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The pathophysiology and natural course of childhood food allergies (FAs) remains largely elusive. Recent findings have implicated resolvins, omega-3 metabolites, in the pathogenesis and resolution of FAs, highlighting their potential clinical significance. This investigation aimed to elucidate the clinical implications of resolvins in the manifestation and resolution of childhood FAs. Serum samples were collected from a cohort of children diagnosed with FA and healthy controls upon their first visit to the Severance Children's Hospital (Seoul, Korea). FA persistence was assessed for each patient based on follow-up records. Resolvin D1 (RvD1) levels were measured and their correlation with total immunoglobulin E (IgE) and allergen-specific IgE levels were evaluated. This study included 278 children (mean age 3.28 ± 3.17 years; 62% male), consisting of 92 children with resolved FA (resolved FA group), 113 children with persistent FA (persistent FA group), and 73 children (control group). RvD1 levels were significantly higher in children with FA than in controls (P < 0.001), and were significantly higher in the persistent FA group than in the resolved FA group (P = 0.045). A positive correlation was found between total IgE and RvD1 levels (r = 0.32, P < 0.001), particularly in the persistent FA subgroup. Furthermore, the correlation between RvD1 and total IgE was stronger in children with multiple FAs (r = 0.367, P < 0.001). RvD1 levels were also positively correlated with egg- and milk-specific IgE levels, especially in the persistent FA group. Our findings suggest that RvD1 is a candidate metabolite associated with the persistence of childhood FA, across various food allergens and may provide complementary information to existing clinical features.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease in which eosinophil (Eos) infiltration into polyp tissues is associated with disease prognosis. Our previous study found that linoleic acid is an important differential metabolite. However, lipid metabolism in nasal polyps has been insufficiently investigated. This study aimed to explore the characteristics of lipid metabolism in CRSwNP tissue. This study employed a multi-omics approach by integrating lipidomics and single-cell transcriptomics. The lipidomics analysis was performed using nasal mucosal tissues obtained from 32 patients with nasal polyps and 20 healthy controls. The sequencing findings were validated by using immunofluorescence staining and Western blotting. Phosphatidylethanolamine and phosphatidylcholine were the most abundant lipids expressed in the sinus mucosa, and lysophosphatidylinositol (LPI) was significantly increased in the eosinophilic CRSwNP group compared to the noneosinophilic CRSwNP and the control groups. The LPI levels showed significant positive correlations with the Eos counts and percentages in nasal polyp tissue. The expressions of membrane-bound O-acyltransferase 7 and receptor G-protein coupled receptor 55 in the LPI metabolic pathway were significantly elevated in eosinophilic nasal polyps, and their expression was mainly localized to Eos in polyp tissues. There are differences in the lipidomic patterns between healthy individuals and patients with CRSwNP. The LPI metabolic axis may be associated with Eos activation in polyp tissue. These findings could provide new insights into the pathogenesis and endotyping of CRSwNP.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of invasive infections, yet the genetic basis of its stress adaptation remains partially understood. This study investigates the role of the conserved membrane-associated gene ytrE in MRSA USA300 pathogenesis. While disruption of ytrE did not affect in vitro growth or biofilm formation, the ΔytrE mutant exhibited significant attenuation in a murine systemic infection model, characterized by increased host survival and reduced bacterial burdens in major organs. Phenotypic analyses revealed that loss of ytrE leads to compromised membrane integrity, impaired surface-associated motility, and heightened sensitivity to oxidative stress (H2O2). Furthermore, the mutant showed reduced levels of cell-associated phenol-soluble modulins (PSMs), which may contribute to the impaired colony spreading phenotype. Genetic complementation restored the major altered phenotypes observed in the ΔytrE mutant. These findings suggest that ytrE contributes to MRSA pathogenic fitness by supporting envelope homeostasis and resistance to oxidative stress. Non-essential factors involved in membrane stability may represent potential targets for future anti-virulence studies.
Periostin is a matricellular protein that binds to its receptors, which include several integrin molecules but mainly αvβ3 integrin on cell surfaces, thereby transducing its signals into cells. Almost 20 years have passed since we found that periostin is involved in the pathogenesis of asthma, which marked the first evidence of its involvement in allergic diseases. Over the past 2 decades, cumulative evidence has demonstrated that periostin plays important roles in the onset or progress of many allergic diseases such as chronic rhinitis with nasal polyp, atopic dermatitis (AD), allergic conjunctivitis, eosinophilic esophagitis, eosinophilic otitis media, allergic rhinitis, and eosinophilic granulomatosis with polyangiitis. Starting from the observation of highly expressed periostin in the lesions of these diseases, periostin studies have expanded to include how periostin contributes to the generation of allergic phenotypes, how measurement of periostin is useful as a biomarker for allergic diseases, and recently how periostin inhibitors can improve allergic diseases. Periostin contributes to the generation of allergic phenotypes by acting as a matricellular protein on many cells, including both non-immune and immune cells. Based on the characteristics of periostin as a surrogate biomarker of interleukin-13, a signature cytokine of type 2 inflammation, serum periostin has been used as a biomarker for stratifying endotypes, estimating disease severity, predicting or monitoring the efficacy of therapeutic drugs, and predicting disease relapse or recurrence. Moreover, a lot of attention is now being paid to periostin in body fluids such as tears and sputum as a biomarker directly reflecting type 2 inflammation. Since it has been shown that periostin evokes itch in AD, we hope to see the development of a novel therapeutic agent for AD targeting periostin/αvβ3 integrin. Here we summarize the discovery and characteristics of periostin, as well as questions and/or problems regarding periostin that remain to be resolved.
Synthetic riboswitches provide protein-independent, modular control of gene expression, yet selecting aptamers that reliably couple ligand binding to regulatory switching remains challenging. Here, we identify and mechanistically characterise G12, a doxycycline-binding aptamer with remarkably high regulatory performance in yeast and human cells. We provide evidence that RNA Capture-SELEX efficiently enriches aptamers with ligand-responsive conformational switching. We compared conventional SELEX and RNA Capture-SELEX using the same starting library followed by NGS analysis and in vivo screening, which led to the identification of G12. G12 binds doxycycline with low-nanomolar affinity and strict discrimination against close derivatives, thus enabling high-dynamic-range riboswitch control of translation in yeast and splicing in human cells. Single-molecule force spectroscopy with optical tweezers revealed that doxycycline stabilises a folding intermediate independent of the closing stem P1, which primarily acts as a scaffold for correct aptamer folding. Mutational analysis and chemical probing identified tertiary contacts between loops L2 and L3 in this intermediate state. Stopped-flow fluorescence spectroscopy further supported a two-step binding mechanism consistent with efficient regulatory switching. Together, these findings deepen our understanding of regulatory aptamer selection and function and expand the synthetic biology toolbox with a high-performance doxycycline-responsive riboswitch.
Objective: To investigate the clinicopathological, immunophenotypic, and molecular characteristics of gastrointestinal Langerhans cell histiocytosis (LCH). Methods: A total of 12 patients diagnosed with gastrointestinal LCH from July 2021 to September 2025 were retrieved from the pathological archive database of the First Affiliated Hospital, Zhejiang University School of Medicine, among whom 10 cases were external consultation specimens. Clinical data of these patients were collected, lesion locations, endoscopic findings, histopathologic features, treatment strategies, and follow-up outcomes were systematically analyzed for all cases. Immunohistochemical staining was performed to detect the expression of CD1a, Langerin, S-100, cyclin D1, BRAF V600E and so on, followed by a comprehensive review of relevant literatures. Results: A total of 12 patients were enrolled, including 9 males and 3 females, with an age of 34.5 (26.0, 51.0) years. Lesions predominantly involved the upper gastrointestinal tract (11 out of 12 cases, gastric involvement observed in 10 cases). Endoscopically, 6 of 12 cases presented as polypoid lesions, 3 of 12 cases were flat/depressed lesions and no obvious mucosal lesions were identified in the remaining 3 patients. The key histological findings were sheets of tumor cells displaying reniform or coffee bean-shaped nuclei, and the adjacent stroma was associated with mixed inflammatory cell infiltration, with eosinophils as a prominent constituent. Immunophenotypically, all 12 cases were positive for CD1a, Langerin and S-100; cyclin D1 was positive in 8 out of 10 cases, and BRAF V600E was positive in 6 out of 10 cases. One case showed BRAF V600E point mutation by ARMS-PCR. All patients were diagnosed via biopsy and subsequently received local treatment or regular follow-up observation. The follow-up duration ranged from 3 to 54 months. All patients remained disease-free during follow-up, except for one case that developed multifocal lesions within the same system. Conclusions: Gastrointestinal LCH follows an indolent clinical course with a favorable prognosis. Characteristic histopathologic features include tumor cells with reniform or coffee bean-shaped nuclei and stromal infiltration by eosinophils. The triple immunohistochemistry panel consisting of CD1a, Langerin and S-100 serves as the cornerstone for definitive diagnosis, whereas combined assessment of cyclin D1 and BRAF V600E help confirm the neoplastic nature of the lesion. 目的： 探讨消化道朗格汉斯细胞组织细胞增生症（LCH）的临床病理、免疫表型及分子特征。 方法： 回顾性分析浙江大学医学院附属第一医院病理科2021年7月至2025年9月确诊的消化道LCH病例共12例，其中10例为外院会诊病例。收集患者的临床资料，系统分析其病变部位、胃肠镜表现、病理形态、治疗方案及随访结局；采用免疫组织化学染色检测CD1a、Langerin、S-100蛋白、cyclin D1及BRAF V600E等的表达水平并复习相关文献。 结果： 12例患者中男性9例，女性3例，年龄34.5（26.0，51.0）岁，病变以累及上消化道为主（11/12，其中累及胃10例）。胃肠镜下6例表现为隆起性病变，3例为平坦/凹陷性病变，3例未见明显病灶。组织学特征为瘤细胞核呈肾形或咖啡豆样，片状生长，间质伴嗜酸性粒细胞浸润的混合性炎性细胞；免疫表型：瘤细胞CD1a、Langerin、S-100蛋白12例阳性表达，8例cyclin D1和6例BRAF V600E免疫组织化学染色阳性。扩增阻滞突变系统PCR检测显示1例BRAF V600E突变。12例患者均行活检确诊，予局部治疗或定期随访观察；随访3~54个月，除1例出现同系统多灶性病变外，均无进展、复发及其他系统病变。 结论： 消化道LCH呈惰性生长，预后较好。病理特征以肾形核和咖啡豆样核为显著特征，间质伴嗜酸性粒细胞浸润。CD1a、Langerin、S-100蛋白三联免疫组织化学检测可作为确诊核心手段，cyclin D1与BRAF V600E联合检测可辅助明确肿瘤性增生。.
To compare clinical outcomes between urinary and non-urinary tract sepsis in nonagenarians and centenarians admitted to intensive care units (ICUs). Retrospective propensity score-matched multicentre cohort study. Adult ICUs participating in the Australian and New Zealand Intensive Care Society Adult Patient Database across Australia and New Zealand (2010-2023). We included all ICU admissions for sepsis in patients aged 90 years or older, classified as urinary or non-urinary tract sepsis using Acute Physiology and Chronic Health Evaluation III-J diagnostic codes. After 1:1 nearest neighbour propensity score matching, 1130 patients (565 per group) were included. The primary outcome was all-cause mortality within 180 days and beyond 180 days. Secondary outcomes included ICU mortality, hospital mortality, ICU length of stay and hospital length of stay. Of 1669 patients, 573 had urinary tract sepsis and 1096 had non-urinary tract sepsis. After matching, 1130 patients were included (565 per group). In the matched cohort, non-urinary tract sepsis was associated with higher mortality within 180 days than urinary tract sepsis (HR 1.67, 95% CI 1.33 to 2.09, p<0.001), whereas mortality beyond 180 days did not differ (HR 1.03, 95% CI 0.80 to 1.34, p=0.816). ICU and hospital length of stay were similar between groups. Among nonagenarian and centenarian ICU patients with sepsis, infection source was an important determinant of early but not late mortality, with non-urinary tract sepsis conferring a higher risk than urinary tract sepsis. Incorporating infection source and simple physiological markers alongside illness severity scores may improve prognostication and support shared decision-making in this very old population.
Objective: To investigate the clinicopathological and molecular features of atypical spindle cell/pleomorphic lipomatous tumor (ASPLT). Methods: A retrospective analysis was conducted on nine cases of ASPLT diagnosed at the Fourth Affiliated Hospital of Soochow University and the First Hospital of Jilin University from February 2023 to September 2025. The clinical, histopathologic, immunohistochemical, and molecular genetic features were analyzed, supplemented by a comprehensive literature review. Results: The cohort comprised seven males and two females with an age of 59.0 (54.0, 63.0) years. Tumor arose in the neck, buttock, abdominal wall, face, and axilla. Histologically, the tumors exhibited a variable mixture of atypical spindle cells, adipocytes, pleomorphic/multinucleated cells, and lipoblasts embedded within a collagenous-to-myxoid stroma. Distinctive ropy collagen bundles were identified in seven cases. Mitotic activity was negligible, and tumor necrosis or dedifferentiation was consistently absent. Immunohistochemically, all cases showed diffuse CD34 expression and loss of nuclear RB1 expression. The Ki-67 proliferative index was 1%-2%, and p53 immunostaining demonstrated a wild-type expression pattern in all eight tested cases. Fluorescence in situ hybridization confirmed RB1 gene deletion in all five tested cases. Conclusions: ASPLT is a rare adipocytic neoplasm characterized by a broad morphologic spectrum, distinctive genetic alterations, and an indolent clinical course. Due to substantial morphological overlap with other lipomatous tumors, diagnosis can be challenging. Accurate identification relies on meticulous microscopic evaluation combined with ancillary testing, specifically, CD34 positivity, immunohistochemical loss of RB1 expression, and/or molecular detection of RB1 gene deletion, to ensure correct classification and prevent overtreatment. 目的： 探讨非典型梭形细胞/多形性脂肪瘤样肿瘤的临床病理及分子遗传学特征。 方法： 收集苏州大学附属第四医院和吉林大学第一医院2023年2月至2025年9月诊断为非典型梭形细胞/多形性脂肪瘤样肿瘤病例9例（包括会诊病例3例），分析其临床特征、组织病理学、免疫组织化学及分子遗传学特征，探讨其鉴别诊断并进行文献复习。 结果： 9例患者中男性7例、女性2例，年龄59.0（54.0，63.0）岁。肿瘤发生于颈部、右臀部、腹壁、面部及右腋窝。所有病例均见非典型梭形细胞、脂肪细胞、多形性/多核细胞以及脂肪母细胞，各成分比例和细胞丰富程度不一。肿瘤间质表现为纯胶原性间质至混合性黏液样-胶原性间质，7例可见绳索样胶原束。核分裂象罕见，未见肿瘤坏死及去分化。9例肿瘤均弥漫表达CD34，并出现RB1失表达，Ki-67阳性指数1%~2%。8例检测p53表达，均显示野生型表达模式。5例行荧光原位杂交，均检测到RB1基因缺失。 结论： 非典型梭形细胞/多形性脂肪瘤样肿瘤是一种罕见的脂肪细胞性肿瘤，具有宽泛的形态学谱系及独特的分子遗传学特征，生物学行为较温和，组织病理学诊断具有挑战性，结合CD34和RB1免疫组织化学和/或分子检测有助于精确诊断和鉴别，避免误诊和过治疗。.
The Jagged1 (JAG1) gene is essential for cardiac development, yet its tissue-specific transcriptional regulation remains poorly understood. In this study we used an integrative screening approach to identify 19 candidate enhancers within the ±100 kb region flanking the JAG1 locus, among which R7 exhibited the highest activity in dual-luciferase assays. CRISPR/Cas9-mediated deletion of R7 in AC16 cells significantly reduced JAG1 expression, decreased proliferative and migratory capacities, and increased apoptosis. Mechanistically, R7 deletion altered local chromatin contacts and reduced accessibility at CTCF-bound regions near the JAG1 promoter, accompanied by decreased H3K27ac, H3K4me3, RNA polymerase II, and SRF occupancy. These findings identify R7 as a cardiac-associated promoter-proximal regulatory element with enhancer-like activity that contributes to local chromatin organization and transcriptional activity at the JAG1 locus.
Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure (ICP) and typically affects young women with obesity. Patients are at risk of permanent visual loss due to papilloedema. Some require emergency intervention to rapidly reduce papilloedema and preserve vision. The international standard of care for patients with sight-threatening IIH is cerebrospinal fluid (CSF) shunting. However, dural venous sinus stenting (DVSS) is an emerging procedure that is offered at many neuroscience centres internationally as the primary intervention. Currently, there are no randomised controlled trial data supporting the efficacy of any interventional approach for preserving vision in sight-threatening IIH. IIH Intervention is a UK-based two-arm, open-label, multicentre, randomised controlled phase IIb clinical trial with integrated health economic evaluation to compare CSF shunting with DVSS in patients who have confirmed IIH and are at risk of permanent visual loss due to severe papilloedema. The primary outcome is the global thickness of the peripapillary retinal nerve fibre layer (RNFL), an indicator of papilloedema, measured by optical coherence tomography (OCT) over a 6-month period. Secondary outcomes are global thickness of the RNFL over 12 and 24 months, as well as macular ganglion cell layer volume, perimetric mean deviation, headache outcomes, intervention reporting measures (including complications and revisions) and patient-reported outcomes over 6, 12 and 24 months. The protocol was approved initially on 12 December 2022 by West Midlands-South Birmingham Research Ethics Committee (ref: 22/WM/0230). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications. ISRCTN57142415.
国际脉管异常研究学会（ISSVA）分类2025修订版对脉管畸形进行了重大结构调整，从分类标准、疾病归属、诊断术语等方面进行明确定义，尤其注重临床影像学、病理学和遗传学特征在分类制定中多维度评估的重要作用。本文结合2025版新分类对脉管畸形的分类标准和诊断思路进行解读，以期加深和提高病理医师在该组疾病诊断中的认识。.
Belimumab has been proven to be effective for treating refractory lupus nephritis. However, the meaningful renal response is still far from satisfactory. This study sought to identify immunological biomarkers to stratify patients who are likely to benefit from belimumab therapy. We retrospectively reviewed the medical records of patients with refractory lupus nephritis who received 6 months belimumab treatment. Complete response (CR), partial response (PR) and no response (NR) were evaluated, and the predictors of CR were identified. A total of 28 patients with refractory LN were enrolled. The proportions of CR, PR and NR at 6 months were 39.29%, 32.14% and 28.57%, respectively. The baseline CD19+B cell proportions were significantly higher in CR patients than those in non-CR patients (19.30% vs 10.72%, p<0.001). In the binary logistic regression, baseline CD19+B cell proportion was identified as a predictor of CR in both univariate analysis (OR 1.359, 95% CI 1.098 to 1.683, p=0.005) and exploratory multivariate analysis adjusting for 24-hour urinary protein (OR 1.349, 95% CI 1.092 to 1.665, p=0.005). Receiver operating characteristic showed that the cut-off level of CD19+B cell proportion was 15.12%, with a sensitivity of 90.90%, specificity of 88.20% and an area under curve of 0.888 (95% CI 0.759 to 1.000, p=0.001). Findings support the baseline CD19+B cell proportion could be used to predict CR to treatment with belimumab in refractory lupus nephritis patients.
Leptospirosis is a zoonotic infection caused by the bacterium Leptospira, which typically enters humans through contact with water or soil contaminated with infected urine. One of the most important causes of death due to leptospirosis is leptospirosis pulmonary haemorrhage syndrome (LPHS). LPHS occurs due to an inappropriate immune response, resulting in excessive release of cytokines/chemokines or direct damage to alveoli by bacteria. Mortality remains high in LPHS, and management strategies of this deadly complication are under-investigated. Survivors have minimal residual lung injury, necessitating evidence-based treatment to improve mortality in LPHS. Steroids and plasmapheresis have been tried in many case series but lack robust evidence. Plasmapheresis has become a standard practice in Sri Lanka for managing LPHS, guided by expert opinion. This study will try to determine the effect of moderate-dose or high-dose steroid combination with plasmapheresis compared with plasmapheresis alone as a treatment for LPHS. This open-label, randomised controlled trial will enrol LPHS patients from four selected tertiary care hospitals in Sri Lanka. Participants will be randomly assigned to three groups in a 1:1:1 ratio to receive plasmapheresis alone, plasmapheresis with 150 mg/day methylprednisolone for 3 days or plasmapheresis with 1000 mg/day methylprednisolone for 3 days. Recruitment will consist of 28 participants to each arm of the trial. Diagnosis will be confirmed by Leptospira-specific PCR and microscopic agglutination test. Analysis will follow intention-to-treat principles with adjustment for multiple comparisons. Primary outcome is all-cause mortality at 28 days. Secondary outcomes include hospital-acquired infections, duration of respiratory support, duration of intensive care unit stay, duration of hospital stay and side effects of steroid therapy. The ethical approval was obtained from the Research Ethics Committee of the University of Sri Jayewardenepura (ERC 20/24) and the trial has been registered in the Sri Lanka Clinical Trials Registry (SLCTR/2024/037). Trial is approved by the National Medicines Regulatory Authority in Sri Lanka (NMRA/CTRD/PA4/54). Study findings will be disseminated through peer-reviewed publications and conference presentations. Sri Lanka Clinical Trials Registry, Number SLCTR/2024/037.
This review analyzes the structure and content of the two-axis classification systems for hyperkinetic disorders. The first classification was developed for dystonia in 2013, a tremor classification appeared in 2018, and a myoclonus classification in 2025, together with a revision of the 2013 dystonia classification. In all these classifications, Axis I refers to clinical characteristics, and Axis II to etiology. However, for myoclonus there is also an Axis Ib dedicated to neurophysiology. The clinical features of dystonia are recognized by clinical assessment, whereas in the case of tremor, and particularly of myoclonus, neurophysiology plays a relevant role. In the tremor and myoclonus classifications, neurophysiology is included as an Axis I descriptor aside clinical assessment. The positioning of other laboratory tests differs among classifications. Neuroimaging is an etiological Axis II division in dystonia, whereas it is included aside other laboratory tests under Axis I in the tremor and myoclonus classifications. The results of genetic testing are included under Axis II in the dystonia and tremor classifications, instead under Axis I in the myoclonus classification. The positioning of functional movement disorders also differs, and for myoclonus a new Axis II etiology of "functional neurological disorders" has been added. These classification exercises highlight the specificity of different hyperkinetic disorders on the background of a comparable two-axis structure.
Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system that typically follows viral or bacterial infections. There are only two known case reports that describe an association with ADEM post rickettsial infection. A female in her 80s presented with progressive neurological decline, including dysarthria, dysphagia and hemiparesis, following recent treatment in Hong Kong for rickettsial infection. Initial CT brain imaging showed a right subcortical infarct. She deteriorated with encephalopathy and respiratory failure, requiring intubation. MRI revealed extensive brain and spinal demyelination. Infectious, autoimmune and paraneoplastic investigations were negative, while serology revealed markedly elevated spotted fever group antibodies. Treatment with high-dose corticosteroids and plasma exchange therapy resulted in significant neurological recovery. She was discharged after rehabilitation with a good recovery at 70%-80% of pre-morbid function. This case supports a possible post-infectious immune-mediated mechanism linking rickettsia and ADEM and underscores the importance of early recognition and treatment of ADEM.
Dysmenorrhoea is one of the most frequent manifestations of chronic pelvic pain. Endometriosis and adenomyosis are among the most common pathological causes of secondary dysmenorrhoea. Symptoms often persist despite treatment, so individuals frequently engage in self-management strategies. One self-management approach that may have potential benefits for chronic pain is whole-body thermal therapy, which involves exposure to heat or cold stimuli inducing systemic physiological responses. The aim of this scoping review is to map and synthesise the available literature on the use and reported benefits of whole-body thermal therapies in individuals assigned female at birth (AFAB) with chronic pelvic pain, dysmenorrhoea, endometriosis and adenomyosis. The proposed scoping review will adhere to the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analysis, Extension for Scoping Reviews) checklist. We will search the Embase, Scopus, Medline, American Psychological Association (APA) PsycINFO, Web of Science and CINAHL Ultimate electronic databases for primary studies published in English from the year 2000. All articles will be independently assessed by two reviewers for eligibility. Data will be synthesised using framework synthesis and findings will be presented descriptively in tabular and narrative format. The proposed study does not require ethical approval as it is a scoping review of the existing literature and will only describe and synthesise previously published data. We will consult with an established patient and public involvement (PPI) panel who will assist in interpreting and disseminating the findings. We will produce and disseminate creative outputs (eg, visual illustrations) that capture discussions during PPI panel meetings. Findings will be disseminated in a peer-reviewed journal, at conferences and via webinars with relevant networks. This protocol has been registered as a preprint on the Open Science Framework platform: https://osf.io/zxp3j.
Chromosome-scale genome assemblies in gymnosperms have lagged behind those of angiosperms, likely due to their large genomes. Coniferous tree species, which belong to the gymnosperms, are important resources for wood production in the forestry industry. To elucidate the evolution and speciation of these species and establish genome resources for breeding, we integrated draft assemblies with optical and genetic mapping to construct chromosome-scale genomes for Japanese cypress (Chamaecyparis obtusa, 8.7 Gb), Japanese cedar (Cryptomeria japonica, 9.6 Gb), and Chinese fir (Cunninghamia lanceolata, 13.4 Gb). Additionally, we assembled and annotated their chloroplast and mitochondrial genomes. Comparative analysis of the nuclear genomes revealed that while synteny is largely conserved, distinct translocations and inversions occurred in chromosomes 2, 6, and 9. Notably, the significantly larger genome of Cu. lanceolata was associated with frequent tandem gene duplications rather than transposon expansion. These findings suggest that chromosomal rearrangements and segmental duplications played key roles in the divergence of these species. The genomic resources presented here including chromosome-scale sequences, gene annotations, and genetic maps will facilitate advanced conifer genetics and accelerate forest tree breeding programmes.
Metabolic bone diseases are diverse disorders marked by impaired bone turnover or mineralization, causing fragility and fractures. Interventional radiology (IR) plays a key role by offering minimally invasive treatments for pain relief, stabilization, and early mobilization. Vertebroplasty is effective for painful osteoporotic vertebral fractures without deformity, while kyphoplasty or expandable devices suit cases with collapse or kyphosis. In Kümmell's disease, targeted cement augmentation provides rapid improvement. Sacral insufficiency fractures can be safely treated with computed tomography-guided sacroplasty, enabling early ambulation. Complex sacral fractures may require combined fixation and sacroplasty. Overall, IR enhances outcomes and reduces complications in frail patients.
Swine leukocyte antigens (SLA) may be a new type of xenoantigen. Previous studies on SLA have primarily focused on their cross-reactivity with HLA. However, the role of SLA in stimulating xenogeneic immune responses after xenotransplantation remains unclear. In our recent kidney xenotransplantation study in rhesus monkeys using GTKO/hCD55 or GTKO/β4GalNT2KO/hCD55/hTBM pigs as donors, 5 of 13 recipients experienced early AMR accompanied by a marked increase in anti-donor pig antibodies. Flow cytometry analysis showed that the terminal sera of these recipients contained significant de novo anti-SLA antibodies, as evidenced by reduced antibody binding to GTKO/SLA-I/II KO pig PBMCs. Using GTKO/β4GalNT2KO pAECs with or without pIFN-γ stimulation as target cells, we found that the binding levels of the terminal sera to pAECs were positively correlated with SLA expression. IP-MS analysis identified multiple SLA class I and class II epitopes targeted by recipient IgG antibodies, with SLA-2 emerging as a dominant immunogenic antigen. In addition, xenogeneic MLR assays revealed that deletion of SLA, particularly SLA class II, markedly attenuated human anti-pig T-cell proliferation. These results demonstrate that induced anti-SLA antibodies can be generated in the early period after pig-to-monkey kidney xenotransplantation and may play a significant role in the development of AMR.