Distinct B‐cell populations contribute to vaccine antigen‐specific antibody production in a transgenic mouse model

The generation of memory B cells by vaccination plays a critical role in maintaining antigen-specific antibodies and producing antibody responses upon re-exposure to a pathogen. B-cell populations contributing to antibody production and protection by vaccination remain poorly defined. We used influenza virus-like particle (VLP) vaccine in a transgenic mouse model that would identify germinal centre-derived memory B cells with the expression of yellow fluorescent protein (YFP⁺ cells). Immunization with influenza VLP vaccine did not induce significant increases in YFP⁺ cells although vaccine antigen-specific antibodies in sera were found to confer protection against a lethal dose of influenza A virus (A/PR8). In addition, CD43⁺ B220⁻ populations with low YFP⁺ cells mainly contributed to the production of vaccine antigen-specific IgG isotype-switched antibodies whereas CD43⁻ B220⁺ populations with high YFP⁺ cells were able to produce vaccine antigen-specific IgM antibodies. Challenge infection of immunized transgenic mice with live influenza A virus resulted in significant increases in YFP⁺ cells in the B220⁻ populations of spleen and bone marrow cells. These results suggest that CD43⁺ B220⁻ B cells generated by vaccination are important for producing influenza vaccine antigen-specific antibodies and conferring protection.     

Toll-like receptor 6 gene polymorphisms increase the risk of bovine tuberculosis in Chinese Holstein cattle

Our present study aimed to investigate the effect of four SNPs (G1793A, C1859A, A1980G, G1934A) in toll-like receptor 6 (TLR6) on bovine tuberculosis (bTB) resistance in a case–control study. A total of 603 Chinese Holstein cattle (264 from a dairy farm of Henan province, 339 from Hubei province) were selected to analyze the genotype of TLR6 gene by PCR-RFLP. Genotype frequencies of C1859A and A1980G site differed significantly between bTB-infected and non-infected cows (χ² = 6.062, P = 0.048 and χ² = 6.749, P = 0.034, respectively). Relative risk of tuberculosis incidence result showed that genotypes of AA or CA had greater relative risk (OR = 2.730, 95%CI = 0.869–8.573; OR = 1.547, 95CI% = 0.803–2.982, respectively) than those with genotype CC at C1859A site between bTB-infected and non-infected animals. Genotypes of GG or GA had greater relative risk (OR = 2.986, 95%CI = 1.245–7.165; OR = 1.582, 95%CI = 0.734–3.409, respectively) than those with genotype AA at A1980G site. No significant association can be inferred from G1793A and G1934A polymorphism site. The present study suggests that variants in the TLR6 gene are associated with susceptibility to bTB and the TLR6 gene may be considered as a candidate gene for bTB resistance.     

Differential classical conditioning selectively heightens response gain of neural population activity in human visual cortex

Neutral cues, after being reliably paired with noxious events, prompt defensive engagement and amplified sensory responses. To examine the neurophysiology underlying these adaptive changes, we quantified the contrast‐response function of visual cortical population activity during differential aversive conditioning. Steady‐state visual evoked potentials (ssVEPs) were recorded while participants discriminated the orientation of rapidly flickering grating stimuli. During each trial, luminance contrast of the gratings was slowly increased and then decreased. Right‐tilted gratings (CS+) were paired with loud white noise but left‐tilted gratings (CS?) were not. The contrast‐following waveform envelope of ssVEPs showed selective amplification of the CS+ only during the high‐contrast stage of the viewing epoch. Findings support the notion that motivational relevance, learned in a time frame of minutes, affects vision through a response gain mechanism.     

Water-soluble lanthanide coordination polymers particles with white-light emission and color tuning

Water-soluble polymer particles (PPs) with strong fluorescence emission were prepared from hyperbranched poly(ethylenimine) (PEI) and terpyridine-bearing aldehyde (TPy) via Schiff base reaction and self-assembly in aqueous phase. TPy/PEI PPs were then used to develop a series of luminescent lanthanide coordination polymers particles (Ln-CPPs). The optical properties of these Ln-CPPs are readily modulated over a wide spectrum in water systems. Finally, water-soluble white-emitting Ln-CPPs were achieved by controlling the lanthanide ion stoichiometry. This Ln-CPPs design approach offers a robust pathway for white-luminescent materials in water systems.

Water-soluble polymer particles (PPs) with strong fluorescence emission were prepared from hyperbranched poly(ethylenimine) (PEI) and terpyridine-bearing aldehyde (TPy) via Schiff base reaction and self-assembly in aqueous phase.

In recent decades, dynamic metal coordination polymers (M-CPs) have attracted great interest in catalysis, drug delivery, chemical sensors and bioanalysis applications.^1–7 M-CPs are constructed from metal ions and organic ligands with a variety of structures and interesting properties for many potential applications. M-CPs acting as chemical sensors are mainly explored by making use of their luminescence properties.^8–10 The luminescent M-CPs can emit a stable and intense luminescent emission, so some substances can be detected by observing changes in luminescence intensity. It is well known that lanthanide ions have high color purity and long lifetime excitation lifetime, and the emission covers the entire visible range of 400 to 700 nm. In particular, Eu(iii) and Tb(iii) ions can emit intense red and green light, respectively. Lanthanide coordination polymers (Ln-CPs) are promising luminescent materials because lanthanide ions have similar chemical properties and two or more lanthanide ions can be randomly distributed in coordination polymers with metal sites, which can modulate the color and brightness of the emission.¹¹ For the above reasons, Ln-CPs have attracted the attention of many scientists and have been effectively used to design multiple color and white light emitting materials. For example, He and co-workers¹² developed a new fluorophore that exhibits white light by combining an Eu(iii) moiety (red emission) with an organic ligand (blue and green emission). Ma et al.¹³ reported a white-light-emitting La(iii)/Tb(iii)/Eu(iii) coordination polymers based on combination of blue-emitting ligand/La(iii), green-emitting Tb(iii) and red-emitting Eu(iii) units. Song et al.¹⁴ developed a white-light-emitting compound by doping a Eu(iii) ion into the Gd(iii) framework.Meanwhile, the selection of suitable ligands plays a crucial role in the synthesis of Ln-CPs with good luminescent properties, since organic ligands can be used not only as building blocks for the construction of new backbones of Ln-CPs, but also as effective sensitizer for Ln(iii) ions.^15,16 However, ligands are generally poorly water soluble, which limits the practical sensing application in environmental and biological systems.¹⁷ An efficient strategy to promote dispersion in water is to prepare Lanthanide coordination polymer particles (Ln-CPPs) by miniemulsion method, reprecipitation method, and so on.¹⁸ Nevertheless, several drawbacks still exist for their preparation and application, such as sophisticated multistep synthetic pathways, use of environmentally unfriendly organic solvents, and the possibility of fluorescence self-quenching in aqueous solution. Therefore, the systematic investigation of water-soluble Ln-CPPs with white-light emission is quite rare. More research studies are urgently needed to accelerate the development of white-light luminescent Ln-CPPs in the water system.Based on the above considerations, we rationally designed water-soluble polymer particles with blue emission and selected Tb(iii)/Eu(iii) to construct white-light-emitting Ln-CPPs (Fig. 1). The water-soluble polymer particles were constructed from hyperbranched poly(ethylenimine) (PEI) and terpyridine-bearing aldehyde (TPy) via Schiff base reaction and self-assembly. Structural characterization and luminescence properties in the water system of Ln-CPPs are studied in detail. An important clue could be obtained from the result that Ln-CPPs constructed by terpyridine ligands can maintain their structural and luminescent properties in the water system. This research also provides a basis for realizing the controllability of water-soluble white-light-emitting Ln-CPPs in the future.Open in a separate windowFig. 1Schematic preparation of TPy/PEI PPs and Ln(III) coordination-based luminescent polymer particles (Ln-CPPs) under UV light (λ_ex = 365 nm).Synthesis of the TPy/PEI PPs is based on facile Schiff base reaction, which refers to the reaction between primary amine on PEI and aldehyde group on TPy, resulting in a product containing C N bonds. Moreover, the diluted TPy/PEI PPs solution emits blue fluorescence under a 365 nm UV lamp. Fig. 2A displays the fluorescence excitation and emission spectra of the TPy/PEI PPs solution, and the maximum excitation and emission wavelengths are 330 and 448 nm, respectively. The UV-vis absorption spectra of TPy/PEI PPs, PEI and TPy were shown in Fig. S4.^† Compared with TPy, the absorption peak at 250 nm in TPy/PEI PPs solution is weakened, which may be due to the decolorization effect caused by the formation of copolymer by TPy and PEI. In addition, the absorption peak at 335 nm in TPy/PEI PPs solution is attributed to n → π* transitions of C N bonds.^18,19 These phenomena indicated TPy/PEI PPs were a newly generated subject.Open in a separate windowFig. 2(A) Fluorescence excitation and emission spectra of TPy/PEI PPs (0.01 g mL⁻¹). (Inset) Photographs of TPy/PEI PPs under visible light and UV light of 365 nm. (B) FT-IR spectra of TPy/PEI, PEI, and TPy.The morphologies of TPy/PEI PPs were characterized by transmission electron microscopy (TEM), Fig. S5A^† is a TEM image and reveals that the TPy/PEI PPs are monodisperse spherical shape with the size distribution in the range of 26–50 nm. Formation of water-soluble nanoparticles is due to the following factors. In TPy/PEI copolymer, ample amine groups and pyridinium groups are hydrophilic, whereas Schiff base bonds are hydrophobic. As a result, the hyperbranched structure of TPy/PEI copolymer tends to fold and collapse, shrinking and self-assembling into uniform polymer nanoparticles in aqueous medium.¹⁸ Many hydrophilic groups on the surface of TPy/PEI PPs make the excellent water dispersity possible. To further explore the chemical composition of TPy/PEI PPs, we performed FT-IR spectra of PEI, TPy, and TPy/PEI PPs (Fig. 2B). Several featured vibration bands at 3284 and 1590 cm⁻¹ in PEI are associated with the stretching vibration of N–H bond, and their intensity is decreased in TPy/PEI PPs, which indicates that some amine groups have reacted with TPy. In addition, another remarkable new peak at 1630 cm⁻¹ was observed in TPy/PEI PPs, which can be assigned to the C N bond.^20–25 Meanwhile, a new peak at 8.37 ppm was observed in the ¹H NMR spectra of TPy/PEI PPs (Fig. S6^†), which can be assigned to N CH protons.²⁶ The monitoring of the aldehyde conversion into imine units can be carried out by measuring the CH̲O/CH̲ N integral ratio, and the conversion rate of the aldehyde into imine units is 69%. The estimation of the conversion rate from the ¹H-NMR spectrum agrees well with the calculation from the weighting measurements with a conversion rate of 73%. These analysis results well demonstrated the formation of Schiff base bonds between TPy and PEI.TPy/PEI PPs possess intrinsic fluorescence, good water solubility, and functional terpyridine structure unit, allowing us to incorporate the Ln(iii)-TPy coordination complexes into polymer networks. With the incremental addition of Tb(NO₃)₃ to the TPy/PEI PPs solution (2% v/v), the TPy : Ln ratio is 2 : 1, which produces green-luminescent Ln-CPPs, GL CPPs (τ = 0.35 ms, Φ = 4.3%, CIE coordinates (0.27, 0.36), Fig. S7, S8 and Table S1^†). In the corresponding emission spectrum, a decrease in the luminescence intensity of the ligand centred emission band at 448 nm with the concomitant emergence of sharp bands at 489 nm, 544 nm, 583 nm, and 622 nm was observed (Fig. S7^†). A decrease in the luminescence intensity of the central emission band of the ligand was observed. These emission bands were assigned to ⁵D₄–⁷F₆, ⁵D₄–⁷F₅, ⁵D₄–⁷F₄, and ⁵D₄–⁷F₃ based transitions, respectively, for Tb(iii).^27–30 A similar procedure was observed upon addition of Eu(NO₃)₃ to the TPy/PEI PPs solution with the occurrence of five characteristic Eu(iii)-based emission bands having maxima at 579 nm (⁵D₀–⁷F₀), 592 nm (⁵D₀–⁷F₁), 617 nm (⁵D₀–⁷F₂), 649 nm (⁵D₀–⁷F₃), and 687 nm (⁵D₀–⁷F₄), resulting in a clear red-luminescent Ln-CPPs, RL CPPs (τ = 0.81 ms, Φ = 11.3%, CIE coordinates (0.52, 0.29)). These emission spectra demonstrate that Ln³⁺ (Eu³⁺ or Tb³⁺) ions were successfully doped to the TPy/PEI PPs. More importantly, strong fluorescence could still be detected even after these Ln-CPPs were stored for over a week, implying that the coordination between the TPy/PEI PPs and Ln³⁺ ions is very stable. The interactions between the TPy/PEI PPs and Ln³⁺ ions were further monitored by FT-IR spectroscopy (Fig. S9^†). Strong absorbent bands at 3256, 1549 and 1398 cm⁻¹ in TPy/PEI PPs are attributed to the stretching vibrations of N–H bond.^18,19 After the formation of RL CPPs, GL CPPs or WL CPPs using Ln³⁺ ions, a dramatically red shift appeared, which indicated the coordination of the TPy/PEI PPs to Ln³⁺ ions. The medium-to-weak bands at 760 cm⁻¹ for RL CPPs, 769 cm⁻¹ for GL CPPs and 765 cm⁻¹ for WL CPPs are observed as additional evidence of the Ln–N formation.³¹Next we investigated how to modulate the emission of polymer particles by adjusting the stoichiometry of the two lanthanide chromophores. Titration of the Tb/Eu molar ratio resulted in a series of Ln-CPPs with a broad spectrum of emission under UV irradiation (Fig. 3A). By testing the emission spectrum (Fig. 3B and C), it was found that the intensity of the green band at 544 nm increased gradually at the expense of the intensity of the red band at 616 nm as a function of Tb/Eu molar ratio. Interestingly, an intense white-luminescent Ln-CPPs, WL CPPs (CIE coordinates (0.33, 0.34)), were observed when the Eu/Tb molar ratio was 1 : 4. The smart illumination control strategy here provides a simple design approach for broad-spectrum color adjustment of luminescent polymer materials.Open in a separate windowFig. 3Luminescence tuning: (A) photographs of Ln-CPPs under UV irradiation, corresponding CIE coordinates are mentioned below; (B) emission spectra (λ_ex = 330 nm) of Ln-CPPs and (C) Job''s plot showing the peak emission intensity of the red band at 544 nm and green band at 616 nm as a function of the Tb/Eu molar ratio (1 : 1, 2 : 1, 3 : 1, 4 : 1, 5 : 1, 6 : 1, 7 : 1, and 8 : 1).In conclusion, we created polymer particles with blue emission from PEI and TPy via Schiff base reaction and self-assembly under mild conditions. The structural characterization and the fundamental properties of the TPy/PEI PPs have been studied. Because of the specific structure, the TPy/PEI PPs exhibit excellent water solubility. Furthermore, we have used the TPy/PEI PPs to develop a series of luminescent Ln-CPPs with Eu(iii), Tb(iii), and mixed Eu(iii)/Tb(iii) in aqueous medium. The individual Ln-CPPs exhibited bright red (Eu-CPPs) and green (Tb-CPPs) fluorescence upon exposure to UV light (λ_ex = 365 nm). Careful tuning of the stoichiometric ratio of Eu(iii) and Tb(iii) helped in achieving water-soluble white-emitting Ln-CPPs, which could offer a suitable pathway for preparing white-luminescent materials in water systems. Due to their stability in water, in our next work efforts will be focused on exploring their potential applications in biological and environmental areas as luminescence sensing and quantitative detection materials.     

High acidity cellulose sulfuric acid from sulfur trioxide: a highly efficient catalyst for the one step synthesis of xanthene and dihydroquinazolinone derivatives

A cellulose sulfonate catalyst (HS-cellulose sulfonate) with high stability, excellent catalytic activity and high acidity value (about 1.55 mmol g⁻¹) was successfully prepared by SO₃ gas phase sulfonation. The basic morphology and nanostructure of the catalyst were determined by HRTEM, XRD, IR, TG, etc. In addition, the catalyst was applied to the catalytic reaction of a dihydroquinazolinone derivative and a xanthene compound, and very valuable results were obtained. The development and preparation of cellulose sulfonate catalysts provide a good approach for the development and application of cellulose, and also an important application of green organic catalytic synthesis methodology.

The HS-cellulose sulfonate catalysed green and efficient one-step synthesis of xanthene and dihydroquinazolinone derivatives.     

An ultrasensitive Fano resonance biosensor using two dimensional hexagonal boron nitride nanosheets: theoretical analysis

This study proposed a novel Fano resonance (FR) biosensor with ultrahigh detection sensitivity by integrating two dimensional (2D) hexagonal boron nitride (h-BN) nanosheets with a plasmonic silver film–silicon hybrid nanostructure. Owing to its ultralow-loss in surface plasmon polaritons (SPPs), 2D h-BN nanosheets can act as a planar photon waveguide (PWG) for generating energy level splitting. Notably, both asymmetric FR sharp lines and plasmon induced transparency (PIT) can be produced by modulating the coupling strength between the planar PWG mode provided by h-BN nanosheets and the surface plasmon polariton (SPP) mode in the silver film–silicon hybrid nanostructure. Compared with conventional phase-modulation SPR biosensors, our proposed configuration based on Fano resonance can produce ultrahigh reflectivity of 0.934 and overcome the limitation of quasi-darkness reflectivity which is difficult for further phase extraction. More importantly, our proposed FR configuration can provide a promising phase detection sensitivity as high as 3.13 × 10⁶ degree per RIU (refractive index unit, RIU), which is enhanced by almost 100 times compared with conventional phase-modulation SPR biosensors. In addition, our proposed configuration has also shown the characteristics of multiple-order Fano resonances, largely depending on the partial coupling between the SPP mode and the different-order PWG mode. Our proposed FR biosensor can provide a highly promising candidate for designing a multiple-order FR platform for performing ultrasensitive detection.

This paper proposed an ultrasensitive FR biosensor with multiple-order characteristics using two dimensional hexagonal boron nitride nanosheets in the visible region.     

Branched polyethyleneimine-assisted 3-carboxybenzoboroxole improved Wulff-type boronic acid functionalized magnetic nanoparticles for the specific capture of cis-diol-containing flavonoids under neutral conditions

Flavonoids have shown a variety of biological activities such as antimicrobial, antibacterial, antifungal, antiviral, antiinflammatory, antitumor, antiatherogenic, and antihyperglycemic activities. A lot of important flavonoids contain cis-diols such as rutin (Ru), quercetin (Qu), luteolin (Lu), myricetin (Myr) and baicalein (Ba) and so on. It is necessary to establish a simple, low-cost and efficient purification method for cis-diol-containing flavonoids from plant extracts. Boronate affinity materials are able to reversibly bind the cis-diols via boronic acids by forming a five- or six-membered boronic cyclic ester in aqueous media. However, conventional boronate affinity materials have to be used in alkaline media, which can lead to the oxidation of cis-diols in compounds. In this study, the polyethyleneimine (PEI)-assisted 3-carboxybenzoboroxole-functionalized magnetic nanoparticles (MNPs) were prepared to achieve efficient capture of cis-diol-containing flavonoids under neutral conditions. Branched PEI was applied as a scaffold to amplify the number of boronic acid moieties, while 3-carboxybenzoboroxole, exhibiting high affinity and excellent water solubility toward flavonoids, was used as an affinity ligand. The prepared boronate affinity MNPs exhibited high binding capacity and fast binding kinetics (equilibrium in 3 min) under neutral conditions. In addition, the obtained boronate affinity MNPs exhibited high binding affinity (K_d ≈ 10⁻⁴ M), low binding pH (pH ≥ 6.0) and tolerance of the interference to abundant sugars.

Flavonoids have shown a variety of biological activities such as antimicrobial, antibacterial, antifungal, antiviral, antiinflammatory, antitumor, antiatherogenic, and antihyperglycemic activities.     

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE) and hepatic arterial infusion chemotherapy(HAIC) have shown promising local benefits for advanced hepatocellular carcinoma(HCC). S-1, a composite preparation of a 5-fluorouracil prodrug, has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC.AIM To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC.METHODS In this single-center, open-label, prospective, randomized controlled trial, 117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with(TACE/HAIC + S-1, n = 56) or without(TACE/HAIC, n = 61) oral S-1 between December 2013 and September 2017. Two participants were excluded from final analysis for withdrawing consent. The primary endpoint was progression-free survival(PFS) and secondary endpoints included overall survival(OS), objective response rate, disease control rate and safety.RESULTS In total, 115 participants(100 males and 15 females; mean age, 57.7 years ± 11.9) were analyzed. The median PFS and OS were 5.0 mo(0.4–58.6 mo)(95% confidence interval(CI): 3.82 to 6.18) vs 4.4 mo(1.1–54.4 mo)(95%CI: 2.54 to 6.26; P = 0.585) and 8.4 mo(0.4–58.6 mo)(95%CI: 6.88 to 9.92) vs 8.3 mo(1.4–54.4 m)(95%CI: 5.71 to 10.96; P = 0.985) in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. The objective response rate and disease control rate were 30.9% vs 18.4% and 72.7% vs 56.7% in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. Grade 3/4 adverse events had a similar frequency in both treatment groups.CONCLUSION No improvements in tumor response rates, PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC. Both treatment regimens had a similar safety profile.     

单节段颈前路椎间盘切除植骨融合术后颈椎椎间高度和整体曲率的影像学变化

目的 本研究旨在探讨单节段颈椎前路椎间盘切除减压植骨融合术(anterior cervical discectomy and fusion, ACDF)后颈椎椎间高度及颈椎整体曲度的变化。方法 回顾性分析接受单节段ACDF治疗的119名脊髓型颈椎病患者的病例及影像学资料。通过使用患者的颈椎X线平片测量融合前后椎间隙的高度。同时测量侧位片上第2颈椎至第7颈椎的Cobb角,以评估颈椎的整体曲度。通过比较术前和术后的影像学资料,以说明置入椎间融合器对颈椎椎间高度和整体曲度的影响。结果 术后神经功能JOA及Nurick评分较术前明显改善（P<0.01）。术前椎间前高度（anterior intervertebral height, AIH）和椎间后高度（posterior intervertebral height, PIH）均明显低于正常椎间高度（P<0.01）,术后AIH明显升高,恢复正常;术后PIH与术前相比同样明显增加。术后颈椎曲度[（22.36±5.07）°]较术前[（16.53±6.85）°]明显增加（P<0.01）,但是并未恢复至正常曲度。结论 ACDF手术能够完成有效的神经减压改善神经功能,并且该手术能够恢复颈椎退变节段的椎间高度及改善颈椎整体曲度。