Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness. To experimentally demonstrate the epidemiological results, we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2. Remarkably, high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss, weakness, piloerection, hunched back and abdominal respiration, as well as severe pneumonia, pulmonary edema, consolidation, and fibrosis. In contrast with the males, the female hamsters showed much lower shedding viral titers, moderate symptoms, and relatively mild lung pathogenesis. The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.

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Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine comprised of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both Th1- and Th2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.

The abscisic acid (ABA)-responsive element binding factors (ABFs) play important regulatory roles in multiple abiotic stresses responses. However, information on the stress tolerance functions of ABF genes in sweetpotato ( Ipomoea batatas [L.] Lam) remains limited. In the present study, we isolated and functionally characterized the sweetpotato IbABF4 gene, which encodes an abiotic stress-inducible basic leucine zipper (bZIP) transcription factor. Sequence analysis showed that the IbABF4 protein contains a typical bZIP domain and five conserved Ser/Thr kinase phosphorylation sites (RXXS/T). The IbABF4 gene was constitutively expressed in leaf, petiole, stem, and root, with the highest expression in storage root body. Expression of IbABF4 was induced by ABA and several environmental stresses including drought, salt, and heat shock. The IbABF4 protein localized to the nucleus, exhibited transcriptional activation activity, and showed binding to the cis -acting ABA-responsive element (ABRE) in vitro . Overexpression of IbABF4 in Arabidopsis thaliana not only increased ABA sensitivity but also enhanced drought and salt stress tolerance. Furthermore, transgenic sweetpotato plants (hereafter referred to as SA plants) overexpressing IbABF4 , generated in this study, exhibited increased tolerance to drought, salt, and oxidative stresses on the whole plant level. This phenotype was associated with higher photosynthetic efficiency and lower malondialdehyde and hydrogen peroxide content. Levels of endogenous ABA content and ABA/stress-responsive gene expression were significantly upregulated in transgenic Arabidopsis and sweetpotato plants compared with wild-type plants under drought stress. Our results suggest that the expression of IbABF4 in Arabidopsis and sweetpotato enhances tolerance to multiple abiotic stresses through the ABA signaling pathway.

Radiotherapy is a traditional method for cancer therapy but may become ineffective likely due to the radiation-induced immunosuppression. Instead of simply increasing the radiation dose, reactivation of immunosuppression in the tumor microenvironment is an alternative strategy for successful cancer treatment. In this work, we synthesized bismuth sulfide nanoparticles (BiNP) and conjugated with immunoactive Ganoderma lucidum polysaccharide (GLP). GLP-BiNP were able to increase the sensitivity of radiotherapy, attributing to the efficient X-ray absorption of bismuth element. BiNP alone can mildly activate dendritic cells (DC) in vitro, while GLP-BiNP further enhanced the level of DC maturation, shown as the increase in phenotypic maturation markers, cytokine release, acid phosphatase activity, and T cell proliferation in DC/ T cell co-culture. Compared to BiNP, GLP-BiNP altered the tissue distribution with faster accumulation in the tumor. Meanwhile, mature DC greatly increased in both tumor and spleen by GLP-BiNP within 24 h. GLP-BiNP combination with radiation achieved remarkable inhibition of tumor growth through apoptosis. Alternatively, lung metastasis was largely prohibited by GLP-BiNP, shown as a reduced amount of tumor nodules and cancer cell invasion by pathological findings. Mechanistically, GLP-BiNP altered the tumor immunosuppression microenvironment by preferably increasing the number of intratumor CD8 + T cell proliferation, as well as the improved immunobalance shown as the increased serum interferon-γ/interleukin-4 ratio. Specifically, GLP conjugation seemed to protect the kidney from injury occasionally introduced by bare BiNP. As a result, GLP-BiNP play a dual role in tumor treatment through radiosensitization and immunoactivities.

Objectives: To investigate the subclinical imaging changes in terms of myocardial inflammation and fibrosis and to explore the risk factors associated with myocardial fibrosis by cardiac magnetic resonance (CMR) approach in a Chinese HIV/AIDS cohort.Methods: We evaluated myocardial function (cine), myocardial inflammation (T1, T2), and myocardial fibrosis (through extracellular volume fraction [ECV] and late gadolinium enhancement [LGE]) by a multiparametric CMR scan protocol in a total of 68 participants, including 47 HIV-infected individuals, who were divided into two groups: asymptomatic HIV (HIV+) (n = 30), and acquired immunodeficiency syndrome (AIDS) (n = 17), and 21 healthy controls.Results: HIV-infected patients had lower left (55.3 ± 6.5 vs. 63.0 ± 7.9%, P < 0.001) and right ventricular systolic function (35.9 ± 15.7 vs. 50.8 ± 9.3%, P < 0.001). Radial systolic strain (30.7 ± 9.3 vs. 39.3 ± 9.4%, P = 0.001), circumferential systolic strain (−17.5 ± 2.6 vs. −19.4 ± 2.7%, P = 0.008), and longitudinal systolic strain (−9.4 ± 5.7 vs. −12.8 ± 3.1%, P = 0.012) were also decreased in HIV. Native T1 relaxation time (1,337.2 ± 70.2 vs. 1,249.5 ± 47.0 ms, P < 0.001), ECV value (33.5 ± 6.2 vs. 28.5 ± 2.9 ms, P = 0.026), and T2 relaxation time (45.2 ± 3.5 vs. 42.0 ± 2.6 ms, P = 0.001) were higher in HIV-infected patients compared with controls. Myocardial fibrosis, predominantly in the mid-inferior wall, was detected in 24.4% of the HIV-infected patients. HIV+ had a significantly lower value of ECV [29.1 (26.1, 31.8) vs. 35.2 (31.8, 41.9) %, P < 0.001] and frequency of LGE [3/25 (8%) vs. 7/16 (43.8%), P = 0.014)] compared with AIDS. AIDS was associated with myocardial fibrosis.Conclusions: HIV-infected patients were associated with changes in myocardial function and higher rates of subclinical myocardial inflammation and fibrosis, which were more abnormal with greater severity of the disease. AIDS was associated with myocardial fibrosis, where the observations supported earlier initiation of antiretroviral therapy in the Chinese HIV/AIDS cohort.

Radiotherapy was considered to induce an abscopal effect initiated through antigen release and presented by dendritic cells (DC), while the immunosuppressive tumor microenvironment (TEM) attenuated the effects. Herein, we utilized bioactive polysaccharides extracted from the natural herb Astragalus membranaceus and developed polysaccharide nanoparticles (ANPs) that can reverse TEM and, accordingly, enhance the radiation-induced abscopal effect. ANP showed ability to prolong the survival rate of tumor-bearing mice. In addition, ANP dramatically inhibited the growth of the primary tumor subjected to radiation as well as the secondary tumor distant from the primary lesion. Mechanistic study demonstrated that an ANP-induced immune response was mainly reflected by DC activation, represented by phenotypic maturation and enhanced antigen presentation through the TLR4 signaling pathway. Mature DC induced by ANP migrated to the tumor-draining lymph node and initiated T-cell expansion. Specifically, DC activation was successfully translated into an increase in CD4+ T/Treg and CD8+ T/Treg ratios within both primary (irradiated) and secondary (unirradiated) tumors. Our results also indicated that the systemic antitumor immune response and immune memory were enhanced with the increase in IFN-γ production and effector memory T-cell population. Our work provided a novel strategy to facilitate the incorporation of immunoactive macromolecules purified from natural herbs into modern nanotechnology in the era of immunotherapy.