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PubMed2026

Comparison of posterior cellular bonegraft options for single-level lumbar spinal fusion: a randomized trial.

BACKGROUND: Iliac bone autograft (IBG) is osteoinductive/osteogenic/osteoconductive but requires an additional harvesting procedure with known morbidities. Bone morphogenic protein (BMP) is osteoinductive and effective in obtaining fusion but is used off label for posterior fusion, has multiple side effects, and is expensive. Stem cell bone products, both auto- and allograft are attractive osteoinductive alternatives that avoid morbidity related to the graft donor site and may have a better safety profile than BMP. Morcelized allograft bone is osteoconductive but not osteoinductive or osteogenic. PURPOSE: Evaluate and compare the effectiveness of 6 types of viable or osteoinductive bone graft material in obtaining a solid posterior spinal fusion (PSF) for single level anterior/posterior lumbar spinal fusion. The bone grafts were IBG, BMP, autogenous stem cells (MSC) from concentrated bone marrow aspirate (BMA), allograft MSC from bone marrow, adipose tissue, or amniotic fluid, combined with inert cancellous allograft (Allo). STUDY DESIGN/SETTING: Prospective, single-blinded randomized study of 6 cohorts and inert historical control. PATIENT SAMPLE: Elective anterior-posterior lumbar spinal fusion of 175 patients. OUTCOME MEASURES: Assessments included pre and postoperative back and leg pain (VAS) scores, pain drawing, disability (ODI) scores, pain medication usage, and 1-year postoperative thin-cut CT scans (read by blinded radiologists). METHODS: Patients who were surgical candidates for a 1-level anterior/posterior lumbar fusion were randomized to 1 of 6 types of posterior bone graft alternatives: IBG, BMP, BMA, allograft MSC derived from bone marrow combined with morcelized Allo (cAlloBone), adipose derived MSC combined with morcelized Allo (cAlloFat), or amnion derived MSC combined with morcelized Allo (cAlloAm). Historical Allo patients served as a negative control group. Each group (n 27) had prospective outcomes and were followed for a minimum of 2 years. Fusion rate and outcomes were compared and referenced to Allo group. RESULTS: All but 5 patients had a solid ASF. The posterior fusion rates were 98% for IBG, 94% for BMP, 85% for BMA, 67% for cAlloBone, 64% for cAlloFat, 62% for cAlloAm, and 50% for Allo. Outcomes were significantly improved for all measures for all groups and there was no difference between groups except cAlloFat had slightly greater improvement in back pain in the 7-12 month follow-up period. BMP was the most expensive graft material; cellular allografts had a high-cost relative to fusion rate. CONCLUSIONS: For single level ASF/PSF, the PSF fusion rate was significantly greater for IBG and BMP followed by BMA. Various allograft MSC bone graft options resulted in lower fusion rates but may be greater than Allo. Outcomes were uniformly improved regardless of the type of graft used or the fusion status of the posterior fusion as long as the interbody fusion was solid. If bone graft cost savings is a consideration for PSF, then IBG has the greatest radiographic value, and Allo the greatest clinical value as long as the anterior interbody fusion is solid.

Humans↗

PubMed2026

Genomic insights into end-use grain quality and nutritional traits of an ancient Indian dwarf wheat ( Triticum sphaerococcum Percival) population using a multi-locus genome-wide association study.

BACKGROUND: Triticum sphaerococcum, an ancient hexaploid wheat species, is renowned for its stress resilience and superior nutritional quality. A panel of 116 T. sphaerococcum accessions (the largest known collection at a single site globally), with six bread wheat released varieties, was evaluated for its potential for genetic quality improvement. Field experiments were conducted under standard, heat and moisture-deficit conditions across two cropping seasons for ten grain end-use quality and nutritional traits. RESULTS: Genotypes showed highly significant differences (P ≤ 0.001) for measured traits, with high broad-sense heritability resulting from substantial genotypic variance contributions. Triticum sphaerococcum consistently outperformed T. aestivum across environments, with moisture-deficit stress proving more detrimental to quality parameters than heat stress, while micronutrient content increased under stressed conditions. Trait correlations revealed that the gluten index (GI) correlated negatively with the grain hardness index (GHI), wet gluten (WG), and water-binding capacity (WB), while positively correlating with dry gluten (DG) and protein content (PRO), whereas grain iron (GFE), zinc (GZN), and protein showed consistent positive interrelationships. Two superior accessions, PAUTS10 (WG 35.13%, DG 13.71%, PRO 16.42%, GZN 50.89 ppm) and Sonamoti (WG 33.33%, DG 12.92%, PRO 16.27%, GZN 56.03 ppm), were identified, surpassing the best check variety HD3226 for quality and nutritional parameters. Multi-locus genome-wide association studies identified 30 stable quantitative trait nucleotides across environments, with candidate gene analysis revealing genes involved in transcription regulation, biosynthetic processes, metal ion homeostasis, and transport. CONCLUSIONS: Triticum sphaerococcum demonstrated superior grain quality and micronutrient potential compared with modern wheat, highlighting its value as a genetic resource for biofortification. The identification of elite accessions and stable quantitative trait nucleotides (QTNs) provides useful targets for breeding programs aimed at improving protein and micronutrient content. Integrating ancient germplasm with modern genomic tools can accelerate the development of nutritionally enhanced wheat varieties. © 2026 Society of Chemical Industry.

Triticum↗

PubMed2026

Integrated exome and mitochondrial genome sequencing reveals the genetic landscape of primary mitochondrial diseases: findings from a large Tunisian cohort.

Primary mitochondrial diseases are a heterogeneous group of neurometabolic disorders recognized as the most common metabolic genetic diseases. They manifest at any age, affecting any tissue or organ, especially those with high energy demands, and are caused by pathogenic variants in both mitochondrial and nuclear genomes. Here, we aimed to describe the genetic spectrum of a Tunisian pediatric cohort with suspected mitochondrial diseases. We recruited 47 unrelated families who underwent exome sequencing as a first-tier test followed by whole mitochondrial genome sequencing for unsolved cases. Dedicated bioinformatic pipelines and prediction tools were used to determine the potential disease-causing variants. Sanger sequencing confirmed the presence and segregation within parents. For the newly identified variants, structural modeling was conducted to study the impact of these variants on protein structure and motions. Dual genome sequencing yielded a molecular diagnosis in 33/47 families (70%) and 18/47 (38%) showed disease-causing variants in genes encoding mitochondrial proteins. Among them, four families disclosed novel variants in FASTKD2, SERAC1 and GATB, which were supported by in-depth in silico and structural analyses demonstrating their deleterious effect. The remaining families (32%, 15/47) disclosed other metabolic and neurological disorders. An exome-first strategy delivers a high diagnostic yield in Tunisia, where consanguinity remains high and simultaneously captures mitochondrial and non-mitochondrial etiologies. Mitochondrial sequencing remains indispensable in the case of an inconclusive exome. Thus, our data expand the clinical and genetic spectrum of primary mitochondrial diseases in Tunisia, an underrepresented and admixed population.

Humans↗

PubMed2026

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia↗

PubMed2026

Exploratory proteomic and metabolomic profiling of pleural effusions identifies histone H4 and alanine as promising complementary markers for pleural tuberculosis.

The diagnosis of pleural tuberculosis (Pl-TB) remains challenging. Histopathological analysis and pathogen detection in pleural biopsies are informative but limited. We investigated differentially expressed proteins and metabolites in pleural effusions from patients with Pl-TB, malignancies, and other pathologies. A proteomic analysis of pooled pleural effusions identified 45 proteins exclusively detected or upregulated in Pl-TB samples, many linked to infectious processes. Conversely, 18 proteins were uniquely found or upregulated in malignant pleural effusions, mainly associated with detoxification and hemostasis. To validate these findings, we employed targeted proteomics in individual samples. Eight proteins were validated: S100-A9, histone H4, insulin-like growth factor-binding protein 2, fibrinogen beta chain, ficolin-3, immunoglobulin heavy constant alpha 1, sulfhydryl oxidase 1, and histidine-rich glycoprotein. Additionally, NMR-based metabolomics identified 13 metabolites with differential abundance between Pl-TB and non-TB samples. Notably, N-acetyl-glycoprotein and the branched-chain amino acids, alanine and lysine differed between groups. Proteomic and metabolomic analyses revealed distinct molecular profiles between Pl-TB and non-TB patients, despite intra-group variability. To address this, we applied classification models. Histone H4 and alanine consistently emerged as discriminative features. Overall, this study provides novel insights into the molecular landscape of Pl-TB. The combined quantification of proteins and metabolites may improve differential diagnosis, although should be further validated in larger, independent cohorts before clinical application.

Humans↗

PubMed2026

In Situ Hybridization and RT-PCR Detection of Nervous Necrosis Virus in Fourfinger Threadfin, Eleutheronema tetradactylum, in Taiwan.

Between April and July 2020, suspected outbreaks of nervous necrosis virus (NNV) infection were observed in fourfinger threadfin (Eleutheronema tetradactylum) fingerling hatcheries in Pingtung County, southern Taiwan. Affected fish exhibited spiral swimming behaviour and abdominal distension, resulting in mortality rates between 50% and 100%. Histopathological examination showed severe vacuolation in the brain and ocular tissues, with large oval and/or irregular basophilic cytoplasmic inclusion bodies in the brain. Phylogenetic analysis of the viral replicase (RNA1) and capsid protein (RNA2) genes revealed high nucleotide sequence identities among the isolates in this study, with sequence similarity rates of 96.9%-99% for RNA1 and 98.2%-99.0% for RNA2 compared to RGNNV reference strains available in the NCBI GenBank database. This is the first detection of betanodavirus in fourfinger threadfin in Taiwan, using RT-PCR and ISH. A positive correlation between elevated water temperatures and disease severity indicates the need for year-round surveillance and genomic analysis to clarify the epidemiology of FTNNV. The data suggest that infected eggs may facilitate the vertical transmission of Betanodavirus. Crucially, utilising virus-free broodstock, alongside routine health screening and environmental control, is essential for mitigating NNV risks in fourfinger threadfin aquaculture.

Animals↗

PubMed2026

Venetoclax added to dose-adjusted EPOCH-R for newly diagnosed double-hit lymphomas: phase 2 results from ALLIANCE A051701, an open-label, randomised, controlled, phase 2-3 trial.

BACKGROUND: High-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, known as double-hit lymphoma, is a highly aggressive malignancy with poor outcomes after standard chemoimmunotherapy. We aimed to study whether the addition of the BCL2-inhibitor venetoclax to chemoimmunotherapy in patients with double-hit lymphoma resulted in superior efficacy compared with chemotherapy alone. METHODS: ALLIANCE A051701 is an open-label, randomised, controlled, phase 2-3 trial in separate cohorts of patients with double-hit lymphoma and patients with double-expressor lymphoma. In this analysis, we report phase 2 results from the double-hit lymphoma cohort. Patients aged 18-80 years with newly diagnosed double-hit lymphoma and Eastern Cooperative Oncology Group (ECOG) performance status 0-2 were recruited from 41 hospitals and outpatient clinics in the USA. Patients were randomly assigned (1:1) to receive DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) either alone (DA-EPOCH-R group) or with venetoclax (DA-EPOCH-R plus venetoclax group) using permuted block randomisation schedule. All patients and investigators were aware of group assignment. DA-EPOCH-R was administered on a 21-day schedule for up to six total cycles. Venetoclax was given as 600 mg by mouth daily on days 4-8 of cycle 1 and on days 1-5 of cycles 2-6. The primary endpoint was progression-free survival in the modified intent-to-treat population inclusive of all eligible patients with centrally confirmed double-hit lymphoma. The safety analysis population consisted of all evaluable patients who received at least one dose of protocol treatment. This trial is registered with ClinicalTrials.gov (NCT03984448) and is closed to enrolment. FINDINGS: 36 patients were randomly assigned to the DA-EPOCH-R group and 37 to the DA-EPOCH-R plus venetoclax group between Oct 22, 2019, and Sept 18, 2020. Median age was 65 years (IQR 56-73) and baseline demographic factors were well balanced between groups, with 30 (45%) female and 36 (55%) male patients. Most patients (59 [89%]) were white, two (3%) were Asian, one (2%) was Black or African American, and four (6%) had unknown or unreported ethnicity. The majority of patients had MYC-BCL2 double-hit lymphoma (59 [89%] patients), advanced stage disease (57 [86%] patients), and high-intermediate/high-risk IPI score (42 [64%] patients). Median follow-up was 34·7 months (IQR 30·1-36·8). Median progression-free survival was 28·4 months (95% CI 5·2-not estimable) in the DA-EPOCH-R group (n=30) and 7·7 months (95% CI 4·7-NE) in the DA-EPOCH-R plus venetoclax group (n=36; hazard ratio [HR] 1·13, 95% CI 0·53-2·37; p=0·75). Deaths on treatment occurred in one (3%) patient in the DA-EPOCH-R group (due to dyspnoea; possibly related to treatment) and six (17%) patients in the DA-EPOCH-R plus venetoclax group (four due to sepsis [three at least possible related and one unrelated], two due to cardiac arrest [at least possibly related]), prompting early closure of the double-hit lymphoma cohort. The most common grade 3-4 non-haematological adverse event was febrile neutropenia, occurring in 15 (43%) of 35 patients in the DA-EPOCH-R plus venetoclax group and 11 (37%) of 30 patients in the DA-EPOCH-R group. The median overall survival has not been reached in either group. The 24-month overall survival estimates were 72% (95% CI 52-85) in the DA-EPOCH-R group compared with 52% (95% CI 33-68) in the DA-EPOCH-R plus venetoclax group (HR 2·49, 95% CI 1·03-6·04; p=0·038). INTERPRETATION: The addition of venetoclax to DA-EPOCH-R resulted in excess mortality, prompting early study closure. Robust accrual shows that prospective multicentre trials are feasible in double-hit lymphoma, and the outcomes in the DA-EPOCH-R group serve as a benchmark for future studies. FUNDING: National Cancer Institute of the National Institutes of Health.

Humans↗

PubMed2026

Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.

Central nervous system (CNS) injuries are the leading cause of permanent disability and premature death in adults worldwide, with their incidence continuing to rise amid social development. These injuries not only severely impair the quality of life but also impose a heavy burden on the global public health system. Current clinical interventions, such as decompression and thrombolysis, can alleviate primary injury but fail to effectively reverse the secondary neuroinflammatory damage. Traditional anti-inflammatory therapies, which cannot block the upstream source of the inflammatory cascade, have led to repeated failures in global clinical translation research over the past decades. Gasdermins were first characterized in studies of systemic inflammatory diseases. These proteins form transmembrane pores to drive the release of proinflammatory factors and inflammatory cell death, serving as key mediators of host innate immunity. Recent studies have revealed that gasdermins play critical roles in regulating the initiation and amplification of neuroinflammation following CNS injury. To clarify the therapeutic potential of gasdermins as targets for injury repair, this review systematically summarizes the structure and function of gasdermins, as well as their cell-specific activation and regulatory mechanisms. We further elaborate on their pathological roles in these injuries and the corresponding therapeutic strategies, aiming to provide a theoretical reference for basic research and clinical translation in this field.

Humans↗

PubMed2026

Malaria rapid diagnostic tests: performance, pitfalls, and progress.

PURPOSE OF REVIEW: Malaria rapid diagnostic tests (RDTs) have revolutionized malaria diagnosis in endemic settings. RDTs are simple to use and accurate for clinical cases, although sensitivity is reduced at parasite densities below 200 parasites/μl. However, increasing prevalence of hrp2/3 gene deletions in certain areas threaten utility of histidine-rich protein 2 (HRP2)-based RDTs, and lingering HRP2 antigenemia can generate false-positive results after parasite clearance. This review summarizes current performance of malaria RDTs, threats to their validity, and recent innovations to improve their performance and continued role in malaria diagnosis. RECENT FINDINGS: Most World Health Organization (WHO) prequalified RDTs perform well for clinical diagnosis, with only occasional exceptions, including a recently reported issue affecting several countries. RDT sensitivity is generally related to malaria transmission intensity, with higher proportions of false-negative results in lower-transmission areas. Newly prequalified lactate dehydrogenase (pLDH)-based RDTs perform well for both Plasmodium falciparum in areas with >5% hrp2/3 gene deletions and for Plasmodium vivax diagnosis. Several point-of-care alternatives to RDTs, including micro-fluidic devices, hemozoin-detecting devices, and automated hematology analyzers, have shown promising results in small studies, but require larger-scale trials before widespread use. SUMMARY: RDTs remain a critical tool in clinical diagnosis of malaria, and newer pLDH-based tests perform well in areas where hrp2/3 gene deletions threaten validity of HRP2-based RDTs.

Humans↗

PubMed2026

Genome-Wide Characterization of β-Glucosidase (TaBGLU) Genes in Bread Wheat and Their Expression Under Drought, Cold, and Combined Stress.

Glycoside hydrolase 1 (GH1) β-glucosidases were known to activate hormone conjugates and defense metabolites, yet their genomic organization and stress-response dynamics in wheat remained incompletely defined. We therefore performed an integrated characterization of TaBGLUs spanning phylogeny, gene structure and conserved motifs, subcellular localization, promoter cis-elements, Gene Ontology enrichment, protein-protein interaction networks, and targeted expression profiling. Wheat TaBGLUs partitioned into well-supported clades that shared canonical GH1 catalytic residues and a largely conserved motif scaffold. Subcellular localization predictions indicated predominant nuclear and chloroplast targeting, with a smaller cohort directed to secretory or endomembrane compartments. Promoters were enriched for light-responsive, hormone-related (ABA, JA/SA, auxin, GA) and stress-associated (MYB/WRKY, heat, low temperature) cis-elements, and functional annotations were consistent with roles in carbohydrate and cell-wall metabolism, hormone homeostasis, and defense. Network analysis revealed a densely connected TaBGLU submodule embedded within broader carbohydrate and defense interaction networks, suggesting coordinated or cooperative functions. Expression profiling under cold, drought, and combined drought and cold demonstrated broad stress inducibility, with early activation detected by 6 h, cold-responsive maxima typically at 12 h, drought-responsive peaks predominating at 24 h, and combined stress eliciting both earlier and more sustained expression maxima between 12-24 h. Representative strongly responsive genes included TaBGLU20, TaBGLU44, TaBGLU6, and TaBGLU23, which showed pronounced late induction under combined stress, TaBGLU30, which exhibited an earlier combined-stress peak, and TaBGLU12, which displayed a marked late drought-specific response. Taken together, this integrated genomic, regulatory, and expression atlas refined the wheat BGLU repertoire relative to previous gene model inventories, highlighted candidate TaBGLUs with central network positions and strong stress inducibility, and provided concrete entry points for functional validation and breeding for improved stress resilience.

Triticum↗

PubMed2026

A novel peptide encoded by circTLL1 drives osimertinib resistance in lung cancer by modulating the NT5C2/Ras/PI3K axis.

BACKGROUND: Acquired resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). Although circular RNAs (circRNAs) have been increasingly implicated in drug resistance, most studies have focused on their canonical role as microRNA sponges, while their capacity to encode functional micropeptides remains largely unexplored. This study aimed to identify novel circRNAs involved in osimertinib resistance and to characterize their regulatory functions at the protein level. METHODS: Osimertinib-resistant (OR) NSCLC cell lines were established and validated. High-throughput RNA sequencing was performed to compare the circRNA expression profiles between parental and OR cells. The function of the candidate circRNA was assessed through a series of in vitro and in vivo experiments, including cell viability assays, apoptosis analysis, and xenograft mouse models. Mechanistic investigations involved mass spectrometry, co-immunoprecipitation and western blotting to explore its protein-coding potential and downstream signaling pathways. RESULTS: We identified a novel circRNA, termed circTLL1, that was stably and significantly upregulated in OR-NSCLC cells. Functionally, overexpression of circTLL1 promoted osimertinib resistance, whereas its knockdown restored drug sensitivity both in vitro and in vivo. Mechanistically, we discovered that circTLL1 harbors an open reading frame (ORF) that is translated into a novel 90-amino-acid protein, which we designated circTLL1-90aa. Further investigation revealed that circTLL1-90aa directly interacts with and promotes the degradation of 5'-nucleotidase, cytosolic II (NT5C2), thereby uncoupling nucleotide metabolism from its normal regulatory constraints. The consequent downregulation of NT5C2 leads to elevated GTP levels and leading to the sustained activation of the downstream Ras/PI3K/AKT signaling pathway. CONCLUSION: Our findings unveil a previously unrecognized circRNA/micropeptide/metabolism cascade underlying osimertinib resistance. The identification of the circTLL1-90aa/NT5C2/Ras/PI3K axis not only expands the functional repertoire of the non-coding genome but also provides new insights into the complexity of drug resistance. Given its selective upregulation in resistant cells, circTLL1-90aa holds promise both as a predictive biomarker for treatment stratification and as an actionable therapeutic target, offering a novel strategy to overcome osimertinib resistance in NSCLC patients.

Pyrimidines↗

PubMed2026

Feasibility and Efficacy of Lorlatinib in Japanese Patients With Relapsed/Refractory ALK-Aberrant Neuroblastoma.

Lorlatinib, a third-generation ALK inhibitor, was administered off-label to five heavily pretreated patients with relapsed or refractory ALK-aberrant neuroblastoma. ALK alterations included F1174L, R1275Q, BEND5::ALK fusion, and ALK amplification; three patients had MYCN amplification. Best responses were three partial responses and two disease progressions. The longest progression-free survival (6.7 months) occurred in a patient with F1174L and non-amplified MYCN, whereas rapid progression was observed in two MYCN-amplified cases. Lorlatinib was generally well tolerated with manageable adverse events. These findings suggest that lorlatinib is a feasible therapeutic option in ALK-aberrant neuroblastoma and that clinical heterogeneity in treatment response warrants further investigation.

Humans↗

PubMed2026

Nonviral transposon‑engineered stem cells characterization: dose‑dependency between vector copy number and transgene expression.

Genetically engineered stem cells hold substantial promises for advancing regenerative medicine, yet ensuring their genomic safety remains a critical challenge. A key safety concern is vector copy number (VCN), which defines the number of integrated transgene copies per genome. Although ddPCR is used to assess VCN in virally transduced cells, its application in transposon‑engineered systems is limited. In this study, we extended VCN determination to non‑viral, transposon‑engineered stem cells. In alignment with FDA recommendations, the primary objective was to establish a robust and quantitative framework for interim VCN determination at the time of lot release. Specifically, we demonstrate that reliable interim VCN estimates increase in a dose‑dependent manner with increasing plasmid input. In addition, strong linear correlations between VCN and both EGFP median fluorescence intensity (MFI) and gene‑of‑interest (GOI) protein expression validate the accuracy of this framework. Furthermore, comparison of two distinct GOIs revealed gene‑specific differences in expression efficiency. Together, these findings validate a standardized VCN determination workflow that quantitatively links plasmid dose, genomic integration, and functional transgene expression. This workflow provides a systematic characterization of engineered cells, offering comprehensive information to support downstream risk‑based analyses to ensure the genomic safety and stability of the final cell product.

Transgenes↗

PubMed2026

Integrated transcriptomic and metabolomic analysis of fluoride tolerance-related pathways and differentially expressed genes in silkworm strain XSKD.

XueSong KD (XSKD) silkworm strain exhibits prominent fluoride tolerance, yet the underlying molecular mechanisms of fluoride tolerance remains unclear. In the present study, fourth-instar pre-molting XSKD silkworms were used as experimental materials for integrated transcriptomic and untargeted metabolomic analyses. In total, 572 differentially expressed genes and 90 differential metabolites were screened. GO enrichment and KEGG enrichment based on the hypergeometric distribution model revealed that 13-Hydroxy-9Z,11E-octadecadienoic acid (13-(S)-HODE) acts as the core differential metabolite, which is significantly enriched in the linoleic acid metabolism pathway. Within this pathway, LOC101737302 and CYP338A1 display opposite expression trends and show correlations with pathway metabolites. Based on multi-omics data, this study preliminarily characterizes the lipid metabolic response under fluoride stress, providing omics dataset support for further in-depth exploration of the molecular mechanism of fluoride tolerance in silkworms.

Animals↗

PubMed2026

Mesenchymal Stem Cell-Derived Exosomes Combined With 3-Dimensional Hyaluronan-Based Scaffold Promote Tendon-to-Bone Tunnel Healing.

PURPOSE: Tendon-to-bone healing remains a major clinical challenge due to poor regenerative capacity at the enthesis. This study aimed to evaluate the effects of mesenchymal stem cell-derived exosomes combined with a 3-dimensional hyaluronan-based scaffold on graft healing within bone tunnels. This study was conducted in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines. METHODS: A total of 128 tendon-bone models were created in 64 Sprague-Dawley rats, randomized into four groups: control, exosome-only, scaffold-only, and exosome-loaded scaffold. At weeks 4 and 8 postoperatively, samples were analyzed histologically (hematoxylin-eosin, Masson Trichrome), immunohistochemically (fibroblast growth factor 2, bone morphogenetic protein 2), and biomechanically (maximum failure load). RESULTS: At both time points, the exosome-loaded scaffold group demonstrated significantly enhanced vascularization, cellular activity, and collagen fiber continuity and parallelism compared to all other groups (P < .05). Fibroblast growth factor 2 and bone morphogenetic protein 2 expression levels were highest in the exosome-loaded scaffold group, indicating early activation of proregenerative pathways. Biomechanically, this group also exhibited the greatest maximum failure load (15.64 ± 0.86 N at week 4; 22.97 ± 2.86 N at week 8), suggesting superior tendon-to-bone integration. The exosome-only group showed delayed but comparable improvements by week 8. CONCLUSIONS: Combining mesenchymal stem cell-derived exosomes with a 3-dimensional hyaluronan-based polycaprolactone/tricalcium phosphate scaffold enhances early and sustained healing at the tendon-bone interface. This cell-free, biocompatible strategy significantly improves vascularization, growth factor expression, collagen organization, and mechanical strength. These findings support its potential as a clinically translatable approach for improving tendon-to-bone healing outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Animals↗

PubMed2026

Pangenome-wide identification and expression analysis of the chalcone synthase (CHS) gene family in five yellowhorn spp.

Chalcone synthase (CHS) is a pivotal enzyme in flavonoid biosynthesis involved in plant development, defense, and secondary metabolism. Xanthoceras sorbifolium (yellowhorn) is a medicinal and ornamental species with high resistance to environmental stresses, but its CHS gene family remains uncharacterized. We performed a pangenome-wide identification of CHS genes across five yellowhorn genomes (Xzs4, Xwf8, Xjg, Xg11, and Xzg2). Across the five yellowhorn genomes, 27 CHS genes were identified and classified into four core pangenes, present in all five genomes, and two dispensable genes, present only in a subset of genomes. Phylogenetic analysis grouped these genes into three major clades, and chromosomal mapping and duplication analyses identified four tandemly duplicated gene pairs under purifying selection. The analyses of conserved structural features, including protein motifs and exon-intron organization, together with promoter cis-regulatory elements and gene ontology annotation, further indicated the potential involvement of CHS genes in flavonoid biosynthesis and stress-responsive mechanisms. Gene expression profiling identified significant upregulation of Xg11_CHS1 and Xg11_CHS3 under cold and drought stress, with tissue-specific expression patterns. These findings provide valuable insights into the evolution, functional diversification, and stress-responsive roles of the CHS gene family, identifying candidate genes for future studies targeting stress tolerance and flavonoid biosynthesis in yellowhorn.

Acyltransferases↗

PubMed2026

Exploratory identification and cellular functional characterization of ppiabl as a candidate gene associated with growth traits in Paralichthys olivaceus.

The Japanese flounder (Paralichthys olivaceus) is an important mariculture species. However, the genetic mechanisms underlying its growth traits remain poorly understood. To explore the genetic basis of growth variation, whole-genome resequencing was performed in a cultured cohort of 60 individuals, followed by exploratory genome-wide association analysis and candidate-gene prioritization. The results revealed heritability estimates of 0.40 for body weight and 0.24 for body length, with substantial overlap in associated loci between the two traits. Exploratory association and variant-annotation analyses prioritized ppiabl, which carries a nonconservative missense variant, as a candidate gene for further investigation. Tissue expression analysis showed that ppiabl was highly expressed in muscle tissue. This gene encodes a protein belonging to the conserved peptidyl-prolyl cis-trans isomerase family. In Japanese flounder primary muscle cells, ppiabl knockdown was associated with altered expression of growth-related genes and an increased G1-phase fraction, whereas overexpression produced changes in the opposite direction. In line with this, fast-growing individuals were found to have significantly larger muscle fiber areas than slow-growing ones. These findings suggest that ppiabl may be involved in muscle-related cellular processes associated with growth variation in Japanese flounder, although its contribution to whole-animal growth requires further validation. Overall, this exploratory study prioritizes ppiabl as a candidate gene potentially associated with growth-related cellular processes in Japanese flounder, although validation in larger independent populations and in vivo models is required.

Animals↗

PubMed2026

Whole-Genome Deep Learning Predicts Chemotherapy Response in Colorectal Cancer.

Chemotherapy response in colorectal cancer (CRC) exhibits significant heterogeneity, with current clinical predictors failing to capture complex genomic determinants of resistance. We developed a hybrid deep learning framework integrating convolutional neural networks (CNNs) and bidirectional long short-term memory (BiLSTM) networks to analyze whole-genome somatic mutations, evolutionary conservation, chromatin accessibility, and 3D genome architecture in 2,546 TCGA patients. An attention mechanism identified predictive genomic regions. The model achieved an AUC of 0.92 (95% CI: 0.89-0.94) in cross-validation and 0.88 (95% CI: 0.85-0.91) in independent validation, outperforming clinical models (ΔAUC = +0.18, p < 0.001). Key predictors included non-coding variants in TP53, KRAS, and PIK3CA regulatory regions. Triple-positive patients (mutations in all 3 regions) had significantly worse progression-free survival (HR = 4.7, p < 0.001). Our framework enables accurate chemotherapy response prediction and reveals novel non-coding resistance mechanisms, advancing precision oncology in CRC.

Humans↗