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Background and purpose Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths. The once highly anticipated antibody-based pathway-targeted therapies have not achieved promising outcomes, due to drugs' low intrinsic anticancer activity and low penetration across the dense physiological barrier of PDAC tumors. Here, an ultra-small-sized (50 kDa), bispecific protein, called Bi-fp50, that can penetrate deep tumor tissue and effectively inhibit PDAC tumor growth is reported. Methods Bi-fp50 was constructed by a typical synthetic biology method and target both EGFR and VEGF of PDAC cells simultaneously. Characteristics for example binding affinity of Bi-fp50 were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), enzyme-linked immunosorbent assay (ELISA) and fourier transform infrared spectra (FTIR). Different cell lines (Bxpc3, Aspc1) were used to test the in vitro targeting effect and anticancer ability of Bi-fp50. The orthotopic PDAC tumor model and subcutaneous PDAC tumor model were used to assess in vivo circulation and antitumor effect of Bi-fp50. Results Bi-fp50 with an ultra-small size of 50 kDa (5 ~ 6 nm) had shown a high target binding capacity and in vitro anticancer effect with significant cell killing for Bxpc3 and Aspc1 human PDAC cells. In vivo imaging had shown that Bi-fp50 could vastly enrich deep tumor tissue and had excellent penetration and accumulation when it was injected into orthotopic Bxpc3 xenograft mice. Bi-fp50 also had a high inhibition effect of tumor growth in vivo, accompanied by vascular normalization. No noticeable side effect of Bi-fp50 was found both in vitro and in vivo. Conclusion Compared with scFv2, anti-EGFR scFv, anti-VEGF scFv and Bi-fp50x group, Bi-fp50 with the ultra-small size had the highest binding affinity to both EGFR and VEGF targets. Since Bi-fp50 could penetrate deep pancreatic tumor tissue and had a high antitumor effect in vivo. Our work demonstrates that Bi-fp50 could be a potential candidate as a PDAC tumor suppressor.

An accumulating number of studies have highlighted the importance of interpersonal neural synchronization (INS) between interlocutors in successful verbal communications. The opportunities for communication across different language contexts are rapidly expanding, thanks to the frequent interactions among people all over the world. However, whether the INS changes in different language contexts and how language choice affects the INS remain scarcely explored. The study recruited twenty pairs of participants to communicate in the first language (L1), second language (L2) and interlingual contexts. Using functional near-infrared spectroscopy (fNIRS), we examined the neural activities of interlocutors and analyzed their wavelet transform coherence to assess the INS of dyads. Results showed that as compared to the resting state, stronger INS was observed at the left inferior temporal gyrus, middle temporal gyrus, pre-motor and supplementary motor cortex, dorsolateral prefrontal cortex, and inferior frontal gyrus in L1; at the left middle temporal gyrus, superior temporal gyrus, and inferior frontal gyrus in L2; at the left inferior temporal gyrus and inferior frontal gyrus in interlingual context. Additionally, INS at the left inferior frontal gyrus was significantly stronger in L2 than in L1. These findings reveal the differences of the INS in different language contexts and confirm the importance of language choice for the INS changes.

Individual passenger travel patterns have significant value in understanding passenger’s behavior, such as learning the hidden clusters of locations, time, and passengers. The learned clusters further enable commercially beneficial actions such as customized services, promotions, data-driven urban-use planning, peak hour discovery, and so on. However, the individualized passenger modeling is very challenging for the following reasons: 1) The individual passenger travel data are multi-dimensional spatiotemporal big data, including at least the origin, destination, and time dimensions; 2) Moreover, individualized passenger travel patterns usually depend on the external environment, such as the distances and functions of locations, which are ignored in most current works. This work proposes a multi-clustering model to learn the latent clusters along the multiple dimensions of Origin, Destination, Time, and eventually, Passenger (ODT-P). We develop a graph-regularized tensor Latent Dirichlet Allocation (LDA) model by first extending the traditional LDA model into a tensor version and then applies to individual travel data. Then, the external information of stations is formulated as semantic graphs and incorporated as the Laplacian regularizations; Furthermore, to improve the model scalability when dealing with massive data, an online stochastic learning method based on tensorized variational Expectation-Maximization algorithm is developed. Finally, a case study based on passengers in the Hong Kong metro system is conducted and demonstrates that a better clustering performance is achieved compared to state-of-the-arts with the improvement in point-wise mutual information index and algorithm convergence speed by a factor of two.

Background As the main cause of cancer death, lung cancer imposes seriously health and economic burdens on individuals, families, and the health system. In China, there is no national study analyzing the hospitalization expenditures of different payment methods by lung cancer inpatients. Based on the 2010–2016 database of insured urban resident lung cancer inpatients from the China Medical Insurance Research Association (CHIRA), this paper aims to investigate the characteristics and cost of hospitalized lung cancer patient, to examine the differences in hospital expenses and patient out-of-pocket (OOP) expenses under four medical insurance payment methods: fee-for-service (FFS), per-diem payments, capitation payments (CAP) and case-based payments, and to explore the medical insurance payment method that can be conducive to controlling the cost of lung cancer. Method This is a 2010–2016, 7-year cross-sectional study. CHIRA data are not available to researchers after 2016. The Medical Insurance Database of CHIRA was screened using the international disease classification system to yield 28,200 inpatients diagnosed with lung cancer (ICD-10: C34, C34.0, C34.1, C34.2, C34.3, C34.8, C34.9). The study includes descriptive analysis and regression analysis based on generalized linear models (GLM). Results The average patient age was 63.4 years and the average length of hospital stay (ALOS) was 14.2 day; 60.7% of patients were from tertiary hospitals; and 45% were insured by FFS. The per-diem payment had the lowest hospital expenses (RMB7496.00/US$1176.87), while CAP had the lowest OOP expenses (RMB1328.18/US$208.52). Compared with FFS hospital expenses, per-diem was 21.3% lower (95% CI = -0.265, -0.215) and case-based payment was 8.4% lower (95% CI = -0.151, -0.024). Compared with the FFS, OOP expenses, per-diem payments were 9.2% lower (95% CI = -0.130, -0.063) and CAP was 15.1% lower (95% CI = -0.151, -0.024). Conclusion For lung cancer patients, per-diem payment generated the lowest hospital expenses, while CAP meant patients bore the lowest OOP costs. Policy makers are suggested to give priority to case-based payments to achieve a tripartite balance among medical insurers, hospitals, and insured members. We also recommend future studies comparing the disparities of various diseases for the cause of different medical insurance schemes.

The microorganisms and allelochemicals in Pontederia cordata planting water may have a synergistic inhibitory effect on algae. To study this synergy, an algae-inhibiting organism was isolated and identified, and its growth and feeding characteristics were studied. The organism was identified as Poterioochromonas malhamensis yzs924 based on both its morphology and molecular barcoding employing 18S rDNA gene sequences.The growth and feeding of P. malhamensis were affected by environmental factors and the state of its prey. (1) P. malhamensis is a mixotrophic flagellate. Its heterotrophic growth was the fastest in a wheat grain medium, and its growth rate in this study reached 2.5 day

In this work, lead-free (1−x)(Bi0.5Na0.5)0.94Ba0.06TiO3−xBi(Mg0.5Ti0.5)O3 (abbreviated as BNBT-xBMT, x = 0.3, 0.4, 0.5 and 0.6) thin films were prepared on Pt/Ti/SiO2/Si substrates using sol–gel method. The microstructures, dielectric, and energy storage properties were investigated. The results showed that the addition of BMT disrupted the long-range ferroelectric order and enhanced the relaxor behavior of BNBT-xBMT thin films. In addition, the leakage current density of thin films was also reduced by the doping of a moderate amount of BMT. A high recoverable energy density of 34.36 J/cm3 with an efficiency of 56.63% was achieved in the BNBT-0.5BMT thin film under the electric field of 2149 kV/cm. Furthermore, BNBT-0.5BMT thin film exhibited superior stability in the temperature range of 30 °C–145 °C and frequency range of 500 Hz–5 kHz, as well as long-term fatigue durability after 1 × 105 cycles. These results suggest that BNBT-0.5BMT thin film may be a promising material for lead-free dielectric energy storage applications.

Waste magnesia-carbon bricks (MCB) exhibit great potential for being reutilized as MgO additive for iron ore sintering due to their main composition of high activity magnesia and extra carbon content. In this paper, the combustion characteristics of the carbon component of waste MCB were first studied by thermogravimetric, derivative thermogravimetric and differential scanning calorimetry thermal analysis. The influence of waste MCB utilization as MgO additive on the mineralization of sinter raw materials was also systematically investigated. The main conclusions are shown as below: (1) Compared with anthracite, the carbon component of waste MCB has relatively worse flammability and combustibility, and its combustion heat per unit mass is less; (2) As the MgO content of sinter increases from 2.0 to 3.0 wt%, the advantage of using waste MCB, compared with dolomite, as MgO additive in the crystallinity degree of sinter gradually appears; (3) At the MgO content of 3.0 wt%, the sinter using the combination of waste MCB and dolomite as MgO additive has higher content of calcium ferrite, and the distributions of main mineral compositions and pores are more uniform than the sinter totally using dolomite or waste MCB as MgO additive.

Self-assembled photonic systems with well-organized spatial arrangement and engineered optical properties can be used as efficient energy materials and as effective biomedical agents. The lessons learned from natural light-harvesting antennas have inspired the design and synthesis of a series of biomimetic photonic complexes, including those containing strongly coupled dye aggregates with dense molecular packing and unique spectroscopic features. These photoactive components provide excellent features that could be coupled to multiple applications including light-harvesting, energy transfer, biosensing, bioimaging, and cancer therapy. Meanwhile, nanoscale DNA assemblies have been employed as programmable and addressable templates to guide the formation of DNA-directed multi-pigment complexes, which can be used to enhance the complexity and precision of artificial photonic systems and show the potential for energy and biomedical applications. This review focuses on the interface of DNA nanotechnology and biomimetic photonic systems. We summarized the recent progress in the design, synthesis, and applications of bioinspired photonic systems, highlighted the advantages of the utilization of DNA nanostructures, and discussed the challenges and opportunities they provide.Graphical Abstract

The programmable synthesis of rationally engineered crystal architectures for the precise arrangement of molecular species is a foundational goal in nanotechnology, and DNA has become one of the most prominent molecules for the construction of these materials. In particular, branched DNA junctions have been used as the central building block for the assembly of 3D lattices. Here, crystallography is used to probe the effect of all 36 immobile Holliday junction sequences on self-assembling DNA crystals. Contrary to the established paradigm in the field, most junctions yield crystals, with some enhancing the resolution or resulting in unique crystal symmetries. Unexpectedly, even the sequence adjacent to the junction has a significant effect on the crystal assemblies. Six of the immobile junction sequences are completely resistant to crystallization and thus deemed “fatal,” and molecular dynamics simulations reveal that these junctions invariably lack two discrete ion binding sites that are pivotal for crystal formation. The structures and dynamics detailed here could be used to inform future designs of both crystals and DNA nanostructures more broadly, and have potential implications for the molecular engineering of applied nanoelectronics, nanophotonics, and catalysis within the crystalline context.

Controlled transport of biomolecules across lipid bilayer membranes is of profound significance in biological processes. In cells, cargo exchange is mediated by dedicated channels that respond to triggers, undergo a nanomechanical change to reversibly open, and thus regulate cargo flux. Replicating these processes with simple yet programmable chemical means is of fundamental scientific interest. Artificial systems that go beyond nature’s remit in transport control and cargo are also of considerable interest for biotechnological applications but challenging to build. Here, we describe a synthetic channel that allows precisely timed, stimulus-controlled transport of folded and functional proteins across bilayer membranes. The channel is made via DNA nanotechnology design principles and features a 416 nm2opening cross-section and a nanomechanical lid which can be controllably closed and re-opened via a lock-and-key mechanism. We envision that the functional DNA device may be used in highly sensitive biosensing, drug delivery of proteins, and the creation of artificial cell networks.