Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines.

Tularemia is a highly contagious disease caused by infection with Francisella tularensis (Ft), a pathogenic intracellular gram-negative bacterium that infects a wide range of animals and causes severe disease and death in people, making it a public health concern. Vaccines are the most effective way to prevent tularemia. However, there are no Food and Drug Administration (FDA)-approved Ft vaccines thus far due to safety concerns. Herein, three membrane proteins of Ft, Tul4, OmpA, and FopA, and a molecular chaperone, DnaK, were identified as potential protective antigens using a multifactor protective antigen platform. Moreover, the recombinant DnaK, FopA, and Tul4 protein vaccines elicited a high level of IgG antibodies but did not protect against challenge. In contrast, protective immunity was elicited by a replication-defective human type 5 adenovirus (Ad5) encoding the Tul4, OmpA, FopA, and DnaK proteins (Ad5-Tul4, Ad5-OmpA, Ad5-FopA, and Ad5-DnaK) after a single immunization, and all Ad5-based vaccines stimulated a Th1-biased immune response. Moreover, intramuscular and intranasal vaccination with Ad5-Tul4 using the prime-boost strategy effectively eliminated Ft lung, spleen and liver colonization and provided nearly 80% protection against intranasal challenge with the Ft live vaccine strain (LVS). Only intramuscular, not intranasal vaccination, with Ad5-Tul4 protected mice from intraperitoneal challenge. This study provides a comprehensive comparison of protective immunity against Ft provided by subunit or adenovirus-vectored vaccines and suggests that mucosal vaccination with Ad5-Tul4 may yield desirable protective efficacy against mucosal infection, while intramuscular vaccination offers greater overall protection against intraperitoneal tularemia.

A seroepidemiological survey of adenovirus type 7 circulation among healthy adults in China and in Sierra Leone, West Africa.

Adenovirus type 7 (HAdV7) is one of the most pathogenic human adenoviruses (HAdVs) and can cause severe illness and even death, particularly in people with weakened immune systems. Many countries worldwide have experienced epidemics of this highly contagious pathogen, including China and Sierra Leone; however, studies describing the seroprevalence of anti-HAdV7 neutralizing antibodies (nAbs) are still lacking. Herein, we established an efficient neutralization assay based on a recombinant luciferase-expressing HAdV7 virus (HAd7-Luc) to monitor historical HAdV7 infections and predict outbreak distributions. Among the 2,350 serum samples collected from eight sites in China and Sierra Leone in this cross-sectional serological survey, the overall proportion of anti-HAdV7-seropositive individuals was nearly 60%, with higher seroprevalence rates in Sierra Leone than in China. Regionally, HAdV7 nAb titers were higher in China than in Sierra Leone and showed a geographic variation across different regions. Regardless of the location, the seropositive rate of HAdV7 nAb was lower than that of HAdV5 nAb, as was the nAb titer. The prevalence rates of antibodies against HAdV7 and HAdV5 were both related to age but not to sex. In addition, serologic cross-reactions were rarely observed among people infected with HAdV7 and HAdV5. These results indicate a humoral immune response acquired through endemic HAdV7 infection and enrich the understanding of not only the epidemiological prevention and control of HAdV7 but also the clinical application of HAdV7-based vaccines or gene therapy tools.

Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease of unknown etiology. At present, the mortality rate of the deadly disease is still very high, while the existing treatments only delay the progression of the disease and improve the quality of life of patients. Lung cancer (LC) is the most fatal disease in the world. In recent years, IPF has been considered to be an independent risk factor for the development of LC. The incidence of lung cancer is increased in the patients with IPF and the mortality is also significantly increased in the patients inflicted with the two diseases. In this study, we evaluated an animal model of pulmonary fibrosis complicated with LC by implanting LC cells orthotopically into the lungs of mice several days after bleomycin induction of the pulmonary fibrosis in the same mice. In vivo studies with the model showed that exogenous recombinant human thymosin beta 4 (exo-rhTß4) alleviated the impairment of lung function and severity of damage of the alveolar structure by the pulmonary fibrosis and inhibited the proliferation of LC tumor growth. In addition, in vitro studies showed that exo-rhTß4 inhibited the proliferation and migration of A549 and Mlg cells. Furthermore, our results also showed that rhTß4 could effectively inhibit the JAK2-STAT3 signaling pathway and this might exert an anti-IPF-LC effect. The establishment of the IPF-LC animal model will be helpful for the development of drugs for the treatment of IPF-LC. Exogenous rhTß4 can be potentially used for the treatment of IPF and LC.

Nursing influences on motor function recovery in patients on post stroke hemiplegia / Influências da enfermagem na recuperação da função motora em pacientes com hemiplegia pós-ave / Influencias de la enfermería en la recuperación de la función motora en pacientes con hemiplejia post ictus

ABSTRACT Introduction: The motor function of the lower limbs is of great importance for the recovery of hemiplegics post stroke. Objective: Study the influence of nursing during motor rehabilitation on the recovery of lower limb motor function in patients with hemiplegia after stroke. Methods: In this study, the 28 patients were treated with nursing intervention for motor rehabilitation in the experimental group, while the control group was treated only with a conventional rehabilitation program, and the results were compared before and after the experiment. Results: After eight weeks of the experiment, the FMA-LE scale score in the experimental group increased from 19.65 to 30.51; the TUGT assessment score increased from 38.45s to 28.61s; the FAC rating test was upgraded from 1.86 to 2.98. The maximum weight percentage on the hemiplegic side increased from 27.54±10.14% to 79.51±7.52%; the fastest 5m return speed increased from 0.22±0.03m/s to 0.54±0.07m/s. The improvement effect was less evident in the control group. Conclusion: Rehabilitation nursing promotes a positive effect on improving lower limb motor function in hemiplegic patients. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A função motora dos membros inferiores é de grande importância para a recuperação de hemiplégicos pós-acidente vascular encefálico. Objetivo: Estudar a influência da enfermagem durante a reabilitação motora na recuperação da função motora dos membros inferiores em pacientes com hemiplegia após o acidente vascular encefálico. Métodos: Neste estudo, os 28 pacientes foram tratados com intervenção de enfermagem para reabilitação motora no grupo experimental, enquanto o grupo controle foi tratado apenas com um programa de reabilitação convencional, sendo que os resultados foram comparados antes e depois do experimento. Resultados: Após 8 semanas do experimento, a pontuação da escala FMA-LE no grupo experimental aumentou de 19,65 para 30,51; a pontuação da avaliação TUGT aumentou de 38,45s para 28,61s; o teste de classificação FAC foi atualizado de 1,86 para 2,98. A porcentagem máxima de peso do lado hemiplégico passou de 27,54±10,14% para 79,51±7,52%; a velocidade de retorno mais rápida de 5m passou de 0,22±0,03m/s para 0,54±0,07m/s. O efeito de melhoria foi menos evidente no grupo controle. Conclusão: O trabalho de enfermagem de reabilitação tem um efeito positivo na melhoria da função motora dos membros inferiores em pacientes com hemiplegia. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La función motora de los miembros inferiores es de gran importancia para la recuperación de los hemipléjicos post ictus. Objetivo: Estudiar la influencia de la enfermería durante la rehabilitación motora en la recuperación de la función motora de los miembros inferiores en pacientes con hemiplejia post ictus. Métodos: En este estudio, los 28 pacientes fueron tratados con intervención de enfermería para la rehabilitación motora en el grupo experimental, mientras que el grupo de control fue tratado sólo con un programa de rehabilitación convencional, y se compararon los resultados antes y después del experimento. Resultados: Tras 8 semanas de experimento, la puntuación de la escala FMA-LE en el grupo experimental aumentó de 19,65 a 30,51; la puntuación de la evaluación TUGT aumentó de 38,45s a 28,61s; la prueba de valoración FAC se mejoró de 1,86 a 2,98. El porcentaje de peso máximo en el lado hemipléjico aumentó de 27,54±10,14% a 79,51±7,52%; la velocidad de retorno más rápida de 5m aumentó de 0,22±0,03m/s a 0,54±0,07m/s. El efecto de mejora fue menos evidente en el grupo de control. Conclusión: El trabajo de enfermería de rehabilitación tiene un efecto positivo en la mejora de la función motora de las extremidades inferiores en pacientes con hemiplejia. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Enabling High-Voltage "Superconcentrated Ionogel-in-Ceramic" Hybrid Electrolyte with Ultrahigh Ionic Conductivity and Single Li+ -Ion Transference Number.

High room-temperature ionic conductivities, large Li+ -ion transference numbers, and good compatibility with both Li-metal anodes and high-voltage cathodes of the solid electrolytes are the essential requirements for practical solid-state lithium-metal batteries. Herein, a unique "superconcentrated ionogel-in-ceramic" (SIC) electrolyte prepared by an in situ thermally initiated radical polymerization is reported. Solid-state static 7 Li NMR and molecular dynamics simulation reveal the roles of ceramic in Li+ local environments and transport in the SIC electrolyte. The SIC electrolyte not only exhibits an ultrahigh ionic conductivity of 1.33 × 10-3 S cm-1 at 25 °C, but also a Li+ -ion transference number as high as 0.89, together with a low electronic conductivity of 3.14 × 10-10 S cm-1 and a wide electrochemical stability window of 5.5 V versus Li/Li+ . Applications of the SIC electrolyte in Li||LiNi0.5 Co0.2 Mn0.3 O2 and Li||LiFePO4 batteries further demonstrate the high rate and long cycle life. This study, therefore, provides a promising hybrid electrolyte for safe and high-energy lithium-metal batteries.

Recombinant Human Thymosin ß4 (rhTß4) Modulates the Anti-Inflammatory Responses to Alleviate Benzalkonium Chloride (BAC)-Induced Dry Eye Disease.

Dry eye disease (DED) is a multifactorial ocular disorder that interferes with daily living and reduces quality of life. However, there is no most ideal therapeutic treatment to address all the deleterious defects of DED. The purpose of this study was to investigate the ability of recombinant human thymosin ß4 (rhTß4) to promote healing in a benzalkonium chloride (BAC)-induced mice DED model and the anti-inflammatory effects involved in that process. Eye drops consisting of 0.05% and 0.1% rhTß4 were used for treatment of DED. Tear volume and corneal staining scores were measured after 7 days. Periodic acid-Schiff staining for gobleT cells in conjunctiva, immunohistochemical staining for CD4+ T cells, TUNEL assay for apoptotic positive cells in cornea and conjunctiva, qRT-PCR and ELISA assays for multiple cytokines were performed. All clinical parameters showed improvement in both the 0.05% and 0.1% rhTß4 groups. Specifically, topical application of rhTß4 significantly increased conjunctival gobleT cells and reduced apoptotic cells in conjunctiva. Mechanically, the rhTß4 groups showed significantly reduced inflammatory cytokine levels and CD4+ T cells in conjunctiva by blocking NF-κB (nuclear factor kappa B) activation, suggesting that 0.05-0.1% rhTß4 eye drops may be used as a potential therapeutic treatment for DED.

Synthesis and properties of poly(1,3-dioxolane) in situ quasi-solid-state electrolytes via a rare-earth triflate catalyst.

We report a rare-earth triflate catalyst Sc(OTf)3 for the ring-opening polymerization of 1,3-dioxolane and the in situ production of a quasi-solid-state poly(1,3-dioxolane) electrolyte, which not only demonstrates a superior ionic conductivity of 1.07 mS cm-1 at room temperature, but achieves dendrite-free lithium deposition and a high Coulombic efficiency of 92.3% over 200 Li plating/striping cycles.

Recombinant human thymosin beta-4 (rhTß4) improved scalp condition and microbiome homeostasis in seborrheic dermatitis.

Seborrheic dermatitis (SD) is a recurrent common inflammatory skin disease that affects all ethnic groups in all regions worldwide. However, no specific treatment or preventive measure is yet available. Identifying effective treatments with acceptable safety and tolerability is desirable. In this study, scalp microbiota alterations were measured in SD, showing significantly greater abundance of Malassezia and Staphylococcus and diminished fungal and bacterial diversity compared with healthy controls. We investigated the benefit of a 4-week treatment with 0.5 mg ml-1 recombinant human thymosin ß4 (rhTß4) gel or 2% ketoconazole lotion on the scalp condition of 71 patients with SD compared with 21 healthy individuals. Clinical assessment (Adherent Scalp Flaking Score, and the Maximum Erythema Area) and physiological conditions (transepidermal water loss, hydration, and sebum secretion) were evaluated. The rhTß4 treatment provided significantly greater efficacy than ketoconazole and a sustained effect in the treatment of scalp SD. More importantly, rhTß4 dramatically improved the microbiome homeostasis and prompted a shift of scalp microflora towards healthy composition, helping symptoms and ameliorating physiological conditions more effectively and durably than ketoconazole. Our research demonstrated the scalp microbe dysbiosis of SD and highlighted rhTß4 as a promising therapeutic strategy in the prevention and treatment of SD.

Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection.

Coronaviruses (CoVs) are enveloped and harbor an unusually large (30-32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (Tß4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. Tß4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether Tß4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human Tß4 (rhTß4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhTß4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host's immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhTß4 to the treatment of human CoV diseases such as COVID-19.

A facile method for the synthesis of a sintering dense nano-grained Na3Zr2Si2PO12 Na+-ion solid-state electrolyte.

We report dense Na3Zr2Si2PO12 with an average grain size of 546 ± 58 nm and prepared by a facile method. The nano-grained Na3Zr2Si2PO12 exhibits an extremely high conductivity of 1.02 × 10-3 S cm-1 and low interfacial resistance of 35 Ω cm2 at 25 °C. Such processing facilitates the exploration of nanocrystalline conductors.

The STING phase-separator suppresses innate immune signalling.

Biomolecular condensates (biocondensates) formed via liquid-liquid phase-separation of soluble proteins have been studied extensively. However, neither the phase-separation of endoplasmic reticulum (ER) transmembrane protein nor a biocondensate with organized membranous structures has been reported. Here, we have discovered a spherical ER membranous biocondensate with puzzle-like structures caused by condensation of the ER-resident stimulator of interferon genes (STING) in DNA virus-infected or 2'3'-cGAMP (cyclic GMP-AMP)-treated cells, which required STING transmembrane domains, an intrinsically disordered region (IDR) and a dimerization domain. Intracellular 2'3'-cGAMP concentrations determined STING translocation or condensation. STING biocondensates constrained STING and TBK1 (TANK binding protein 1) to prevent innate immunity from overactivation, presumably acting like a 'STING-TBK1-cGAMP sponge'. Cells expressing STING-E336G/E337G showed notably enhanced innate immune responses due to impaired STING condensation after viral infection at later stages. Microtubule inhibitors impeded the STING condensate gel-like transition and augmented type I-interferon production in DNA virus-infected cells. This membranous biocondensate was therefore named the STING phase-separator.

Psychometric Properties of Achievement Goal Constructs for Chinese Students.

In Chinese schools, classes are organized with special monitors and teachers contributing to the achievement goal structure for students. This study aimed to examine the psychometric properties of perception of teachers' achievement goal structure constructs with 3,149 Chinese students from grades 3-8. The results showed that the internal consistencies of the whole scale and subscales were low to marginal. Eight models were examined to check the constructs of the achievement goal structure (mastery, performance, and performance avoidance). Two-factor structures proved to be the best fit. Additionally, a multilevel confirmatory factor analysis proved that the achievement goal structure existed at the same time in the class student levels. Our findings supported the hypothesis that achievement goal structures are different for students with different cultures, which implies that teaching approaches should be adapted in consideration of culturally distinct learning.

Seroepidemiological investigation of HAdV-4 infection among healthy adults in China and in Sierra Leone, West Africa.

An apparent increase in the frequency of human adenovirus type 4 (HAdV-4) infections among general populations has been observed over the past 10 years. However, available epidemiological data that may reflect previous viral circulation and assist in predicting potential outbreaks are sparse, particularly in mainland China and Africa. In this study, a convenient neutralization assay for use in the surveillance of historical HAdV-4 infections was established based on a recombinant luciferase-expressing virus. Subsequently, the neutralizing antibodies (nAbs) of 1013 healthy adult serum samples from China and Sierra Leone were evaluated. Our results showed that over 50% of the participants from China and nearly 70% of donors from Sierra Leone had detectable nAbs against HAdV-4 despite the few infection cases officially reported in these regions. Furthermore, the prevalence of nAbs to HAdV-4 is lower than that to HAdV-5, and both varied by geographic location. In addition, the seropositive rates of both HAdV-4 and HAdV-5 nAbs increased with age. However, the nAbs stimulated by HAdV-4 remained stable at low (≤200) levels among the different age groups, whereas moderate (201-1000) or high (>1000) nAb levels were produced by HAdV-5 and tended to decrease with age. These results elucidate the human humoral immune response against HAdV-4 and revealed that this virus may be an underestimated causative agent of respiratory disease among adults in China and West Africa, demonstrating the importance of HAdV-4 surveillance and providing useful insights for the future development of HAdV-4-based vaccines.

Estimating soil organic carbon content with visible-near-infrared (vis-NIR) spectroscopy.

The selection of a calibration method is one of the main factors influencing measurement accuracy with visible-near-infrared (Vis-NIR, 350-2500 nm) spectroscopy. This study, based on both air-dried unground (DU) and air-dried ground (DG) soil samples, used nine spectral preprocessing methods and their combinations, with the aim to compare the commonly used partial least squares regression (PLSR) method with the new machine learning method of support vector machine regression (SVMR) to find a robust method for soil organic carbon (SOC) content estimation, and to further explore an effective Vis-NIR spectral preprocessing strategy. In total, 100 heterogeneous soil samples collected from Southeast China were used as the dataset for the model calibration and independent validation. The determination coefficient (R(2)), root mean square error (RMSE), residual prediction deviation (RPD), and ratio of performance to interquartile range were used for the model evaluation. The results of this study show that both the PLSR and SVMR models were significantly improved by the absorbance transformation (LOG), standard normal variate with wavelet detrending (SW), first derivative (FD), and mean centering (MC) spectral preprocessing methods and their combinations. SVMR obtained optimal models for both the DU and DG soil, with R(2), RMSE, and RPD values of 0.72, 2.48 g/kg, and 1.83 for DU soil and 0.86, 1.84 g/kg, and 2.60 for DG soil, respectively. Among all the PLSR and SVMR models, SVMR showed a more stable performance than PLSR, and it also outperformed PLSR, with a smaller mean RMSE of 0.69 g/kg for DU soil and 0.50 g/kg for DG soil. This study concludes that PLSR is an effective linear algorithm, but it might not be sufficient when dealing with a nonlinear relationship, and SVMR turned out to be a more suitable nonlinear regression method for SOC estimation. Effective SOC estimation was obtained based on the DG soil samples, but the accurate estimation of SOC with DU soil samples needs to be further explored. In addition, LOG, SW, FD, and MC are valuable spectral preprocessing methods for Vis-NIR optimization, and choosing two of them (except for FD + SW and LOG + FD) in a simple combination is a good way to get acceptable results.

Total longitudinal momentum in a dispersive optical waveguide.

Using the Lorentz force law, we derived simpler expressions for the total longitudinal (conserved) momentum and the mechanical momentums associated with an optical pulse propagating along a dispersive optical waveguide. These expressions can be applied to an arbitrary non-absorptive optical waveguide having continuous translational symmetry. Our simulation using finite difference time domain (FDTD) method verified that the total momentum formula is valid in a two-dimensional infinite waveguide. We studied the conservation of the total momentum and the transfer of the momentum to the waveguide for the case when an optical pulse travels from a finite waveguide to vacuum. We found that neither the Abraham nor the Minkowski momentum expression for an electromagnetic wave in a waveguide represents the complete total (conserved) momentum. Only the total momentum as we derived for a mode propagating in a dispersive optical waveguides is the 'true' conserved momentum. This total momentum can be expressed as PTot = -U Die/(vg) + neff (U/c). It has three contributions: (1) the Abraham momentum; (2) the momentum from the Abraham force, which equals to the difference between the Abraham momentum and the Minkowski momentum; and (3) the momentum from the dipole force which can be expressed as -UDie/vg. The last two contributions constitute the mechanical momentum. Compared with FDTD-Lorentz-force method, the presently derived total momentum formula provides a better method in terms of analyzing the permanent transfer of optical momentum to a waveguide.