations and TP53 mutations. Matching mutations between paired tumours were observed in 1 (2.4%) patient for P20. The genotypes were all EGFR L858R mutations, but the pathological type of P20T1 was lepidic predominant, and P20T2 was adenocarcinoma in situ. In the phylogenetic tree, genetic variations were divided into trunk, shared and branch subtypes. Branch mutations accounted for 91.09% of variations in sMPLA, while the ratio of trunk (4.95%) and shared (3.96%) variations was significantly lower.ConclusionsRemarkable intertumoural heterogeneity and frequent branch mutations were found in synchronous multiple primary lung adenocarcinomas.

Current treatments for Parkinson’s disease (PD) provide only symptomatic relief, with no disease-modifying therapies identified to date. Repurposing FDA-approved drugs to treat PD could significantly shorten the time needed for and reduce the costs of drug development compared with conventional approaches. We developed an efficient strategy to screen for modulators of β-glucocerebrosidase (GCase), a lysosomal enzyme that exhibits decreased activity in patients with PD, leading to accumulation of the substrate glucosylceramide and oxidized dopamine and α-synuclein, which contribute to PD pathogenesis. Using a GCase fluorescent probe and affinity-based fluorescence polarization assay, we screened 1280 structurally diverse, bioactive, and cell-permeable FDA-approved drugs and found that the antipsychotic quetiapine bound GCase with high affinity. Moreover, quetiapine treatment of induced pluripotent stem cell–derived (iPSC-derived) dopaminergic neurons from patients carrying mutations in GBA1 or LRRK2 led to increased wild-type GCase protein levels and activity and partially lowered accumulation of oxidized dopamine, glucosylceramide, and α-synuclein. Similarly, quetiapine led to activation of wild-type GCase and reduction of α-synuclein in a GBA mutant mouse model (Gba1D409V/+ mice). Together, these results suggest that repurposing quetiapine as a modulator of GCase may be beneficial for patients with PD exhibiting decreased GCase activity.

Trichosanthes anguina L. (family Cucurbitaceae) is a monoecious and diclinous plant that can be consumed as a vegetable and has anti-inflammatory and antioxidant effects. The chemical composition and content of volatile compounds in female and male buds of T. anguina were explored by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology combined with multivariate statistical analysis. The results showed that the content of the volatile compounds was different between female and male buds. 2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran-3-ol and 2,2,6-trimethyl-6-vinyldihydro-2H-pyran-3(4H)-one were the main volatile compounds in both female and male buds. Based on the multivariate statistical analysis of orthogonal projections to latent structures discriminant analysis (OPLS-DA) and t-test, the content of seven compounds was significantly different between female and male buds. The content of three compounds in male buds was higher than that in female, i.e., (E)-4,8-dimethyl-1,3,7-nonatriene, 1,5,9,9-tetramethyl-1,4,7-cycloundecatriene, and (E)-caryophyllene. Conversely, the content of (Z)-4-hexen-1-ol, (Z)-3-hexenyl benzoate, (Z)-3-hexenyl salicylate, and 2-hexen-1-ol in female buds was higher than that in male buds. This is the first report on the difference in the volatile compounds between female and male buds of T. anguina, which enriches the basic research on the monoecious and diclinous plant and provides a reference for the study of plant sex differentiation.

Fructus Rosae Roxburghii (FRR) has been considered as edible and medicinal fruit possessing antiatherosclerotic effect [1–5], but the mechanism is still unclear. Hyperlipidemia (HLP) is the material basis for atherosclerosis (AS) formation [6,7]. In this study, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), lower high-density lipoprotein (HDL) and atherosclerotic index (ASI) in mice were analyzed under the action of FRR juice. Then differentially expressed proteins in liver were further analyzed by using TMT labeling and LC-MS/MS for better understanding the effect and molecular mechanism of FRR on diet-induced hyperlipidemic mice [8]. After the protein extraction and trypsin digestion, TMT labeling proteomic analysis were performed. The functions and KEGG signaling pathways of differentially expressed proteins were analyzed by bioinformatics methods. Hence, the potential antiatherosclerotic mechanism of FRR regulating blood lipids from protein level has great significance to explore new drug targets for AS.

Abstract Electrochemical sensors have the high sensitivity, fast response, and simple operation for applications in biological, medical, and chemical detection, but limited by the poor stability and high cost of the electrode materials. In this work, we used PtNi lagged-like nanowire for caffeic acid (CA) electrochemical detection. The removal of outer layer Ni during reaction process contributed to the rehabilitation of active Pt sites at the surface, leading to the excellent electrocatalytic behavior of CA sensing. Carbon-supported PtNi-modified glassy carbon electrode (PtNi/C electrode) showed a broad CA detecting range (from 0.75 to 591.783 μM), a low detection limit (0.5 μM), and excellent stability. The electrode preserved high electrocatalytic performance with 86.98% of the initial oxidation peak current retained after 4000 potential cycles in 0.5 mM caffeic acid solution. It also demonstrates excellent anti-interference capability and is ready for use in the real sample analysis.

To comprehensively evaluate the quality of medicinal and edible Ziziphi Spinosae Semen (ZSS, the dried ripe seeds of Ziziphus jujuba var. spinosa) before and after rancidity during storage, some indicators including traditional sensory properties, physicochemical characteristics, and volatile compounds were analyzed. As a result, compared with the normal samples, the rancid samples of ZSS produced a darker color, a bitter taste, and an irritating odor, increased moisture content, electrical conductivity, fatty oil content, and acid value, and decreased water- and alcohol-soluble extract contents and pH value. Among them, the acid value had significant difference (p < 0.01) from 3.90 of normal ZSS to 18.68 mg/g of rancid ZSS. A total of 39 volatile compounds were identified in samples, including 20 in normal ZSS and 38 compounds in rancid ZSS. Nineteen common compounds were identified in normal and rancid samples. Among them, the content of 10 compounds such as δ-limonene, (R,R)-2,3-butanediol, and (R,S)-2,3-butanediol was decreased but that of nine compounds such as acetic acid, n-octanoic acid, and n-nonanoic acid was increased in rancid ZSS. Nineteen unique compounds such as β-phellandrene, α-pinene, and 3-carene were detected and only one compound, δ-cadinene, was not detected in rancid ZSS. In addition, eight short-chain organic acids, acetic, propanoic, butanoic, pentanoic, hexanoic, heptanoic, octanoic, and nonanoic acids, were new products in rancid ZSS, and it was speculated that the production of a series of organic acids might be the material basis of irritating odor after normal ZSS became rancid. This is the first report that a series of short-chain organic acids have been found in a rancid substance. In conclusion, there was a significant difference between normal and rancid ZSS. These indicators could be used as an early warning for judging the rancidity phenomenon of medicinal and edible ZSS. In addition, this is the first comprehensive evaluation about the rancidity process of a medicinal and edible substance.

Abstract A high‐performance liquid chromatography (HPLC) fingerprint method with multivariate statistical analyses was applied to discriminate the male and female barks of Populus tomentosa for the first time. The samples of 11 male and 13 female barks of mature P. tomentosa were collected in Beijing. The chemical fingerprint of methanol extract was established by HPLC method with diode array detector (DAD). The principal component analysis (PCA), hierarchical clustering analysis (HCA), and supervised orthogonal partial least squares discriminant analysis (OPLS‐DA) were applied to discriminate male and female barks based on the area of common peaks identified in HPLC fingerprints. A clear grouping trend (R2X, 0.83; Q2, 0.595) among the male and female samples was exhibited by PCA score plot. Two groups were clearly divided into male and female samples by HCA. Both male and female samples were well discriminated with OPLS‐DA (R2X, 0.775; Q2, 0.795). Seven potential chemical markers were screened by variable importance in projection (VIP values >1.0) of OPLS‐DA model and four of them were identified as micranthoside, siebolside B, sakuranin, and isosakuranin. The HPLC fingerprint combined with multivariate statistical analyses could be used to discriminate the gender of barks of P. tomentosa and revealed the differences in chemical components, which enriched the basic studies on dioecious plant.

Ischemic cerebral infarction represents a significant cause of disability and death worldwide. Caspase-1 is activated by the NLRP3/ASC pathway and inflammasomes, thus triggering pyroptosis, a programmed cell death. In particular, this death is mediated by gasdermin D (GSDMD), which induces secretion of interleukin (IL)-1β and IL-18. Accordingly, inhibition of caspase-1 prevents the development and worsening of multiple neurodegenerative diseases. However, it is not clear whether inhibition of caspase-1 can preserve blood-brain barrier (BBB) integrity following cerebral infarction. This study therefore aimed at understanding the effect of caspase-1 on BBB dysfunction and its underlying mechanisms in permanent middle cerebral artery occlusion (MCAO). Our findings in rat models revealed that expression of caspase-1 was upregulated following MCAO-induced injury in rats. Consequently, pharmacologic inhibition of caspase-1 using vx-765 ameliorated ischemia-induced infarction, neurological deficits, and neuronal injury. Furthermore, inhibition of caspase-1 enhanced the encapsulation rate of pericytes at the ischemic edge, decreased leakage of both Evans Blue (EB) and matrix metalloproteinase (MMP) proteins, and upregulated the levels of tight junctions (TJs) and tissue inhibitors of metalloproteinases (TIMPs) in MCAO-injured rats. This in turn improved the permeability of the BBB. Meanwhile, vx-765 blocked the activation of ischemia-induced pyroptosis and reduced the expression level of inflammatory factors such as caspase-1, NLRP3, ASC, GSDMD, IL-1β, and IL-18. Similarly, vx-765 treatment significantly reduced the expression levels of inflammation-related receptor for advanced glycation end products (RAGE), high-mobility family box 1 (HMGB1), mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB). Evidently, inhibition of caspase-1 significantly improves ischemia-associated BBB permeability and integrity by suppressing pyroptosis activation and the RAGE/MAPK pathway.

A graph’s entropy is a functional one, based on both the graph itself and the distribution of probability on its vertex set. In the theory of information, graph entropy has its origins. Hex-derived networks have a variety of important applications in medication store, hardware, and system administration. In this article, we discuss hex-derived network of type 1 and 2, written as HDN 1n and HDN 2n, respectively of order n. We also compute some degree-based entropies such as Randić, ABC, and GA entropy of HDN 1n and HDN 2n.

Non-small cell lung cancer (NSCLC) is still challenging for treatment owing to immune tolerance and evasion. MicroRNA-138 (miR-138) not only acts as a tumor suppressor to inhibit tumor cell proliferation and migration but also regulates immune response. The regulatory mechanism of miR-138 in NSCLC remains not very clear. Herein, we demonstrated that miR-138-5p treatment decreased the growth of tumor cells and increased the number of tumor-infiltrated DCs. miR-138-5p not only down-regulated the expression of cyclin D3 (CCND3), CCD20, Ki67, and MCM in A549/3LL cells, but also regulated the maturation of DCs in A549-bearing nude mice and the 3LL-bearing C57BL/6 mouse model, and DCs’ capability to enhance T cells to kill tumor cells. Furthermore, miR-138-5p was found to target PD-L1 to down-regulate PD-L1 on tumor cells to reduce the expression of Ki67 and MCM in tumor cells and decrease the tolerance effect on DCs. miR-138-5p also directly down-regulates the expression of PD-L1 and PD-1 on DCs and T cells. Similar results were obtained from isolated human non-small cell lung cancer (NSCLC) cells and DCs. Thus, miR-138-5p inhibits tumor growth and activates the immune system by down-regulating PD-1/PD-L1 and it is a promising therapeutic target for NSCLC.

The heterotrophic microalgae Crypthecodinium cohnii was usually cultivated in complex medium containing glucose, yeast extract and sea salt. For the preparation of DHA with highest purity, a new defined medium without the yeast extract was developed. Different inoculated densities, C/N ratios, temperatures, culture volumes and glucose additions were investigated to optimize the algal growth rate and DHA production. The growth period in C. cohnii was shortened from 12-14 days to 7-8 days, the OD600 was enhanced from 2.0 to 3.0, the glucose consumption was accelerated and used up on day 3-4, and the DHA content in culture were increased from 10 to 45 nmoles/300 μl batch. It was found that C. cohnii had optimal growth and DHA accumulation in 25 °C, 0.2 inoculated density, 5-10 C/N ratio, 5:1 air/culture volume ratio. This is the first time DHA production using C.cohnii has been optimized in synthetic medium. This allows preparation of uniformly radiolabeled 13C- and 14C-DHA.

Herpetospermum pedunculosum (Ser.) C. B. Clarke (Family Cucurbitaceae) is a dioecious plant and has been used as a traditional Tibetan medicine for the treatment of hepatobiliary diseases. The component, content, and difference in volatile compounds in the female and male buds of H. pedunculosum were explored by using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology and multivariate statistical analysis. The results showed that isoamyl alcohol was the main compound in both female and male buds and its content in males was higher than that in females; 18 compounds were identified in female buds including 6 unique compounds such as (E)-4-hexenol and isoamyl acetate, and 32 compounds were identified in male buds, including 20 unique compounds such as (Z)-3-methylbutyraldehyde oxime and benzyl alcohol. (Z)-3-methylbutyraldehyde oxime and (E)-3-methylbutyraldehyde oxime were found in male buds, which only occurred in night-flowering plants. In total, 9 differential volatile compounds between female and male buds were screened out, including isoamyl alcohol, (Z)-3-methylbutanal oxime, and 1-nitropentane based on multivariate statistical analysis such as principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). This is the first time to report the volatile components of H. pedunculosum, which not only find characteristic difference between female and male buds, but also point out the correlation between volatile compounds, floral odor, and plant physiology. This study enriches the basic theory of dioecious plants and has guiding significance for the production and development of H. pedunculosum germplasm resources.

The differences in metabolites in male and female individuals of dioecious Morus alba L. (Moraceae) are usually ignored and lack study. In the present study, 58 leaves and 61 stem barks from male and female individuals were analyzed by untargeted metabolomics via headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) coupled with chemometrics, including principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). A total of 66 and 44 metabolites were identified from leaves and stem barks, respectively. Four and eight differential metabolites among candidate metabolites in leaves and stem barks from male and female individuals were identified. Moreover, females possessed stronger antioxidant activity than males. This is the first report where untargeted metabolomics coupled with chemometrics was used to analyze the different metabolites and to discriminate the gender of leaves and stem barks of dioecious M. alba. It provided the basis for further study of M. alba and reference value for researching dioecious plants.

1H Nuclear Magnetic Resonance (1H NMR) combined with multivariate statistics was adopted to discriminate female and male flower buds of Populus tomentosa in the study. Samples of 11 female and 16 male flower buds of P. tomentosa were collected in Beijing, China. 1H NMR spectra were acquired on a 400 MHz spectrometer. In total, 30 chemical compounds were identified with standards and literature according to chemical shifts, peak areas, and multiplicity. Principal component analysis (PCA), hierarchical clustering analysis (HCA), and supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to discriminate female and male flower buds. An apparent grouping trend (R2X, 0.809; Q2, 0.903) between female and male groups was exhibited with PCA and HCA. The two groups were also well discriminated with OPLS-DA (R2X, 0.808; R2Y, 0.976; Q2, 0.960). Combined with variable importance in projection (VIP) > 1.0 and p < 0.05 of OPLS-DA, it was found that the content of daucosterol, β-sitosterol, ursolic acid, and betulonic acid in male group was higher than that in female, which should be the key differences of chemical constituents in female and male flower buds of P. tomentosa. The study demonstrated that 1H NMR combined with multivariate statistics could be used to discriminate female and male plants and clarify differences, which provided a novel method to identify the gender of dioecious plants.

Abstract Background Serum carcinoembryonic antigen (CEA) levels are a predictor of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) efficacy and are associated with epidermal growth factor receptor (EGFR) gene mutations. However, the clinical significance of plasma CEA level changes during different cycles of target therapy is unknown for lung adenocarcinoma patients with sensitizing EGFR mutations. Methods In total, 155 patients with lung adenocarcinoma were enrolled in this retrospective study between 2011 and 2015. EGFR mutations were detected by RT-PCR (real-time quantitative PCR). Plasma CEA levels were measured prior to different EGFR-TKI treatment cycles. Computed tomography (CT) scans were conducted every 2 months to assess the therapeutic efficacy. Results Serum CEA concentrations were significantly associated with EGFR mutations (p

Background and Objectives: An accurate delineation of the primary clinical target volume (CTVp) in esophageal squamous cell carcinoma (ESCC) significantly affects the outcomes of radiotherapy. However, when basing the CTVp on the primary gross tumor volume, there are no consistent guidelines for the size of the margin. We compared preoperative 18F-fluorodeoxyglucose (FDG) PET/CT images and large slices of resected pathological ESCC specimens for evidence and prediction of subclinical lesions. We also investigated associations between the maximum standardized uptake value (SUVmax), metabolic tumor volumes (MTVs), and lesions to improve estimates of the CTVp.Methods:55 patients underwent FDG PET/CT before surgery, and the SUVmax and MTVs were determined. To ensure that the in situ distances between the primary and secondary tumors were preserved, the esophageal specimens collected during radical surgery were processed to minimize shrinkage, and subclinical lesions were characterized by pathological examination. A 2-dimensional logistic regression model was used to assess the associations between clinicopathological features and microscopic spread of the lesions.Results: Subclinical lesions in pathological specimens were characterized as direct invasion, multicentric occurrence lesions, intra-mural metastasis, vascular invasion, and perineural invasion in 56.4, 40.0, 30.9, 21.8, and 18.2% of patients, respectively. The mean distances of the subclinical lesions from the primary tumor were 0.79 ± 1.28 cm and 0.87 ± 1.00 cm in the cranial and caudal directions, respectively. Together the SUVmax and MTV values could predict the presence of subclinical lesions that were not detectable in PET/CT images.Conclusions: To cover 94.5% of ESCC subclinical lesions in the CTVp, a 3-cm margin along the cranial-caudal axis should be added to the primary gross tumor volume as defined by FDG-PET/CT, as well as a cutoff SUVmax value of 2.5. Although preoperative FDG PET/CT images may not reveal lesions directly, the SUVmax and MTV measurements together could predict their presence.

Tracheal intubation general anesthesia technique is widely used in video-assisted thoracic surgery (VATS) because it can improve the safety of VATS, but the complications of tracheal intubation can not be avoided. How to develop a "minimally invasive" surgery (including micro anesthesia) has become a hot topic in the field of minimally invasive surgery. Along with the progress of the anesthesia management technology and the risk management in the operation, the technology of non-intubated anesthesia was successfully applied to VATS, namely using local anesthesia to maintain patients intraoperative independent ventilation and intraoperative only mild sedation or fully conscious state of implementation of thoracoscope surgery, therefore is also called awake VATS. The anesthesia method not only reduces the anesthesia injury of tracheal intubation, but also conforms to the idea of rapid rehabilitation surgery. Based on non-intubated anesthesia in VATS in the brief history of development, the anesthesia selection, operation advantages and risks are reviewed in this paper.

Abstract Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson’s disease (PD), respectively, which manifested with the selective vulnerability of neuronal cells in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.

Parkinson’s disease (PD) is one of the most affected neurodegenerative diseases in the world. Deregulation of cyclin-dependent kinase 5 (Cdk5) is believed to play an important role in neurodegenerative diseases including PD. p25 is a cleavage peptide of p35, a physiologic activator of Cdk5. p25 combines to Cdk5 and leads to the hyperactivity of Cdk5, which in turn hyperphosphorylates downstream substrates and leads to neuroinflammation and apoptosis of neurons. Previously, we have demonstrated that adeno-associated virus serotype-9 (AAV9) mediated Cdk5 inhibitory peptide (CIP) inhibits the activity of Cdk5/p25 complex and alleviates pathologic and behavioral changes in Alzheimer’s disease mouse model. In this study, we evaluated whether AAV9-CIP protected dopaminergic (DA) neurons in 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine-probenecid (MPTP/p) induced PD mouse model. The data showed that administration of AAV9-CIP by intracerebroventricular injection 1 week before MPTP/p exposure protected loss of DA neurons in substantia nigra compact of the model mice. Importantly, AAV9-CIP also alleviated the motor and anxiety-like symptoms of the disease animals. In summary, AAV9 mediated CIP might be a potential intervention for PD.

Kai-Xin-San (KXS), a Chinese herbal decoction, has been applied to medical care of depression for thousands of years. It is composed of two functional paired-herbs: Ginseng Radix et Rhizoma (GR)-Polygalae Radix (PR) and Acori Tatarinowii Rhizoma (ATR)-Poria (PO). The compatibility of the paired-herbs has been frequently changed to meet the criteria of syndrome differentiation and treatment variation. Currently, a modified KXS (namely KXS2012) was prepared by optimizing the combinations of GR-PR and ATR-PO: the new herbal formula was shown to be very effective in animal studies. However, the cellular mechanism of KXS2012 against depression has not been fully investigated. Here, the study on KXS2012-induced neuronal differentiation in cultured PC12 cells was analyzed. In PC12 cultures, single application of KXS2012 showed no effect on the neuronal differentiation, but which showed robust effects in potentiating nerve growth factor (NGF)-induced neurite outgrowth and neurofilament expression. The potentiating effect of KXS2012 was mediated through NGF receptor, tropomyosin receptor kinase (Trk) A: because the receptor expression and activity was markedly up-regulated in the presence of KXS2012, and the potentiating effect was blocked by k252a, an inhibitor of Trk A. Our current results in cell cultures fully support the therapeutic efficacy of KXS2012 against depression.

Uridine diphosphate glycosyltransferases (UGTs) are multifunctional detoxification enzymes, which are involved in metabolizing various chemicals and contribute to the development of insecticide resistance. However, the possible roles of UGTs in chlorantraniliprole resistance in Chilo suppressalis have rarely been studied in detail. Based on genome data, 24 UGT genes in C. suppressalis belonging to 11 families were identified, which were designated by the UGT nomenclature committee. Synergism assay data suggested that UGTs are potentially involved in chlorantraniliprole resistance in C. suppressalis. CsUGT40AL1 and CsUGT33AG3 were significantly overexpressed in the chlorantraniliprole resistant strain (12.36- and 5.34-fold, respectively). The two UGTs were highly expressed in the larval Malpighian tubules, fat body, and midgut; however, expression was lowest in the head. Injection of individual dsRNAs reduced the expression of the two target genes (by 69.34% and 48.74%, respectively) and caused significant higher larval mortality (81.33% and 54.67%, respectively). Overexpression of CsUGT40AL1 and CsUGT33AG3 was potentially involved in chlorantraniliprole resistance in C. suppressalis, as confirmed by the RNAi assay. Our findings suggest that overexpression of UGTs may contribute to chlorantraniliprole resistance in C. suppressalis.

Lung cancer is one of the common malignancies with an extremely poor prognosis, because of the current diagnostic techniques are not easy to find micrometastases. Melanoma associated antigens genes (MAGE) are tumor specific antigen genes, closely related to the occurrence, development and prognosis of lung cancer. The research of MAGE genes provide a new direction for the diagnosis and treatment of lung cancer.

Carbon quantum dots (CQDs) as a rising star of carbon nanomaterials have extensive applications due to their excellent characteristics. In this work, we introduce a simple and green method to prepare nitrogen-doped lignin carbon quantum dots (N-L-CQDs) by using alkali lignin carbon sources and deep eutectic solvent (DES) as solution and nitrogen source. The physiochemical characterization results suggested that N-L-CQDs with diameters ranging from 4 to 12 nm were successfully synthesized. The optical properties data indicated that the as-prepared N-L-CQDs with a quantum yield of 7.95% exhibited excellent optoelectronic properties, excitation-dependent and pH stability. After that, we have investigated the N-L-CQDs used as fluorescent probes to detect iron ions, which suggested that the as-prepared N-L-CQDs exhibited excellent sensitivity and selectivity for Fe3+ with a detection limit of 0.44 μM. Besides, cytotoxicity of N-L-CQDs was also evaluated by MTT assay. These results demonstrated that the as-prepared N-L-CQDs with excellent properties have potential applications in environment and biomedicine.

The differentially co-expressed proteins in N-deprived and N-enriched I. galbana were comparatively analyzed by using two dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight-mass spectrometry (MALDI-TOF/TOF-MS) with the aim of better understanding lipid metabolism in this oleaginous microalga. Forty-five of the 900 protein spots showed dramatic changes in N-deprived I. galbana compared with the N-enriched cells. Of these, 36 protein spots were analyzed and 27 proteins were successfully identified. The identified proteins were classified into seven groups by their molecular functions, including the proteins related to energy production and transformation, substance metabolism, signal transduction, molecular chaperone, transcription and translation, immune defense and cytoskeleton. These altered proteins slowed cell growth and photosynthesis of I. galbana directly or indirectly, but at the same time increased lipid accumulation. Eight key enzymes involved in lipid metabolism via different pathways were identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), enolase, aspartate aminotransferase (AST), fumarate hydratase (FH), citrate synthase (CS), O-acetyl-serine lyase (OAS-L) and ATP sulfurylase (ATPS). The results suggested that the glycolytic pathway and citrate transport system might be the main routes for lipid anabolism in N-deprived I. galbana, and that the tricarboxylic acid (TCA) cycle, glyoxylate cycle and sulfur assimilation system might be the major pathways involved in lipid catabolism.