Homologous cancer cell membrane-camouflaged nanoparticles target drug delivery and enhance the chemotherapy efficacy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common digestive tract malignancy that seriously threatens human life and health. Early HCC may be treated by intervention, surgery, and internal radiotherapy, while the choice for late HCC is primarily chemotherapy to prolong patient survival. Lenvatinib (LT) is a Food and Drug Administration (FDA)-approved frontline drug for the treatment of advanced liver cancer and has achieved excellent clinical efficacy. However, its poor solubility and severe side effects cannot be ignored. In this study, a bionic nanodrug delivery platform was successfully constructed. The platform consists of a core of Lenvatinib wrapped with a pH-sensitive polymer, namely, poly(ß-amino ester)-polyethylene glycol-amine (PAE-PEG-NH2), and a shell formed by a cancer cell membrane (CCM). The prepared nanodrugs have high drug loading capacity, long-term stability, good biocompatibility, and a long retention time. In addition, the targeting effect of tumor cell membranes and the pH-responsive characteristics of the polymer materials enable them to precisely target tumor cells and achieve responsive release in the tumor microenvironment, which makes them suitable for effective drug delivery. In vivo experiments revealed that the nanodrug showed superior tumor accumulation and therapeutic effects in subcutaneous tumor mice model and could effectively eliminate tumors within 21 days. As a result, it opens up a new way to reduce side effects and improve the specific therapeutic effect of first-line clinical medications to treat tumors.

Identification and prognostic analysis of biomarkers to predict the progression of pancreatic cancer patients.

BACKGROUND: Pancreatic cancer (PC) is a malignancy with a poor prognosis and high mortality. Surgical resection is the only "curative" treatment. However, only a minority of patients with PC can obtain surgery. Improving the overall survival (OS) rate of patients with PC is still a major challenge. Molecular biomarkers are a significant approach for diagnostic and predictive use in PCs. Several prediction models have been developed for patients newly diagnosed with PC that is operable or patients with advanced and metastatic PC; however, these models require further validation. Therefore, precise biomarkers are urgently required to increase the efficiency of predicting a disease-free survival (DFS), OS, and sensitivity to immunotherapy in PC patients and to improve the prognosis of PC. METHODS: In the present study, we first evaluated the highly and selectively expressed targets in PC, using the GeoMxTM Digital Spatial Profiler (DSP) and then, we analyzed the roles of these targets in PCs using TCGA database. RESULTS: LAMB3, FN1, KRT17, KRT19, and ANXA1 were defined as the top five upregulated targets in PC compared with paracancer. The TCGA database results confirmed the expression pattern of LAMB3, FN1, KRT17, KRT19, and ANXA1 in PCs. Significantly, LAMB3, FN1, KRT19, and ANXA1 but not KRT17 can be considered as biomarkers for survival analysis, univariate and multivariate Cox proportional hazards model, and risk model analysis. Furthermore, in combination, LAMB3, FN1, KRT19, and ANXA1 predict the DFS and, in combination, LAMB3, KRT19, and ANXA1 predict the OS. Immunotherapy is significant for PCs that are inoperable. The immune checkpoint blockade (ICB) analysis indicated that higher expressions of FN1 or ANXA1 are correlated with lower ICB response. In contrast, there are no significant differences in the ICB response between high and low expression of LAMB3 and KRT19. CONCLUSIONS: In conclusion, LAMB3, FN1, KRT19, and ANXA1 are good predictors of PC prognosis. Furthermore, FN1 and ANXA1 can be predictors of immunotherapy in PCs.

Graphene-Modulated Terahertz Metasurfaces for Selective and Active Control of Dual-Band Electromagnetic Induced Reflection (EIR) Windows.

Currently, metasurfaces (MSs) integrating with different active materials have been widely explored to actively manipulate the resonance intensity of multi-band electromagnetic induced transparency (EIT) windows. Unfortunately, these hybrid MSs can only realize the global control of multi-EIT windows rather than selective control. Here, a graphene-functionalized complementary terahertz MS, composed of a dipole slot and two graphene-integrated quadrupole slots with different sizes, is proposed to execute selective and active control of dual-band electromagnetic induced reflection (EIR) windows. In this structure, dual-band EIR windows arise from the destructive interference caused by the near field coupling between the bright dipole slot and dark quadrupole slot. By embedding graphene ribbons beneath two quadrupole slots, the resonance intensity of two windows can be selectively and actively modulated by adjusting Fermi energy of the corresponding graphene ribbons via electrostatic doping. The theoretical model and field distributions demonstrate that the active tuning behavior can be ascribed to the change in the damper factor of the corresponding dark mode. In addition, the active control of the group delay is further investigated to develop compact slow light devices. Therefore, the selective and active control scheme introduced here can offer new opportunities and platforms for designing multifunctional terahertz devices.

Genome-wide analysis of pseudogenes reveals HBBP1's human-specific essentiality in erythropoiesis and implication in ß-thalassemia.

The human genome harbors 14,000 duplicated or retroposed pseudogenes. Given their functionality as regulatory RNAs and low conservation, we hypothesized that pseudogenes could shape human-specific phenotypes. To test this, we performed co-expression analyses and found that pseudogene exhibited tissue-specific expression, especially in the bone marrow. By incorporating genetic data, we identified a bone-marrow-specific duplicated pseudogene, HBBP1 (η-globin), which has been implicated in ß-thalassemia. Extensive functional assays demonstrated that HBBP1 is essential for erythropoiesis by binding the RNA-binding protein (RBP), HNRNPA1, to upregulate TAL1, a key regulator of erythropoiesis. The HBBP1/TAL1 interaction contributes to a milder symptom in ß-thalassemia patients. Comparative studies further indicated that the HBBP1/TAL1 interaction is human-specific. Genome-wide analyses showed that duplicated pseudogenes are often bound by RBPs and less commonly bound by microRNAs compared with retropseudogenes. Taken together, we not only demonstrate that pseudogenes can drive human evolution but also provide insights on their functional landscapes.

hnRNPLL controls pluripotency exit of embryonic stem cells by modulating alternative splicing of Tbx3 and Bptf.

The regulatory circuitry underlying embryonic stem (ES) cell self-renewal is well defined, but how this circuitry is disintegrated to enable lineage specification is unclear. RNA-binding proteins (RBPs) have essential roles in RNA-mediated gene regulation, and preliminary data suggest that they might regulate ES cell fate. By combining bioinformatic analyses with functional screening, we identified seven RBPs played important roles for the exit from pluripotency of ES cells. We characterized hnRNPLL, which mainly functions as a global regulator of alternative splicing in ES cells. Specifically, hnRNPLL promotes multiple ES cell-preferred exon skipping events during the onset of ES cell differentiation. hnRNPLL depletion thus leads to sustained expression of ES cell-preferred isoforms, resulting in a differentiation deficiency that causes developmental defects and growth impairment in hnRNPLL-KO mice. In particular, hnRNPLL-mediated alternative splicing of two transcription factors, Bptf and Tbx3, is important for pluripotency exit. These data uncover the critical role of RBPs in pluripotency exit and suggest the application of targeting RBPs in controlling ES cell fate.

Complete mitochondrial genome and phylogenetic analysis of Cyathostomum tetracanthum (Rhabditida: Cyathostominae).

The complete mitochondrial genome sequence of Cyathostomum tetracanthum was sequenced in the present study. It was determined to be 13,839 bp bases. The overall base composition was 30.93% A, 45.75% T, 6.97% C, and 16.35% G, with a very strong A + T bias (76.65%). The nucleotide sequence data of 12 protein-coding genes of C. tetracanthum and other 16 Strongylidae species were used for phylogenetic analyses. Cyathostomum tetracanthum was closely related with Cylicocyclus species rather than other Cyathostomum species. The complete mitogenome will facilitate taxonomy and systematics studies of Cyathostominae nematodes.

The complete mitochondrial genome of Coronocyclus labratus (Rhabditida: Cyathostominae).

The complete mitochondrial genome sequence of Coronocyclus labratus was sequenced in the present study. It was determined to be 13,856 bp in length, containing 12 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 2 non-coding regions. The nucleotide sequence data of 12 protein-coding genes of C. labratus and other 16 Strongylidae species were used for phylogenetic analyses. Coronocyclu labratus formed a monophyletic cluster with the remaining Strongylidae species. Coronocyclus genus was present in the same clade with high statistical support. The mitogenome sequences will facilitate taxonomy as well as systematic studies of Cyathostominae nematodes.

Facile Synthesis of Self-Assembled NiFe Layered Double Hydroxide-Based Azobenzene Composite Films with Photoisomerization and Chemical Gas Sensor Performances.

Two kinds of layered double hydroxide (LDH) Langmuir composite films containing azobenzene (Azo) groups were successfully prepared by Langmuir-Blodgett (LB) technology. Then, an X-ray diffractometer (XRD), a transmission electron microscope (TEM), and an atomic force microscope (AFM) were used to investigate the structures of NiFe-LDH and the uniform morphologies of the composite LB films. The photoisomerization and acid-base gas sensor performances of the obtained thin film samples were tested by infrared visible (FTIR) spectroscropy and ultraviolet visible (UV-vis) spectroscropy. It is proved that the Azo dye molecules in the composite film are relatively stable to photoisomerization. In addition, the prepared composite films have high sensing sensitivity and good recyclability for acid-base response gases. The present research proposes a new clue for designing thin film materials for chemical gas response with good stability and sensitivity.

Delivery of carbon, nitrogen, and sulfur to the silicate Earth by a giant impact.

Earth's status as the only life-sustaining planet is a result of the timing and delivery mechanism of carbon (C), nitrogen (N), sulfur (S), and hydrogen (H). On the basis of their isotopic signatures, terrestrial volatiles are thought to have derived from carbonaceous chondrites, while the isotopic compositions of nonvolatile major and trace elements suggest that enstatite chondrite-like materials are the primary building blocks of Earth. However, the C/N ratio of the bulk silicate Earth (BSE) is superchondritic, which rules out volatile delivery by a chondritic late veneer. In addition, if delivered during the main phase of Earth's accretion, then, owing to the greater siderophile (metal loving) nature of C relative to N, core formation should have left behind a subchondritic C/N ratio in the BSE. Here, we present high pressure-temperature experiments to constrain the fate of mixed C-N-S volatiles during core-mantle segregation in the planetary embryo magma oceans and show that C becomes much less siderophile in N-bearing and S-rich alloys, while the siderophile character of N remains largely unaffected in the presence of S. Using the new data and inverse Monte Carlo simulations, we show that the impact of a Mars-sized planet, having minimal contributions from carbonaceous chondrite-like material and coinciding with the Moon-forming event, can be the source of major volatiles in the BSE.

[Study on Myelopoietic Functions of miR-191 by Using Zebrafish Model].

OBJECTIVES: To establish a method of gene analysis via zebrafish model to explore the effect of microRNA-191(miR-191) on myelopoiesis. METHODS: The hsa-miR-191 or cel-miR-67 was microinjected into the fertilized eggs of zebrafish, then the total RNA of embryos was extracted at 10 s, 24, 36 and 48 hpf for qRT-PCR to detect the expression levels of erythroid and granulocytic genes. Then embryos at the time-point of 24 hpf were collected for whole mount in situ hybridization to detect spatiotemporal expression of those genes. RESULTS: The antisense RNA probes with high sensitivity and specificity of erythroid genes (gata 1, scl, hbbe 3, lmo 2) and myelomonocytic genes (pu.1, L-plastin, mpx, cebpα) in zebrafish were obtained by molecular cloning and T7 RNA polymerase reaction; the expression levels of the erythroid and myelomonocytic genes of zebrafish microinjected with miR-191 mimics displayed higher than those in control group at the time-points of 24 hpf and 36 hpf. The spatiotemporal expression level of L-plastin at the time-point of 24 hpf was up-regulated, and the other genes were not significantly changed. It was worth mentioning that the mRNA expression level of mpx was significantly up-regulated by 10-20 times at the time-point of 10 s. CONCLUSION: The genetic analysis method of embryonic myeloid differentiation has been set up via zebrafish. Preliminary analysis of regulation in zebrafish myelopoiesis shows that miR-191 may be involved in the regulation of erythroid and myelomonocytic differentiation. The mechanism and corresponding function of mpx regulated by the other factors need to be further studied.

Cyclane-aminol 10-hydroxycamptothecin analogs as novel DNA topoisomerase I inhibitors induce apoptosis selectively in tumor cells.

A novel series of cyclane-aminol 10-hydroxycamptothecin (HCPT) analogs was designed and synthesized through the Mannich reaction using HCPT as the lead compound, such as 10-hydroxyl-9-L-prolinol (+) methylcamptothecin (PRPT), 10-hydroxyl-9-(4'-hydroxy) piperidinylmethylcamptothecin (PPPT), and 10-hydroxy-9-(4'-hydroxyethyl)-piperazinylmethycamptothecin (QPPT). Three kinds of new cyclane-aminols were introduced into the structure of HCPT, which modified strong cytotoxic HCPT into cyclane-aminol HCPT analogs with moderate cytotoxicity and improved selectivity toward DNA topoisomerase I inhibition in tumor cells. Special metabolic pathways for cyclane-aminol HCPT analogs in rats were discovered, which differed from other HCPT analogs. Cyclane-aminol HCPT analogs can capture O2 and cause an increase in intracellular hydrogen peroxide levels with selective induction of apoptosis in tumor cells rather than in normal peripheral blood mononuclear cells. Among them, PPPT has a much better druggability than topotecan (TPT) and has the potential to be developed into an antitumor agent.

catena-Poly[(chloridozinc)-µ-5-(1-methyl-1H-benzimidazol-2-yl-κN(3))-1,2,3-triazol-1-ido-κ(2)N(1):N(3)].

In the title complex, [Zn(C(10)H(8)N(5))Cl](n), the Zn(II) ion is four-coordinated by one Cl atom and three N atoms from two in situ-generated deprotonated 5-(1-methyl-1H-benzimidazol-2-yl-κN(3))-1,2,3-triazol-1-ide ligands in a slightly distorted tetra-hedral geometry. The Zn(II) ions are bridged by the ligands, forming a helical chain along [001]. C-H⋯N and C-H⋯Cl hydrogen bonds and π-π inter-actions between the imidazole rings [centroid-centroid distance = 3.4244 (10) Å] assemble the chains into a three-dimensional supra-molecular network.

Decyl-ammonium octa-noate.

The title compound, C(10)H(24)N(+)·C(8)H(15)O(2) (-), forms a layered structure in which inter-molecular N(+)-H⋯O hydrogen bonds connect anions and cations, forming a two-dimensional network parallel to (010). The n-alkyl chains of the decyl-ammonium cations pack according to an ortho-rhom-bic 'subcell' with approximate dimensions 5.1 × 7.3 Å, and they are significantly distorted from planarity.

Bulk and adsorbed monolayer phase behavior of binary mixtures of undecanoic acid and undecylamine: catanionic monolayers.

Differential scanning calorimetry (DSC) and X-ray powder diffraction (PXRD) have been used to determine the phase behavior of the binary mixtures of undecanoic acid (A) and undecylamine (B) in the bulk. In addition, we report DSC data that indicates very similar behavior for the solid monolayers of these materials adsorbed on the surface of graphite. The two species are found to form a series of stoichiometric complexes of the type AB, A(2)B, and A(3)B on the acid rich side of the phase diagram. Interestingly, no similar series of complexes is evident on the amine rich side. As a result of this complexation, the solid monolayers of the binary mixtures exhibit a very pronounced enhancement in stability relative to the pure adsorbates.

Observation of a two-dimensional halogen-bonded cocrystal at sub-monolayer coverage using synchrotron X-ray diffraction.

The formation of two-dimensional halogen-bonded layers of 4,4'-bipyridyl and 1,4-diiodotetrafluorobenzene was observed on a graphite surface at sub-monolayer coverage using synchrotron X-ray diffraction; the use of the diffraction technique enabled, for the first time, the measurement of I···N halogen bonding distances in a two-dimensional cocrystal and the identification of the halogen bonding interaction in the monolayer.

Barriers to TB care for rural-to-urban migrant TB patients in Shanghai: a qualitative study.

OBJECTIVE: To understand barriers to tuberculosis (TB) care among migrant TB patients in Shanghai after the introduction of the TB-free treatment policy which has applied to migrants since 2003, and to provide policy recommendations to improve TB control in migrant populations in big cities. METHODS: In-depth interviews were conducted with 34 migrant patients who registered on the Shanghai TB programme as new bacteria positive pulmonary TB cases. Patients were purposively selected across six districts of Shanghai to give a balance of gender and TB treatment phase. RESULTS: Financial constraints were reported as the biggest barriers to TB service among migrant patients. Many migrant patients experienced high medical costs both before and after their TB diagnosis. The government free treatment policy only covered a small fraction of patients' total costs. However, respondents tended to stay in Shanghai for treatment because their families were in Shanghai, they were more confident with the quality of medical care there or they felt they could not earn cash at home. Migrant patients had a limited knowledge of TB and the free TB treatment policy, and reported being laid off from work or avoided after having TB. CONCLUSIONS: Health system problems caused the biggest barrier to migrant patients' access to TB care. The free treatment policy alone has little, if any, effect in reducing migrant patients' financial stress: it is also essential to provide social welfare, including living subsidies, for poor migrant TB patients.