A fluorescent probe based on cyclochalcone for detecting peroxynitrite.

A novel cyclic chalcone fluorescent probe C-PN was synthesized to detect ONOO-. After reaction with peroxynitrite, the double bond of C-PN in the cyclic chalcone structure was disconnected, which caused the change of intramolecular charge transfer (ICT) effect, emitting blue fluorescence and quenching orange red fluorescence. Visible to the naked eye, the color of the probe solution changed. The probe showed low sensitivity (detection limit = 20.2 nm), short response time (less than 60 s) at low concentration of ONOO-, good visibility, and good selectivity and stability for ONOO-.

An experimental study of a novel external fixator based on universal joints for the rapid initial stabilization of mandibular comminuted fractures.

PURPOSE: Shaping and assembling contemporary external fixators rapidly for the severe mandibular fractures remains a challenge, especially in emergency circumstance. We designed a novel external fixator that incorporates universal joints to provide the stabilization for mandibular comminuted fractures. This study aims to confirm the efficacy of this novel external fixator through biomechanical tests in vitro and animal experiments. METHODS: In vitro biomechanical tests were conducted using 6 fresh canine with mandibular defect to simulate critical comminuted fractures. Three mandibles were stabilized by the novel external fixator and other mandibles were fixed by 2.5 mm reconstruction plates. All fixed mandibles were subjected to loads of 350 N on the anterior regions of teeth and 550 N on the first molar of the unaffected side. The stability was evaluated based on the maximum displacement and the slope of the load-displacement curve. In animal experiments, 9 beagles with comminuted mandibular fractures were divided into 3 groups, which were treated with the novel external fixation, reconstruction plate, and dental arch bar, respectively. The general observation, the changes in animals' weight, and the surgical duration were recorded and compared among 3 groups. The CT scans were performed at various intervals of 0 day (immediately after the surgery), 3 days, 7 days, 14 days, 21 days, and 28 days to analyze the displacement of feature points on the canine mandible and situation of fracture healing at 28 days. The statistical significance was assessed by the two-way analysis of variance test followed by the Bonferroni test, enabling multiple comparisons for all tests using GraphPad Prism10.1.0 (GraphPad Inc, USA). RESULTS: The outcomes of the biomechanical tests indicated that no statistically significant differences were found in terms of the maximum displacement (p = 0.496, 0.079) and the slope of load displacement curves (p = 0.374, 0.349) under 2 load modes between the external and internal fixation groups. The animal experiment data showed that there were minor displacements of feature points between the external and internal fixation groups without statistic difference, while the arch bar group demonstrated inferior stability. The CT analysis revealed that the best fracture healing happened in the internal fixation group, followed by the external fixation and arch baring at 28 days after fixation. The external fixation group had the shortest fixation duration (25.67 ± 3.79) min compared to internal fixation ((70.67 ± 4.51) min, p < 0.001) and arch baring ((42.00 ± 3.00) min, p = 0.046). CONCLUSION: The conclusion of this study highlighted the efficacy and reliability of this novel external fixator in managing mandibular fractures rapidly, offering a viable option for the initial stabilization of comminuted mandibular fractures in the setting of emergency rescue.

[Intelligent material classification of traditional Chinese medicine based on semantic analysis].

A method for material classification of traditional Chinese medicines based on the physical properties of powder has been established by our research group. This method involves pre-treatment of traditional Chinese medicine decoction pieces, powder preparation, and determination of physical properties, being cumbersome. In this study, the word segmentation logic of semantic analysis was adopted to establish the thesaurus and local standardized semantic word segmentation database with the macroscopic and microscopic characteristics of 36 model traditional Chinese medicines as the basic data. The physical properties of these medicines have been determined and the classification of these medicines is clear in the cluster analysis. A total of 55 keywords for powdery, fibrous, sugary, oily, and brittle materials were screened by association rules and the set inclusion and exclusion criteria, and the weights of the keywords were calculated. Furthermore, the algorithms of the keyword matching scores and the computation rules of the single or multiple material classification were established for building the intelligent model of semantic analysis for the material classification. The semantic classification results of the other 35 TCMs except Pseudostellariae Radix(multi-material medicine) agreed with the clustering results based on the physical properties of the powder, with an agreement rate of 97.22%. In model validation, the prediction results of semantic classification of traditional Chinese medicines were consistent with the clustering results based on the physical properties of powder, with an agreement rate of 83.33%. The results showed that the method of material classification based on semantic analysis was feasible, which laid a foundation for the development of intelligent decision-making technology for personalized traditional Chinese medicine preparations.

Genomic evolution and the impact of SLIT2 mutation in relapsed intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is aggressive and has high rates of relapse, conferring poor long-term survival after curative resection. Little is known about the genomic evolution that occurs during ICC relapse. APPROACH AND RESULTS: We conducted whole-exome sequencing of 30 paired primary and relapsed tumors from 10 patients with ICC who received curative resection. We sought to identify frequently altered genes, infer tumor subclonal architectures, and track genomic evolution from primary to relapsed tumors. We examined functional effects and the mechanism of action of SLIT2, a gene specifically mutated in relapsed tumors, on tumor growth and metastasis and the tumor microenvironment. Our results indicated that relapsed ICCs were genetically derived from intrahepatic dissemination of primary tumors. However, they acquired additional mutations while maintaining most drivers, such as TP53 and IDH1. Multiregion sequencing suggested polyclonal seeding of ICC dissemination. Four of 10 relapsed ICCs acquired SLIT2 mutations that were not present in the corresponding primary tumors. Validation in an expanded sample revealed SLIT2 mutations in 2.3% (1/44) of primary ICCs and 29.5% (13/44) of relapsed ICCs. Biofunctional investigations revealed that inactivating mutation of SLIT2 resulted in activation of PI3K-Akt signaling in ICC cells, directly enhanced neutrophil chemotaxis, mediated tumor-associated neutrophil infiltration, and contributed to ICC growth and metastasis. CONCLUSIONS: We characterized genomic evolution during ICC relapse and identified SLIT2 as a driver of tumor dissemination and tumor-associated neutrophil infiltration.

Research Progress on the Structural Modification of Magnolol and Honokiol and the Biological Activities of Their Derivatives.

Magnolol and Honokiol are the primary active components that have been identified and extracted from Magnolia officinalis, and several investigations have demonstrated that they have significant pharmacological effects. Despite their therapeutic benefits for a wide range of illnesses, research on and the implementation of these compounds have been hindered by their poor water solubility and low bioavailability. Researchers are continually using chemical methods to alter their structures to make them more effective in treating and preventing diseases. Researchers are also continuously developing derivative drugs with high efficacy and few adverse effects. This article summarizes and analyzes derivatives with significant biological activities reported in recent research obtained by structural modification. The modification sites have mainly focused on the phenolic hydroxy groups, benzene rings, and diene bonds. Changes to the allyl bisphenol structure will result in unexpected benefits, including high activity, low toxicity, and good bioavailability. Furthermore, alongside earlier experimental research in our laboratory, the structure-activity relationships of magnolol and honokiol were preliminarily summarized, providing experimental evidence for improving their development and utilization.

The spatial distribution of immune cell subpopulations in hepatocellular carcinoma.

Infiltrating immune cells in the tumor microenvironment (TME) influence tumor progression and patient prognosis, making them attractive therapeutic targets for immunotherapy research. A deeper understanding of immune cell distributions in the TME in hepatocellular carcinoma (HCC) is needed to identify interactions among different immune cell types that might impact the effectiveness of potential immunotherapies. We performed multiplex immunohistochemistry using a tissue microarray of samples from 302 patients with HCC to elucidate the spatial distributions of immune cell subpopulations (CD3+ , CD4+ , CD8+ , CD66b+ , and CD68+ ) in HCC and normal liver tissues. We analyzed the associations between different immune subpopulations using Pearson's correlation. G(r) functions, K(r) functions and Euclidean distance were applied to characterize the bivariate distribution patterns among the immune cell types. Cox regression and Kaplan-Meier analysis were used to evaluate the associations between tumor infiltration by different immune cells and patient outcomes after curative surgery. We also analyzed the relationship between the spatial distribution of different immune cell subpopulations with HCC patient prognosis. We found that the immune cell spatial distribution in the HCC TME is heterogeneous. Our study provides a theoretical basis for HCC immunotherapy.

Enhancing probe's sensitivity for peroxynitrite through alkoxy modification of dicyanovinylchromene.

An intramolecular charge transfer (ICT)-based fluorescent probe P-ONOO- was synthesized to detect ONOO-. After responding to peroxynitrite, the dicyano-vinyl group of P-ONOO- generates the aldehyde group, emitting strong green fluorescence accompanied by quenching of the yellow fluorescence. According to the calculated Fukui function, the modification of the alkoxy group can enhance the f+ of P-ONOO-, which can enhance the probe's nucleophilic addition reactivity with ONOO-. It has been experimentally verified that P-ONOO- shows fast response (within 30 s), excellent sensitivity (the detection limit = 10.4 nM), and good selectivity towards ONOO-. Additionally, the probe P-ONOO- has high membrane permeability and good biocompatibility, which can image endogenous ONOO- and exogenous ONOO- in HeLa cells.

Associations among the mutational landscape, immune microenvironment, and prognosis in Chinese patients with hepatocellular carcinoma.

Recent studies suggested that the immune microenvironment and mutational landscape are associated with the response to immune-based therapy in several types of cancer. The roles of those factors in Chinese HCC remain largely unknown. In this study, we obtained 182 FFPE samples of HCC cohort that were previously subjected to NGS (49 WGS, 18 WES, and 115 targeted sequencing). We performed immunohistochemistry to detect CD3, CD4, CD8, CD57, Foxp3, CD68, CD66b, and PD-L1 expression in the samples. We identified diverse associations between the mutational landscape and the immune microenvironment in the HCC samples. High mutational burden and an aristolochic acid-dominated mutational signature were both correlated with elevated tumoral PD-L1 expression and CD3+ T-cell infiltration and high numbers of CD68+ TAMs and CD66b+ TANs. CD4+ and CD8+ T cells exhibited lower infiltration levels in tumors with mutations in AXIN1/CTNNB1 and in tumors with aflatoxin-dominant mutational signatures. Moreover, tumors with TP53 mutations had less CD8+ T-cell infiltration and more Foxp3+ Treg-cell infiltration than those without TP53 mutations. Kaplan-Meier survival analysis revealed that the presence of CD8+, Foxp3+, CD66b+, or CD68+ immune cells; tumoral PD-L1 expression alone; or the presence of CD8+ or Foxp3+ cells combined with TP53 mutation were predictive of recurrence and poor overall survival after curative resection. In conclusion, the association between the mutational landscape and the immune microenvironment warrants further analysis to determine its impact on patient outcomes to guide personalized immune-based therapy for Chinese patients with HCC.

Rab32 GTPase, as a direct target of miR-30b/c, controls the intracellular survival of Burkholderia pseudomallei by regulating phagosome maturation.

Burkholderia pseudomallei is a gram-negative, facultative intracellular bacterium, which causes a disease known as melioidosis. Professional phagocytes represent a crucial first line of innate defense against invading pathogens. Uptake of pathogens by these cells involves the formation of a phagosome that matures by fusing with early and late endocytic vesicles, resulting in killing of ingested microbes. Host Rab GTPases are central regulators of vesicular trafficking following pathogen phagocytosis. However, it is unclear how Rab GTPases interact with B. pseudomallei to regulate the transport and maturation of bacterial-containing phagosomes. Here, we showed that the host Rab32 plays an important role in mediating antimicrobial activity by promoting phagosome maturation at an early phase of infection with B. pseudomallei. And we demonstrated that the expression level of Rab32 is increased through the downregulation of the synthesis of miR-30b/30c in B. pseudomallei infected macrophages. Subsequently, we showed that B. pseudomallei resides temporarily in Rab32-positive compartments with late endocytic features. And Rab32 enhances phagosome acidification and promotes the fusion of B. pseudomallei-containing phagosomes with lysosomes to activate cathepsin D, resulting in restricted intracellular growth of B. pseudomallei. Additionally, Rab32 mediates phagosome maturation depending on its guanosine triphosphate/guanosine diphosphate (GTP/GDP) binding state. Finally, we report the previously unrecognized role of miR-30b/30c in regulating B. pseudomallei-containing phagosome maturation by targeting Rab32 in macrophages. Altogether, we provide a novel insight into the host immune-regulated cellular pathway against B. pseudomallei infection is partially dependent on Rab32 trafficking pathway, which regulates phagosome maturation and enhances the killing of this bacterium in macrophages.

Circular RNA Sequencing Identifies CircASAP1 as a Key Regulator in Hepatocellular Carcinoma Metastasis.

BACKGROUND AND AIMS: There is growing evidence that single-stranded, circular RNA (circRNA) plays a key role in the development of certain cancers, including hepatocellular carcinoma (HCC). It is less clear, however, what role circRNA plays in HCC metastasis. APPROACH AND RESULTS: In this study, through circRNA sequencing, we identified a circRNA: circASAP1 (a circRNA derived from exons 2 and 3 of the ASAP1 gene, hsa_circ_0085616), which is associated with pulmonary metastasis after curative resection in patients with HCC. CircASAP1 was overexpressed in HCC cell lines with high metastatic potential and in metastatic HCCs. In vitro, circASAP1 promoted cell proliferation, colony formation, migration, and invasion, and in vivo, it enhanced tumor growth and pulmonary metastasis. Mechanism studies showed that circASAP1 acts as a competing endogenous RNA for microRNA 326 (miR-326) and microRNA 532-5p (miR-532-5p), both of which are tumor suppressors in HCC. We found that mitogen-activated protein kinase (MAPK) 1 and colony stimulating factor (CSF)-1 were direct common targets for microRNA 326 (miR-326) and microRNA 532-5p (miR-532-5p), which were regulated by circASAP1. CircASAP1 promotes HCC cell proliferation and invasion by regulating miR-326/miR-532-5p-MAPK1 signaling and, furthermore, mediates tumor-associated macrophage infiltration by regulating the miR-326/miR-532-5p-CSF-1 pathway. Clinical HCC samples exhibited a positive correlation between circASAP1 expression and levels of CSF-1, MAPK1, and CD68+ tumor-associated macrophages, all of which were predictive of patient outcomes. CONCLUSION: We identified circASAP1 as a key regulator of HCC metastasis that acts on miR-326/miR-532-5p-MAPK1/CSF-1 signaling and serves as a prognostic predictor in patients with HCC.

MicroRNA-146a inhibits autophagy to maintain the intracellular survival of Burkholderia pseudomallei by targeting LIPA.

Burkholderia pseudomallei is the etiological agent of melioidosis, which is an emerging infectious disease endemic to many tropical regions. Autophagy is an intrinsic cellular process that degrades cytoplasmic components and plays an important role in protecting the host against pathogens. Like many intracellular pathogens, B. pseudomallei can evade the autophagy-dependent cellular clearance. However, the underlying mechanism remains unclear. In this study, we applied a combination of multiple assays to monitor autophagy processes and found that B. pseudomallei induced an incomplete autophagic flux and eliminate autophagy clearance in macrophages by blocking autophagosome-lysosome fusion. Based on a high-throughput microarray screening, we found that LIPA (lysosomal acid LIPAse A) was downregulated during B. pseudomallei infection. MiR-146a was then identified to be specifically upregulated upon infection with B. pseudomallei and further regulated LIPA expression by interacting with 3'UTR of LIPA. Furthermore, overexpression of miR-146a contributed to the defect of autophagic flux caused by B. pseudomallei and was beneficial for the survival of B. pseudomallei in macrophages. Therefore, our findings suggest that miR-146a inhibits autophagy via posttranscriptional suppression of LIPA expression to maintain B. pseudomallei survival in macrophages.

[Preparation of personalized traditional Chinese medicine condensed water pill without excipients based on correlation between concentrate viscosity and molding quality].

To explore the correlation between concentrate viscosity and molding quality of personalized traditional Chinese medicine(TCM) condensed water pill, this study established a concentrate viscosity characterization method with rotational rheometry. Seven model prescriptions were respectively concentrated to different degrees and the viscosity of each concentrate was determined. The pre-sence of 'viscosity jump' in the middle stage of 'flag hanging' of all the model prescriptions implied that there might be an ideal viscosity range in the preparation of condensed water pill. The further study of 22 model prescriptions demonstrated that the optimum viscosity range of concentrate was 5-15 Pa·s(25 ℃) for approximately 82% of the prescriptions. About 18% of the prescriptions had a wide range, which might be caused by the high proportions of mineral and crustacean drugs in the crushing part and sugar and fibrous drugs in the decocting part. This study clarified the optimum viscosity range for concentrates of personalized TCM condensed water pills and achieved a preparation technology without any excipient, laying a foundation for the on-line control of the preparation.

A Positive Feedback Loop Between Cancer Stem-Like Cells and Tumor-Associated Neutrophils Controls Hepatocellular Carcinoma Progression.

Tumor-associated neutrophils (TANs) play a crucial role in tumor development and progression in the cancer microenvironment. Despite increased understanding of TAN contributions to hepatocellular carcinoma (HCC) progression and prognosis, the direct interaction between TANs and HCC cells is not fully understood. In this study, we tested the effect of TANs on HCC cells in vitro and in vivo and investigated the mechanism of interaction between them. Our results showed that TANs secreted bone morphogenetic protein 2 and transforming growth factor beta 2 and triggered microRNA 301b-3p (miR-301-3p) expression in HCC cells, subsequently suppressed gene expression of limbic system-associated membrane protein (LSAMP) and CYLD lysine 63 deubiquitinase (CYLD), and increased stem cell characteristics in HCC cells. These TAN-induced HCC stem-like cells were hyperactive in nuclear factor kappa B signaling, secreted higher levels of chemokine (C-X-C motif) ligand 5 (CXCL5), and recruited more TAN infiltration, suggesting a positive feedback loop. In clinical HCC samples, increased TANs correlated with elevated miR-301b-3p, decreased LSAMP and CYLD expression, and increased nuclear p65 accumulation and CXCL5 expression, all of which predicted patient outcome. Conclusion: Our work identified a positive feedback loop governing cancer stem-like cells and TANs in HCC that controls tumor progression and patient outcome.

Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. METHODS: To evaluate pDCs' distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. RESULTS: Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. CONCLUSIONS: Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

A diazabenzoperylene derivative as ratiometric fluorescent probe for cysteine with super large Stokes shift.

Biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play key roles in biological processes, and detecting such thiols selectively is critical for understanding functions of biothiols. In this work, a pyridazine annelated perylene-based fluorescent probe PAPC is synthesized for highly selective detection of Cys. PAPC exhibits strong blue emission in PBS, while the red emission at 605 nm can be observed in the presence of Cys. The probe PAPC shows ratiometric fluorescence (I605/I460) detection of Cys with wide linear range of 1-120 µM and low detection limit of 0.19 µM. Super large Stokes shift (170 nm) and ratiometric fluorescence endow the probe low background signal. The discrimination of Cys over Hcy and GSH can be achieved through the difference of the ratiometric fluorescence. In addition, the probe has been proven to track Cys in real samples such as urine and HeLa cells. Therefore, PAPC probe is a promising candidate for detecting Cys in practical application. Graphical abstract.

New insight into BIRC3: A novel prognostic indicator and a potential therapeutic target for liver cancer.

BACKGROUND: Prognosis of hepatocellular carcinoma (HCC) remains poor due to high recurrence rate and ineffective treatment options, highlighting the need to better understand the mechanism of recurrence and metastasis in HCC. METHODS: We first collected messenger RNA (mRNA) expression data from 442 cases of HCC patients from The Cancer Genome Atlas (TCGA) database as well as 251 HCC patients from Zhongshan Hospital during 2009 and 2010 to analyze the expression pattern from tissue microarray (TMA) of baculoviral IAP repeat containing 3 (BIRC3). Then, we used BIRC3 gain-of-function (overexpression) and loss-of-function (knockdown) studies to examine the effect of BIRC3 on HCC cell proliferation and invasion. In addition, we also investigated the undying mechanism by which BIRC3 contributes to HCC tumor progression. Functionally, we also used a BIRC3-specific inhibitor AT-406 in HCC xenograft model to explore the potential therapeutic benefit of targeting BIRC3 in liver cancer. RESULTS: BIRC3 serves as a novel prognostic indicator for HCC patients undergoing curative resection. BIRC3 promotes HCC epithelial-mesenchymal transition (EMT), cell migration, and metastasis via upregulating MAP3K7, therefore, inducing ERK1/2 phosphorylation. The specific BIRC3 inhibitor AT-406 can inhibit HCC cell proliferation and reduce pulmonary metastases. CONCLUSION: BIRC3 induces tumor proliferation and metastasis in vitro and in vivo. BIRC3 may serve as a novel therapeutic target for liver cancer.

Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence.

BACKGROUND & AIMS: Early recurrence of hepatocellular carcinoma (HCC) after curative resection is common. However, the association between genetic mechanisms and early HCC recurrence, especially in Chinese patients, remains largely unknown. METHODS: We performed whole-genome sequencing (49 cases), whole-exome sequencing (18 cases), and deep targeted sequencing (115 cases) on 182 primary HCC samples. Focusing on WNK2, we used Sanger sequencing and qPCR to evaluate all the coding exons and copy numbers of that gene in an additional 554 HCC samples. We also explored the functional effect and mechanism of WNK2 on tumor growth and metastasis. RESULTS: We identified 5 genes (WNK2, RUNX1T1, CTNNB1, TSC1, and TP53) harboring somatic mutations that correlated with early tumor recurrence after curative resection in 182 primary HCC samples. Focusing on WNK2, the overall somatic mutation and copy number loss occurred in 5.3% (39/736) and 27.2% (200/736), respectively, of the total 736 HCC samples. Both types of variation were associated with lower WNK2 protein levels, higher rates of early tumor recurrence, and shorter overall survival. Biofunctional investigations revealed a tumor-suppressor role of WNK2: its inactivation led to ERK1/2 signaling activation in HCC cells, tumor-associated macrophage infiltration, and tumor growth and metastasis. CONCLUSIONS: Our results delineate genomic events that characterize Chinese HCCs and identify WNK2 as a driver of early HCC recurrence after curative resection. LAY SUMMARY: We applied next-generation sequencing and conducted an in-depth genomic analysis of hepatocellular carcinomas from a Chinese patient cohort. The results delineate the genomic events that characterize hepatocellular carcinomas in Chinese patients and identify WNK2 as a driver associated with early tumor recurrence after curative resection.

KLF7 promotes polyamine biosynthesis and glioma development through transcriptionally activating ASL.

Krüppel-like factors (KLFs) are zinc-finger transcriptional factors that regulate target gene expression. Recent studies have shown that KLFs play essential roles in cancer development, whereas the function of KLF7 in glioma remains unclear. In this study, we showed that KLF7 was up-regulated in glioma tissues and its expression was inversely correlated with the patients' survival. Functional experiments demonstrated that KLF7 promoted the proliferation, migration and tumorigenesis of glioma cells. Mechanistically, KLF7 transcriptionally activated argininosuccinate lyase (ASL), which was observed highly expressed in glioma tissues. The biosynthesis of polyamine, a urea cycle metabolite, was enhanced by KLF7 in glioma cells. In addition, ASL contributed to the growth of glioma cells triggered by KLF7. Our findings demonstrate KLF7 as an oncogene and link KLF7 to ASL-mediated polyamine metabolism in glioma.

Intratumoral plasmacytoid dendritic cells as a poor prognostic factor for hepatocellular carcinoma following curative resection.

Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated the distribution, prognostic value, and potential function of pDCs in HCC patients undergoing curative resection. We performed immunohistochemical analyses of whole tumor sections from 224 patients to assess the expression of BDCA2, CD3, CD4, CD8, Foxp3, granzyme B, IL-17, and CD34. The findings were validated using tissue microarrays from another two independent cohorts totaling 841 HCC patients undergoing curative resection. Our results demonstrated that high numbers of BDCA2+ pDCs within tumors correlated with high alpha-fetoprotein levels, greater vascular invasion, advanced tumor-node-metastasis stage, shorter overall survival, and a higher recurrence rate. However, patient outcomes were not associated with pDCs in peritumoral stromal or nontumor tissues. Furthermore, an increase in intratumoral pDCs was associated with increased intratumoral infiltration of Foxp3+ regulatory T cells and IL-17-producing cells and correlated with tumor vascular density. Univariate and multivariate analyses revealed that the presence of intratumoral pDCs alone or in combination with regulatory T and/or IL-17-producing cells was an independent predictor of time to recurrence and overall survival. In conclusion, our study demonstrated that intratumoral infiltration by pDCs is a novel indicator for poor prognosis in patients with HCC, possibly through the induction of an immune tolerogenic and inflammatory tumor microenvironment comprising regulatory T and IL-17-producing cells. An assessment of the combination of these cells represents a superior predictor of patient outcome.

[Development status and research strategy of traditional Chinese medicine temporary prescription preparation technology].

Temporary prescription preparation is the preparation processed into different dosage forms by relevant pharmacist according to the temporary preparation requirement and the personalized prescription made by the doctor in accordance with the syndrome differentiation and drug performance.It is an important part in personalized pharmaceutical services.Rational design of process route,production equipment and quality control method for the temporary prescription preparation,and establishment of technology research strategy and mode in accordance with the characteristics of traditional Chinese medicine temporary prescription preparations play an important role in promoting the development of the temporary prescription preparations.To promote the normalization,standardization and intelligent development of temporary prescription preparations,we would comprehensively summarize the significance,policy,technology characteristics,technology research status quo and existing problems in this paper,and put forward the research direction of temporary prescription preparation technology based on the physical properties of raw materials,equipment research strategy,and intelligent manufacturing technology.Thus it will push the inheritance and innovation of temporary prescription preparation.