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1.
BMC Cancer ; 24(1): 754, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907215

ABSTRACT

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Brain Neoplasms , Glioma , Pyridines , Temozolomide , Humans , Temozolomide/administration & dosage , Temozolomide/therapeutic use , Temozolomide/adverse effects , Female , Male , Adult , Pyridines/administration & dosage , Pyridines/adverse effects , Pyridines/therapeutic use , Glioma/drug therapy , Glioma/pathology , Adolescent , Retrospective Studies , Child , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child, Preschool , Middle Aged , Treatment Outcome
2.
Angew Chem Int Ed Engl ; : e202405520, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896428

ABSTRACT

Functionalization of Si-bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon-stereogenic architectures by functionalization of Si-bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5-palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5-palladium migration reaction. The key to the success is the discovery and fine-tuning of the different substituents of α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based phosphoramidites, which ensure the enantioselectivity and desired reactivity.

3.
Molecules ; 28(11)2023 May 31.
Article in English | MEDLINE | ID: mdl-37298944

ABSTRACT

Versatile and concise Pd-catalyzed oxidative N-alkenylation of N-aryl phosphoramidates with alkenes is described in this study, a reaction that is of great significance but surprisingly unexploited. The transformation proceeds under mild reaction conditions, using O2 as a green oxidant and TBAB as an effective additive. An efficient catalytic system allows a variety of drug-related substrates to participate in these transformations, which is of great interest in the drug discovery and development of phosphoramidates.


Subject(s)
Alkenes , Palladium , Amination , Molecular Structure , Catalysis
4.
Angew Chem Int Ed Engl ; 62(41): e202306185, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37507837

ABSTRACT

Prussian blue (PB) has emerged as a promising cathode material in aqueous batteries. It possesses two distinct redox centers, and the potassium ions (K+ ) are unevenly distributed throughout the compound, adding complexity to the interpretation of the K+ insertion/de-insertion kinetic mechanism. Traditional ensemble-averaged measurements are limited in uncovering the precise kinetic information of the PB particles, as the results are influenced by the construction of the porous composite electrode and the redox behavior from different particles. In this study, the electrochemical processes of individual PB particles were investigated using nano-impact electrochemistry. By varying the potentials, different types of transient current signals were obtained that revealed the kinetic mechanism of each oxidation/reduction reaction in combination with theoretical simulation. Additionally, a partially contradictory conclusion between single-particle analysis and the ensemble-averaged measurement was discussed. These findings contribute to a better understanding of the electrochemical processes of cathode materials with multiple redox centers, which facilitates the development of effective strategies to optimize these materials.

5.
Vet Res ; 53(1): 46, 2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35733156

ABSTRACT

A universal vaccine protecting against multiple serotypes of Streptococcus suis is urgently needed to improve animal welfare and reduce the consumption of antibiotics. In this study, a dual antigen expression cassette consisting of SS2-SaoA and SS9-Eno was delivered by a recombinant Salmonella Choleraesuis vector to form the vaccine candidate rSC0016(pS-SE). SaoA and Eno were simultaneously synthesized in rSC0016(pS-SE) without affecting the colonization of the recombinant vector in the lymphatic system. In addition, the antiserum of mice immunized with rSC0016(pS-SE) produced a broader and potent opsonophagocytic response against multiple serotypes of S. suis. Finally, rSC0016(pS-SE) provided mice with a 100% protection against a lethal dose of parent S. suis serotype 2 and serotype 9, and provided 90% and 80% protection against heterologous S. suis serotype 7 or 1/2. These values were significantly higher than those obtained with rSC0016(pS-SaoA) or rSC0016(pS-Eno). Together, this study serves as a foundation for developing a universal vaccine against multiple serotypes of S. suis.


Subject(s)
Bacterial Vaccines , Cross Protection , Salmonella enterica , Streptococcal Infections , Streptococcus suis , Animals , Bacterial Vaccines/immunology , Cross Protection/immunology , Disease Models, Animal , Mice , Salmonella enterica/genetics , Salmonella enterica/immunology , Serogroup , Streptococcal Infections/prevention & control , Streptococcal Infections/veterinary , Streptococcus suis/genetics , Streptococcus suis/immunology
6.
BMC Public Health ; 21(1): 226, 2021 01 27.
Article in English | MEDLINE | ID: mdl-33504339

ABSTRACT

BACKGROUND: As COVID-19 continues to spread around the world, understanding how patterns of human mobility and connectivity affect outbreak dynamics, especially before outbreaks establish locally, is critical for informing response efforts. In Taiwan, most cases to date were imported or linked to imported cases. METHODS: In collaboration with Facebook Data for Good, we characterized changes in movement patterns in Taiwan since February 2020, and built metapopulation models that incorporate human movement data to identify the high risk areas of disease spread and assess the potential effects of local travel restrictions in Taiwan. RESULTS: We found that mobility changed with the number of local cases in Taiwan in the past few months. For each city, we identified the most highly connected areas that may serve as sources of importation during an outbreak. We showed that the risk of an outbreak in Taiwan is enhanced if initial infections occur around holidays. Intracity travel reductions have a higher impact on the risk of an outbreak than intercity travel reductions, while intercity travel reductions can narrow the scope of the outbreak and help target resources. The timing, duration, and level of travel reduction together determine the impact of travel reductions on the number of infections, and multiple combinations of these can result in similar impact. CONCLUSIONS: To prepare for the potential spread within Taiwan, we utilized Facebook's aggregated and anonymized movement and colocation data to identify cities with higher risk of infection and regional importation. We developed an interactive application that allows users to vary inputs and assumptions and shows the spatial spread of the disease and the impact of intercity and intracity travel reduction under different initial conditions. Our results can be used readily if local transmission occurs in Taiwan after relaxation of border control, providing important insights into future disease surveillance and policies for travel restrictions.


Subject(s)
COVID-19/epidemiology , Communicable Diseases, Imported/epidemiology , Disease Outbreaks , Travel/statistics & numerical data , Forecasting , Humans , Models, Biological , Risk , Social Media , Taiwan/epidemiology , Travel/legislation & jurisprudence
7.
BMC Vet Res ; 16(1): 129, 2020 May 07.
Article in English | MEDLINE | ID: mdl-32381017

ABSTRACT

BACKGROUND: Recombinant Salmonella enterica serotype Choleraesuis (S. Choleraesuis) vaccine vector could be used to deliver heterologous antigens to prevent and control pig diseases. We have previously shown that a live-attenuated S. Choleraesuis vaccine candidate strain rSC0011 (ΔPcrp527::TT araC PBADcrp Δpmi-2426 ΔrelA199::araC PBADlacI TT ΔasdA33, Δ, deletion, TT, terminator) delivering SaoA, a conserved surface protein in most of S. suis serotypes, provided excellent protection against S. suis challenge, but occasionally lead to morbidity (enteritidis) in vaccinated mice (approximately 1 in every 10 mice). Thus, alternated attenuation method was sought to reduce the reactogenicity of strain rSC0011. Herein, we described another recombinant attenuated S. Choleraesuis vector, rSC0012 (ΔPfur88:: TT araC PBADfur Δpmi-2426 ΔrelA199:: araC PBADlacI TT ΔasdA33) with regulated delayed fur mutation to avoid inducing disease symptoms while exhibiting a high degree of immunogenicity. RESULTS: The strain rSC0012 strain with the ΔPfur88::TT araC PBADfur mutation induced less production of inflammatory cytokines than strain rSC0011 with the ΔPcrp527::TT araC PBADcrp mutation in mice. When delivering the same pS-SaoA plasmid, the intraperitoneal LD50 of rSC0012 was 18.2 times higher than that of rSC0011 in 3-week-old BALB/C mice. rSC0012 with either pS-SaoA or pYA3493 was cleared from spleen and liver tissues 7 days earlier than rSC0011 with same vectors after oral inoculation. The strain rSC0012 synthesizing SaoA induced high titers of anti-SaoA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes) sites, as well as increased level of IL-4, the facilitator of Th2-type T cell immune response in mice. The recombinant vaccine rSC0012(pS-SaoA) conferred high percentage of protection against S. suis or S. Choleraesuis challenge in BALB/C mice. CONCLUSIONS: The live-attenuated Salmonella enterica serotype Choleraesuis vaccine rSC0012(pS-SaoA) with regulated delayed fur mutation provides a foundation for the development of a safe and effective vaccine against S. Choleraesuis and S. suis.


Subject(s)
Salmonella enterica/genetics , Streptococcal Infections/immunology , Streptococcus suis/immunology , Animals , Female , Mice, Inbred BALB C , Mutation , Salmonella Vaccines/adverse effects , Salmonella Vaccines/genetics , Salmonella Vaccines/immunology , Serogroup , Streptococcus suis/genetics , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
8.
Vet Res ; 48(1): 89, 2017 12 21.
Article in English | MEDLINE | ID: mdl-29268787

ABSTRACT

Streptococcus suis is one of the major pathogens that cause economic losses in the swine industry worldwide. However, current bacterins only provide limited prophylactic protection in the field. An ideal vaccine against S. suis should protect pigs against the clinical diseases caused by multiple serotypes, or at least protect against the dominant serotype in a given geographic region. A new recombinant Salmonella enterica serotype Choleraesuis vaccine vector, rSC0011, that is based on the regulated delayed attenuation system and regulated delayed antigen synthesis system, was developed recently. In this study, an improved recombinant attenuated Salmonella Choleraesuis vector, rSC0016, was developed by incorporating a sopB mutation to ensure adequate safety and maximal immunogenicity. In the spleens of mice, rSC0016 colonized less than rSC0011. rSC0016 and rSC0011 colonized similarly in Peyer's patches of mice. The recombinant vaccine rSC0016(pS-SaoA) induced stronger cellular, humoral, and mucosal immune responses in mice and swine against SaoA, a conserved surface protein that is present in many S. suis serotypes, than did rSC0011(pS-SaoA) without sopB or rSC0018(pS-SaoA), which is an avirulent, chemically attenuated vaccine strain. rSC0016(pS-SaoA) provided 100% protection against S. suis serotype 2 in mice and pigs, and full cross-protection against SS7 in pigs. This new vaccine vector provides a foundation for the development of a universal vaccine against multiple serotypes of S. suis in pigs.


Subject(s)
Antigens, Bacterial/pharmacology , Salmonella enterica/immunology , Streptococcal Infections/veterinary , Streptococcal Vaccines/pharmacology , Streptococcus suis/immunology , Swine Diseases/prevention & control , Animals , Streptococcal Infections/immunology , Swine , Swine Diseases/immunology , Vaccines, Synthetic/immunology
9.
Pathol Res Pract ; 258: 155349, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38772115

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. Emerging evidence suggests that inflammation plays a crucial role in the pathogenesis of PD, with the NLRP3 inflammasome implicated as a key mediator. Nfon-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have recently garnered attention for their regulatory roles in various biological processes, including inflammation. This review aims to provide a mechanistic insight into how ncRNAs function as regulators of inflammatory pathways in PD, with a specific focus on the NLRP3 inflammasome. We discuss the dysregulation of miRNAs and lncRNAs in PD pathogenesis and their impact on neuroinflammation through modulation of NLRP3 activation, cytokine production, and microglial activation. Additionally, we explore the crosstalk between ncRNAs, alpha-synuclein pathology, and mitochondrial dysfunction, further elucidating the intricate network underlying PD-associated inflammation. Understanding the mechanistic roles of ncRNAs in regulating inflammatory pathways may offer novel therapeutic targets for the treatment of PD and provide insights into the broader implications of ncRNA-mediated regulation in neuroinflammatory diseases.


Subject(s)
Parkinson Disease , RNA, Untranslated , Parkinson Disease/genetics , Parkinson Disease/pathology , Parkinson Disease/metabolism , Humans , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , Inflammasomes/metabolism , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Inflammation/genetics , Inflammation/pathology , Inflammation/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Neuroinflammatory Diseases/pathology , Neuroinflammatory Diseases/genetics , Neuroinflammatory Diseases/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism
10.
Vet Microbiol ; 294: 110131, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38805917

ABSTRACT

Outer membrane vesicles (OMVs) are membranous structures frequently observed in Gram-negative bacteria that contain bioactive substances. These vesicles are rich in bacterial antigens that can activate the host's immune system, making them a promising candidate vaccine to prevent and manage bacterial infections. The aim of this study was to assess the immunogenicity and protective efficacy of OMVs derived from Salmonella enterica serovar Typhimurium and S. Choleraesuis, while also focusing on enhancing OMV production. Initial experiments showed that OMVs from wild-type strains did not provide complete protection against homologous Salmonella challenge, possible due to the presence of flagella in the purified OMVs samples, which may elicit an unnecessary immune response. To address this, flagellin-deficient mutants of S. Typhimurium and S. Choleraesuis were constructed, designated rSC0196 and rSC0199, respectively. These mutants exhibited reduced cell motility and their OMVs were found to be flagellin-free. Immunization with non-flagellin OMVs derived from rSC0196 induced robust antibody responses and improved survival rates in mice, as compared to the OMVs derived from the wild-type UK-1. In order to enhance OMV production, deletions of ompA or tolR were introduced into rSC0196. The deletion of tolR not only increase the yield of OMVs, but also conferred complete protection against homologous S. Typhimurium challenge in mice. Collectively, these findings indicate that the flagellin-deficient OMVs with a tolR mutation have the potential to serve as a versatile vaccine platform, capable of inducing broad-spectrum protection against significant pathogens.


Subject(s)
Bacterial Outer Membrane Proteins , Mice, Inbred BALB C , Salmonella Vaccines , Salmonella typhimurium , Animals , Salmonella typhimurium/immunology , Salmonella typhimurium/genetics , Mice , Salmonella Vaccines/immunology , Bacterial Outer Membrane Proteins/immunology , Bacterial Outer Membrane Proteins/genetics , Female , Flagellin/immunology , Flagellin/genetics , Salmonella Infections, Animal/prevention & control , Salmonella Infections, Animal/microbiology , Salmonella Infections, Animal/immunology , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Bacterial Outer Membrane/immunology , Salmonella/immunology , Salmonella/genetics , Immunogenicity, Vaccine , Antigens, Bacterial/immunology
11.
Langmuir ; 29(26): 8433-9, 2013 Jul 02.
Article in English | MEDLINE | ID: mdl-23758652

ABSTRACT

This work demonstrates a fast process to decorate silver (Ag) nanoparticles onto the functionalized few-walled carbon nanotubes (f-FWCNTs) and graphene nanosheets (f-GNs). The Ag-coated carbon nanomaterials were used as fillers, which mixed with poly(3,4-ethylenedioxythiophene)-poly(4-stryensulfonate) (PEDOT:PSS) for preparing high optoelectronic performances of flexible transparent conductive films (TCFs). The Ag nanoparticles with a particle size of approximate 5 nm were uniformly distributed on the surfaces of the f-FWCNTs (Ag@f-FWCNTs) and the f-GNs (Ag@f-GNs). The Ag ions play the role of electron acceptors during the reduction process, which increases the hole concentrations in PEDOT:PSS, f-FWCNTs, and f-GNs, therefore enhancing the electrical conductivity of the TCFs. Additionally, the Schottky barrier was decreased because of the increase of work functions of the carbon fillers caused by Ag decoration. The X-ray diffraction spectrum of Ag@f-GNs depicts the formations of the face-centered cubic Ag nanoparticles, and the peak of the (002) graphene plane slightly shifted to the lower frequency, indicating that the f-GN interlayer was intercalated with Ag ions or Ag nanoparticles. When the mixture of 2.0 wt % Ag@f-FWCNTs and 8.0 wt % Ag@f-GNs containing PEDOT:PSS dispersant was coated onto a poly(ethylene terephthalate) (PET) substrate, outstanding optoelectronic properties with a sheet resistance of 50.3 Ω/sq and a transmittance of 79.73% at a wavelength of 550 nm were achieved.

12.
Adv Sci (Weinh) ; 10(33): e2303568, 2023 11.
Article in English | MEDLINE | ID: mdl-37867213

ABSTRACT

Engineered vector-based in vivo protein delivery platforms have made significant progress for both prophylactic and therapeutic applications. However, the lack of effective release strategies results in foreign cargo being trapped within the vector, restricting the provision of significant performance benefits and enhanced therapeutic results compared to traditional vaccines. Herein, the development of a Salmonella mRNA interferase regulation vector (SIRV) system is reported to overcome this challenge. The genetic circuits are engineered that (1) induce self-lysis to release foreign antigens into target cells and (2) activate the cytosolic surveillance cGAS-STING axis by releasing DNA into the cytoplasm. Delayed synthesis of the MazF interferase regulates differential mRNA cleavage, resulting in a 36-fold increase in the delivery of foreign antigens and modest activation of the inflammasome, which collectively contribute to the marked maturation of antigen-presenting cells (APCs). Bacteria delivering the protective antigen SaoA exhibits excellent immunogenicity and safety in mouse and pig models, significantly improving the survival rate of animals challenged with multiple serotypes of Streptococcus suis. Thus, the SIRV system enables the effective integration of various modular components and antigen cargos, allowing for the generation of an extensive range of intracellular protein delivery systems using multiple bacterial species in a highly efficient manner.


Subject(s)
Antigens, Bacterial , Bacterial Vaccines , Animals , Mice , Swine , Bacterial Vaccines/genetics , Antigens, Bacterial/genetics , Antigens, Bacterial/metabolism , RNA, Messenger , Cell Death , Bacteria
13.
Vet Microbiol ; 287: 109915, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38000209

ABSTRACT

The adjuvant and/or vector significantly affect a vaccine's efficacy. Although traditional adjuvants such as alum have contributed to vaccine development, deficiencies in the induction of cellular and mucosal immunity have limited their further promotion. Salmonella vectors have unique advantages for establishing cellular and mucosal immunity due to mucosal pathways of invasion and intracellular parasitism. In addition, Salmonella vectors can activate multiple innate immune pathways, thereby promoting adaptive immune responses. In this work, the attenuated Salmonella enterica serovar Choleraesuis (S. Choleraesuis) vector rSC0016 was used to deliver the conserved protective antigen HPS_06257 of Glaesserella parasuis (G. parasuis), generating a novel recombinant strain rSC0016(pS-HPS_06257). The rSC0016(pS-HPS_06257) can express and deliver the HPS_06257 protein to the lymphatic system of the host. In comparison to HPS_06257 adjuvanted with alum, rSC0016(pS-HPS_06257) significantly increased TLR4 and TLR5 activation in mice as well as the levels of proinflammatory cytokines. In addition, rSC0016 promoted a greater degree of maturation in bone marrow-derived dendritic cells (BMDCs) than alum. The specific humoral, mucosal, and cellular immune responses against HPS_06257 in mice immunized with rSC0016(pS-HPS_06257) were significantly higher than those of HPS_06257 adjuvanted with alum. HPS_06257 delivered by the S. Choleraesuis vector induces a Th1-biased Th1/Th2 mixed immune response, while HPS adjuvanted with alum can only induce a Th2-biased immune response. HPS_06257 adjuvanted with alum only causes opsonophagocytic activity (OPA) responses against a homologous strain (G. parasuis serotype 5, GPS5), whereas rSC0016(pS-HPS_06257) could generate cross-OPA responses against a homologous strain and a heterologous strain (G. parasuis serotype 12, GPS12). Ultimately, HPS_06257 adjuvanted with alum protected mice against lethal doses of GPS5 challenge by 60 % but failed to protect mice against lethal doses of GPS12. In contrast, mice immunized with rSC0016(pS-HPS_06257) had 100 % or 80 % survival when challenged with lethal doses of GPS5 or GPS12, respectively. Altogether, the S. Choleraesuis vector rSC0016 could potentially generate an improved innate immune response and an improved adaptive immunological response compared to the traditional alum adjuvant, offering a novel concept for the development of a universal G. parasuis vaccine.


Subject(s)
Salmonella enterica , Vaccines , Mice , Animals , Serogroup , Adjuvants, Immunologic , Immunity, Cellular , Mice, Inbred BALB C
14.
Biomolecules ; 13(12)2023 11 30.
Article in English | MEDLINE | ID: mdl-38136597

ABSTRACT

Edema disease (ED) is a severe and lethal infectious ailment in swine, stemming from Shiga-toxin-producing Escherichia coli (STEC). An efficient, user-friendly, and safe vaccine against ED is urgently required to improve animal welfare and decrease antibiotic consumption. Recombinant attenuated Salmonella vaccines (RASV) administered orally induce both humoral and mucosal immune responses to the immunizing antigen. Their potential for inducing protective immunity against ED is significant through the delivery of STEC antigens. rSC0016 represents an enhanced recombinant attenuated vaccine vector designed for Salmonella enterica serotype Choleraesuis. It combines sopB mutations with a regulated delay system to strike a well-balanced equilibrium between host safety and immunogenicity. We generated recombinant vaccine strains, namely rSC0016 (pS-FedF) and rSC0016 (pS-rStx2eA), and assessed their safety and immunogenicity in vivo. The findings demonstrated that the mouse models immunized with rSC0016 (pS-FedF) and rSC0016 (pS-rStx2eA) generated substantial IgG antibody responses to FedF and rStx2eA, while also provoking robust mucosal and cellular immune responses against both FedF and rStx2eA. The protective impact of rSC0016 (pS-FedF) against Shiga-toxin-producing Escherichia coli surpassed that of rSC0016 (pS-rStx2eA), with percentages of 83.3%. These findings underscore that FedF has greater suitability for vaccine delivery via recombinant attenuated Salmonella vaccines (RASVs). Overall, this study provides a promising candidate vaccine for infection with STEC.


Subject(s)
Escherichia coli Infections , Salmonella Vaccines , Salmonella enterica , Shiga-Toxigenic Escherichia coli , Animals , Mice , Swine , Shiga-Toxigenic Escherichia coli/genetics , Salmonella , Vaccines, Synthetic/genetics , Immunization
15.
Front Chem ; 10: 917371, 2022.
Article in English | MEDLINE | ID: mdl-35707457

ABSTRACT

A simple and practical strategy for intermolecular aminohalogenation of quinone with alkyl amines and NXS was developed, in which haloamines generated in situ were employed as bifunctional reagents. The reaction system is reliable, efficient and wide in substrate range, which is suitable for the two-fold aminochlorination of 1, 4-benzoquinones, large-scale reaction and late-stage modification of pharmaceuticals.

16.
Vaccine ; 40(33): 4732-4741, 2022 08 05.
Article in English | MEDLINE | ID: mdl-35773121

ABSTRACT

The virus-like particles (VLPs) of porcine circovirus type 2 (PCV2) is an attractive vaccine candidate that retains the natural conformation of the virion but lacks the viral genome to replicate, thus balancing safety and immunogenicity. However, the assembly of VLPs requires cumbersome subsequent processes, hindering the development of related vaccines. In addition, as a subunit antigen, VLPs are defective in inducing cellular and mucosal immune responses. In this study, the capsid (Cap) protein of PCV2 was synthesized and self-assembled into VLPs in the recombinant attenuated S. Choleraesuis vector, rSC0016(pS-Cap). Furthermore, rSC0016(pS-Cap) induced a Cap-specific Th1-dominant immune response, mucosal immune responses, and neutralizing antibodies against PCV2. Finally, the virus genome copies in mice immunized with the rSC0016(pS-Cap) were significantly lower than those of the empty vector control group after challenge with PCV2. In conclusion, our study demonstrates the potential of using S. Choleraesuis vectors to delivery VLPs, providing new ideas for the development of PCV2 vaccines.


Subject(s)
Circoviridae Infections , Circovirus , Salmonella enterica , Viral Vaccines , Animals , Antibodies, Viral , Capsid Proteins , Circoviridae Infections/prevention & control , Circovirus/genetics , Immunity , Mice , Serogroup , Swine
17.
Front Psychol ; 13: 837885, 2022.
Article in English | MEDLINE | ID: mdl-35558693

ABSTRACT

The pattern and scale of commerce worldwide have been greatly transformed by the Fourth Industrial Revolution and technological advancement; digital trade has become the primary form of trade in the digital economy. On the basis of information network infrastructure, information technology level, digital industrialization level, and industrial digitalization level, this study establishes a comprehensive assessment system that applies an entropy-TOPSIS model to evaluate digital trade development level in China. The results indicate that digital trade in China was steadily growing between 2010 and 2019. A principal component analysis is conducted to identify factors affecting the digital trade development level in China. The analysis results suggest that Internet development, population income, industrial structure, payment convenience level, fixed asset investment, online transaction scale, and economic development all have positive effects on the digital trade development level in China, with payment convenience level having the greatest influence. By contrast, state intervention and degree of dependence on foreign trade have a negative effect on digital trade development.

18.
Disabil Rehabil ; 44(18): 5060-5068, 2022 09.
Article in English | MEDLINE | ID: mdl-33984249

ABSTRACT

PURPOSE: We aimed to determine the global effects of the Chêneau brace combined with Schroth exercises on adolescent idiopathic scoliosis (AIS). METHODS: We analyzed 192 patients with AIS who underwent the Chêneau brace treatment alone or combined with Schroth best practice (SBP) from June 2013 to October 2019. There were 138 patients in the Brace group and 54 patients in the Brace + SBP group. Radiographs were obtained at various treatment durations. Answers to the health-related quality of life (HRQoL) questionnaire were recorded before the intervention and at the time of treatment wean. RESULTS: The Cobb angle (-3.55°; p < 0.001) and C7-CSVL (-3.03 mm; p < 0.001) significantly decreased in the Brace + SBP group. Thoracic kyphosis (TK) decreased in both the Brace + SBP group (-1.85°; p = 0.0152) and the Brace group (-5.06; p < 0.001). Changes before and after treatment of TK were significantly different between groups (p < 0.001). The 22-item Scoliosis Research Society function score, self-image, mental health, and EuroQol 5-Dimension scores were significantly higher in the Brace + SBP group. The satisfaction score was higher in the Brace + SBP group (3.77 ± 0.63 vs. 3.13 ± 0.79; p < 0.001). CONCLUSIONS: Compared to bracing alone, the Schroth exercises plus bracing had a better effect on coronal balance. Schroth exercises improve flatback deformity caused by bracing and positively influence the HRQoL in AIS patients who received the Chêneau brace treatment.Implications for RehabilitationBracing and physiotherapy are common treatments for adolescent idiopathic scoliosis (AIS).The Chêneau brace treatment causes flatback deformity and muscle stiffness in AIS patients.The Schroth method helps patients increase muscle strength, halt curve progression, increase vital capacity, and maintain improved posture.The Schroth exercises could improve flatback deformity caused by bracing and positively influence the health-related quality of life in AIS patients who received the Chêneau brace treatment.


Subject(s)
Kyphosis , Scoliosis , Adolescent , Humans , Kyphosis/therapy , Quality of Life , Retrospective Studies , Scoliosis/diagnostic imaging , Scoliosis/therapy , Treatment Outcome
19.
Front Chem ; 9: 828964, 2021.
Article in English | MEDLINE | ID: mdl-35178380

ABSTRACT

Cobalt-nitride-carbide (Co-N-C) catalysts are promising cost-efficient transition metal catalysts for electrocatalytic hydrogen evolution, but few works investigate the metal-support interaction (MSI) effect on hydrogen evolution reaction (HER) performance. Herein, efficient Co-N-CX catalysts with controllable MSI between encapsulated Co nanoparticles and nitrogen-doped graphitic carbon nanosheets were synthesized via a facile organic-inorganic hybridization method. Results demonstrate that the Co-N-C0.025M catalyst with the coexistence of single-atom Co sites and Co nanoparticles prepared by 0.025 M cobalt nitrate shows excellent HER performance, achieving a low overpotential of 145 mV to reach 10 mA cm-2 in 0.5 M sulfuric acid, which is mainly because the optimal MSI, which leads to a moderate hydrogen adsorption energy and improved electroactive sites, not only facilitates the charge transfer to improve the HER kinetics, but also improves the durability of the catalyst by Co-N bond anchoring and encapsulation of active Co species. This work provides guidance to further reveal the influence of MSI on their catalytic activity.

20.
medRxiv ; 2020 Aug 12.
Article in English | MEDLINE | ID: mdl-32817972

ABSTRACT

Background As COVID-19 continues to spread around the world, understanding how patterns of human mobility and connectivity affect outbreak dynamics, especially before outbreaks establish locally, is critical for informing response efforts. In Taiwan, most cases to date were imported or linked to imported cases. Methods In collaboration with Facebook Data for Good, we characterized changes in movement patterns in Taiwan since February 2020, and built metapopulation models that incorporate human movement data to identify the high risk areas of disease spread and assess the potential effects of local travel restrictions in Taiwan. Results We found that mobility changed with the number of local cases in Taiwan in the past few months. For each city, we identified the most highly connected areas that may serve as sources of importation during an outbreak. We showed that the risk of an outbreak in Taiwan is enhanced if initial infections occur around holidays. Intracity travel reductions have a higher impact on the risk of an outbreak than intercity travel reductions, while intercity travel reductions can narrow the scope of the outbreak and help target resources. The timing, duration, and level of travel reduction together determine the impact of travel reductions on the number of infections, and multiple combinations of these can result in similar impact. Conclusions To prepare for the potential spread within Taiwan, we utilized Facebook's aggregated and anonymized movement and colocation data to identify cities with higher risk of infection and regional importation. We developed an interactive application that allows users to vary inputs and assumptions and shows the spatial spread of the disease and the impact of intercity and intracity travel reduction under different initial conditions. Our results can be used readily if local transmission occurs in Taiwan after relaxation of border control, providing important insights into future disease surveillance and policies for travel restrictions.

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