Development of an RBD-Fc fusion vaccine for COVID-19.

Although the global pandemic of SARS-CoV-2 has passed, there are still regional outbreaks that continue to jeopardize human health. Hence, there is still a great deal of interest in developing an efficient vaccine that can quickly and effectively prevent reemerging outbreaks of SARS-CoV-2. Delta variant was once a dominant strain in the world in 2021, and we first constructed a recombinant RBDdelta-Fc fusion vaccine by coupling the RBD of Delta variant with the human Fc fragment. This Fc fusion strategy increases the immunogenicity of the recombinant RBD vaccine, with a long-lasting high level of IgG antibodies and neutralizing antibodies induced by RBDdelta-Fc vaccine. This RBDdelta-Fc vaccine, as well as the RBD-Fc vaccine prepared in our previously study, could trigger a durable immune effect by the heterologous boosting immunity, and the RBD-Fc induced a quicker humoral immune response than the homologous immunization with inactivated vaccines. In conclusion, the Fc fusion strategy has a significant role in enhancing the immunogenicity of recombinant protein vaccines, thus promising the development of a safe and efficient vaccine for the heterologous boosting against SARS-CoV-2.

Simulation and Experiment on the Low-Velocity Impact Response of Flax Fabric Reinforced Composites.

Natural fiber reinforced composites are increasingly used to fabricate structural components prone to suffering low-velocity impacts. The low-velocity impact response of flax fabric reinforced composites under different impact energies is experimentally studied and numerically simulated. A multi-scale finite element analysis strategy for the progressive damage prediction of flax fabric reinforced composites is developed. Micro- and meso-scale analyses are conducted to predict the effective properties of the woven unit cell. Macro-scale analysis is carried out subsequently to predict the impact response of composite laminates using the results of micro- and meso-scale analyses as inputs. Simulation results and experimental results both show that most of the impact energy is absorbed by the specimens when the impact energy is lower than 4 J, and the absorption ratio of impact energy slightly increases with the increase in impact energy. On the contrary, a dramatic decrease occurs in the absorption ratio when the impact energy is 6 J, due to the severe damage to the specimen. In addition, simulation results indicate that matrix shear damage and interlaminar damage are the primary failure modes of composites under high impact energy. The numerical results of impact force, absorbed energy, and damage morphologies on both sides for all specimens show good agreement with the experimental results.

Modulation of Myeloid-derived Suppressor Cells by Long Non-coding RNAs in the Tumor Microenvironment and Tumorigenesis.

Myeloid-derived suppressor cells (MDSCs) constitute an important component in regulating immune responses in cancer. Long non-coding RNAs (lncRNAs) are untranslated functional RNA molecules. There is growing evidence that lncRNAs are involved in modulating transcriptional factors to become complex regulatory networks that regulate the immune function and activity of MDSCs in the immunosuppressive tumor microenvironment. This review focuses on the emerging role of lncRNAs in MDSCs activity. We summarize how lncRNAs modulate the differentiation, expansion, and immunosuppressive functions of MDSCs and the underlying mechanisms. It is hoped that lncRNAs targeting may prevent the growth and development of MDSCs in the immunosuppressive tumor microenvironment.

Ultrasound-Guided Dry Needling for Trigger Point Inactivation in the Treatment of Postherpetic Neuralgia Mixed with Myofascial Pain Syndrome: A Prospective and Controlled Clinical Study.

Objective: To evaluate the safety and effectiveness of ultrasound-guided dry needling for trigger point inactivation in the treatment of postherpetic neuralgia (PHN) mixed with myofascial pain syndrome (MPS). Methods: A prospective and controlled clinical study was conducted. From January 2020 to December 2020, among the 100 patients who received PHN treatment in the pain department, 54 patients complicated with MPS were randomly divided into the dry needling group D (n = 28) and pharmacotherapeutic group P (n = 26). Visual analogue score (VAS) and McGill Pain Questionnaire (MPQ) were taken as primary indicators. Ultrasound-guided inactivation of myofascial trigger points (MTrPs) with dry needling and intradermal needling combined with press needling were applied on group D and pharmacotherapeutic only treatment on group P respectively. The VAS score <3 and/or the MPQ score <2 represents effective treatment. The VAS score >3 and/or the MPQ score >2 represents recurrent in follow-up study three months after the treatment. Results: After four weeks treatment, the effective rate of one month later of the group D was 92.9% and the effective rate of group P was 38.5%, respectively. The recurrent rate of group D was 7.1% and 34.6% for group P, respectively, for follow-up three months later. The satisfactory rate of group D was higher than that of group P. Conclusion: Ultrasound-guided dry needling and intradermal needling combined with press needling were more effective than only pharmacotherapeutic treatment for PHN mixed with MPS, with lower recurrent rate and higher patient's satisfactory rate.

The distribution of high-quality internal standard lines and their selection method based on the Q-value in portable laser-induced breakdown spectroscopy.

Internal standard lines play a crucial role in the univariate quantitative analysis in portable laser-induced breakdown spectroscopy (LIBS) technology. To overcome the uncertainty of the conventional internal standard method, the distribution principles of high-quality internal standard lines were studied and revealed at the macro and micro levels, and an automatic internal standard line selection method based on the Q-value was proposed. Using this method, in the quantitative analysis of Si in low-alloy steel samples, the average relative error of cross-validation (ARECV), root mean squared error of cross-validation (RMSECV), and the limit of detection (LoD) were decreased significantly from 27.42%, 0.041 wt%, and 1060 µg g-1 to 18.65%, 0.026 wt%, and 680 µg g-1, respectively. The quantitative analysis results of Cr, Cu and Ni showed that it has excellent generalization ability. The results indicate that this method can screen out the optimal internal standard lines efficiently and accurately, which provides a new approach to improve the performance of univariate quantitative analysis in portable LIBS.

Metabolic Reprogramming of Myeloid-derived Suppressor Cells in the Tumor Microenvironment.

A large number of studies on the metabolism of immune cells in anti-tumor response have been carried out in recent years. It is proved that metabolic reprogramming can determine the differentiation and functions of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells in the tumor microenvironment (TME). They can significantly inhibit the anti-tumor response of T cells and play an important role in promoting tumor growth, metastasis, and invasion. This review summarizes the energy metabolic pathways of MDSCs in the TME, such as fatty acid oxidation (FAO), glycolysis, and amino acids (AAs) metabolism, and highlights the importance of metabolic reprogramming of MDSCs for its immunosuppressive functions.

Targeting myeloid-derived suppressive cells in the tumor microenvironment to enhance the efficacy of cancer immunotherapy.

Myeloid-derived suppressor cells (MDSCs) are immature suppressive cells partly influencing the efficacy of cancer immunotherapies. The crosstalk between MDSCs and immune cells mediates a potently immunosuppressive network within the tumor microenvironment to attenuate the anti-tumor response. Targeting MDSCs could be a potential therapeutic approach to overcome the limitation of immunotherapies. In this article, we will review available information on how MDSCs exert their immunosuppressive function and summarize the therapeutic strategies targeting them to enhance the efficacy of cancer immunotherapies.

Modulation of cancer immunotherapy efficacy by gut microbiota.

The microbial community is present abundantly in mucosal organs including the intestine, the oral cavity, and the vagina, and is referred to as the microbiota. The microbiota is composed of commensal bacteria and other microorganisms. Intestinal colonization by commensal microorganisms is essential for host physiological functions from the maintenance of barrier homeostasis locally to the regulation of metabolism, hematopoiesis, inflammation, immune development, and other functions systemically. Evidence is growing that the gut microbiota can modulate the host response to cancer immunotherapy. In this review, we discuss the evidence for the ability of the microbiota to modulate immunotherapy, their mechanisms of action, and the possibility of altering the microbiota to improve immunotherapy efficacy.

[Retrospective cohort study on period of incubation and survival among former commercial plasma donors infected with HIV in Hebei province].

OBJECTIVE: To examine the state of incubation period and survival time of former commercial plasma donors (FCPDs) infected with HIV. METHODS: All objects infected with HIV were from Hebei province and found from general investigation for FCPDs in 1995. The infector cohort by 142 cases was used to estimate incubation period. In the infector cohort, the time which infectors entered the cohort was their infection time, which was the middle value of the origin date, which was January 1, 1995. The onset of AIDS was defined as an outcome event. End point of observation was Dec 31, 2010. There were 192 months in all from beginning to end. The AIDS cohort by 57 cases was used to estimate the survival of the patients. In the patient cohort, the time of AIDS onset was defined as the time entering the cohort, and death of AIDS was defined as an outcome event. The cumulative incidence ratio, cumulative mortality, illness intensity and mortality intensity were analyzed through Kaplan-Meier. RESULTS: During the observation period, 123 cases of 142 infectors developed into AIDS, the cumulative incidence was 86.42% (123/142) and the intensity was 8.53/100 person-years and the median time of incubation period was 112.0 months (95%CI: 108.8 - 115.2). The death dates of 57 patients were from 1 to 24 months after onset. The cumulative mortality was 100%, and the intensity was 250.66/100 person-years and the median survival time was 3.0 months (95%CI: 1.8 - 4.2). It was estimated that the median time was 115.0 months (9.6 years) from infection to death. CONCLUSION: The median times of incubation and median survival time were 112.0 and 3.0 months, respectively.

[Immunoregulatory effects of periplocin from Cortex Periplocae in tumor-bearing mice].

AIM: To investigate the immune mechanisms for Periplocin from Cortex Periplocae (CPP) in tumor-bearing mice. METHODS: H(22) tumor-bearing model BALB/c mice were applied to evaluated in vivo immunoregulatory effect of CPP. The influence of different dose CPP (0.25, 0.50 and 1.00 mg/kg) on immune organs in tumor-bearing mice were observed. T cell subsets of mice spleen were detected by flow cytometry. MTT assay was used to determine the influence of CPP on lymphocyte proliferation of mice spleen stimulated by ConA. The levels of TNF-alpha, IL-2 and IL-12 in serum from mice were detected by means of ELISA. RESULTS: Thymus index and spleen index of H(22) tumor-bearing model control mice became less than that of normal mice (P<0.05). Compared to both model and normal control groups, thymus index and spleen index of H(22) tumor-bearing mice treated with CPP increased obviously (P<0.05). CPP had no influence on the number of CD8(+) T cells, but up-regulated markedly the number of CD3(+), CD4(+) T cells and the ratio of CD4(+)/CD8(+) in tumor-bearing mice. In CPP-treated mice, the percentage of CD3(+), CD4(+) T cells were not different from normal mice (P<0.05), the ratio of CD4(+)/CD8(+) was higher than that of normal mice (P<0.05). CPP enhanced obviously lymphocyte proliferation of mice spleen induced by ConA, the SI scores were even higher than that of normal mice. The levels of TNF-alpha, IL-2 and IL-12 in serum from CPP-treated mice, increased significantly compared to model control group (P<0.05) in a dose-dependent manner, were similar to or higher than that of normal mice. CONCLUSION: CPP protected immune organs of tumor-bearing mice, increased obviously the percentage of CD4(+) and CD4(+)/CD8(+) among the T cell line, and enhanced lymphocyte proliferation of mice spleen significantly, stimulated the production of TNF-alpha, IL-2 and IL-12. The results suggested that CPP possessed potent immunoregulatory effect.

[The effect on the differentiation and maturation of dendritic cells by lupane acetate of cortex periplocae].

AIM: To investigate the effect of lupane acetate of cortex periplocae (CPLA) on the differentiation, maturation and immune activity of human peripheral blood mononuclear cell (PBMC)-derived dendritic cells (DCs) in vitro. METHODS: PBMC isolated from human peripheral blood was cultured with GM-CSF, IL-4 for 5 d and stimulated with TNF-alpha (as positive control) or CPLA to induce DCs. The morphological characteristics of DC were observed under inverted microscope and transmisson electron microscope. The expressions of CD1a, CD83, CD80 and CD86 were analyzed by flow cytometry. IL-12, IFN-gamma production in the culture supernatant of DCs was detected by ELISA. MTT method was used to determine the proliferation of T cells stimulated by DCs. RESULTS: After 10-days culture with cytokines and CPLA, PBMC developed into mature DCs with typical morphological characteristics and high expressions of CD1a, CD83, CD80 and CD86 on the cellular surface (P<0.05). CPLA enhanced IL-12 and IFN-gamma production by DCs (P<0.05). CPLA-treated DCs markedly stimulated proliferation of T cells (P<0.05). CONCLUSION: CPLA may induce the differentiation and maturation of DC, up-regulate cytokines production and increase the immune activity of DC.