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PubMed2026

Influence of ovarian maturity, age, and mating status on the antennal responses of wild and laboratory reared Xyleborus affinis (Coleoptera: Curculionidae: Scolytinae) to ethanol.

Xyleborus affinis Eichthoff is a neotropical ambrosia beetle that, in certain regions such as the United States and Mexico, has been associated with exotic phytopathogenic fungi causing extensive tree mortality. Although studies relating its olfactory response to volatile compounds and trapping systems have been published, factors such as the insect's physiological condition, which can affect its recognition or response to odors, have not been studied. Here, we evaluated the electroantennographic (EAG) response of wild and laboratory reared X. affinis females to 70% ethanol, a compound known to attract these insects. The experimental design was developed to consider and compare the following conditions: (i) females collected inside and outside host-galleries, (ii) sexual maturity (with mature and immature ovaries), (iii) age (0, 1, 3, and 5 d after emergence), and (iv) mating status (virgins and mated). Our results indicate that most of the wild females located outside the galleries were sexually mature but exhibited significantly lower EAG response than those inside the galleries. Regarding mating status, mated females exhibited significantly stronger antennal responses compared to virgins, whereas age did not affect antennal sensitivity. Finally, we provide images of the hitherto undescribed reproductive system of X. affinis females, a key element that enabled this investigation. The information generated offers a useful foundation for future studies aimed at understanding the physiological mechanisms and other critical factors related to sensory perception and reproductive condition. For example, factors that may influence the behavior and attraction of X. affinis females to host semiochemicals.

Animals↗

PubMed2026

A systematic review and meta-analysis to estimate the global prevalence of leptospirosis in sheep.

Leptospirosis in sheep is a zoonotic concern considering sheep may act as potential reservoirs for Leptospira spp. infection to humans. This study aimed to estimate the pooled prevalence of leptospirosis in sheep worldwide. A comprehensive literature search was conducted across databases following PRISMA guidelines. Meta-analyses were performed using a random effect model in R software (version 4.3.1) to calculate pooled prevalence with 95% confidence intervals (CI). Subgroup analyses were performed based on prevalence types, diagnostic methods and continental regions to explore sources of heterogeneity. A total of 138 studies comprising 54,174 samples and 10,299 positive detections were included in this study. The global pooled prevalence of leptospirosis in sheep was 15.69% (95% CI: 12.69-19.25) with overall heterogeneity (I2) 98%. The prediction interval ranged from 1.09% to 75.91%, indicating wide inter-study variability. The seroprevalence was 16.16% (95% CI: 12.91-20.04) and infection prevalence was 12.98% (95% CI: 8.07-20.22), showing no significant difference (P = 0.40). In addition, the prevalence of leptospirosis in sheep differed significantly across diagnostic methods and continents (P < 0.01), indicating substantial variation influenced by both methodological and geographical factors. The funnel plot revealed marked asymmetry, suggesting potential publication bias which was confirmed by Egger's regression test (P < 0.01). In conclusion, leptospirosis is widely prevalent in sheep globally, with marked geographical and methodological heterogeneity. These findings highlight the epidemiological importance of sheep in leptospirosis transmission and underscore the need for improved surveillance, standardized diagnostic approaches, and targeted control strategies within a One Health framework.

Animals↗

PubMed2026

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12 cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B) ≈ 9, coefficient of variance (CV) < 10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus↗

PubMed2026

Genomic and Molecular Interaction Analysis of NodD1 in a Novel Bradyrhizobium yuanmingense sp. B64 Isolate for Nodulation and Symbiosis of Legume Plants.

Rhizobial bacteria are known for their ability to fix nitrogen for leguminous plants and their essential function for sustainable agriculture. This study characterizes the taxonomic status and functional potential of the Bradyrhizobium B64 isolate using integrated genomic and molecular approaches. The whole genome of the B64 isolate was sequenced via Illumina paired-end technology. Species delimitation was performed using average nucleotide identity (ANI) and digital DNA-DNA Hybridization (dDDH). The NodD1 protein structure was modeled using AlphaFold3 and validated by Ramachandran plot analysis. Molecular docking was then conducted to evaluate interactions between NodD1 and four signaling flavonoids: Apigenin, Daidzein, Genistein, and Naringenin. Genomic analysis revealed a maximum ANI of 94.4% and dDDH values between 51.4 and 62.4%. Since these values fall below the standard prokaryotic thresholds (ANI < 95%; dDDH < 70%), the B64 isolate is identified as a novel species. Physiological assays confirmed nitrogen fixation (1.97 ppm), IAA production (3.67 ppm), and phosphate solubilization (26.10 ppm). Structural validation showed 100% of NodD1 residues in allowed regions, ensuring high model reliability. Docking simulations demonstrated strong binding affinities across all flavonoids, with binding free energies ranging from - 8.8 to - 9.0 kcal/mol. Daidzein exhibited the highest thermodynamic stability (- 9.0 kcal/mol), whereas apigenin showed the most extensive residue interaction network. The B64 isolate is a novel Bradyrhizobium species with a high symbiotic capacity. The stable NodD1-flavonoid interactions provide a molecular basis for efficient nodulation, positioning B64 as a promising candidate for developing lipo-chitooligosaccharide (LCO)-based biofertilizers.

Bradyrhizobium↗

PubMed2025

Efficacy of Janus kinase inhibitor combined with phototherapy in non-segmental vitiligo: systematic review and meta-analysis.

BACKGROUND: Vitiligo is a chronic autoimmune disease causing skin depigmentation and psychosocial issues. Non-segmental vitiligo often shows limited response to standard therapies. The IFN-γ-JAK-STAT pathway plays a key role, and combining JAK inhibitors with NB-UVB may improve repigmentation. AIM: To evaluate the efficacy of JAK inhibitors (baricitinib or tofacitinib) plus NB-UVB versus NB-UVB without JAK inhibitors in adult NSV. METHODS: PubMed, Cochrane, and ClinicalTrials.gov were searched till August 2024 for randomized controlled trials. Four studies, comprising 217 adults (121 in the combination group and 96 in the control group), were analyzed using RevMan 5.4. Bias was assessed via Newcastle-Ottawa, Cochrane ROB-2, and ROBINS-I tools. RESULTS: Combination therapy significantly reduced total VASI compared to controls (MD = -4.96, 95% CI [-9.29, -0.63], p = 0.02), with a greater effect on sensitivity analysis (MD = -6.84, p = 0.0007). Significant reductions were seen in face/neck (MD = -0.17, p = 0.002), trunk (MD = -3.62, p = 0.0001); acral (MD = -0.85, p = 0.0002) and extremity (MD = -4.61, p < 0.00001) regions after sensitivity analysis. Patients were more likely to achieve ≥50% (RR = 6.87, p < 0.00001) and ≥75% (RR = 15.13, p = 0.006) repigmentation. CONCLUSIONS: JAK inhibitor plus NB-UVB markedly improves the repigmentation in adult NSV compared to NB-UVB alone.

Humans↗

PubMed2026

Adductor Canal Block and Local Anesthetic Versus Local Anesthetic Alone in ACL Reconstruction: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Effective postoperative analgesia is crucial for early recovery after anterior cruciate ligament reconstruction (ACLR). Local infiltration analgesia (LIA) and adductor canal block (ACB) are common regional techniques, but their combined efficacy remains unclear. PURPOSE: To compare the effectiveness of LIA alone versus LIA combined with ACB in patients undergoing ACLR, with primary outcomes including postoperative opioid consumption and quadriceps function. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A double-blind randomized controlled trial enrolled 100 patients undergoing ACLR under general anesthesia. Patients were randomized into 2 groups: LIA + sham (saline injection) (n = 50) and LIA + ACB (n = 50). The primary outcome was postoperative opioid consumption in the first 24 hours. Secondary outcomes included visual analog scale (VAS) pain score, quadriceps function assessed by straight leg raise (SLR) at 3 hours, Quality of Recovery-15 (QoR-15) score, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 1 week. Statistical analysis was performed using t tests and chi-square tests with a P value <.05 considered significant. RESULTS: There was no significant difference in 24-hour opioid consumption between the LIA + ACB and LIA-only groups (P = .109). Similarly, VAS pain scores at 24 hours postoperatively showed no significant differences between the groups (P = .0804). Early functional recovery, assessed by SLR performance at 3 hours, was equivalent between groups (P = .6711). Additionally, QoR-15 scores on postoperative day 1 and KOOS values at 1 week demonstrated no significant differences (P = .6486 and P = .9054, respectively). Intraoperative opioid consumption was not different between the groups (P = .127). CONCLUSION: These findings indicate that the addition of ACB to LIA does not yield postoperative analgesic in ACLR. Consequently, LIA alone suffices for routine ACLR, potentially enabling clinicians to optimize perioperative workflows without incurring the additional time, financial burden, and resources associated with routine ACB administration. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04721119.

Humans↗

PubMed2026

Viral surveillance beyond detection: JMTV and the need for ensemble approaches in emerging virus discovery.

The recent report by T. Murillo, L. E. Enrique Chaves-González, S. Temmam, S. Bermúdez, et al. (Microbiol Spectr 14:e04078-25, 2026, https://doi.org/10.1128/spectrum.04078-25) expands the known geographic and ecological range of Jingmen tick virus (JMTV) by detecting the virus in Amblyomma mixtum ticks collected from horses in Costa Rica. This is an important finding because A. mixtum can feed on wildlife, domestic animals, and humans, creating a possible interface for virus movement across various hosts. The study also places the Costa Rican virus in a wider phylogenetic context, linking it to JMTV diversity reported from other regions. However, the detection of viral RNA in ticks should not be interpreted as proof of local disease, human infection, or active transmission, especially in the absence of supporting results. Instead, it reflects an important signal for careful viral surveillance. Here, I discuss how JMTV illustrates the need for ensemble approaches that combine field sampling, phylogeny, segment-level genome analysis, serology, experimental validation, and data-driven virus discovery tools.

emerging viruses↗

PubMed2026

Genetic overlap between estimated glomerular filtration rate and cardiovascular disease identifies potential targets for cardiorenal syndrome.

Heart and kidney diseases frequently coexist, but the genetic basis of this relationship remains unclear. We analyzed genetic data from large-scale studies to investigate how kidney function (estimated glomerular filtration rate, eGFR) and six common cardiovascular diseases share genetic risk factors. Using MiXeR method, and conjunctional false discovery rate (conjFDR) to identify overlapping genetic regions, we found 478 shared genomic loci between eGFR and cardiovascular diseases. These shared genes are involved in tissue development and structure. We also identified 29 genes that could be targeted by existing medications approved by the US Food and Drug Administration, such as PRKAG2, PDE1A, and IGF1R. Among these, genetically predicted higher level of IGF1R expression is associated with a higher eGFR, which reflects good kidney function and is protective against cardiorenal diseases, such as atrial fibrillation, and myocardial infarction. These findings reveal genetic overlap between kidney function and cardiovascular diseases, highlighting potential targets for understanding and treating cardiorenal syndrome.

Humans↗

PubMed2026

Performance comparison of rapid and native barcoding methods for Oxford Nanopore sequencing of Poliovirus Viral Protein 1 (VP1) amplicons.

Accurate and timely sequencing of poliovirus is critical for global eradication efforts, particularly for molecular epidemiology based on the typing region of the genome, viral protein 1 (VP1). While Oxford Nanopore Technologies (ONT) sequencing has expanded capabilities for poliovirus surveillance, the relative performance of different ONT library preparation methods, including ligation-based (Native Barcoding) and transposase-based (Rapid Barcoding) approaches, has not been systematically evaluated. In this study, we compared rapid barcoding and native barcoding workflows for sequencing VP1 amplicons from 17 type 2 poliovirus-positive samples, each processed in triplicate. Native barcoding generated significantly more sequencing output, producing approximately 2.3-fold greater total read yield than rapid barcoding, and demonstrated higher run-to-run reproducibility (R2 = 0.979-0.998 vs. 0.847-0.929, respectively; p < 0.001). In addition, native barcoding generated 80% of the total yield achieved by rapid barcoding within approximately 7 h, whereas rapid barcoding required approximately 40 h to reach the same output. Despite these differences, both methods produced identical VP1 consensus sequences across all samples, with comparable read quality (median per-base Q-scores of approximately Q17-Q18). Rapid barcoding provided substantial practical advantages, reducing hands-on library preparation time (55 vs. 200 min) and per-sample cost ($12.82 vs. $16.54), while simplifying workflow and reducing technical complexity. These findings indicate that sequencing yield may not be a determinant of downstream analytical outcomes for poliovirus VP1 ONT sequencing. Rapid barcoding therefore represents a cost-effective and efficient approach for routine poliovirus surveillance, whereas native barcoding remains advantageous in applications requiring rapid data generation or maximal sequencing depth.

Poliovirus↗

PubMed2026

A proteomic analysis of the PHF-forming tau fragment (tau297-391) following uptake into differentiated human neuronal SHSY5Y cells.

Tau self-assembly and intracellular deposition are associated with a group of neurodegenerative diseases called tauopathies, which include Alzheimer's disease (AD) and Pick's disease. Here, we measured the proteome response in human neuronal cells (differentiated SH-SY5Y) following the addition of a spontaneously amyloidogenic region of tau known as dGAE (tau297-391), which forms AD-like paired helical filaments in vitro, and proteomic analysis showed increased endogenous tau expression. Further interactome analysis uncovered increased association between tau and proteins associated with nuclear chromatin, the nucleolus, and the spliceosome, as well as the thiol-peroxidase, PRDX6, alongside an increase in reactive oxygen species. The present work highlights a method to identify proteome pathways that may play an important role in the development of tau pathology and reveals an oxidative stress response to dGAE.

Humans↗

PubMed2026

De Novo 2.2 Mb 19q13.42-q13.43 Microdeletion Encompassing U2AF2: Support for a Haploinsufficiency Model.

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor involved in the early stages of pre-mRNA splicing. To date, multiple individuals have been reported with predominantly heterozygous missense variants presenting intellectual disability, speech and motor delays, seizures, hypotonia, and thin or hypoplastic corpus callosum. Here, we describe a patient with a de novo 2.2 Mb interstitial deletion involving chromosome 19q13.42-q13.43, encompassing U2AF2, presenting with intellectual disability, epilepsy, corpus callosum hypoplasia, dysmorphic features, and congenital heart disease. The patient's clinical features overlap substantially with those reported in individuals harboring heterozygous U2AF2 variants, supporting haploinsufficiency as a plausible disease mechanism. To our knowledge, this represents the first postnatal report of complete U2AF2 gene deletion. In addition, this is the first detailed phenotypic characterization of a distal 19q chromosomal interstitial deletion, further delineating the clinical spectrum associated with this genomic region.

Humans↗

PubMed2026

A Dynamic Nomogram to Predict Metabolic Dysfunction-Associated Fatty Liver Disease in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) involves multiple metabolic disorders. This study aimed to identify high-risk populations for metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with MetS and to establish a dynamic predictive nomogram. METHODS: A total of 627 patients with MetS from six regions in Zhejiang Province were enrolled and categorized into MAFLD and non-MAFLD groups, then randomly assigned to training and validation sets at a ratio of 7:3. Independent predictors of MAFLD were identified using least absolute shrinkage and selection operator regression and multivariable logistic regression analyses. These predictors were then used to construct a dynamic nomogram. RESULTS: A total of 627 patients with MetS were included in the final analysis, of whom 77.0% (483/627) were diagnosed with MAFLD. Multivariable logistic regression analysis identified body mass index (BMI), waist circumference (WC), total cholesterol (TC), alanine aminotransferase (ALT), MetS-defined dysglycemia, and education level as independent risk factors for MAFLD. MetS-defined dysglycemia showed the highest odds ratio (OR) for MAFLD development [OR = 1.87, 95% confidence interval (CI): 1.07-3.29]. Although the number of MetS components and the metabolic syndrome score were significantly associated with MAFLD in univariate analysis, they were not independently associated with MAFLD in the multivariate model. A dynamic nomogram for predicting MAFLD risk in patients with MetS was developed and internally validated. The area under the receiver operating characteristic curve was 0.834 (95% CI: 0.787-0.880) in the training set and 0.839 (95% CI: 0.771-0.899) in the validation set, indicating strong predictive performance. Bootstrap internal validation demonstrated good agreement between predicted and observed outcomes in calibration curves. Decision curve analysis further indicated favorable clinical applicability of the nomogram. CONCLUSION: BMI, WC, TC, ALT, MetS-defined dysglycemia, and education level are independent risk factors for MAFLD. A dynamic nomogram for predicting MAFLD risk in patients with MetS was successfully developed and validated.

Humans↗

PubMed2026

Whole-Exome Sequencing in a Consanguinity-Enriched South Indian Retinitis Pigmentosa Cohort: Diagnostic Yield and Molecular Spectrum.

PURPOSE: To determine the molecular diagnostic yield, variant spectrum, inheritance architecture, and influence of consanguinity on whole-exome sequencing outcomes in a South Indian retinitis pigmentosa (RP) cohort. DESIGN: Prospective, registry-based cohort study. SUBJECTS: A total of 113 affected participants were enrolled through the Aravind Registry for Inherited Diseases of the Eye, including 109 unrelated probands and 4 affected relatives from already represented families. Primary analyses were restricted to the 109 unrelated probands. METHODS: Whole-exome sequencing was performed using a clinical exome workflow. Variants were interpreted using American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria and cases were categorized as solved, possibly solved, inconclusive, or unsolved using prespecified inheritance-aware rules. MAIN OUTCOME MEASURES: Molecular diagnostic yield, distribution of implicated genes and variant classes, inheritance architecture, and diagnostic yield stratified by consanguinity status. RESULTS: Among the 109 unrelated probands, mean age at testing was 39.3 ± 14.1 years and 58.7% were male. Whole-exome sequencing identified 186 distinct rare variants across 92 inherited retinal disease genes, including 26 pathogenic and 33 likely pathogenic variants. A molecular diagnosis was established in 50 of 109 probands (45.9%), including 42 solved and 8 possibly solved cases; 45 (41.3%) were inconclusive and 14 (12.8%) remained unsolved, including 4 (3.7%) in whom no candidate variant was identified. EYS, USH2A, and ADGRV1 were the most frequently implicated genes. Autosomal recessive (AR) disease predominated (44/50, 88.0%). Consanguineous AR cases were exclusively homozygous (17/17); notably, 68.0% of nonconsanguineous AR cases were also homozygous (P = 0.013). Diagnostic yield was higher in consanguineous probands (51.4% vs. 41.7%), without reaching significance. Recurrent alleles included an established South Asian founder variant (MFSD8 c.1361T>C) and candidate founder alleles in EYS (c.4321C>T) and ADGRV1 (c.14329C>T). CONCLUSIONS: Whole-exome sequencing established a molecular diagnosis in nearly half of this South Indian RP cohort and revealed a predominantly recessive, homozygosity-enriched architecture shaped by consanguinity. These findings define a region-specific variant landscape to support clinical interpretation, genetic counseling, and future trial enrollment in this underrepresented population. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.

Consanguinity↗

PubMed2026

TNFα-dependent modulation of WT1-MMP9 regulatory axis links developmental and inflammatory pathways in glaucoma.

Glaucomas are heterogeneous optic neuropathies associated with extracellular matrix dysregulation, abnormal ocular morphogenesis, and inflammatory signaling. Targeted deep sequencing of 586 primary congenital glaucoma (PCG) cases and 1,757 controls identified rare pathogenic variants in multiple genes, including WT1 and MMP9. Notably, WT1 variants clustered within the nuclear export sequence. Further, functional analyses showed that combined wt1-pax6 suppression in zebrafish disrupted ocular morphogenesis, highlighting developmental interdependence. In human trabecular meshwork cells, WT1 acted as a transcriptional repressor of MMP9, while TNF-α signaling triggered nitric oxide-dependent nuclear export of WT1, resulting in delayed MMP9 upregulation. This effect was reversible by inhibiting nuclear export or nitric oxide synthase. A patient-derived mutation in the nuclear-export region of WT1, disrupted this regulatory switch, causing abnormal MMP9 expression. These findings position WT1 as an important regulator linking developmental and inflammatory mechanisms in glaucoma pathogenesis.

anterior segment dysgenesis↗

PubMed2026

Adaptive Sports Exposure Across Physical Medicine and Rehabilitation Residency and Sports Medicine Fellowship Programs: A National Cross-Sectional Website Analysis.

Adaptive sports improve health and quality of life for people with disabilities, yet the extent of adaptive sports exposure in physical medicine and rehabilitation (PM&R) training is unclear. This cross-sectional study reviewed the public websites of 115 accredited physical medicine and rehabilitation residency programs and 26 sports medicine fellowship programs for any mention of adaptive sports, characterizing exposure type, target populations, and associated program characteristics. Adaptive sports were mentioned by 32 residency programs (27.8%) and 8 fellowship programs (30.8%). Mention varied significantly by geographic region in both cohorts (residency, West 64% vs. South 19%, P=.017; fellowship, Midwest 80% vs. South 0%, P=.035) and, among residencies, was associated with larger program size and a greater number of associated subspecialty fellowships. Residency exposure was predominantly volunteer-based, whereas fellowship exposure was exclusively clinical or undisclosed; target populations served were frequently unspecified. Programs have an opportunity to expand structured adaptive sports training and to clearly convey these opportunities to applicants and patients.

Adaptive sports↗

PubMed2026

The return of measles: a dangerous comeback.

PURPOSE OF REVIEW: Measles has reemerged as a significant global public health threat, with increasing morbidity and mortality associated with declining vaccination rates. This review summarizes current global outbreaks, history of measles, vaccination and elimination status, vaccine hesitancy, and outbreak response and lessons learned highlighting different novel digital epidemiological tools. RECENT FINDINGS: Measles continues to surge worldwide with an estimated 11 million infections in 2024, which is more than prepandemic levels. Developing and developed countries are both facing measles outbreaks, with the United States at risk of losing measles elimination status. Recent studies have showed that worldwide percentages of two-dose measles vaccination were lower than 95% that is required to interrupt measles transmission in all WHO regions. Novel epidemiological tools such as interactive simulators, real-time use of dynamic models, serosurveillance, and others are transforming measles outbreak response and enable earlier outbreak detection, tracking, and targeted public health interventions. SUMMARY: Vaccine hesitancy is one of the top global health threats and developing a tailored evidence-based approach is necessary to establish and maintain measles elimination.

Humans↗

PubMed2026

A validated sensitive LC-MS/MS method and its application in elucidating the unique ocular pharmacokinetic profile of 0.01% atropine underpinning its clinical utility for myopia.

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify atropine in ten rabbit ocular tissues enabling systematic characterization of the ocular pharmacokinetic profile of 0.01% atropine sulfate eye drops after a single topical administration. The method demonstrated excellent linearity (coefficient of determination, R2 ≥ 0.9908) across all matrices, with lower limits of quantification (LLOQ) of 0.05 ng/mL for most tissues and 0.10 ng/mL for retina and lens; intra- and inter-day accuracy, precision, matrix effects, extraction recoveries, and stability all met the acceptance criteria. Following a single bilateral topical dose (50 μL/eye) in New Zealand White rabbits, atropine distributed rapidly into all 12 ocular compartments (the sclera further divided into three anatomical regions) with marked heterogeneity-the highest exposures were found in conjunctiva and cornea, a distinct anterior-to-posterior concentration gradient was observed in the sclera, sustained retention was noted in the retina (mean residence time from zero to the last measurable time point, MRT0-t 3.30 h), while aqueous and vitreous humor eliminated rapidly (elimination half-life, t₁/₂ < 0.7 h), and all tissues except aqueous humor followed a two-compartment model. This validated method and the comprehensive pharmacokinetic data reveal that topically applied 0.01% atropine achieves sustained exposure in key myopia-regulating tissues (retina, choroid, posterior sclera) with low exposure in side-effect target tissues (iris, ciliary body, lens).

Animals↗

PubMed2026

Molecular mechanisms of natural de novo shoot organogenesis and their applications.

Natural de novo shoot organogenesis (DNSO) is the spontaneous regeneration of shoots from wound sites outside the shoot apical region through endogenous developmental programs. This regenerative capacity enables plants to recover from severe tissue damage by re-establishing the shoot-root axis. Here, we review current knowledge about the molecular mechanisms of natural DNSO, focusing on transcriptomic and physiological studies in model plants. Accumulating evidence suggests that natural DNSO proceeds through three sequential phases: (i) early wound responses, characterized by the activation of the WIND1-ESR1 module and the establishment of apical-basal auxin asymmetry; (ii) cellular proliferation driven by metabolic and cell-cycle reprogramming; and (iii) cytokinin-mediated establishment of shoot apical meristem identity. We also discuss how these mechanistic insights have been harnessed for practical applications, including tissue culture-free transformation systems such as the cut-dip-budding (CDB) method, and developmental reprogramming strategies that employ ectopic expression of developmental regulator (DR) genes to induce DNSO in otherwise recalcitrant species. Together, these advances illustrate how understanding natural regeneration can guide the development of simplified, broadly applicable plant transformation technologies.

Plant Shoots↗