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Desmoplastic small round cell tumor (DSRCT) is an extremely rare and highly aggressive soft-tissue sarcoma that predominantly affects adolescents and young male patients. This malignancy is defined by the t(11;22) (p13;q12) chromosomal translocation, which generates the EWSR1-WT1 fusion gene. Owing to its rarity and aggressive clinical behavior, standardized treatment strategies for DSRCT have not yet been established. A 13-year-old boy presented with increased defecation frequency and progressive weight loss. Serum cancer antigen 125 (CA125) levels were markedly elevated at 187.00 U/mL. Contrast-enhanced abdominal computed tomography (CT) revealed a large heterogeneous mass with calcifications in the left epigastrium, invading the adjacent intestinal loops. CT-guided biopsy combined with immunohistochemical staining demonstrated positive expression of desmin, cytokeratin pan (CKpan), and vimentin in the tumor. Targeted next-generation sequencing (NGS) confirmed the presence of EWSR1-WT1 fusion, supporting the diagnosis of DSRCT. The patient received comprehensive multimodal treatment, including neoadjuvant chemotherapy, cytoreductive surgery, multiple lines of systemic chemotherapy, combined chemoimmunotherapy, and tyrosine kinase inhibitor (TKI) therapy. Nevertheless, the tumor relapsed repeatedly, and chemotherapy resistance gradually emerged during sequential treatment. We report a pediatric case of intra-abdominal DSRCT harboring EWSR1-WT1 fusion. The patient was diagnosed with an advanced stage disease at the initial presentation. Immunohistochemical and molecular analyses revealed a WT1-negative phenotype and dual EWSR1-WT1 fusion breakpoints, which are atypical findings compared with most reported DSRCT cases. Despite these unusual molecular features, a definitive diagnosis of DSRCT was established. The tumor inevitably progressed despite intensive multimodal intervention. This case further demonstrates the highly aggressive nature of DSRCT, which is associated with a high risk of local recurrence and distant metastasis. Novel systemic and targeted therapies are urgently needed to improve the clinical outcomes of affected patients.

Trichosanthes cucumeroides (Cucurbitaceae) is a rich source of cucurbitacin-type triterpenoids, known for their diverse pharmacological effects. This study aimed to isolate compounds from the roots of T. cucumeroides and to evaluate their cytotoxic activities and potential protein-binding interactions. The characterization of the isolated compounds was accomplished using spectroscopic and spectrometric approaches, including 1D/2D NMR, ECD, UV, IR, HR-ESI-MS, and X-ray crystallography. The antitumor effects were studied against different cell lines (MDA-MB-231, SKOV3, T24, and HUVEC) via MTT assays. Phytochemical investigation of T. cucumeroides yielded 25 compounds (1-25), including 11 undescribed kugualiansu A-K (1-11) and 14 known compounds (12-25). Additionally, the X-ray structures of compounds 2, 13, 17, and 20 were also reported. All compounds were assessed for cytotoxic activity against four cell lines, and their SARs were discussed. The MTT assay showed that some compounds exhibited significant effects with IC50 values from 0.051 to >20 μM. Moreover, compounds 19, 24, and 25 showed the most significant cytotoxicity against MDA-MB-231, SKOV3, and T24, with IC50 values of 0.098 ± 0.010, 0.054 ± 0.010, and 0.051 ± 0.010 μM, respectively. Furthermore, molecular docking studies were conducted for all compounds to analyze protein-ligand interactions and were supported by SPR and CETSA studies.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric plots featured in Fig. 4 on p. 3748 were strikingly similar to plots that had appeared in a pair of articles written by different authors at different research institutes that had already been submitted for publication/published in the journal Medical Science Monitor, and a further paper with which the above paper shared flow cytometric data was identified as having been submitted to the journal Oncology Letters. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 3744‑3750, 2018; DOI: 10.3892/mmr.2018.9358].

Several Clostridium perfringens toxinotypes may cause disease in both humans and animals. The role of non-native wildlife as carriers of this pathogen has not been fully investigated. Direct PCR toxinotyping on intestinal content of clinically healthy individuals of the invasive American mink (Neogale vison) in southern Chile, detected the genes encoding alpha, beta, epsilon, iota, enterotoxin and necrotic-enteritis b-like toxins. No microscopic lesions associated with these toxins were observed in samples of intestinal tissue, but the study confirms that minks are exposed to and can harbor C. perfringens toxigenic strains in their intestinal contents, serving as a baseline for future epidemiological monitoring.

Polymeric (p) immunoglobulins (Igs) and their secretory (S) forms are critical to vertebrate immunity. The pIgs and SIgs comprise a molecularly diverse family of antibodies that contain multiple Ig monomers, up to one joining chain (JC), and up to one secretory component. A subset of pIgs function in circulation whereas SIgs populate mucosal barriers. The pIgs and SIgs exhibit unique functions compared to monomeric Igs, yet their underlying molecular structures remained largely elusive until 2020 when cryo-electron microscopy revealed SIgA and SIgM to be remarkably asymmetric antibody assemblies. More recent reports have uncovered IgM and IgA complexes with host receptors and pathogenic virulence factors, species-specific structural differences, and conformational relationships between pIgs' structural cores and antigen binding fragments. Together, these findings highlight pIg and SIg conformational asymmetry as a key feature and establish a foundation to advance our understanding of pIg and SIg structure-function relationships critical for understanding immunity.

Pregnancy in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) is uncommon but clinically challenging. Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are clonal hematopoietic stem cell disorders characterized by myeloid proliferation, JAK-STAT pathway activation, and an increased risk of thrombotic and hemorrhagic complications. Pregnancy itself is a hypercoagulable state, and when it occurs in patients with MPNs, maternal and fetal complications are more frequent than in the general population. The most common fetal complications are first trimester pregnancy loss, placental insufficiency, fetal growth restriction, preeclampsia, preterm delivery, and stillbirth. Maternal complications include venous and arterial thrombosis, bleeding, acquired von Willebrand syndrome, and postpartum thromboembolism. ET is the most frequently encountered MPN in pregnancy and generally carries the most favorable prognosis. PV is associated with higher thrombotic and placental risk, largely related to erythrocytosis and hyperviscosity. Pregnancy in PMF is rare, and available data are limited to small series and case reports, making management particularly dependent on expert opinion. The mainstay of treatment is risk-adapted therapy with low-dose aspirin, low-molecular-weight heparin, phlebotomy for PV, and interferon-based cytoreduction when needed. Hydroxyurea, anagrelide, and JAK inhibitors are generally avoided due to limited fetal safety data. Given the paucity of prospective evidence, management should be individualized and coordinated by hematology and maternal-fetal medicine specialists. This review summarizes current data on MPN pregnancy outcomes and provides a practical approach to preconception counseling, antepartum management, delivery planning, postpartum care, and future research priorities.

Electroporation has birthed two massive parallel universes of applications: medicine and food processing. Despite operating on the same fundamental physics, these fields fail to crosspollinate, limiting their advancement. The classical "aqueous pore" model and threshold-based definitions fail to explain the highly complex, multiparameter realities of molecular transport, cell death mechanisms, and tissue-level physiological responses. The fields often struggle to translate in vitro findings-where even varying cell lines yield conflicting results-into predictive clinical and industrial outcomes. Upscaling from small animals to humans, as well as from laboratory to industrial scale, often fails due to increasing biological complexity and variability. This translational chasm is exacerbated by a lack of multiscale and multiphysics modeling that couples electric fields with thermodynamics, fluid dynamics, and electrochemistry and most of all downstream effects of electroporation like cell death and changes in mass transport. Emerging clinical applications like Pulsed Field Ablation and therapies based on gene delivery represents a perplexing, multiparameter optimization problem that must balance electrical, thermal, and electrochemical constraints. This paper highlights critical deficiencies, explores the sharp boundary between reversible and irreversible electroporation, and calls for better reporting, standardized nomenclature, and interdisciplinary collaboration to elevate electroporation from an empirical to a universally predictive, robust science.

Primary ovarian synovial sarcoma is an exceedingly rare malignancy that may mimic more common ovarian tumors, particularly in adolescents, posing significant diagnostic challenges. A 14-year-old girl presented with progressive abdominal distension and respiratory compromise. Imaging revealed a large mixed solid-cystic adnexal mass with ascites and pleural effusion. Serum CA-125 was elevated, while AFP and CEA were normal. The patient underwent right salpingo-oophorectomy and omentectomy. Histopathology showed a monophasic spindle cell neoplasm with focal cartilaginous differentiation. Immunohistochemistry demonstrated diffuse nuclear positivity for SS18 and TLE1, with co-expression of BCL-2, CD99, and EMA, while inhibin, calretinin, and WT-1 were negative. The positive SS18 immunohistochemical staining provided additional diagnostic confirmation of synovial sarcoma, supporting the diagnosis in conjunction with the characteristic histopathologic findings. The patient deteriorated rapidly and died before initiation of chemotherapy. Primary ovarian synovial sarcoma is a rare and aggressive tumor that can mimic germ cell neoplasms. Accurate diagnosis requires careful integration of histopathology and immunohistochemistry. Although molecular confirmation remains the diagnostic gold standard, SS18 fusion-specific immunohistochemistry provides a reliable diagnostic surrogate when molecular testing is unavailable.

Neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative diseases in childhood. This study aimed to investigate the phenotypic and genetic spectrum of NCLs in Egypt. This descriptive study involved children with NCLs diagnosed and managed at five Egyptian centers between 2019 and 2024. Demographic, clinical, brain imaging, and genetic data were systematically evaluated. Identified variants in NCL-related genes were classified following the American College of Medical Genetics and Genomics guidelines. The cohort included 64 Egyptian children (from 57 families) with eight NCL types. The most commonly identified genotype was CLN2 (17/64, 27%), followed by CLN1 and CLN7 (12/64, 19% each). Patients generally exhibited the classic manifestations of NCLs, particularly motor regression (64/64, 100%), cognitive decline (64/64, 100%), language impairment (64/64, 100%), epilepsy (57/64, 89%), and vision loss (47/64, 73%). Notably, developmental regression (12/17, 71%) was the predominant presenting symptom for CLN2. Brain imaging generally showed typical cerebral and cerebellar atrophy in 95% (61/64) and 84% (54/64) of cases, respectively. Nevertheless, thalamic abnormalities were observed in only 16% (10/64) of cases. A total of 46 distinct variants were identified across eight NCL-related genes, including 23 novel ones, with the majority (33/46, 72%) being private. There was a median diagnostic delay of 2 years, and none of the patients received specific therapy. This study reports the largest cohort of children with NCLs from Egypt, including 12 patients with the less-commonly reported CLN7 subtype, which expands the demographic, clinical, and molecular spectrum of these diseases.

Pleural mesothelioma (PM) is an aggressive cancer with limited therapeutic options and poor prognosis, necessitating comprehensive model systems for mechanistic studies and drug discovery. Tumor cells were isolated from malignant pleural effusion of PM patients and subjected to primary culture and continuous passaging. Cell lines were successfully established after more than 40 continuous passages in vitro. Cell identification included morphological analysis, species identification, short tandem repeat (STR) profiling, mycoplasma detection, in vitro proliferation assays, in vivo tumorigenicity testing in NOD/SCID mice, and immunohistochemical characterization. Genomic landscapes and transcriptomic profiling were defined by whole-exome, whole-genome sequencing, and RNA-sequencing. Three Chinese-derived pleural mesothelioma cell lines (PUMC-MESO1, PUMC-MESO3, and PUMC-MESO4) were successfully established. All three cell lines exhibited epithelioid morphology with adherent growth patterns. Upon subcutaneous transplantation into NOD/SCID mice, PUMC-MESO1 and PUMC-MESO4 demonstrated tumorigenicity, while PUMC-MESO3 remained non-tumorigenic after 3 months of observation. Histopathological examination confirmed their mesothelioma origin through positive staining for mesothelial markers including calretinin, WT-1, and D2-40. Genomic analysis revealed characteristic PM genomic alterations including mutations in BAP1, NF2, and TP53, along with CDKN2A deletions. Transcriptomic analyses revealed heterogeneous molecular features among the three cell lines. Although the PUMC-MESO cell lines displayed distinct clustering patterns relative to the CCLE mesothelioma cohort, each retained transcriptomic similarities to specific established mesothelioma models. Drug sensitivity assays further demonstrated heterogeneous responses to standard therapeutic agents. This study reports the establishment and characterization of three novel PM cell lines. These models recapitulate key aspects of PM biology, exhibit diverse therapeutic responses, and provide a valuable new resource for investigating disease mechanisms and advancing precision oncology research.

General population-based studies addressing the association between occupational exposure to irritants and allergens and hand eczema (HE) are limited, or only focus on specific occupations using self-reported exposure data. To assess the association between occupational exposure to irritants and allergens and moderate-to-very severe HE, by using the Occupational Asthma-specific job exposure matrix (OasJEM) within the Dutch general population, and to address the applicability of this approach. Within the Lifelines Cohort Study, participants with moderate-to-very severe HE at worst in the past year vs. no HE in lifetime were identified based on self-reports. The OasJEM was used to link occupations with occupational exposure to irritants and sensitizers, relying on expert-based classification. In total, 56,978 (41.9%) participants were included. The multivariate binary logistic regression analyses showed associations between occupational exposure to irritants [Odds ratio (OR): 1.19 (95% CI: 1.06-1.33)], high molecular weight sensitizers [OR: 1.20 (95% CI: 1.06-1.36)], mites [OR: 1.41 (95% CI: 1.16-1.73)] and disinfectants and cleaning products [1.25 (95% CI: 1.11-1.42)], and moderate-to-very severe HE. While associations between several irritants and allergens and HE were found by applying the OasJEM, which may provide insights into occupational exposure patterns and highlight the general relevance of occupational exposure in relation to HE and its prevention, several methodological and conceptual challenges must be acknowledged. A JEM not specifically designed for HE, like the OasJEM, may not fully capture the complex interplay between occupational exposure and HE, particularly in reflecting direct skin contact, the primary exposure route relevant for HE. However, in the absence of widely available and reliable HE-specific exposure assessment tools, the use of non-HE-specific JEMs may be considered a pragmatic alternative, while acknowledging certain limitations. Future studies should focus on task-based and HE-specific exposure data, providing more accurate insights into occupational exposure and HE.

CD30 positivity serves as a critical diagnostic hallmark for anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK+ ALCL); however, rare cases with partial or complete loss of CD30 expression present diagnostic challenges. We report a unique case with two morphologically and immunophenotypically distinct subpopulations within the same tumor: A typical CD30-positive component and a CD30-negative counterpart. Comparative genetic analysis revealed overlapping but divergent molecular features, including nucleophosmin 1-ALK (NPM1-ALK) fusion, notch receptor 1 mutations, and differential gene amplifications involving MYC proto-oncogene and BCL2-like 1. These findings offer insights into the regulatory mechanisms of CD30 and highlight that loss of CD30 expression alone should not preclude the diagnosis of ALK-positive ALCL, underscoring the importance of integrated histopathological and molecular evaluation in diagnostically challenging cases. Meanwhile, it provides a basis for optimizing the diagnostic process of clinically suspected cases.

Epstein-Barr virus-associated gastric cancer (EBVaGC) is a relatively rare clinical subtype. Despite its generally favorable prognosis, preoperative diagnosis remains challenging, and no established consensus exists regarding postoperative adjuvant treatment strategies for early-stage patients with high-risk pathological factors. This study reports a female case of early-stage EBVaGC of the lymphoepithelioma-like carcinoma subtype complicated with perineural invasion (a high-risk factor), and systematically explores the etiology, pathological features, key diagnostic points, individualized adjuvant therapy options, and prognosis of EBVaGC. The aim is to improve clinicians' understanding of this gastric cancer subtype, reduce its misdiagnosis rate, and accelerate the development of standardized diagnostic and treatment pathways. A case of a 60-year-old female patient admitted with "abdominal pain and distension for more than 1 year" was reported, and postoperative pathology confirmed EBVaGC. The clinical manifestations and diagnostic and treatment process were analyzed in combination with a review of relevant literature from recent years. Preoperative gastroscopic biopsy revealed poorly differentiated adenocarcinoma of the gastric mucosa. The patient underwent laparoscopic radical subtotal gastrectomy with lymph node dissection. Postoperative pathology confirmed EBVaGC. After symptomatic treatment, the patient improved and was discharged from the hospital. One month after surgery, no disease progression was observed and the SOX regimen was administered. The patient tolerated the treatment well, and the next cycle of chemotherapy is currently planned. EBVaGC lacks specific clinical manifestations, and laboratory findings may be within normal ranges at the time of onset. Reliance solely on conventional gastroscopy and histopathological biopsy can easily lead to misdiagnosis and inappropriate treatment. Epstein-Barr virus-encoded RNA in situ hybridization is the core diagnostic modality for definitive diagnosis. This subtype generally has a favorable prognosis. However, for patients with high-risk pathological factors such as perineural invasion and tumor invasion into the muscularis propria, standardized postoperative individualized adjuvant therapy should be administered based on tumor stage and molecular profiles.

Vaccination-induced granuloma is a common clinical diagnosis, but few reports have described the diagnostic utility of comprehensive pathological and microbiological examinations. This report details a case of DTaP-IPV vaccination-induced granuloma where the use of multi-virus/microbial real-time polymerase chain reaction (PCR) enabled a definitive molecular diagnosis. This advanced testing method confirmed the presence in the excised tissue of Bordetella pertussis and poliovirus genes from the vaccine components, a novel finding for this type of lesion. In cases requiring a definitive diagnosis, especially those where malignancy is a differential, surgical excision followed by multiplex PCR testing is a reliable option.

Syndromic inborn errors of immunity (IEIs) are a heterogeneous group of disorders characterized by immune dysfunction associated with congenital anomalies and multisystem involvement. Tricho-hepato-enteric syndrome (THES) is an ultra-rare autosomal recessive syndromic IEI caused by biallelic pathogenic variants in TTC37 or SKIV2L. Delayed recognition is common because of its broad clinical spectrum. To describe the clinical, immunologic, genetic, and histopathologic characteristics of two children with THES and to highlight a structured diagnostic approach for syndromic immunodeficiencies. We retrospectively reviewed the clinical presentation, laboratory investigations, immune phenotyping, endoscopic and histopathologic findings, and molecular analyses of two unrelated children diagnosed with THES at a tertiary pediatric immunology center. Molecular confirmation was obtained by whole-exome sequencing. Both patients presented during early infancy with intractable diarrhea, severe failure to thrive, characteristic dysmorphic features, brittle woolly hair, and inflammatory enteropathy requiring prolonged nutritional support. Immunologic evaluation demonstrated immune dysregulation, including inverted CD4/CD8 ratios, abnormalities of humoral immunity, and impaired vaccine-specific antibody responses. Histopathology revealed chronic active colitis with crypt distortion, inflammatory infiltrates, and crypt abscesses, consistent with very-early-onset inflammatory bowel disease-like enteropathy. Whole-exome sequencing identified homozygous pathogenic variants in SKIV2L in one patient and TTC37 in the other, establishing the diagnosis. Management included nutritional support, immunoglobulin replacement, antimicrobial prophylaxis, and immunomodulatory therapy. Recognition of syndromic phenotype combined with comprehensive immune evaluation and early genomic testing facilitates prompt diagnosis, multidisciplinary management, genetic counseling, and consideration of emerging targeted therapies.

Klebsiella pneumoniae (KP) has emerged as a formidable nosocomial pathogen in the era of antimicrobial resistance, with mortality from pneumonia caused by carbapenem-resistant strains exceeding 50%. Phage therapy has re-emerged as a promising alternative or adjunctive strategy for managing refractory KP infections. This review consolidates the current preclinical and clinical evidence base, outlines the molecular mechanisms of phage-host interactions, and appraises evolving therapeutic approaches. Preclinical investigations in murine pneumonia models have consistently demonstrated that intranasal or nebulization phage administration markedly reduces pulmonary bacterial burden, attenuates inflammatory lung injury, and improves survival, often exhibiting synergistic effects when combined with conventional antibiotics. Clinical case reports and small compassionate-use series have further provided preliminary yet compelling evidence supporting the safety and therapeutic promise of personalized phage formulations in critically ill patients with multidrug-resistant KP pneumonia who have exhausted standard treatment options. Mechanistically, phage tropism is mediated through the specific recognition of bacterial surface receptors-principally capsular polysaccharide and, to a lesser extent, lipopolysaccharide-by phage-encoded receptor-binding proteins, culminating in bacterial lysis. In response, KP has evolved a multilayered defensive arsenal encompassing receptor modification to impede adsorption, nucleic acid interference systems (e.g., CRISPR-Cas and restriction-modification), and abortive infection mechanisms that curtail phage propagation at the population level. To surmount the inherent limitations of narrow host range and the inevitable emergence of phage-resistant mutants, a suite of optimization strategies is under active refinement, including rationally designed phage cocktails, genetically engineered phages with extended tropism, artificial intelligence-assisted host-range prediction, and innovative delivery platforms such as hydrogel encapsulation to enhance pulmonary bioavailability. Despite ongoing challenges in mechanistic complexity, manufacturing standardization, and regulatory uncertainty, current initiatives- such as the establishment of geographically diverse phage libraries, real-time surveillance of phage resistance, and the development of phage-derived enzyme products-hold promise for establishing precision phage therapy as a viable and sustainable component of the antimicrobial stewardship armamentarium. 在抗菌药物耐药时代，肺炎克雷伯菌（Klebsiella pneumoniae，KP）已成为一种棘手的院内病原体，碳青霉烯耐药菌株所致肺炎的病死率超过50%。噬菌体疗法已重新成为治疗难治性KP感染的替代或辅助策略。本综述系统梳理了当前临床前与临床证据基础，阐明了噬菌体-宿主相互作用的分子机制，并评估了不断演进的治疗策略。尽管在机制复杂性、生产标准化及监管不确定性方面仍面临持续挑战，但正在推进的各项举措——包括建立覆盖不同地域的噬菌体库、开展噬菌体耐药性的实时监测以及开发噬菌体衍生酶类产品——有望使精准噬菌体疗法成为抗菌药物管理体系中切实可行且可持续的组成部分。.

Down syndrome (DS) is the most common chromosomal abnormality in the human population, most frequently caused by trisomy 21 due to meiotic nondisjunction. Rarely, DS may result from an isochromosome or a Robertsonian translocation, this being the least common variant. We present a rare prenatal case of Down syndrome caused by a derivative chromosome 21, together with a case-based review of previously reported prenatal der(21;21)/i(21q) rearrangements. We report a case of prenatal diagnosis of DS in a 13-week female fetus, characterized by a derivative chromosome 21, der(21;21)(q10;q10), identified by conventional karyotyping and subsequently confirmed by fluorescence in situ hybridization (FISH). First-trimester ultrasonography showed bilateral jugular lymphatic sacs, marked tricuspid regurgitation, and a single umbilical artery. Quantitative fluorescence polymerase chain reaction (QF-PCR) failed to detect the structural chromosomal abnormality. The rearrangement was considered likely de novo based on normal parental karyotypes. Consequently, the empirical recurrence risk is 1% for de novo cases, whereas in families with a parental 21q;21q rearrangement the recurrence risk may approach 100%. This case highlights the importance of integrating detailed ultrasound screening with molecular and cytogenetic techniques, including QF-PCR, conventional karyotyping, and FISH, for accurate prenatal diagnosis of DS. Precise determination of the underlying chromosomal abnormality is essential for providing accurate genetic counseling, estimating recurrence risk, and facilitating informed reproductive planning for the parents.

Bone marrow failure syndromes (BMFs) comprise a heterogeneous group of genetic disorders characterized by impaired hematopoiesis and multisystem involvement. Dyskeratosis congenita (DC) is a telomere biology disorder caused by defects in telomerase or telomere maintenance, leading to progressive BMF and variable extra-hematopoietic manifestations. To describe the clinical, immunologic, genetic, and telomere biology findings in a patient with DC caused by a novel biallelic telomerase reverse transcriptase (TERT) mutation, and to highlight diagnostic and therapeutic considerations in telomere-associated BMFs. We assessed cellular and humoral immune functions. Genetic analysis was conducted using whole-exome sequencing (WES) with segregation analysis. Telomere length was assessed by flow-FISH. Functional and radiologic evaluations were performed to define disease extent. A 2-year old male born to consanguineous parents presented with multisystemic clinical features, and hypocellular bone marrow. WES identified a novel homozygous TERT missense variant (c.3052G>A; p.Ala109Thr) supported by markedly shortened telomeres. Neuroimaging revealed cerebellar hypoplasia consistent with Hoyeraal-Hreidarsson syndrome. Immunologic evaluation demonstrated skewed CD4:CD8 ratios. An incidental heterozygous MEN1 variant was also detected. We expand the clinical and genetic spectrum of TERT-associated DC and illustrate the critical role of genomic diagnostics and telomere assessment in BMFs. Early molecular diagnosis enables targeted evaluation, informs prognosis, and guides personalized management in telomere biology disorders. In addition, the identification of actionable secondary variants further highlights both the power and complexity of comprehensive genomic testing.

Armillaria mellea (Vahl) P. Kumm. and related species in the A. mellea sensu lato complex are ecologically important basidiomycetes and key fungal partners in the cultivation of the fully mycoheterotrophic orchid Gastrodia elata. Because many historical reports labelled isolates simply as A. mellea before modern molecular delimitation, biological and applied conclusions require careful taxonomic interpretation. This critical review synthesizes literature on taxonomy, G. elata symbiosis, stress adaptation, selenium enrichment and applications. This review highlights four key findings. First, species delimitation cannot rely on morphology or ITS alone; authenticated vouchers, culture deposition and multigene or phylogenomic evidence are needed. Second, the Armillaria-G. elata association is a conditional interaction shaped by rhizomorph formation, enzymatic decomposition of woody substrates, host digestion of hyphae and cultivation environment. Third, stress tolerance and selenium enrichment are promising but remain under-standardized, with limited cross-strain comparisons, selenium speciation data and toxicity thresholds. Fourth, medicinal, food and enzyme-related claims are supported mainly by chemical, in vitro or cultivation data rather than mechanistic or clinical validation. Future work should integrate authenticated strain banks, isotope tracing, comparative genomics, standardized stress assays, selenium speciation and techno-economic evaluation. Accurate taxonomy is therefore essential not only for reproducible biological inference, but also for reliable strain selection, regulatory assessment and the safe commercial development of Armillaria-derived products.