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Background Post-vaccination myopericarditis is reported after immunization with coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. The effect of inadvertent intravenous injection of this vaccine on the heart is unknown. Methods We compared the clinical manifestations, histopathological changes, tissue mRNA expression, and serum levels of cytokine/chemokine and troponin in Balb/c mice at different time points after intravenous (IV) or intramuscular (IM) vaccine injection with normal saline (NS) control. Results Although significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1–2 days post-injection (dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis, and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, although evidence of coronary artery or other cardiac pathologies was absent. Serum troponin level was significantly higher in IV group. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of interleukin (IL)-1β, interferon (IFN)-β, IL-6, and tumor necrosis factor (TNF)-α increased significantly from 1 dpi to 2 dpi in the IV group but not the IM group, compatible with presence of myopericarditis in the IV group. Ballooning degeneration of hepatocytes was consistently found in the IV group. All other organs appeared normal. Conclusions This study provided in vivo evidence that inadvertent intravenous injection of COVID-19 mRNA vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.

Background The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pathogenesis of testicular damage is uncertain. Methods We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by wild-type SARS-CoV-2 and its variants with intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control. Results Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, serum testosterone and inhibin B at 4–7 days after infection; and chronic reduction in testicular size and weight, and serum sex hormone at 42–120 days after infection. Acute histopathological damage with worsening degree of testicular inflammation, hemorrhage, necrosis, degeneration of seminiferous tubules, and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and death of Sertoli and Leydig cells were found. Although viral loads and SARS-CoV-2 nucleocapsid protein expression were markedly lower in testicular than in lung tissues, direct intratesticular injection of SARS-CoV-2 demonstrated nucleocapsid expressing interstitial cells and epididymal epithelial cells, While intranasal or intratesticular challenge by A(H1N1)pdm09 control showed no testicular infection or damage. From 7 to 120 days after infection, degeneration and apoptosis of seminiferous tubules, immune complex deposition, and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. This testicular damage can be prevented by vaccination. Conclusions SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent coronavirus disease 2019 in men.

CsPbI3 is considered to one potential material in the future resistive random access memory(RRAM). There are four crystal types of CsPbI3, among which δ phase is the most stable and available to commercialize. However, the inherent defect of δ-CsPbI3 results in its inferior switching performance to other crystal types. Here, we present a new structure to solve this problem. Carbon nanotube (CNT) was inserted into the two interfaces of Ag/δ-CsPbI3/ITO and Ag/δ-CsPbI3/FTO to adjust its resistance switching performance. It is found that the introduction of carbon nanotube layer can effectively control durability of RRAM devices through influencing strength of conductive filaments. These findings present a new strategy for the future design of δ-CsPbI3 memory.

We demonstrate high contrast optical-resolution photoacoustic microscopy (OR-PAM) imaging by using biocompatible, indirect band gap silicon nanoparticles (SiNPs) as contrast agents. The SiNPs were synthesized by high energy ball milling of crystalline silicon wafers, followed by hydrosilylation with bifunctional olefinic ligands to enable water solubility and bioconjugation. When uniformly dispersed in water, the SiNPs with an average particle size about 114 nm showed remarkably high extinction coefficients, more than 2 × 1010 M−1 cm−1, from the visible to near-infrared spectral range. For the first OR-PAM imaging demonstration, the SiNPs were microinjected to live zebrafish embryonic cells. As the embryo developed, the distribution of the cells carrying the SiNPs can be clearly traced by the spread of the photoacoustic signals. Secondly, photoacoustic-fluorescence dual-modality imaging was demonstrated on live zebrafish larvae which were microinjected with a mixture of the SiNPs and dextran-rhodamine dye...

Piperaquine (PQ) is one of the major components of artemisinin-based combination therapy for malaria. However, the mechanism of PQ resistance has remained unclear. In this study, we infected mice with PQ-resistant Plasmodium berghei ANKA strain line (PbPQR) or PQ-sensitive P. berghei ANKA strain line (PbPQS) and their survival rates, parasitemia, and spleen sizes were compared. In addition, we constructed genomic DNA subtractive library of spleens from the infected mice, and screened the potential PQ-resistant related genes from genomic DNA of PbPQR line using the representational difference analysis (RDA) method. Clones of the subtractive library were screened by PCR, and related genes were sequenced and analyzed using BLAST software of NCBI. Compared to PbPQS-infected mice, PbPQR-infected mice survived significantly longer, and had significantly lowered parasitemia rate and significantly increased splenomegaly. Among the total of 502 clones picked, 494 were sequenced and 96 unique PCR fragments were obtained; in which 24 DNA fragments were homologous to chromosomes related to immune function of mice. ORF Finder blasting showed that at the protein level, 26 encoded proteins were homologous to 18 hypothetical PbANKA proteins and 13 encoded proteins were homologous to “ferlin-like protein” family of PbANKA. In addition, there were more immune-related DNA molecules, ubiquitous PbANKA homology at the ORF fragment level, and enriched ferlin-like protein families identified from PbPQR-infected mice than those from PbPQS-infected mice. These findings suggest that PbPQR may induce stronger protective immune response than that of PbPQS in infected mice.

A miniature endoscope capable of imaging multiple tissue contrasts in high resolution is highly attractive, because it can provide complementary and detailed tissue information of internal organs. Here we present a photoacoustic (PA)-fluorescence (FL) endoscope for optical-resolution PA microscopy (PAM) and FL microscopy (FLM). The endoscope with a diameter of 2.8 mm achieves high lateral resolutions of 5.5 and 6.3 µm for PAM and FLM modes, respectively. In vivo imaging of zebrafish larvae and a mouse ear is conducted, and high-quality images are obtained. Additionally, in vivo endoscopic imaging of a rat rectum is demonstrated, showing the endoscopic imaging capability of our endoscope. By providing dual contrasts with high resolution, the endoscope may open up new opportunities for clinical endoscopic imaging applications.

Post-vaccination myopericarditis is reported after immunization with coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. The effect of inadvertent intravenous injection of this vaccine on the heart is unknown.We compared the clinical manifestations, histopathological changes, tissue mRNA expression, and serum levels of cytokine/chemokine and troponin in Balb/c mice at different time points after intravenous (IV) or intramuscular (IM) vaccine injection with normal saline (NS) control.Although significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1-2 days post-injection (dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis, and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, although evidence of coronary artery or other cardiac pathologies was absent. Serum troponin level was significantly higher in IV group. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of interleukin (IL)-1β, interferon (IFN)-β, IL-6, and tumor necrosis factor (TNF)-α increased significantly from 1 dpi to 2 dpi in the IV group but not the IM group, compatible with presence of myopericarditis in the IV group. Ballooning degeneration of hepatocytes was consistently found in the IV group. All other organs appeared normal.This study provided in vivo evidence that inadvertent intravenous injection of COVID-19 mRNA vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.

Background Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the coronavirus disease-2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. Methods Two-dose (14 days apart) vaccination regimen with formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a 1-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters. Results The 1-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titers in the lung and nasal turbinate, inflammatory changes in intestines, and a higher serum neutralizing antibody or IgG titer against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1, and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titer of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titer. Conclusions Vaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.

Background Although Plasmodium parasites and intestinal helminths share common endemic areas, the mechanisms of these co-infections on the host immune response remain not fully understood. Liver involvement in severe Plasmodium falciparum infections is a significant cause of morbidity and mortality. However, the effect of pre-existing Trichinella spiralis infection on the immune response and liver immune-pathogenesis in P. berghei ANKA (PbANKA)-infected mice needs to be elucidated. Methods Outbred Kunming mice were infected with T. spiralis and 9 days later were challenged with P. berghei ANKA (PbANKA), and the investigation occurred at 13 days after co-infection. Results Compared with PbANKA-mono-infected mice, T. spiralis + PbANKA-co-infected mice had similar survival rate but lower PbANKA parasitaemia; however, there were more severe hepatosplenomegaly, increased liver and spleen indexes, and increased liver pathology observed by hematoxylin and eosin staining; higher expression levels of galectin (Gal)-1, Gal-3, CD68+ macrophages, and elastase-positive neutrophils measured by immunohistochemical staining; upregulated mRNA expression levels of Gal-1, Gal-3, cytokines (interferon-gamma (IFNγ) and interleukin (IL)-6), and M1 macrophage polarization marker (inducible nitric oxide synthase (iNOS)) in the liver, and increased expression levels of Gal-1, IFNγ, IL-6, eosinophil cationic protein, eosinophil protein X, and M1 (IL-1β and iNOS) and M2 (Ym1) macrophage polarization markers in the spleen of co-infected mice detected by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). In vitro study showed that compared with PbANKA-mono-infected mice, there were significantly increased expression levels of Gal-1, Gal-3, IL-6, IL-1β, and iNOS in the peritoneal macrophage isolated from co-infected mice detected by using qRT-PCR. Correlation analysis revealed significant positive correlations between Gal-3 and IL-1β in the peritoneal macrophages isolated from PbANKA-mono-infected mice, between Gal-3 and IFNγ in the spleen of co-infected mice, and between Gal-1 and Ym1 in the peritoneal macrophages isolated from co-infected mice. Conclusions Our data indicate that pre-existing infection of T. spiralis may suppress P. berghei parasitaemia and aggravate malaria-induced liver pathology through stimulating Gal-1 and Gal-3 expression, activating macrophages, neutrophils, and eosinophils, and promoting mediator release and cytokine production.

In this study, a novel photoacoustic microscopy (PAM) probe integrating white-light microscopy (WLM) modality that provides guidance for PAM imaging and complementary information is implemented. One single core of an imaging fiber bundle is employed to deliver a pulsed laser for photoacoustic excitation for PAM mode, which provides high resolution with deep penetration. Meanwhile, for WLM mode, the imaging fiber bundle is used to transmit two-dimensional superficial images. Lateral resolution of 7.2 μm for PAM is achieved. Since miniature components are used, the probe diameter is only 1.7 mm. Imaging of phantom and animals in vivo is conducted to show the imaging capability of the probe. The probe has several advantages by introducing the WLM mode, such as being able to conveniently identify regions of interest and align the focus for PAM mode. The prototype of an endoscope shows potential to facilitate clinical photoacoustic endoscopic applications.