Somatic reversion in Wiskott-Aldrich syndrome: Case reports and mechanistic insights.

This report describes two brothers from India and a Chinese patient with somatic reversion of an inherited deleterious mutation in the WAS gene. Both the Indian siblings had inherited a single nucleotide deletion causing a frameshift mutation (c.1190del, p.Pro397Argfs*48) (variant 1: marked in blue) from the mother. Another variant (variant 2: marked in red), a 12-nucleotide deletion at position 1188-1199 (c.1188_1199del, p.P401_P404del) was also found, which resulted in restoration of the frame and subsequent rescue of the protein sequence. DNA sequencing from buccal mucosal cells revealed only the inherited variant (variant 1), while no reversion mutation was identified in the mucosal cells. Similarly, the Chinese patient was found to have a novel germline 14-base duplication (ACGAAAATGCTTGG) c.120_132 + 1dup (variant 1). This resulted in abolishment of the original splice junction coupled with the creation of a new junction 14 bases 3' and a frameshift mutation with predicted protein truncation p. Thr45Aspfs*. DNA from the patient's PBMC showed co-existence of wild-type and mutated sequences, but only the mutant was present in the buccal cells. Genomic and mRNA analysis of the isolated CD3+ T lymphocytes, CD3- mononuclear cells, and EBV-transformed B lymphocytes indicated that the reverant variant (germline variant was restored to wild-type sequence) were selectively found in CD3+ T lymphocytes.

Non-invasive glucose extraction by a single polarization rotator system in patients with diabetes.

This study utilizes a Mueller matrix-based system to extract accurate glucose levels from human fingertips, addressing challenges in skin complexity. Integration of domain knowledge and data science aims to enhance prediction accuracy using a Random Forest model. The primary goal is to improve glucose level predictions by selecting effective features based on the Pearson product-moment correlation coefficient (PPMCC). The interpolation compensates for delayed glucose concentration. This study integrates domain knowledge and data science, combining a Mueller matrix-based system and a random forest model. It is noted that 16 effective features were identified from 27 test points collected from a healthy volunteer in the laboratory. These features were divided into training and prediction sets in a ratio of 8:2. As a result, the regression coefficient, R2, was 0.8907 and the mean absolute relative difference (MARD) was 6.8%, respectively. This significantly improves prediction accuracy, demonstrating the model's robustness and reliability in accurately forecasting outcomes based on the identified features. In addition, in the Institutional Review Board (IRB) tests at NCKU's hospital, all data passed the same preprocessing and model. The measurement results from an individual diabetic patient demonstrate high accuracy for blood glucose concentrations below 150 mg/dL, with acceptable deviation at higher levels and no severe error zones. Over a three-month period, data from the participating diabetic patient showed a MARD of 4.44% with the R2 of 0.836, and the other patient recorded a MARD of 7.79% with the R2 of 0.855. The study shows the proposed approach accurately extracts glucose levels. Integrating domain knowledge, data science, and effective strategies significantly improves prediction accuracy.

Acute necrotizing encephalopathy in adult patients with influenza: a case report and review of the literature.

The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22-71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted.

Indistinguishable photons from an artificial atom in silicon photonics.

Silicon is the ideal material for building electronic and photonic circuits at scale. Integrated photonic quantum technologies in silicon offer a promising path to scaling by leveraging advanced semiconductor manufacturing and integration capabilities. However, the lack of deterministic quantum light sources and strong photon-photon interactions in silicon poses a challenge to scalability. In this work, we demonstrate an indistinguishable photon source in silicon photonics based on an artificial atom. We show that a G center in a silicon waveguide can generate high-purity telecom-band single photons. We perform high-resolution spectroscopy and time-delayed two-photon interference to demonstrate the indistinguishability of single photons emitted from a G center in a silicon waveguide. Our results show that artificial atoms in silicon photonics can source single photons suitable for photonic quantum networks and processors.

Clinical Features and Vaccination Effects among Children with Post-Acute Sequelae of COVID-19 in Taiwan.

BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) affects patients after recovering from acute coronavirus disease 2019 (COVID-19). This study investigates the impact of SARS-CoV-2 vaccination on PASC symptoms in children in Taiwan during the Omicron pandemic. METHODS: We enrolled children under 18 years with PASC symptoms persisting for more than 4 weeks. Data collected included demographics, clinical information, vaccination status, and symptom persistence. We used logistic regression models to compare symptoms in the acute and post-COVID-19 phases and to assess the association between vaccination and these symptoms. RESULTS: Among 500 PASC children, 292 (58.4%) were vaccinated, 282 (52.8%) were male, and the mean (SD) age was 7.6 (4.6) years. Vaccinated individuals exhibited higher odds of experiencing symptoms in the previous acute phase, such as cough (adjusted odds ratio [AOR] = 1.57; 95% confidence interval [CI]: 1.02-2.42), rhinorrhea/nasal congestion (AOR = 1.74; 95% CI: 1.13-2.67), sneezing (AOR = 1.68; 95% CI: 1.02-2.76), sputum production (AOR = 1.91; 95% CI: 1.15-3.19), headache/dizziness (AOR = 1.73; 95% CI: 1.04-2.87), and muscle soreness (AOR = 2.33; 95% CI: 1.13-4.80). In contrast, there were lower odds of experiencing abdominal pain (AOR = 0.49; 95% CI: 0.25-0.94) and diarrhea (AOR = 0.37; 95% CI: 0.17-0.78) in children who had received vaccination during the post-COVID-19 phase. CONCLUSIONS: This study revealed clinical features and vaccination effects in PASC children in Taiwan. Vaccination may reduce some gastrointestinal symptoms in the post-COVID-19 phase.

Mueller matrix polarimetry approach for noninvasive glucose sensing with absorbance and anisotropic parameters on fingertips.

A Mueller matrix polarimetry system at 532 nm wavelength is developed for noninvasive glucose sensing in turbid media such as human's fingertip. The system extracts mean absorbance and anisotropic properties, demonstrated numerically and experimentally with phantom glucose samples. It is found that mean absorbance ( A e ), depolarization index (Δ), and linear dichroism (LD) show linear variation with glucose concentration 100-500 mg/dL. In addition, LightTools simulations indicate proportional scaling of scattering effects with A e , Δ, and LD. Real-world tests on fingertip show a strong correlation between these properties and blood glucose levels with a mean absolute relative deviation (MARD) of 12.56% and a correlation coefficient (R2) of 0.875 in prediction by a neural network (NN) model, highlighting the advantages of Mueller matrix in extracting more parameters related to blood glucose.

The effects of age and gender and elite levels on perceptual-cognitive skills of adolescent badminton athletes.

Introduction: This study aimed to examine perceptual-cognitive skills across age, gender and elite levels of badminton adolescent athletes. Methods: A total of 57 badminton athletes divided into junior high school athletes (age = 13.36 ± 1.14 years, females = 22, males = 11) and senior high school athletes (age = 16.25 ± 0.84 years, females = 11, males = 13) were evaluated using a cognitive component skills approach. Elite levels were classified as semi-elite (n = 29, score = 3.23) and competitive elite (n = 28, score = 5.84) levels. Each group completed a cognitive test, including an evaluation of their capacity for Corsi block-tapping (CCT) and spatial priming tasks (SPT). Results: No gender effects were found in the perceptual skills of the adolescent players, and the age effect was consistent across gender. For the elite levels, the perceptual-cognitive skills of SPT of reaction time was performed equally in the groups of semi-elite and competitive players, however, in the CCT Span of working-memory (WM), competitive-elite players outperformed semi-elite players. Conclusion: We found that perceptual-cognitive skills of WM play crucial roles in the open-skill sports of badminton. Thus, when developing advanced skills to higher elite levels in adolescent players, perceptual-cognitive skills should be considered.

Differential effects of long- and short-term exposure to PM2.5 on accelerating telomere shortening: from in vitro to epidemiological studies.

Exposure to air pollutants has been associated with DNA damage and increases the risks of respiratory diseases, such as asthma and COPD; however short- and long-term effects of air pollutants on telomere dysfunction remain unclear. We investigated the impact of short- and long-term exposure to fine particulate matter with an aerodynamic diameter below 2.5 µm (PM2.5) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM2.5 exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM2.5 exposure was significantly associated with telomere shortening, along with the downregulation of human telomerase reverse transcriptase (hTERT) mRNA and protein levels. Moreover, long-term exposure to PM2.5 induced proinflammatory cytokine secretion, notably interleukin 6 (IL-6) and IL-8, triggered subG1 cell cycle arrest, and ultimately caused cell death. Long-term exposure to PM2.5 upregulated the LC3-II/ LC3-I ratio but led to p62 protein accumulation in BEAS-2B cells, suggesting a blockade of autophagic flux. Moreover, consistent with our in vitro findings, our epidemiological study found significant association between annual average exposure to higher PM2.5 and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM2.5 and leukocyte telomere length was observed in children. By combining in vitro experimental and epidemiological studies, our findings provide supportive evidence linking potential regulatory mechanisms to population level with respect to long-term PM2.5 exposure to telomere shortening in humans.

Hyperbaric Oxygen Therapy as a Novel Approach to Modulating Macrophage Polarization for the Treatment of Glioblastoma.

Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with a poor prognosis despite current treatments. This is partially attributed to the immunosuppressive environment facilitated by tumor-associated macrophages, which predominantly underlie the tumor-promoting M2 phenotype. This study investigated the potential of hyperbaric oxygen (HBO) therapy, traditionally used to treat conditions such as decompression sickness, in modulating the macrophage phenotype toward the tumoricidal M1 state and disrupting the supportive tumor microenvironment. HBO has direct antiproliferative effects on tumor cells and reduces hypoxia, which may impair angiogenesis and tumor growth. This offers a novel approach to GBM treatment by targeting the role of the immune system within the tumor microenvironment. The effects of HBO on macrophage polarization and GBM cell viability and apoptosis were evaluated in this study. We detected that HBO promoted M1 macrophage cytokine expression while decreasing GBM cell viability and increasing apoptosis using GBM cell lines and THP-1-derived macrophage-conditioned media. These findings suggest that HBO therapy can shift macrophage polarization toward a tumoricidal M1 state. This can improve GBM cell survival and offers a potential therapeutic strategy. In conclusion, HBO can shift macrophages from a tumor-promoting M2 phenotype to a tumoricidal M1 phenotype in GBM. This can facilitate apoptosis and, in turn, improve treatment outcomes.

Seroepidemiology of measles and rubella among Hong Kong young adults and the humoral responses of an MMR booster among participants with low antibody levels.

BACKGROUND: Some individuals may not retain adequate immunity against measles and rubella years after two doses of measles, mumps, and rubella (MMR) vaccination due to vaccine failure. This study aimed to investigate the rates of vaccine failure and seroconversion by administering an MMR booster to young adults. METHODS: We first assessed measles and rubella antibody levels using the Luminex multiplex assay, VIDAS IgG assay, and plaque reduction neutralization test (PRNT) among individuals aged 18-30 years old who had received two doses of MMR vaccine. Participants with low measles and/or rubella antibody levels as confirmed by VIDAS received an MMR booster. Antibody levels were measured at 1-month post-booster. RESULTS: Among 791 participants, the measles and rubella seroprevalence rates were 94.7% (95% CI: 92.9%-96.0%) and 97.3% (95% CI: 96.0%-98.3%), respectively. Lower seroprevalence rates were observed among older participants. 113 participants who received an MMR booster acquired higher measles and rubella antibody levels at 1-month post-booster compared to baseline. CONCLUSIONS: Although measles and rubella vaccine failures were observed among 5.3% and 2.7% of young adults, respectively, an MMR booster triggered a significant antibody response.

Biocompatibility and radiosensitivity of a fiber optical-based dosimeter: biological applications.

This study introduces a cutting-edge fiber-optic dosimetry (FOD) sensor designed for measuring radiation in biological settings. The accuracy and precision of dosimeters for small animals, particularly prolonged exposure to nonuniform radiation fields, are always challenging. A state-of-the-art in-vivo dosimeter utilizing glass-encapsulated Thermoluminescence cylindrical detector (TLD) was introduced. The FODs are implanted into the rat during a prolonged irradiation scenario involving 137Cs where the rat has the freedom to move within a heterogeneous radiation domain. The implantation surgery was verified with X-ray computed tomography (CT) in addition to biochemical and pathological tests to assess the biocompatibility of FOD in vivo. A versatile FOD is designed for industrial and medical fields, which demand accurate and resilient radiation dosimeters. The dose measurements are associated with precise two-dimensional (2D) radiation distribution imaging. Three cylindrical FODs and three standards TLD_100 for each rat were tested. The measurements of peak irradiation before and after exposure reveal greater stability and superior sensitivity when compared to standard thermo-luminescence detectors in an in-vivo animal test. To the best of our knowledge, FOD testing on live animals is presented for the first time in this paper. Regarding the safety and biocompatibility of FOD, no morphological signs with any kind of inflammation or sensitivity toward the FOD material have been remarked. Moreover, with the current FOD, there is no oedema between the epidermal, dermal, and subdermal sections at the site of implantation. The results also show the stable levels of white blood cells (lymphocytes, granulocytes, MID) as blood inflammatory markers before surgery and at the time of extraction of the implanted dosimeters, thus confirming the biocompatibility for each optical fiber cylinder dosimeter. As a result, the new dosimeters have excellent biocompatibility in living tissues and have 100% accurate reusability intensity of the delivered radiation doses compared to TLD_100 which demonstrated a 45% reduction in its intensity accuracy.

Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states.

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

How does urbanization affect the cognitive function among older adults: A geospatial analysis in China.

There has been a plethora of studies on urbanization and older adults, and more recent ones on how older adults adapt to this process with their cognitive competence. Yet it has been unclear about the relationship between them, like how the level and rate of urbanization affect the cognitive function among older adults. This study sourced, formed, and analyzed a set of geospatial big datasets from different sources, such as the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data, and the NPP/VIIRS nighttime light (NTL) data. Results showed a generally negative linear association between the rate of urbanization and cognitive performance among older adults in China. The "U" shaped non-linear relationship between urbanization level and cognitive function, as well as the tipping point, were identified. At the same time, it should be noted that mediators such as education, physical activity, social activity, and community elderly service might be able to mitigate these negative associations. Furthermore, older adults living in eastern regions or urban areas appeared to have better cognitive function than those living in mid-western regions or rural areas in China. The findings also pointed to the importance of focusing on older adults with poor cognitive health status in rapidly urbanizing areas.

Aging and Caring: Exploring Older Adults' Motivation for Informal Caregiving to Other Aging Individuals in Nigeria.

Background and Objectives: Because of the global population aging, more informal carers become older adults. In Nigeria, the African country with the largest population of adults aged 60 years and older, self-construal rooted in the African collectivist philosophy generally shapes informal caregiving for older adults. However, there is a general paucity of studies on older adults' informal caregiving roles, particularly about their motivations for caregiving. This study explored older adults' motives for informal caregiving to their care recipients in urban Southeast Nigeria. Research Design and Methods: This study adopted a hermeneutic phenomenological research design. In-depth interviews were conducted with 30 purposively selected older adults aged 54-88 who were the primary carers of other older adults in the family and community. The collected data were analyzed using van Manen's thematic analysis method, using QSR NVivo 12 software. Results: A total of 4 main themes emerged from the participants' responses: reciprocity of kindness, altruism, a sense of moral responsibility, and eagerness for peaceful longevity. The findings generally showed that religion and culture were the latent factors ingrained in these motivations for informal caregiving. Discussion and Implications: Although the African philosophy emphasizes altruism, reciprocity seems more prominent in specific traditional African communities, as observed in Southeast Nigeria. It serves as a means to prioritize family members' needs. The findings indicate the need for the government to establish sustainable programs and policies that support older people in their caregiving role. Doing so will enable carers to derive psychosocial gains from informal caregiving and sustain the caregiving culture of Nigeria.

Combining brief recall and ketamine treatment prevents stress-primed methamphetamine memory reinstatement via heightening mPFC GABA activity.

This study aimed to assess whether brief recall of methamphetamine (MA) memory, when combined with ketamine (KE) treatment, may prevent stress-primed MA memory reinstatement. Combining 3-min recall and KE facilitated MA memory extinction and resistance to subsequent stress-primed reinstatement. Such combination also produced glutamate metabotropic receptor 5 (mGluR5) upregulation in animals' medial prefrontal cortex (mPFC) γ-amino-butyric acid (GABA) neuron. Accordingly, chemogenetic methods were employed to bi-directionally modulate mPFC GABA activity. Following brief recall and KE-produced MA memory extinction, intra-mPFC mDlx-Gi-coupled-human-muscarinic-receptor 4 (hM4Di)-infused mice receiving compound 21 (C21) treatment showed eminent stress-primed reinstatement, while their GABA mGluR5 expression seemed to be unaltered. Intra-mPFC mDlx-Gq-coupled-human-muscarinic-receptor 3 (hM3Dq)-infused mice undergoing C21 treatment displayed MA memory extinction and resistance to stress-provoked reinstatement. These results suggest that combining a brief recall and KE treatment and exciting mPFC GABA neuron may facilitate MA memory extinction and resistance to stress-primed recall. mPFC GABA neuronal activity plays a role in mediating brief recall/KE-produced effects on curbing the stress-provoked MA seeking.

Effect of pre-hospitalization use of oral antiviral agents on reducing critical illness and mortality for patients with COVID-19 pneumonia.

OBJECTIVES: This study aimed to evaluate the effect of administering nirmatrelvir/ritonavir and molnupiravir before hospitalisation on subsequent critical illness among patients with COVID-19 pneumonia. METHODS: This retrospective cohort study included patients with COVID-19 pneumonia who required hospitalisation between 1 January 1 2022 and 31 August 2022. The primary outcomes were the development of critical illness, including intensive care unit admission, use of mechanical ventilation, or mortality. A multivariate logistic regression analysis was conducted to assess the varying risks of critical illness and mortality. A total of 1,011 COVID-19 patients were analysed. Among them, 304 (30.1%) received molnupiravir and 131 (13.0%) received nirmatrelvir/ritonavir before hospitalisation. RESULTS: There were significant reductions for critical illness (adjusted odds ratio 0.29, 95% confidence interval 0.21-0.39, P < 0.001) and mortality (adjusted odds ratio 0.40, 95% confidence interval 0.27-0.59, P < 0.001) in patients receiving oral antivirals compared with those who did not. No significant differences in critical illness were observed between molnupiravir and nirmatrelvir/ritonavir. The combination of COVID-19 vaccines and oral antivirals can further reduce the risk of critical illness in high-risk populations. CONCLUSION: Administering molnupiravir and nirmatrelvir/ritonavir before hospitalisation reduced the risk of COVID-19 patients with moderate to severe pneumonia progressing to critical illness and mortality.

Transcriptomic features of systemic lupus erythematosus patients in flare and changes during acute in-hospital treatment.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. METHODS: RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analysed and scored to elucidate the transcriptomic changes during treatment. RESULTS: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. CONCLUSIONS: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents.

BACKGROUND: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents. METHODS: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. RESULTS: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions. CONCLUSION: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

Multipole engineering by displacement resonance: a new degree of freedom of Mie resonance.

The canonical studies on Mie scattering unravel strong electric/magnetic optical responses in nanostructures, laying foundation for emerging meta-photonic applications. Conventionally, the morphology-sensitive resonances hinge on the normalized frequency, i.e. particle size over wavelength, but non-paraxial incidence symmetry is overlooked. Here, through confocal reflection microscopy with a tight focus scanning over silicon nanostructures, the scattering point spread functions unveil distinctive spatial patterns featuring that linear scattering efficiency is maximal when the focus is misaligned. The underlying physical mechanism is the excitation of higher-order multipolar modes, not accessible by plane wave irradiation, via displacement resonance, which showcases a significant reduction of nonlinear response threshold, sign flip in all-optical switching, and spatial resolution enhancement. Our result fundamentally extends the century-old light scattering theory, and suggests new dimensions to tailor Mie resonances.