Cost-effectiveness of brentuximab vedotin compared with conventional chemotherapy for relapsed or refractory classic Hodgkin lymphoma in China.

BACKGROUND: Relapsed or refractory classic Hodgkin lymphoma (RRcHL) associates with poor prognosis and heavy disease burden to patients. This study evaluated the cost-effectiveness of brentuximab vedotin (BV) in comparison to conventional chemotherapy in patients with RRcHL, from a Chinese healthcare perspective. METHODS: The lifetime cost and quality adjusted life years (QALYs) were estimated through a partitioned survival model with three health states (progression free, post progression, and death). Two cohorts for each BV arm and chemotherapy arm were built, representing patients with and without transplant after BV or chemotherapy, respectively. Clinical parameters were retrieved from BV trials and the literature. Resource utilization data were mainly collected from local expert surveys and cost parameters were reflecting local unit prices. Utility values were sourced from the literature. A discount rate of 5% was employed according to the Chinese guideline. A series of deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness and uncertainty associated with the model. RESULTS: Results of the base case analysis showed that the incremental cost-effectiveness ratio (ICER) for BV versus chemotherapy was $2,867 (¥19,774). The main model driver was the superior progression-free and overall survival benefits of BV. The ICERs were relatively robust in a series of sensitivity analyses, all under a conventional decision threshold (1 time of Chinese per capita GDP). With this conventional threshold, the probability of BV being cost-effective was 100%. CONCLUSIONS: Brentuximab vedotin can be considered a cost-effective treatment versus conventional chemotherapy in treating relapsed or refractory classic Hodgkin lymphoma in China.

Phenotypic and genomic insights into mutant with high nattokinase-producing activity induced by carbon ion beam irradiation of Bacillus subtilis.

Nattokinase (NK) is found in fermented foods and has high fibrinolytic activity, which makes it promising for biological applications. In this study, a mutant strain (Bacillus subtilis ZT-S1, 5529.56 ± 183.59 U/mL) with high NK-producing activity was obtained using 12C6+ heavy ion beam mutagenesis for the first time. The surface morphology of B. subtilis is also altered by changes in functional groups caused by heavy ion beams. Furthermore, B. subtilis ZT-S1 required more carbon and nitrogen sources and reached stabilization phase later. Comparative genome analysis revealed that most of the mutant implicated genes (oppA, appA, kinA, spoIIP) were related to spore formation. And the affected rpoA is related to the synthesis of the NK-coding gene aprE. In addition, the B. subtilis ZT-S1 obtained by mutagenesis had good genetic stability. This study further explores the factors affecting NK activity and provides a promising microbial resource for NK production in commercial applications.

Insights into the oral microbiota in human systemic cancers.

The oral cavity stands as one of the pivotal interfaces facilitating the intricate interaction between the human body and the external environment. The impact of diverse oral microorganisms on the emergence and progression of various systemic cancers, typified by oral cancer, has garnered increasing attention. The potential pathogenicity of oral bacteria, notably the anaerobic Porphyromonas gingivalis and Fusobacterium nucleatum, has been extensively studied and exhibits obvious correlation with different carcinoma types. Furthermore, oral fungi and viruses are closely linked to oropharyngeal carcinoma. Multiple potential mechanisms of oral microbiota-induced carcinogenesis have been investigated, including heightened inflammatory responses, suppression of the host immune system, influence on the tumor microenvironment, anti-apoptotic activity, and promotion of malignant transformation. The disturbance of microbial equilibrium and the migration of oral microbiota play a pivotal role in facilitating oncogenic functions. This review aims to comprehensively outline the pathogenic mechanisms by which oral microbiota participate in carcinogenesis. Additionally, this review delves into their potential applications in cancer prevention, screening, and treatment. It proves to be a valuable resource for researchers investigating the intricate connection between oral microbiota and systemic cancers.

Preclinical evaluation of the SARS-CoV-2 Mpro inhibitor RAY1216 shows improved pharmacokinetics compared with nirmatrelvir.

Although vaccines are available for SARS-CoV-2, antiviral drugs such as nirmatrelvir are still needed, particularly for individuals in whom vaccines are less effective, such as the immunocompromised, to prevent severe COVID-19. Here we report an α-ketoamide-based peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro), designated RAY1216. Enzyme inhibition kinetic analysis shows that RAY1216 has an inhibition constant of 8.4 nM and suggests that it dissociates about 12 times slower from Mpro compared with nirmatrelvir. The crystal structure of the SARS-CoV-2 Mpro:RAY1216 complex shows that RAY1216 covalently binds to the catalytic Cys145 through the α-ketoamide group. In vitro and using human ACE2 transgenic mouse models, RAY1216 shows antiviral activities against SARS-CoV-2 variants comparable to those of nirmatrelvir. It also shows improved pharmacokinetics in mice and rats, suggesting that RAY1216 could be used without ritonavir, which is co-administered with nirmatrelvir. RAY1216 has been approved as a single-component drug named 'leritrelvir' for COVID-19 treatment in China.

Cryo-EM structures of Mycobacterium tuberculosis polynucleotide phosphorylase suggest a potential mechanism for its RNA substrate degradation.

As one of the oldest infectious diseases in the world, tuberculosis (TB) is the second most deadly infectious disease after COVID-19. Tuberculosis is caused by Mycobacterium tuberculosis (Mtb), which can attack various organs of the human body. Up to now, drug-resistant TB continues to be a public health threat. Pyrazinamide (PZA) is regarded as a sterilizing drug in the treatment of TB due to its distinct ability to target Mtb persisters. Previously we demonstrated that a D67N mutation in Mycobacterium tuberculosis polynucleotide phosphorylase (MtbPNPase, Rv2783c) confers resistance to PZA and Rv2783c is a potential target for PZA, but the mechanism leading to PZA resistance remains unclear. To gain further insight into the MtbPNPase, we determined the cryo-EM structures of apo Rv2783c, its mutant form and its complex with RNA. Our studies revealed the Rv2783c structure at atomic resolution and identified its enzymatic functional groups essential for its phosphorylase activities. We also investigated the molecular mechanisms underlying the resistance to PZA conferred by the mutation. Our research findings provide structural and functional insights enabling the development of new anti-tuberculosis drugs.

In situ bio-mineralized Mn nanoadjuvant enhances anti-influenza immunity of recombinant virus-like particle vaccines.

Virus like particles (VLPs) have been well recognized as one of the most important vaccine platforms due to their structural similarity to natural viruses to induce effective humoral and cellular immune responses. Nevertheless, lack of viral nucleic acids in VLPs usually leads the vaccine candidates less efficient in provoking innate immune against viral infection. Here, we constructed a biomimetic dual antigen hybrid influenza nanovaccines THM-HA@Mn with robust immunogenicity via in situ synthesizing a stimulator of interferon genes (STING) agonist Mn3O4 inside the cavity of a recombinant Hepatitis B core antigen VLP (HBc VLP) having fused SpyTag and influenza M2e antigen peptides (Tag-HBc-M2e, THM for short), followed by conjugating a recombinant hemagglutinin (rHA) antigen on the surface of the nanoparticles through SpyTag/SpyCatcher ligating. Such inside Mn3O4 immunostimulator-outside rHA antigen design, together with the chimeric M2e antigen on the HBc skeleton, enabled the synthesized hybrid nanovaccines THM-HA@Mn to well imitate the spatial distribution of M2e/HA antigens and immunostimulant in natural influenza virus. In vitro cellular experiments indicated that compared with the THM-HA antigen without Mn3O4 and a mixture vaccine consisting of THM-HA + MnOx, the THM-HA@Mn hybrid nanovaccines showed the highest efficacies in dendritic cells uptake and in promoting BMDC maturation, as well as inducing expression of TNF-α and type I interferon IFN-ß. The THM-HA@Mn also displayed the most sustained antigen release at the injection site, the highest efficacies in promoting the DC maturation in lymph nodes and germinal center B cells activation in the spleen of the immunized mice. The co-delivery of immunostimulant and antigens enabled the THM-HA@Mn nanovaccines to induce the highest systemic antigen-specific antibody responses and cellular immunogenicity in mice. Together with the excellent colloid dispersion stability, low cytotoxicity, as well as good biosafety, the synthetic hybrid nanovaccines presented in this study offers a promising strategy to design VLP-based vaccine with robust natural and adaptive immunogenicity against emerging viral pathogens.

Effect of modified okara insoluble dietary fibre on the quality of yoghurt.

The aim of this study was to investigate the potential of adding soya bean dregs insoluble dietary fibre (IDF) modified by jet cavitation combined with cellulase to yoghurt to improve its functional properties (Yoghurt was prepared by adding 10 µL of yoghurt fermenter to 100 mL of milk, fermented to pH 4.5 in a constant temperature incubator at 42 °C, and then stored in a refrigerator at 4 °C after adding IDF separately). The results showed that the modified IDF had a rough structure with high water-holding capacity and sodium cholate adsorption capacity. The addition of modified IDF improved the pH, hardness, and elasticity of the yoghurt. During the entire storage period, the titratable acidity and whey precipitation rate of the modified IDF yoghurt gradually increased, and antioxidant activity gradually decreased, and its titratable acidity, whey precipitation rate, and antioxidant activity had a significant advantage compared with those of the blank group yoghurt. In conclusion, the modified soya bean dregs IDF-added yoghurt prepared by jet cavitation combined with the cellulase method has the potential for sodium cholate adsorption capacity and antioxidant activity, which can confer unique functional properties and improve the pH, texture, and reduce whey precipitation of yoghurt. This study provides a scientific basis for the application of soya bean dregs IDF as a fibre fortifier in yoghurt production and suggests innovative ideas for the design of functional dairy products.

Vitexin Regulates Heat Shock Protein Expression by Modulating ROS Levels Thereby Protecting against Heat-Stress-Induced Apoptosis.

Heat stress due to high temperatures can cause heat stroke, pyrexia, heat cramps, heart disease, and respiratory diseases, which seriously affect human health. Vitexin has been shown to alleviate heat stress; however, its mechanism of action remains unclear. Therefore, in this study, we used Caco-2 cells to establish a heat stress model and vitamin C as a positive control to investigate the regulatory effects of vitexin on heat-stress-induced apoptosis and the related mechanisms using Cell Counting Kit-8, flow cytometry, real-time quantitative polymerase chain reaction, and Western blot. The results showed that the mRNA expressions of Hsp27, Hsp70, and Hsp90 induced by heat stress could be effectively inhibited at vitexin concentrations as low as 30 µM. After heat stress prevention and heat stress amelioration in model cells based on this concentration, intracellular reactive oxygen species (ROS) levels and the mRNA level and the protein expression of heat shock proteins (Hsp70 and Hsp90) and apoptotic proteins were reduced. In addition, compared with the heat stress amelioration group, the expression of BCL2 mRNA and its protein (anti-apoptotic protein Bcl-2) increased in the heat stress prevention group, while the expression of BAX, CYCS, CASP3, and PARP1 mRNAs and their proteins (apoptotic proteins Bax, Cytochrome C, cle-Caspase-3, and cle-PARP1) were decreased. In summary, the heat-stress-preventive effect of vitexin was slightly better than its heat-stress-ameliorating effect, and its mechanism may be through the inhibition of intracellular ROS levels and thus the modulation of the expressions of Hsp70 and Hsp90, which in turn protects against heat-stress-induced apoptosis. This study provides a theoretical basis for the prevention and amelioration of heat stress using vitexin.

Study of self-assembling properties of HBc-VLP derivatives aided by molecular dynamic simulations from a thermodynamic perspective.

Self-assembling protein nanoparticles showed promise for vaccine design due to efficient antigen presentations and safety. However, the unpredictable formations of epitopes-fused protein assemblies remain challenging in the upstream design. This study suggests employing molecular dynamic (MD) simulations to investigate the assembly properties of Hepatitis B core protein (HBc) from thermodynamic perspectives. Eight HBc derivatives were expressed in E. coli, with their self-assembly properties characterised by high-performance liquid chromatography and transmission electron microscopy. MD simulations on the dimers, based on AlphaFold-predicted 3D structures, analysed the derivative at the atomic level. Results revealed that HBc derivatives can form dissociative polymers or large multi-subunit structures due to assembly failures. The instability of the dimer in aqueous solvents or inappropriate intradimer distances could cause major assembly failures. Polar solvation energies played a vital role too in forming assemble-incompetent dimers. Importantly, our study demonstrated that MD simulations on dimers can provide preliminary predictions on the assembly properties of HBc derivatives, thus aiding vaccine design by lowering the risk of self-assembling failures in engineered proteins.Communicated by Ramaswamy H. Sarma.

The position of Spy Tag/Catcher system in hepatitis B core protein particles affects the immunogenicity and stability of the synthetic vaccine.

Presenting exogenous antigens on virus-like particles (VLPs) through "plug-and-display" decoration strategies based on SpyTag/SpyCatcher isopeptide bonding have emerged as attractive technology for vaccine synthesis. However, whether the position of ligation site in VLPs will impose effects on immunogenicity and physiochemical properties of the synthetic vaccine remains rarely investigated. Here in the present work, the well-established hepatitis B core (HBc) protein was used as chassis to construct dual-antigen influenza nanovaccines, with the conserved epitope peptides derived from extracellular domain of matrix protein M2 (M2e) and hemagglutinin (HA) as target antigens. The M2e antigen was genetically fused to the HBc in the MIR region, together with the SpyTag peptide, which was fused either in the MIR region or at the N-terminal of the protein, so that a recombinant HA antigen (rHA) linked to SpyCatcher can be displayed on it, at two different localizations. Both synthetic nanovaccines showed ability in inducing strong M2e and rHA-specific antibodies and cellular immunogenicity; nevertheless, the one in which rHA was conjugated by N-terminal Tag ligation, was superior to another one synthesized by linking the rHA to MIR region SpyTagged-HBc in all aspects, including higher antigen-specific immunogenicity responses, lower anti-HBc carrier antibody, as well as better dispersion stability. Surface charge and hydrophobicity properties of the two synthetic nanovaccines were analyzed, results revealed that linking the rHA to MIR region SpyTagged-HBc lead to more significant and disadvantageous alteration in physiochemical properties of the HBc chassis. This study will expand our knowledge on "plug-and-display" decoration strategies and provide helpful guidance for the rational design of HBc-VLPs based modular vaccines by using SpyTag/Catcher synthesis.

Effects of cavitation-jet technology combined with enzyme treatment on the structure properties and functional properties of OKARA insoluble dietary fiber.

In this study, a new composite modification method utilizing a cavitation jet combined with a composite enzyme (cellulase and xylanase) was developed to modify the insoluble dietary fibre (IDF) of okara (IDF was first treated with the cavitation jet at 0.3 MPa for 10 min, and then 6% of the enzyme was added, the composite enzyme with a 1:1 enzyme activity was hydrolysed for 1.5 h to obtain the modified IDF), and explored the structure-activity relationship between the structural properties, physicochemical properties and biological activities of IDF before and after modification. Under the action of cavitation jet and double enzyme hydrolysis, the modified IDF had a wrinkled and loose porous structure, which improved the thermal stability. Its water holding capacity (10.81 ± 0.17 g/g), oil holding capacity (4.83 ± 0.03 g/g) and swelling capacity (18.60 ± 0.60 mL/g) were significantly higher than those of unmodified IDF. In addition, compared with other IDFs, the combined modified IDF had greater advantages in nitrite adsorption (13.75 ± 0.14 µg/g), glucose adsorption (6.46 ± 0.28 mmol/g) and cholesterol adsorption (16.86 ± 0.83 mg/g), and improved in vitro probiotic activity and in vitro anti-digestion rate. The results show that the cavitation jet combined with compound enzyme modification method can effectively improve the economic value of okara.

Synthesis of a crystalline zeolitic imidazole framework-8 nano-coating on single environment-sensitive viral particles for enhanced immune responses.

Encapsulating antigens with zeolitic imidazole framework-8 (ZIF-8) exhibits many advantages in vaccine development. However, most viral antigens with complex particulate structures are sensitive to pH or ionic strength, which cannot tolerate harsh synthesis conditions of ZIF-8. Balancing the viral integrity and the growth of ZIF-8 crystals is crucial for the successful encapsulation of these environment-sensitive antigens in ZIF-8. Here, we explored the synthesis of ZIF-8 on inactivated foot and mouth disease virus (known as 146S), which is easily disassociated into no immunogenic subunits under the existing ZIF-8 synthesis conditions. Our results showed that intact 146S could be encapsulated into ZIF-8 with high embedding efficiency by lowering the pH of the 2-MIM solution to 9.0. The size and morphology of 146S@ZIF-8 could be further optimized by increasing the amount of Zn2+ or adding cetyltrimethylammonium bromide (CTAB). 146S@ZIF-8 with a uniform diameter of about 49 nm could be synthesized by adding 0.01% CTAB, which was speculated to be composed of single 146S armored with nanometer-scale ZIF-8 crystal networks. Plenty of histidine on the 146S surface forms a unique His-Zn-MIM coordination in the near vicinity of 146S particles, which greatly increases the thermostability of 146S by about 5 °C, and the nano-scale ZIF-8 crystal coating exhibited extraordinary stability to resist EDTE-treatment. More importantly, the well-controlled size and morphology enabled 146S@ZIF-8(0.01% CTAB) to facilitate antigen uptake. The immunization of 146S@ZIF-8(4×Zn2+) or 146S@ZIF-8(0.01% CTAB) significantly enhanced the specific antibody titers and promoted the differentiation of memory T cells without adding another immunopotentiator. This study reported for the first time the strategy of the synthesis of crystalline ZIF-8 on an environment-sensitive antigen and demonstrated that the nano-size and appropriate morphology of ZIF-8 are crucial to exert adjuvant effects, thus expanding the application of MOFs in vaccine delivery.

Microbial nattokinase: from synthesis to potential application.

Nattokinase (NK) is an alkaline serine protease with strong thrombolytic activity produced by Bacillus spp. or Pseudomonas spp. It is a potential therapeutic agent for thrombotic diseases because of its safety, economy, and lack of side effects. Herein, a comprehensive summary and analysis of the reports surrounding NK were presented, and the physical-chemical properties and producers of NK were first described. The process and mechanism of NK synthesis were summarized, but these are vague and not specific enough. Further results may be achieved if detection techniques such as multi-omics are used to explore the process of NK synthesis. The purification of NK has problems such as a complicated operation and low recovery rate, which were found when summarizing the techniques to improve the quality of finished products. If multiple simple and efficient precipitation methods and purification materials are combined to purify NK, it may be possible to solve the current challenges. Additionally, the application potential of NK in biomedicine was reviewed, but functional foods with NK are challenging for acceptance in daily life due to their unpleasant odor. Accordingly, multi-strain combination fermentation or food flavoring agents can improve the odor of fermented foods and increase people's acceptance of them. Finally, the possible future directions focused on NK studies were proposed and provided suggestions for subsequent researchers.

Effect of High Pressure/Heating Combination on the Structure and Texture of Chinese Traditional Pig Trotter Stewed with Soy Sauce.

In order to clarify the effect of a high pressure/heating combination on the texture of Chinese traditional pig trotter with soy sauce, textural parameters (springiness, chewiness, hardness, and gumminess), the secondary structures, cross-links, decorin (DCN), glycosaminoglycans (GAGs) levels, and the histochemical morphology of collagen fibers under different treatments (0.1 MPa, 150 MPa, 300 MPa, 0.1 MPa + 50 °C, 150 MPa + 50 °C, and 300 MPa + 50 °C) were assessed. At room temperature, the 150 and 300 MPa treatments increased the hardness and chewiness of the pig trotter with weak denaturation of collagen proteins compared with the control group. Textural parameters were improved at 300 MPa + 50 °C, accompanied by an ultrastructural collapse of collagen fibers, the reduction in cross-links, DCN and GAGs levels, and unfolded triple-helix structure. We concluded that the positive effects on the textural parameters of pig trotters by a combination of treatments could be attributed to the collapse of collagen structure.

Oil-in-ionic liquid nanoemulsion-based adjuvant simultaneously enhances the stability and immune responses of inactivated foot-and-mouth disease virus.

Maintaining structural integrity and enhancing stability of inactivated foot-and-mouth disease virus (iFMDV) antigen in adjuvants is crucial to ensure the vaccine potency. Unfortunately, formulation with most reported adjuvants leads to the accelerated dissociation of iFMDV into inactive pentamers. Here, an ionic liquid, i.e., choline and niacin ([Cho][Nic]), which was found to stabilize iFMDV against the acid- and thermo- induced dissociation in buffer solution, was applied to construct a novel oil-in-ionic liquid (o/IL) nanoemulsion adjuvant composed of [Cho][Nic], squalene, and Tween 80. The o/IL nanoemulsion formulated with iFMDV has a monodisperse diameter of 135.8 ± 40.4 nm. The thermostability and long-term stability of iFMDV were remarkably enhanced in o/IL nanoemulsion compared with that in the o/w emulsion without [Cho][Nic] and in the commercial Montanide ISA 206 adjuvant. The o/IL nanoemulsion exerted its adjuvant effects by improving the humoral immune responses. Immunization of o/IL nanoemulsion adjuvanted iFMDV induced specific IgG titers similar to that adjuvanted by Montanide ISA 206 and about 4-fold higher than the un-adjuvanted iFMDV, also promoted the activation of B lymphocytes and the secretion of interleukin-4 in the mice model. This [Cho][Nic]-based o/IL nanoemulsion can serve as a promising adjuvant platform for the foot-and-mouth disease vaccine.

Cost-effectiveness analysis of vonoprazan versus proton pump inhibitors in the treatment of reflux esophagitis in China.

Background: Proton pump inhibitors (PPIs) have been recommended as standard of care for reflux esophagitis (RE). Vonoprazan (VPZ), a novel potassium-competitive acid blocker (P-CAB), has been approved in China after demonstrating clinical benefit in RE. However, there are not any published literature reported the cost-effectiveness of VPZ compared with PPI in Chinese healthcare setting. Thus, this study aimed to estimate the cost-effectiveness of VPZ compared with PPIs for the treatment of RE patients in China and take advantage of this result to inform healthcare decision-making. Methods: A Markov model was developed to predict the effectiveness and costs of VPZ for 4 weeks and PPI group for 8 weeks in RE treatment over a 5-year time horizon from a healthcare system perspective. Four health states within healing and maintenance phases were defined in the model: mucosa healed, mucosa unhealed, relapse, and death. Transition probabilities including healing rate and relapse rate were derived from a single-arm meta-analysis and mortality were obtained from Chinese life table. Drug costs and other medical expenses were retrieved from China tendering prices and local clinical expert estimation. Utility parameters were derived from published literature. Both health outcomes and costs were discounted at a rate of 5% annually. Quality-adjusted life years (QALYs), direct medical costs and incremental cost-effectiveness ratios were evaluated. Uncertainty was assessed by one-way and probabilistic sensitivity analysis (PSA). Results: The healing rate for VPZ and PPI were 90% (95% CI: 82-97%) and 74% (95% CI: 71-76%) at week 4 respectively and were 94% (95% CI: 88-99%) and 87% (95% CI: 85-88%) at week 8 respectively. Treatment with VPZ resulted in 4.35 QALYs at a total cost of USD 1,354 over 5 years. Compared with the PPI group, treating RE with VPZ was associated with 0.02 QALYs gained and a cost saving of USD 943. Thus, VPZ should be considered as the dominant treatment option. The model results were deemed robust in sensitivity analyses. Conclusions: VPZ generates incremental QALYs at a lower cost compared with PPI, thus could be considered as an optional choice in the treatment of patients with RE.

Oil-in-ionic liquid nanoemulsion-based intranasal delivery system for influenza split-virus vaccine.

Effective antigen delivery and immune stimulation in nasal mucosa determine the success of mucosal immunity. Here, an oil-in-ionic liquid (o/IL) nanoemulsion formulated with choline and niacin IL ([Cho][Nic]), squalene, and Tween 80 surfactant is explored as a vaccine delivery system for intranasal mucosal immunization. Compared to the o/w emulsion counterpart without the ILs, the o/IL manoemulsion showed a reduced and more uniform size of approximately 168 nm and significantly improved stability. Studies in mice model showed that when was used as an intranasal vaccine delivery system for influenza split-virus antigens, the antigens in the o/IL nanoemulsion induced strong mucosal immune responses with secretory IgA titers 25- and 5.8-fold higher than those of naked and commercial MF59-adjuvanted antigens, respectively. The o/IL nanoemulsion system also induced stronger systemic humoral responses. The excellent mucosal adjuvant effects of the o/IL nanoemulsion mainly benefited from the prolonged retention of antigens in the nasal cavity, enhanced antigen permeation into the submucosa, and the consequently promoted proliferation of CD11b cells and CD4+ T cells in nasal mucosa-associated lymphoid tissue. Moreover, when used as an injection adjuvant, the o/IL nanoemulsion also induced stronger humoral immune responses than MF59. Thus, the [Cho][Nic]-based o/IL nanoemulsion vaccine delivery system can serve as a promising adjuvant platform.

Effects of L1 Transfer Are Profound, Yet Native-Like Processing Strategy Is Attainable: Evidence From Advanced Learners' Production of Complex L2 Chinese Structures.

English as a verb-medial language has a short-before-long preference, whereas Korean and Japanese as verb-final languages show a long-before-short preference. In second language (L2) research, little is known regarding how L1 processing strategies affect the ultimate attainment of target structures. Existing work has shown that native speakers of Chinese strongly prefer to utter demonstrative-classifier (DCL) phrases first in subject-extracted relatives (DCL-SR-N) and DCLs second in object-extracted relatives (OR-DCL-N). But it remains unknown whether L2 learners with typologically different language backgrounds are able to acquire native-like strategies, and how they deviate from native speakers or even among themselves. Using a phrase-assembly task, we investigated advanced L2-Chinese learners whose L1s were English, Korean, and Japanese, because English lacks individual classifiers and has postnominal relative clause (RC), whereas Korean and Japanese have individual classifiers and prenominal RCs. Results showed that the English and Korean groups deviated from the native controls' asymmetric pattern, but the Japanese group approximated native-like performance. Furthermore, compared to the English group, the Korean and Japanese groups favored the DCL-second configuration in SRs and ORs. No differences were found between the Korean and Japanese groups. Overall, our findings suggest that L1 processing strategies play an overarching role in L2 acquisition of asymmetric positioning of DCLs in Chinese RCs.

Cost-Effectiveness Analysis of Vedolizumab Compared With Infliximab in Anti-TNF-α-Naïve Patients With Moderate-to-Severe Ulcerative Colitis in China.

Objective: To evaluate the cost effectiveness of vedolizumab vs. infliximab in the treatment of anti-tumor necrosis factor-alpha (TNF-α)-naïve patients with moderate-to-severe active ulcerative colitis (UC) in China. Methods: The costs and effectiveness of vedolizumab and infliximab in the treatment of anti-TNF-α naïve patients with moderate-to-severe active UC were compared using a hybrid decision tree model and a Markov model. From the perspective of the Chinese healthcare system, this study simulated the lifetime health benefits [quality-adjusted life-years (QALYs)] and costs (USD) for patients with UC from the induction phase to the maintenance phase, with an annual discount rate of 5%. The clinical efficacy and transition probability data were based on a previously published network meta-analysis. The health utility, surgical risk, biologic drug discontinuation rate, and mortality were derived from previous literature and the Chinese statistical yearbook. The cost data were based on China's drug purchase and biding platform and the results of a survey sent to clinicians in 18 tertiary hospitals. One-way and probabilistic sensitivity analyses (PSAs) were performed to validate the robustness of the models' assumptions and specific parameter estimates. Results: The results of the base-case analyses showed that compared with infliximab, vedolizumab led to a gain of 0.25 QALYs (9.56 vs. 9.31 QALYs) and was less expensive by $7,349 ($180,138 vs. 187,487), indicating that the use of vedolizumab was a dominant strategy. The results of one-way sensitivity analyses suggested that the annual discount rate and health-state costs had the greatest impact, but the results were otherwise consistent with those of the base-case analyses. The PSAs suggested that vedolizumab had a 98.6% probability of being effective at a threshold of 3 times the gross domestic product (GDP) per capita in China in 2020. Conclusion: Compared with infliximab, vedolizumab appears to be a more cost-effective option in the treatment of anti-TNF-α naïve adult patients with moderate-to-severe, active UC in China.

Thermal-triggered packing of lipophilic NIR dye IR780 in hepatitis B core at critical ionic strength and cargo-host ratio for improved stability and enhanced cancer phototherapy.

Virus-like particles (VLPs) holding internal cavity with diameter from tens up to one hundred nanometers are attractive platform for drug delivery. Nevertheless, the packing of drugs in the nanocage mainly relies on complicated disassembly-reassembly process. In this study, hepatitis B core protein (HBc) VLPs which can withstand temperature up to 90 °C was employed as carrier to load a lipophilic near infrared dye IR780. It was found that an attaching-dis-atching-diffusing process was involved for the entering of IR780 in the cavity of HBc. The first two steps were associated with the electrostatic interactions between oppositely charged HBc and IR780, which was critically manipulated by ionic strength and HBc/IR780 mass ratio at which they were mixed; while the diffusion of IR780 across the shell of HBc showed a temperature-dependent manner that can be triggered by thermal induced pore-opening of the HBc capsid. At optimized condition, about 1055 IR780 molecules were encapsulated in each HBc by simply mixing them for 10 min at 60 °C. Compared with free IR780, the HBc-IR780 particles showed significantly improved aqueous and photostability, as well as enhanced photothermal and photodynamic performance for cancer therapy. This study provides a novel drug loading strategy and nanomemedicine for cancer phototherapies.