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Background: Novel therapeutic targets in epithelioid glioblastoma (E-GBM) patients are urgently needed. About half of these tumors show the point mutations of the B-Raf proto-oncogene (BRAF). Therefore, this is a target of special interest for this group of patients. Meanwhile, unlike conventional glioblastoma, E-GBM lacks specific prognostic markers.Case presentation: We present a case report of a long-term surviving 37-years-old male patient diagnosed with a BRAF V600E-mutated E–GBM with IDH wild-type. The tumor displayed atypical exophytic growth and an obvious proliferation of vascular endothelial cells. Notably, tumor tissue was found under subarachnoid space. After conventional postoperative treatment options (including radiotherapy and temozolomide chemotherapy) were exhausted, vemurafenib treatment was initiated. The patient maintained clinically stable, and follow-up MRI was consistent with stable disease for the following fifteen months up to now. To identify potential therapeutic targets of E-GBM, we carried out whole exome sequencing analysis and RNA-sequence to study the molecular characteristics of this E-GBM sample. The mutant genes were profiled using glioma RNA-sequencing data from Chinese Glioma Genome Atlas (CGGA) database. We found that CNTNAP3, mTOR, NFATC3, and NOM1 shared by DNA-sequence data and RNA-sequence data were independent prognostic factors. Biological function was associated with phenotypes of focal adhesion and cell cycle. A prognostic risk model was constructed based on the mutant genes for predicting the survival of glioma patients. Survival plot and a nomogram was used to verify that our prognostic risk model is reliable and accurate.Conclusions: Our findings provided a new sight on the BRAF inhibitor, in combination with which CNTNAP3, mTOR, NFATC3, and NOM1 inhibitors seem to be a valuable salvage treatment option for E-GBM.

Data on the occurrences of legacy and alternative per- and polyfluoroalkyl substances (PFASs) in glioma are scarce. It remains unclear if PFASs exposure is related to the prevalence of glioma. A total of 137 glioma and 40 non-glioma brain tissue samples from patients recruited from the Nanfang Hospital, South China were analyzed for 17 PFAS compounds. Perfluorohexanoic acid, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (FOSA), and 6:2 chlorinated polyfluorinated ether sulfonate were frequently detected (60 %) in glioma. The total concentrations (range; median) of 17 PFASs in glioma (0.20-140; 3.1 ng g

Human brain has a complex structure and is able to perform powerful functions. Blood-brain barrier blocks the entry of foreign substances and maintains the homeostasis of the brain. However, some exogenous substances are still able to pass through the blood-brain barrier, with distribution patterns yet to be clarified. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs), a precursor (perfluorooctane sulfonamide that can be degraded to other substances), and emerging PFASs, were analyzed for the first time in living human brain glioma. The target compounds were detected and quantified in 25 out of 26 glioma samples. The concentration range of ∑PFAS was 0.05) in the concentrations of PFASs in the glioma samples. Concentrations of PFASs increased with increasing age, from 0.61 ng g−1 (0–14 years old) to 1.6 ng g−1 (>48 years old), with no significant linear correlation with age. The present study suggested that glioma is an effective indicator for monitoring exogenous contaminants in brain tissues.

A novel procedure to unfold the heavily overlapped valence-shell excitation spectrum of a diatomic molecule has been established. Compared with the traditional least-squares fitting method, the present program repeatedly changes the fitting parameter values by Monte Carlo random walk, which can greatly increase the probability of hunting the global minimum variance. Especially, the modification to the Franck-Condon factors for the vibronic states of an individual electronic state has been introduced, which can surmount the problems caused by the invalidity of Franck-Condon approximation, and improve the reliability of the fitted results. This program is used to determine the optical oscillator strengths of the vibronic states of the electronic states B Σ u + 1 and C Π u 1 of molecular deuterium by the dipole (γ, γ) method. The good agreement of the fitted results with the previous experimental and theoretical ones indicates the validity of this unfolding program.

The oscillator strengths and integral cross sections of the valence-shell excitations of HCl have significant applications in the studies of planetary atmospheres and interstellar gases. In the present work, the generalized oscillator strengths of the valence-shell excitations of HCl have been measured at an incident electron energy of 1500 eV and an energy resolution of 70 meV, and their momentum transfer dependence behaviors have been elucidated. It is observed that the generalized oscillator strength ratios of the b3Π1(ν' = 0) state to the C1Π(ν' = 0) state are a constant and independent of the squared momentum transfer, and this typical behavior in the momentum space is explained by the intraconfiguration mixing of the b3Π1 and C1Π states due to the spin-orbital interaction. The optical oscillator strengths of the valence-shell excitations have been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The present optical oscillator strengths give an independent cross-check to the previous experimental and theoretical results, and it is found that most of the photoabsorption measurements are limited by the line saturation effect. The integral cross sections of the valence-shell excitations of HCl have been obtained systematically from the threshold to 5000 eV with the aid of the BE-scaling method.

The oscillator strengths of the valence–shell excitations of C2H2 are extremely important for testing theoretical models and studying interstellar gases. In this study, the high-resolution inelastic x-ray scattering (IXS) method is adopted to determine the generalized oscillator strengths (GOSs) of the valence–shell excitations of C2H2 at a photon energy of 10 keV. The GOSs are extrapolated to their zero limit to obtain the corresponding optical oscillator strengths (OOSs). Through taking a completely different experimental method of the IXS, the present results offer the high energy limit for electron collision to satisfy the first Born approximation (FBA) and cross-check the previous experimental and theoretical results independently. The comparisons indicate that an electron collision energy of 1500 eV is not enough for C2H2 to satisfy the FBA for the large squared momentum transfer, and the line saturation effect limits the accuracy of the OOSs measured by the photoabsorption method.

The generalized oscillator strengths of the valence-shell excitations from the ground state to the 2 p 5 ( 3 s , 3 s ′ , 3 p , 3 p ′ , 4 s , 4 s ′ ) states of atomic neon have been determined by means of fast electron scattering, with an incident electron energy of 1500 eV and an energy resolution of about 80 meV. The adopted relative flow technique improved accuracy of the experimental measurements prominently. The validity condition of the first Born approximation is clarified by comparing the present measured data with previous experimental and theoretical results. We found that the first Born approximation is not applicable for the monopolar transition in the whole momentum transfer region even at the incident electron energy of 1500 eV. However, the high-order Born terms are found dominating only at the minimum for the dipolar transitions. The good agreement of the present extrapolated optical oscillator strengths with previous available data confirms the reliability of the measurement. With the cross-checked generalized oscillator strengths, the state-resolved integral cross sections in a wide collision energy range have been obtained by adopting the BE-scaling method. The analysis of the feasibility of the BE-scaling method demonstrates that the scaling law applies for the typical dipole-allowed transitions while it would overestimate the cross sections for the dipolar transitions with significant dipole-forbidden components. Present data compilation constitutes a benchmark for developing and testing the theoretical methods or computational codes.

Background: A full spectrum of video capsule endoscopy (VCE) adverse events over the past two decades has not been evaluated. We aimed to determine pooled rates, predictors and temporal-trend of VCE adverse events over the past two decades. Methods: Systematic search of PubMed and EMBASE for English-language publications reporting VCE adverse events (January 1, 2000 to March 31, 2019). Data were extracted independently by two investigators. Pooled VCE adverse event rates were calculated using random-effects model. Predictors and temporal-trend of each adverse event were performed by meta-regression analyses. Results: In total, 402 studies were identified, including 108,079 VCE procedures. Rate of retention, swallow disorder, aspiration, technical failure, and procedural adverse events were 0.73% (95% confidence interval [CI], 0.59%-0.89%), 0.75% (95% CI, 0.43%-1.13%), 0.00% (95% CI, 0.00%-0.00%), 0.94% (95% CI, 0.65%-1.28%), 0.67% (95% CI, 0.32%-1.10%), respectively; incomplete examination rate of esophagus, stomach, small bowel, and colon were 9.05%, 7.69%, 12.08%, 19.19%, respectively. Patency capsule reduced retention rate by 5.04%, whereas known inflammatory bowel disease increased retention rate by 4.29%. Elder was the risk and protective factor for small bowel incomplete examination (0.30%) and swallow disorder (-0.72%), respectively. Rates of retention and small bowel incomplete examination significantly declined over time (P = .0006 and P < .0001).Conclusions: VCE adverse event rates were generally low, and retention and small bowel incomplete examination rates declined over the past two decades. Patients with known inflammatory bowel disease or elder should be alerted to high risk of retention or small bowel incomplete examination (PROSPERO: CRD42019139595).

The placenta is crucial for a successful pregnancy and the health of both the fetus and the pregnant woman. However, how the human trophoblast lineage is regulated, including the categorization of the placental cell subtypes is poorly understood. Here we performed single-cell RNA sequencing (RNA-seq) on sorted placental cells from first- and second-trimester human placentas. New subtypes of cells of the known cytotrophoblast cells (CTBs), extravillous trophoblast cells (EVTs), Hofbauer cells, and mesenchymal stromal cells were identified and cell-type-specific gene signatures were defined. Functionally, this study revealed many previously unknown functions of the human placenta. Notably, 102 polypeptide hormone genes were found to be expressed by various subtypes of placental cells, which suggests a complex and significant role of these hormones in regulating fetal growth and adaptations of maternal physiology to pregnancy. These results document human placental trophoblast differentiation at single-cell resolution and thus advance our understanding of human placentation during the early stage of pregnancy.

The elastic squared form factor of gaseous carbon dioxide was measured for the first time by high resolution X-ray scattering to separate the elastic and inelastic scattering. Bond lengths of rCO = 1.172 ± 0.008 A and rOO = 2.344 ± 0.016 A of CO2 were determined from the measured elastic squared form factors, which are in good agreement with the NIST benchmark data of rCO = 1.1621 A and rOO = 2.3242 A. Moreover, the obtained elastic squared form factor difference shows a clear binding effect in the region of small momentum transfers. The present work shows that high resolution X-ray scattering is a powerful tool to study the binding effect of molecules.

Intestine microbiota and enzyme activities have crucial effects on host's health and behavior. In order to provide evidences for the toxicology of Aflatoxin B1 (AFB1) on human’s health objectively,...

AIM To investigate the diversity of bacterial lactase genes in the intestinal contents of mice with antibiotics-induced diarrhea. METHODS Following 2 d of adaptive feeding, 12 specific pathogen-free Kunming mice were randomly divided into the control group and model group. The mouse model of antibiotics-induced diarrhea was established by gastric perfusion with mixed antibiotics (23.33 mL·kg-1·d-1) composed of gentamicin sulfate and cephradine capsules administered for 5 days, and the control group was treated with an equal amount of sterile water. Contents of the jejunum and ileum were then collected and metagenomic DNA was extracted, after which analysis of bacterial lactase genes using operational taxonomic units (OTUs) was carried out after amplification and sequencing. RESULTS OTUs were 871 and 963 in the model group and control group, respectively, and 690 of these were identical. There were significant differences in Chao1 and ACE indices between the two groups (P < 0.05). Principal component analysis, principal coordination analysis and nonmetric multidimensional scaling analyses showed that OTUs distribution in the control group was relatively intensive, and differences among individuals were small, while in the model group, they were widely dispersed and more diversified. Bacterial lactase genes from the intestinal contents of the control group were related to Proteobacteria, Actinobacteria, Firmicutes and unclassified bacteria. Of these, Proteobacteria was the most abundant phylum. In contrast, the bacterial population was less diverse and abundant in the model group, as the abundance of Bradyrhizobium sp. BTAi1, Agrobacterium sp. H13-3, Acidovorax sp. KKS102, Azoarcus sp. KH32C and Aeromonas caviae was lower than that in the control group. In addition, of the known species, the control group and model group had their own unique genera, respectively. CONCLUSION Antibiotics reduce the diversity of bacterial lactase genes in the intestinal contents, decrease the abundance of lactase gene, change the lactase gene strains, and transform their structures.

The integral cross sections (ICSs) of the electron scattering of nitrogen molecule are of great importance to the understanding of many different aspects of atmospheric physics. In the present work, the generalized oscillator strengths (GOSs) of the valence-shell excitations of b1Πu, b′1Σu+, c31Πu, c4′1Σu+, and o31Πu of nitrogen have been determined by fast-electron scattering at an incident electron energy of 1500 eV and an energy resolution of 70 meV. By crosschecking strictly the present results with the previous electron scattering and inelastic x-ray scattering (IXS) ones, the accuracy and reliability of the GOSs for the corresponding dipole-allowed transitions of nitrogen are tested stringently. Based on the accurate GOSs of these dipole-allowed transitions, their ICSs are obtained systematically from the threshold to 5000 eV for the first time with the aid of the BE-scaling method, and the corresponding ICSs at the moderate and high energies are the only available data to the best of our knowledge.

Dissociative photoionization of 1,2-epoxyoctane was investigated by synchrotron radiation vacuum ultraviolet photons in the energy region of 9.8–16.6 eV under ultrasonic molecular beam. Dissociative fragment ions were measured with reflection time-of-flight mass spectrometer at different photon energies. Appearance potentials of the dominative ion fragments were determined through photoionization efficiency curves. The structures and energies of the parent, ionized and neutral radicals were obtained with G3 calculations. Through comparing the experimental results with the theoretical calculations, we proposed the dissociative channels for the photoionization of 1,2-epoxyoctane.

Front cover: The cover image, by Ming‐Feng Zhou et al., is based on the ORIGINAL ARTICLE Endoplasmic reticulum stress induces apoptosis of arginine vasopressin neurons in central diabetes insipidus via PI3K/Akt pathway. DOI: https://doi.org/10.1111/cns.13089. [Image: see text]

The generalized oscillator strengths of the low-lying valence-shell excitations of N

The vibrationally resolved generalized oscillator strengths of the first and strongest singlet excitation ÃA2″1← X̃

Objective To explore the applied value of modified enzyme digestion method in primary culture of human glioma cells. Methods A traditional enzyme digestion method was modified based on literatures and our work experience. The glioma cells from 32 glioma patients with different grades were primarily cultured by the modified enzyme digestion method. The morphological features of these cells were observed under an inverted phase contrast microscope. The primary cells were purified by differential adhesion during passage. The primary cells were identified by immunofluorescence technique, and the growth curves were drawn by cell proliferation assays (CCK-8 method) for investigating the proliferation of the cells cultured in vitro. Results The primary human glioma cells were successfully cultured and transferred by the new method, with a success rate of 87.5%. The cells cultured successfully in vitro showed good adherent growth, stable morphologies, thus can be passaged. Fluoroimmunoassay showed positive expression of glial fibrillary acidic protein, which confirms the cultured cells were glioma cells. Cell proliferation assays revealed active cell proliferation in vitro, the higher the tumor grade, the higher the proliferative capacity. Conclusion The modified enzyme digestion method is simpler and more efficient for primary culture of human glioma cells, and the success rate is also higher, thus being able to provide a good guarantee for fundamental research of glioma. DOI: 10.11855/j.issn.0577-7402.2016.06.06

The epithelial-to-mesenchymal (-like) transition (EMT), a crucial embryonic development program, has been linked to the regulation of glioblastoma (GBM) progression and invasion. Here, we investigated the role of MIR517C/miR-517c, which belongs to the C19MC microRNA cluster identified in our preliminary studies, in the pathogenesis of GBM. We found that MIR517C was associated with improved prognosis in patients with GBM. Furthermore, following treatment with the autophagy inducer temozolomide (TMZ) and low glucose (LG), MIR517C degraded KPNA2 (karyopherin alpha 2 [RAG cohort 1, importin alpha 1]) and subsequently disturbed the nuclear translocation of TP53 in the GBM cell line U87 in vitro. Interestingly, this microRNA could inhibit autophagy and reduce cell migration and infiltration in U87 cells harboring wild-type (WT) TP53, but not in U251 cells harboring mutant (MU) TP53. Moreover, the expression of epithelial markers (i.e., CDH13/T-cadherin and CLDN1 [claudin 1]) increased, while the expression of mesenchymal markers (i.e., CDH2/N-cadherin, SNAI1/Snail, and VIM [vimentin]) decreased, indicating that the EMT status was blocked by MIR517C in U87 cells. Compared with MIR517C overexpression, MIR517C knockdown promoted infiltration of U87 cells to the surrounding structures in nude mice in vivo. The above phenotypic changes were also observed in TP53(+/+) and TP53(-/-) HCT116 colon cancer cells. In summary, our study provided support for a link between autophagy and EMT status in WT TP53 GBM cells and provided evidence for the signaling pathway (MIR517C-KPNA2-cytoplasmic TP53) involved in attenuating autophagy and eliminating the increased migration and invasion during the EMT.

The generalized oscillator strengths of the valence-shell excitations from the ground state to 3p5(4s, 4s', 4p, 4p', 3d, 3d', 5p, 5p', 5s, 4d) of argon have been determined at an incident electron energy of 1500 eV and an energy resolution about 90 meV. The accuracy of the present generalized oscillator strengths is improved by the adopted relative flow technique. The comprehensive comparison of the present results with the previous experimental and theoretical ones shows that the first Born approximation is satisfied in the lower squared momentum transfer region for the electric dipole excitations, while the deviations from the prediction of the first Born approximation and the inelastic X-ray scattering measurements near the minimum and in the larger K2 region are obvious, which can be attributed to the failure of the first Born approximation in this K2 region. The invalidity of the first Born approximation has also been observed for the electric monopole transitions even at a high impact electron energy of 2500 eV.

For the inelastic electron scattering of atoms and molecules, a consensus has been reached that the first Born approximation is easily approached by decreasing the momentum transfer at the same impact electron energy or increasing the impact electron energy at the same momentum transfer. Although this consensus is applicable for the elastic electron scattering of most atoms and molecules, it is violated for helium where the experimental differential cross sections deviate from the first Born approximation prediction gradually with the decrease of squared momentum transfer at the same impact electron energy. Since this anomalous phenomenon was observed more than 40 years ago, the intrinsic mechanism is not explicit. In the present work, using the high-resolution x-ray scattering, we isolate the scattering contribution from the nucleus and directly obtain the pure electronic structure of helium. Then, the anomalous asymptotic behavior of the elastic electron scattering of helium has been elucidated, i.e., in the small squared momentum transfer region, the scattering contribution from the target's electrons is counteracted by the one from the atomic nucleus, which results in the residual contribution beyond the first Born approximation being drastically enlarged.

The current research tried to investigate the effect of Qiweibaizhu powder (QWBZP) on intestinal mucosa bacterial lactase gene from dysbacterial diarrhea mice, as the good therapeutic mechanism of QWBZP on antibiotics-induced diarrhea. Dysbacterial diarrhea mice model was constructed by gastric perfusion with mixture of cephradine capsules and gentamicin sulfate (23.33 mL kg(−1) day(−1)) for 5 days. After the success of establishing diarrhea, the mice in treatment group were gavaged with QWBZP for 3 days. Intestinal mucosa in each group was collected, and diversity of bacterial lactase genes in intestinal mucosa of mice was carried out by Miseq metagenome sequencing. The results showed the Chao1, ACE, Simpson and Shannon indices in treatment group were lower than model group and were similar to control group. The same result was obtained from the operational taxonomic units (OTUs). There were 298, 435 and 254 OTUs in the control group, model group and treatment group, respectively. Principal component analysis (PCA) indicated that samples distribution in both normal and treatment groups were relatively intensive, distances among individuals were small, while opposite results were observed in model group. Moreover, antibiotics increased the diversity and abundance of bacterial lactase genes at phylum and genus levels. However, they decreased and were similar to control group after treating with QWBZP. Our results indicate that QWBZP has a positive effect on the recovery of bacterial lactase gene diversity to normal level. In addition, QWBZP increase the abundance of Lysobacter and Eukaryota.

A joint experimental and theoretical investigation of the valence-shell excitations of hydrogen has been performed by the high-resolution inelastic x-ray scattering and electron scattering as well as the multireference single- and double-excitation configuration-interaction method. Momentum-transfer-dependent inelastic squared form factors for the vibronic series belonging to the $B{\phantom{\rule{0.16em}{0ex}}}^{1}{\mathrm{\ensuremath{\Sigma}}}_{u}^{+},\phantom{\rule{0.28em}{0ex}}C{\phantom{\rule{0.16em}{0ex}}}^{1}{\mathrm{\ensuremath{\Pi}}}_{u}$, and $EF{\phantom{\rule{0.16em}{0ex}}}^{1}{\mathrm{\ensuremath{\Sigma}}}_{g}^{+}$ electronic states of molecular hydrogen have been derived from the inelastic x-ray scattering method at an impact photon energy around 10 keV, and the electron energy-loss spectra measured at an incident electron energy of 1500 eV. It is found that both the present and the previous calculations cannot satisfactorily reproduce the inelastic squared form-factor profiles for the higher vibronic transitions of the $B{\phantom{\rule{0.16em}{0ex}}}^{1}{\mathrm{\ensuremath{\Sigma}}}_{u}^{+}$ state of molecular hydrogen, which may be due to the electronic-vibrational coupling for the higher vibronic states. For the $C{\phantom{\rule{0.16em}{0ex}}}^{1}{\mathrm{\ensuremath{\Pi}}}_{u}$ state and some vibronic excitations of $EF{\phantom{\rule{0.16em}{0ex}}}^{1}{\mathrm{\ensuremath{\Sigma}}}_{g}^{+}$ state, the present experimental results are in good agreement with the present and previous calculations, while the slight differences between the inelastic x-ray scattering and electron energy-loss spectroscopy results in the larger squared momentum-transfer region may be attributed to the increasing role of the higher-order Born terms in the electron-scattering process.

The current study aimed at exploring the diversity of bacterial lactase genes in the intestinal mucosa of mice with dysbacterial diarrhea induced by antibiotics and to provide experimental basis for antibiotics-induced diarrhea. Mice model of dysbacterial diarrhea was established by gastric perfusion with mixture of cephradine capsules and gentamicin sulfate (23.33 mL kg(−1) d(−1)), twice a day and continuously for 5 days. Intestinal mucosa from jejunum to ileum was collected, and bacterial metagenomic DNA was extracted for Miseq metagenome sequencing to carry out diversity analysis. The results showed that specific operational taxonomic units (OTUs) were 45 in the control group and 159 in the model group. The Chao1, ACE, Shannon and Simpson indices in model group were significantly higher (P

Proper differentiation of trophoblast cells in the human placenta is a prerequisite for a successful pregnancy, and dysregulation of this process may lead to malignant pregnancy outcomes, such as preeclampsia. Finding specific markers for different types of trophoblast cells is essential for understanding trophoblast differentiation. Here, we report that placenta-specific protein 8 (PLAC8) is specifically expressed in the interstitial extravillous trophoblast cells (iEVTs) on the fetomaternal interface. Using model systems, including placental villi-decidua co-culture, iEVTs induction by using primary trophoblast cells or explants, etc., we found that PLAC8 promotes invasion and migration of iEVTs. Mechanistically, time-lapse imaging, GTPase activity assay, co-immunoprecipitation and RNA-seq studies show that PLAC8 increases the Cdc42 and Rac1 activities, and further induces the formation of filopodia at the leading edge of the migratory trophoblast cells. More interestingly, PLAC8 is significantly upregulated under hypoxia and expression of PLAC8 is higher in iEVTs from preeclamptic placentas when compared with those from the normal control placentas. Together, PLAC8 is a new marker for iEVTs and plays an important role in promoting trophoblast invasion and migration., Highlighted Article: Oxygen tension-dependent expression of placenta-specific protein 8 positively regulates trophoblast invasion and migration partially through upregulating the activation of Rac1 and Cdc42.

Delivery and penetration of chemotherapeutic drugs into neoplasm through the tumor vasculature are essential mechanisms to enhance the efficiency of chemotherapy. "Vascular targeting" strategy focuses on promoting the infiltration of chemotherapeutic drugs into neoplastic tissues. In this study, we achieved a targeted therapy by coupling tumor necrosis factor α (TNFα) with TCP-1, a novel vascular-targeting peptide, in an orthotopic colorectal cancer model in mice. High dose of TCP-1-conjugated TNFα (TCP-1/TNFα: 5μg/mouse) displayed potent antitumor activity by inducing apoptosis and reducing microvessel number in tumors than unconjugated TNFα, with no evidence of increased toxicity. In the combined therapy, the antitumor action of 5-fluorouracil (5-FU) was potentiated when the mice were pretreated with a low dose of TNFα (1ng/mouse) and to a greater extent by the same concentration of TCP-1/TNFα. In this regard, TCP-1/TNFα combined with 5-FU synergistically inhibited the tumor growth, induced apoptosis and reduced cell proliferation. More importantly, TCP-1/TNFα normalized the tumor vasculature and facilitated the infiltration of immune cells to neoplasm as well as attenuated the immunosuppressing effects of TNFα in bone marrow and spleen. At the same time, TCP-1/TNFα significantly improved 5-FU absorption into the tumor mass. Taken together, these findings underscore the therapeutic potential of TCP-1 as a drug carrier in cancer therapy. TCP-1 is a novel vascular-targeting peptide and appears to be a promising agent for drug delivery. TCP-1 fused with TNFα holds great promise for colorectal cancer therapy.