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Abstract Background Immune checkpoint therapy (ICT) provides durable responses in select cancer patients, yet resistance remains a significant challenge, prompting the exploration of underlying molecular mechanisms. Tyrosylprotein sulfotransferase-2 (TPST2), known for its role in protein tyrosine O-sulfation, has been suggested to modulate the extracellular protein-protein interactions, but its specific role in cancer immunity remains largely unexplored. Methods To explore tumor cell-intrinsic factors influencing anti-PD1 responsiveness, we conducted a pooled loss-of-function genetic screen in humanized mice engrafted with human immune cells. The responsiveness of cancer cells to interferon-γ (IFNγ) was estimated by evaluating IFNγ-mediated induction of target genes, STAT1 phosphorylation, HLA expression, and cell growth suppression. The sulfotyrosine-modified target gene of TPST2 was identified by co-immunoprecipitation and mass spectrometry. The in vivo effects of TPST2 inhibition were evaluated using mouse syngeneic tumor models and corroborated by bulk and single-cell RNA sequencing analyses. Results Through in vivo genome-wide CRISPR screening, TPST2 loss-of-function emerged as a potential enhancer of anti-PD1 treatment efficacy. TPST2 suppressed IFNγ signaling by sulfating IFNγ receptor 1 at Y397 residue, while its downregulation boosted IFNγ-mediated signaling and antigen presentation. Depletion of TPST2 in cancer cells augmented anti-PD1 antibody efficacy in syngeneic mouse tumor models by enhancing tumor-infiltrating lymphocytes. RNA sequencing data revealed TPST2’s inverse correlation with antigen presentation, and increased TPST2 expression is associated with poor prognosis and altered cancer immunity across cancer types. Conclusions We propose TPST2’s novel role as a suppressor of cancer immunity and advocate for its consideration as a therapeutic target in ICT-based treatments.

Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except “cough,” were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.

Abstract The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyze blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyze their B-cell receptor (BCR) repertoires at six time points in total. The concomitant reactivity to both ancestral and Omicron receptor-binding domain (RBD) is achieved by a limited number of BCR clonotypes depending on the accumulation of somatic hypermutation (SHM) after the third dose. Our findings suggest that SHM accumulation in the BCR space to broaden its specificity for unseen antigens is a counterprotective mechanism against virus variant immune escape.

This study aims to find an eco-friendly dual material to apply toward energy and antibacterial industry, and to identify their active sites. Cu0.1Zn0.9O nanoparticles (NPs) containing 10 % Cu ions into ZnO framework are synthesized using a facile hydrothermal method, and 10, 20, 30, or 40 nm-sized Ag NPs are loaded to obtain Ag@Cu0.1Zn0.9O particles. From the time-dependent increase in photocurrent density, it is confirmed that the Ag NPs has a photoelectron harvesting ability. Unlike ZnO and Cu0.1Zn0.9O, the Ag@Cu0.1Zn0.9O catalyst well splits water to generate hydrogen. Particularly, the catalyst loaded with 30 nm Ag NPs achieves the highest hydrogen production efficiency of 424.54 μmolg−1. This proves that the active sites generating hydrogen during water splitting are the Ag NP surfaces grafted onto the conduction band of the Cu0.1Zn0.9O particles. Contrastingly, antibacterial performances against Bacillus manliponensis are expressed in all samples of ZnO, Cu0.1Zn0.9O, and Ag@Cu0.1Zn0.9O. The antibacterial performance for the Ag NP-loaded sample slightly increases but it is not significant, indicating that the active site exhibiting the antibacterial activity is the hole+ of the valence band of Cu0.1Zn0.9O. In the end, this study revealed that the advantageous photocatalytic activity does not always express effective antibacterial activity because the active sites exhibiting photocatalytic and antibacterial properties may not be the same.

The aim of this study is to enhance comprehension of the different types and features of dementia, including their symptoms, diagnosis and medical treatment, and to propose various evidence-based exercise interventions and their clinical applications tailored to each specific type of dementia. The theoretical review includes the analysis of publications in the scientific databases PubMed/Medline, Ebsco, Scielo, and Google. A total of 177 articles were found, of which 84 were studied in depth. With the prevalence of all forms of dementia projected to increase from 57.4 million in 2019 to 152.8 million in 2050, personalized treatment strategies are needed. This review discusses various forms of dementia, including their pathologies, diagnostic criteria, and prevalence rates. The importance of accurate diagnosis and tailored care is emphasized, as well as the effectiveness of physical exercise in improving cognitive function in dementia patients. For Alzheimer’s, a combination of drug therapies and exercises is recommended to enhance cerebral blood flow and neurotransmitter activity. To improve cognitive and motor functions in Lewy body dementia, a combination of pharmacological and physical therapies is recommended. For managing frontotemporal dementia, a mix of medication and exercises aimed at emotion regulation, including aerobic exercises, and a unified protocol, is suggested. For mild cognitive impairment, aerobic and functional exercises are important in delaying cognitive decline and enhancing cognitive performance. In conclusion, individualized care and treatment plans tailored to the specific characteristics of each disease type can improve the quality of life for individuals with this condition and effectively manage this growing global health issue.

Pediatric palliative care was introduced in South Korea in 2018, with an increased need for care of children with life-limiting conditions, such as leukemia. However, the perspective of parents, who are the primary caregivers, regarding pediatric palliative care has not been explored. This study aimed to describe the pediatric palliative care-related experiences of parents who had lost a child to leukemia to better understand their needs and care outcomes. Ten mothers of children who received pediatric palliative care were recruited. Individual in-depth interviews were conducted. Phenomenology was applied to elucidate parents' experiences during their children's illness and after bereavement. From 179 main statements and 46 meaningful units, 22 themes were derived and grouped into 11 theme clusters and 4 categories. The participants described that the pediatric palliative care team had an indispensable role in providing emotional support to them and their children; this support continued even after the child's death. In addition, the participants were satisfied with their choice to receive pediatric palliative care and hoped that more regions could benefit from the services. The study findings could contribute to advances and the popularization of pediatric palliative care in South Korea. [ABSTRACT FROM AUTHOR]

This scoping review aimed to explore the characteristics of neonatal palliative care in the neonatal intensive care unit, including the features, contents, and experiences of infants, parents, and nurses during palliative care. Five databases (PubMed, Cochrane, CINAHL, Research Information Sharing Service, and Korean Studies Information Service System) were searched to identify relevant articles published between 2011 and 2020. From the systematic search and review process, 13 studies that met the eligibility criteria were selected for the analysis. From the literature review, 2 key principles were found to facilitate neonatal palliative care: family-centered care and integrative care in the neonatal intensive care unit. In addition, the themes found in this review included (1)providing comfortable care to dying infants with respect to infants and offering parents choices, (2) therapeutic communication, (3) support with respect, and (4) bereavement care for parents of dying infants in the neonatal intensive care unit. Caregivers require effective communication, manpower support, emotional support, educational programs, and well-defined protocols. The evidence mapped and synthesized in this review indicates the need to facilitate the provision of palliative care in the neonatal intensive care unit in line with the unique needs of infants, parents, and nurses. [ABSTRACT FROM AUTHOR]