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PubMed2026

A contextual activity score (CAS) for inferring ADAR-associated transcriptional activity across RNA-seq, single-cell, and spatial transcriptomics.

BACKGROUND AND OBJECTIVE: Adenosine-to-inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), is a widespread modification involved in neural function, immune regulation, and cancer. The Alu Editing Index (AEI) is the standard metric to estimate ADAR activity but requires raw sequencing reads and is poorly suited for single-cell and spatial transcriptomic data. This study aimed to develop an alternative framework for inferring ADAR-associated transcriptional activity from gene expression data across diverse transcriptomic technologies. METHODS: We developed the Contextual Activity Score (CAS), a framework based on transcriptional signatures from ADAR perturbation experiments. Context-specific signatures were generated for human neurons, mouse neurons, and cancer models to infer ADAR1 and ADAR2 activity. CAS was computed from normalized gene expression matrices using regulon-based enrichment analysis. Performance was evaluated by comparing with the Alu Editing Index across bulk RNA sequencing datasets, simulated sequencing depths, and library preparation protocols. RESULTS: CAS showed strong concordance with the Alu Editing Index across multiple datasets, while remaining robust to reduced sequencing depth and different library protocols. Unlike the Alu Editing Index, CAS can be applied to single-cell and spatial transcriptomic data and enables the independent assessment of ADAR2 activity. In cancer and neuronal contexts, CAS captured biologically meaningful variations in ADAR-associated transcriptional activity at sample, cell-type, and spatial levels. CONCLUSION: CAS provides a scalable approach applicable across multiple RNA-seq protocols for estimating ADAR-associated transcriptional activity using gene expression data. This method, implemented in an open-source R package for broad adoption, expands the ability to study ADAR-associated transcriptional activity across transcriptomic modalities where direct editing quantification is challenging, such as single-cell and spatial transcriptomics.

Adenosine Deaminase↗

PubMed2026

Engineering bubble structures as Cas12a activators for highly sensitive monitoring of WRN helicase function.

The Werner syndrome helicase (WRN) is a critical synthetic lethal target in microsatellite instability cancers, essential for resolving complex genomic structures like replication bubbles and R-loops. However, strategies to simultaneously discriminate WRN activity on DNA versus DNA-RNA substrates in living cells are lacking. Here, we developed a structure-specific CRISPR/Cas12a biosensing strategy to visualize WRN functional activity by engineering bubble-structure probes. These probes were rationally designed to structurally mimic DNA replication bubbles and R-loop associated DNA-RNA hybrids. Upon specific unwinding by WRN, the probes release a sequestered activator strand that triggers Cas12a trans-cleavage, effectively converting the unwinding event into an amplified fluorescent signal. This assay achieves low picomolar sensitivity (LODs: 5.6-6.0 pM) and exceptional selectivity against homologous RecQ helicases. Uniquely, this strategy enables the parallel quantification of WRN activity on both substrate types, providing insights into distinct WRN-mediated pathways for resolving genomic stress. We further demonstrated the strategy's utility by visualizing endogenous WRN dynamics in living cells and profiling the efficacy of small-molecule inhibitors. This work offers a powerful molecular toolkit for dissecting WRN biology and facilitating high-throughput drug screening in targeted cancer therapy.

Werner Syndrome Helicase↗

PubMed2026

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5 wt%) and increasing Sr contents (0.5, 1.0, 1.5 wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-α and TGF-β; with an enhanced TNF-α secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals↗

PubMed2026

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems↗

PubMed2026

Medication safety in older adults in India: an integrative PhD synthesis of direct evidence and contextual implementation evidence.

BACKGROUND: Unsafe medication practices among older adults are an important global health concern, particularly in low- and middle-income countries where multimorbidity, fragmented care, self-medication, and informal healthcare provision intersect. OBJECTIVE(S): To synthesize direct evidence on medication safety among older adults in India and contextual evidence on deprescribing and community-level provider interventions relevant to safer medication use. METHODS: This PhD synthesis integrates four studies: a record-based cross-sectional study on polypharmacy and cardiovascular autonomic function in Kolkata; a six-city community study of 600 Indian older adults; a systematic review and meta-analysis on deprescribing preventive medications in frail or end-of-life older adults; and a systematic review of informal healthcare provider interventions in low- and middle-income countries. Studies I-II provided direct Indian older-adult evidence, while Studies III-IV provided indirect contextual evidence for their optimization and implementation. RESULTS: Polypharmacy was associated with higher anticholinergic burden and numerically higher cardiac autonomic neuropathy although residual confounding limits causal interpretation. In the multicity study, one-third had polypharmacy, while potentially inappropriate medications, prescribing omissions, and self-medication were common. Risks were higher with multimorbidity, recent hospitalization, care transitions, or living alone. Deprescribing showed no statistically significant increase in mortality, hospitalization, or major cardiovascular events, but heterogeneity was high and certainty low to very low. Informal-provider interventions showed the potential to improve knowledge, referral, case management, and medication-related practices. CONCLUSIONS: Medication safety among older adults in India requires an integrated continuum approach, but direct evidence supports only some components and implementation strategies that need prospective evaluation.

Humans↗

PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗

PubMed2026

Carboxyl group number and acidity of organic acids regulate structural reorganization and low glycemic index in cassava pyrodextrins via molecular interactions.

Transforming high-glycemic cassava starch into functional dietary fiber via pyrodextrinization is a promising way to valorize tuber crops, yet the molecular mechanisms catalyzed by organic acids with different carboxyl numbers and acidity remain unclear. This study investigates how carboxyl number and acidity of acetic acid (AA), tartaric acid (TA), and citric acid (CA) affect structural reorganization and low glycemic properties of cassava pyrodextrins. Compared with AA, TA, and CA with stronger acidity and more carboxyl groups promoted more extensive hydrolysis, transglycosylation, repolymerization, and esterification. These changes increased indigestible glycosidic linkages and the branching degree, while reducing molecular weight. Molecular docking confirmed stronger hydrogen-bonding interactions between TA/CA and starch chains. Furthermore, TA- and CA-catalyzed pyrodextrins exhibited superior anti-digestive properties with resistant starch up to 54.26% and an estimated glycemic index as low as 42.46, highlighting the critical role of carboxyl numbers and acidities in modulating the functionality of pyrodextrins.

Manihot↗

PubMed2026

Inducible flocculation in Komagataella phaffii enables enhanced biomass separation for biopharmaceutical production.

Biomass separation represents a critical bottleneck in Komagataella phaffii-based biopharmaceutical processes, as typically high cell densities of 40 - 50 % create significant operational, technical and economic challenges for harvest operations. Yeast cell aggregation (flocculation) provides a solution to accelerate cell sedimentation by increasing particle size, thus allowing to improve biomass-supernatant separation efficiency during both natural gravity settling and (continuous) centrifugation operations. This study demonstrates successful engineering of K. phaffii strains with an inducible flocculation phenotype using CRISPR/Cas9-based genome editing to integrate the Saccharomyces cerevisiae FLO1 (ScFLO1) gene under control of various regulatory elements, including methanol-inducible and derepressible promoters. Flocculation strength could be enhanced by implementing transcriptional positive feedback circuits based on the methanol-inducible AOX1 promoter. To address methanol-free production requirements, we developed alternative systems to retrofit PAOX1-based ScFLO1 expression and exploited the derepressible PDF promoter, offering broader compatibility with biopharmaceutical manufacturing facilities. Flocculating cells cultivated in a bioreactor demonstrated significantly improved sedimentation behavior, with considerably lower supernatant turbidity after short low-speed centrifugation or gravity sedimentation compared to non-flocculating controls. Crucially, cell flocculation had no negative impact on product amount and quality when expressing a multivalent NANOBODY® VHH molecule with pharmaceutical relevance. Thus, this work establishes the first genetically engineered flocculation system in K. phaffii compatible with recombinant protein production, providing the basis for an innovative approach to streamline harvest operations in biopharmaceutical processes.

Flocculation↗

PubMed2026

Reprogrammed Komagataella phaffii for enhanced secretory expression of human lactoferrin.

Human lactoferrin (hLF) is a multifunctional glycoprotein of the transferrin family derived from milk and mucosal secretions, which exhibits antibacterial, anti-tumor, and immunomodulatory functions, and is an important component of infant formula. Conventional methods for lactoferrin expression are often inefficient, primarily due to inadequate protein synthesis capabilities and poor stability within microbial hosts. Herein, a Komagataella phaffii yeast strain capable of high-level secretory expression of hLF was constructed by reprogramming the endoplasmic reticulum (ER) and vacuole using CRISPR/Cas9 technology. A dual-expression cassette containing the AOX1 promoter, an α-secretion signal peptide, the hLF gene, and a terminator was integrated into three different sites of the K. phaffii genome. The stepwise strategy combining expansion of the ER membrane involved in protein synthesis with knockout of vacuolar proteases further enhanced hLF production. Subsequently, 0.1 g/L FeCl₃ was added to the medium to reduce the toxicity of hLF and improve its stability. After high-density cultivation of K. phaffii through optimization of cultivation conditions in shake flasks and a 5 L bioreactor, the secretory intact hLF titer reached 2214 mg/L, representing a 76.3-fold increase achieved through these engineering strategies. In addition, antibacterial experiments demonstrated that this secretory hLF had a significant inhibitory effect on Escherichia coli, Staphylococcus aureus, and yeast. Overall, the developed K. phaffii protein expression platform enabled efficient production of lactoferrin, demonstrating its potential for expressing other lactoproteins.

Lactoferrin↗

PubMed2026

Multiplexed CRISPR/Cas9 mediated knockdown of BCH gene in potato enhances beta-carotene to combat vitamin A deficiency.

The inadequate amounts of provitamin A carotenoids in crops contribute to the widespread vitamin A deficiency, leading to malnutrition and blindness in humans. Suppression of the β-carotene hydroxylase (BCH) increases β-carotene levels. In the current study, we utilized the multiplexed CRISPR/Cas9 approach by designing three targets against the BCH gene in a local potato cultivar. Transformation efficiency was recorded as 15%, the successful integration of the CRISPR/Cas9-BCH multiplex construct in potatoes was confirmed through PCR. When analysed using TIDE software, Sanger sequencing revealed the highest indel efficacy of 92.1% in plant 7 and 26.6% in plant 1. qRT-PCR (quantitative real-time PCR) analysis indicated a significant 89-fold reduction in BCH transcript levels in genome-edited potato lines compared to control plants. Spectrophotometry demonstrated a notable increase in beta-carotene levels in genome-edited potato plants, ranging from 0.831 µg/mL FW to 4.236 µg/mL FW, compared to the control plant with the lowest beta-carotene concentration (0.344 µg/mL FW). HPLC analysis further confirmed increased beta-carotene levels in genome-edited potato plants, ranging from 0.11 mg/mL FW to 0.36 mg/mL FW, compared to the unmodified control plant with a minimum beta-carotene value of 0.09 mg/mL. Our results revealed that the multiplexed CRISPR-Cas9 approach targeting the BCH gene results in enhanced beta-carotene contents in potato tubers.

Solanum tuberosum↗

PubMed2026

Proteomic characterization of the acquired enamel pellicle under acidic challenges at early and mature formation stages.

OBJECTIVES: This study aimed to characterize acquired enamel pellicle (AEP) proteomic changes after exposure to citric acid (CA) and hydrochloric acid (HCl) under different pellicle formation times (3 and 120 min) in the same volunteers. DESIGN: Nine healthy volunteers participated in this randomized crossover in vivo study. The AEP was allowed to form for 3 or 120 min and subsequently exposed for 10 s to deionized water (control), 1% CA (pH 2.5), or 0.01 M HCl (pH 2.0). Pellicle samples were collected, followed by protein extraction, tryptic digestion, and analysis by nanoliquid chromatography (nanoLC) coupled to mass spectrometry (MS) with MSE (data-independent acquisition; nanoLC-MSᴱ). Label-free quantitative proteomics were performed for relative quantification using t-test (p < 0.05). RESULTS: At 120 min, CA exposure markedly reduced several typical AEP proteins, especially acidic proline-rich proteins (PRPs). Conversely, basic PRPs were upregulated, suggesting acid-resistance protein signature. At 3 min, basal-layer proteins (PRPs, cystatins, histatins and mucins) were more abundant. Hemoglobins increased 6-8-fold (up to 150-fold in 3 min control), suggesting association with early pellicle formation and an acid-resistant protein signature. CA exposures for 120 min also upregulated typical AEP proteins (PRPs, mucins, cystatins, immunoglobulins), while HCl exposure depleted albumins and lactotransferrin. CONCLUSION: Intrinsic and extrinsic acids induce distinct proteomic signatures in the AEP. Hemoglobin and PRPs appear consistently enriched in the early pellicle layer, reflecting an initial acid-resistant protein signature. These findings provide new insights into the molecular remodeling of the AEP following intrinsic and extrinsic acid exposure, highlighting proteins potentially involved in early-stage pellicle formation.

Humans↗

PubMed2026

A dual-dimensional CRISPR toolkit enables one-step high-efficiency multiplex genome editing in Komagataella phaffii.

Against the backdrop of green biomanufacturing, engineering methanol-utilizing Komagataella phaffii (K. phaffii) represents an effective strategy to expand the one carbon (C1) product profile and speed up the industrialization of C1-based bioeconomy. To address the technical challenges of low efficiency and cumbersome experimental procedures for multiplex gene editing and precise large-fragment integration during the reconstruction of complex metabolic pathways in K. phaffii, this study established a CRISPR toolkit - Efficient Multi-Gene Editing System 3.0 (EMGES 3.0) - which enabled one-step large-fragment integration coupled with multiplex gene knockout. EMGES 3.0 was constructed through the synergistic optimization of a repair-engineered chassis and an episomal CRISPR vector. For chassis engineering, five DNA repair modules: Δlig4 (DNA Ligase IV, non-homologous end joining end ligation), ppMRE11(The endogenous MRE11 gene from Pichia pastoris) overexpression (The Meiotic Recombination 11, DNA double-strand break end resection), Δrad9 (Radiation-Sensitive 9, DNA damage checkpoint regulation), Δmph1 (Mutator Phenotype Helicase 1, improvement of homologous recombinant strand extension), and PapRecT-PaSSB co-expression (stabilization of recombination intermediates) were integrated to generate the highly recombinogenic strain Y09. For vector engineering, cenARS was replaced by panARS and the endogenous promoter PGAP was employed to drive the double hammerhead ribozyme-single guide RNA-hepatitis delta virus ribozyme (double HH-sgRNA-HDV: dHgH)-mediated sgRNA expression, yielding the optimized vector Nov_pGAP_panARS_pLAT1_Cas9. These two features on K. phaffii together enhanced the EMGES 3.0 to a higher standard of transformation rate and editing efficiency. According to our results, EMGES 3.0 achieved dual-functional gene knockout efficiencies between 76.6% and 100%. For insertion of medium-long fragments (>4.5 kb), the efficiency achieved 93.3%. In addition, the one-step integration of ultra-long fragments (>16 kb) achieved 14.8%, which was reported for the first time. Furthermore, the efficiency of simultaneous long-fragment integration at three neutral loci reached 38.4% (>15 kb). We applied the system for one-step production of free fatty acids (FFAs, yield: 5.82 ∼ 7.30 mg/L/OD600) and resveratrol (yield: 1.14 ∼ 1.28 mg/L) using methanol as the sole carbon source. EMGES 3.0 provides a robust technical foundation for complex compounds biosynthesis and high-yield industrial strains, while also advancing K. phaffii as an industrial synthetic biology chassis for efficient C1 utilization.

CRISPR-Cas Systems↗

PubMed2026

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4 days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9 ± 12.7; active/sham 50/54). The model yielded a Time × Novelty Seeking interaction (β = -1.70, p = 0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p = 0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans↗

PubMed2026

Mealtime satisfaction in public nursing homes: Associations with sensory, foodservice, and dining-room environment factors.

Satisfaction with meals is commonly used to assess how meals are experienced in nursing homes (NH), although limited evidence compares breakfast, lunch, and dinner within a unified analytical framework. This study examined the sensory and contextual factors associated with satisfaction across meals in public NH. A cross-sectional observational study was conducted using structured interviews with 290 residents aged ≥60 years (median 85 years; Q1-Q3: 81-88; 63.1% women) from 19 facilities in Galicia, Spain. Overall satisfaction and 12 factors related to sensory attributes of the food, foodservice characteristics, and dining-room environment were assessed using a 5-point Likert scale. Descriptive analyses used medians and quartiles, and group comparisons were performed using nonparametric tests. Three multivariable linear regression models, one per meal, were estimated including all factors simultaneously. In adjusted models, the largest standardized coefficients were observed for taste (lunch: β = 0.366; P < 0.001), food temperature at serving (dinner: β = 0.319; P < 0.001), and menu variety (breakfast: β = 0.301; P < 0.001). Taste, food temperature at serving, menu variety, and meal schedule showed statistically significant coefficients in all models. Overall satisfaction was lower at dinner (29.0% ≥ 4) than at breakfast (34.8%) and lunch (34.5%) (P = 0.003). Selected dining-room environment factors showed significant coefficients in meal-specific models. Mealtime satisfaction was mainly associated with sensory and contextual factors related to how meals are perceived. Lower satisfaction at dinner suggests this mealtime as a relevant context for understanding variations in meal perception in NH residents.

Humans↗

PubMed2026

Beyond antigen matching: compatibility intelligence theory for transfusion as an emergent biological system.

BACKGROUND: Despite major advances in serologic testing, extended phenotyping, and blood group genomics, clinically similar transfusion exposures may result in markedly different immune and clinical outcomes. Existing compatibility strategies do not fully explain this biological variability. OBJECTIVES: To examine transfusion compatibility as an emergent donor-recipient biological state and propose a systems-level conceptual framework that integrates established biological determinants into a testable model for future precision transfusion medicine. METHODS: This narrative review critically synthesizes current evidence from blood group genomics, recipient immunobiology, inflammation, disease-specific biology, transfusion medicine, and computational prediction. The proposed framework distinguishes Compatibility Intelligence Theory (CIT) as a biological interpretation from Precision Transfusion Intelligence (PTI) as its potential clinician-supervised translational application. RESULTS: The review argues that transfusion compatibility is shaped by interactions among donor genetics, recipient immune biology, inflammatory physiology, disease context, transfusion history, and longitudinal adaptation rather than by antigen matching alone. CIT provides an organizational framework for integrating these determinants, whereas PTI describes a possible clinician-supervised translation. To address current feasibility, the revised framework separates variables into routinely measurable, contextually available but incompletely standardized, and research-stage domains, and proposes a staged strategy for deriving rather than assuming their quantitative weights. Any clinical implementation would require comparative validation against current serologic, phenotypic, and genotype-based practice. CONCLUSIONS: Compatibility Intelligence Theory offers a testable systems-level framework for understanding transfusion compatibility without replacing established transfusion practices. The framework is not presented as a ready-to-use score: currently measurable variables can be organized for structured risk review, whereas inflammatory, immunogenetic, and multi-omic inputs require prospective standardization and validation. If future studies demonstrate incremental predictive and patient-centered benefit, CIT-informed PTI could support an adaptive, evidence-based extension of current precision transfusion practice.

Humans↗

PubMed2026

Divergent responses of the gill, hepatopancreas, and eyestalk to acute alkalinity stress in Penaeus vannamei: Osmoregulatory compromise, metabolic trade-off, and endocrine disruption.

The expansion of aquaculture into inland saline-alkali waters is constrained by high carbonate alkalinity (CA), a severe environmental stressor for crustaceans. However, the systemic molecular mechanisms underlying its lethal toxicity remain poorly understood. In this study, we employed a comparative transcriptomic approach to investigate the tissue-specific responses of Pacific white shrimp, Penaeus vannamei, under acute lethal stress (48 h-LC50). We focused on three functionally distinct organs: the gill, hepatopancreas, and eyestalk. The results revealed a systemic but highly tissue-specific transcriptomic response. The gill, as the primary interface, exhibited severe structural impairment and critical failure of osmoregulation, highlighted by the significant downregulation of delta-1-pyrroline-5-carboxylate synthetase (P5CS). In contrast, the hepatopancreas initiates a profound metabolic trade-off, sacrificing growth-related pathways to bolster a robust antioxidant defense system, as evidenced by the activation of sulfur metabolism and high protein turnover. The eyestalk displayed a striking disconnect between hyperactivated stress signaling pathways (e.g., mTOR/FoxO) and the collapse of its protein secretory machinery, marked by the suppression of the ER translocon component Sec61. Collectively, our findings suggest that lethal alkalinity toxicity in P. vannamei results from systemic collapse driven by a complex interplay of osmoregulatory failure, metabolic trade-offs, and endocrine disruption. This study provides a comprehensive molecular snapshot of an organism at its physiological limit, offering novel insights into the adaptive strategies and ultimate tolerance boundaries of crustaceans in extreme environments.

Animals↗

PubMed2026

Hyperbaric oxygen for the treatment of traumatic incomplete spinal cord injury: a systematic review and meta-analysis of randomized controlled trials.

The therapeutic efficacy of hyperbaric oxygen therapy for traumatic incomplete spinal cord injury remains a subject of debate. To comprehensively evaluate the impact of hyperbaric oxygen on motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury, we conducted a systematic review and meta-analysis. We performed a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and major Chinese databases for randomized controlled trials published through June 2025. A total of 15 randomized controlled trials were included. The pooled results indicated that hyperbaric oxygen therapy significantly improved the American Spinal Injury Association motor score (mean difference = 10.30, 95% confidence interval: 7.70-12.90), the total American Spinal Injury Association sensory score (mean difference = 29.29, 95% confidence interval: 18.82-39.75), the American Spinal Injury Association light touch score (mean difference = 9.84, 95% confidence interval: 6.15-13.53), and the American Spinal Injury Association pinprick score (mean difference = 8.75, 95% confidence interval: 4.40-13.11). Furthermore, hyperbaric oxygen therapy was associated with significant enhancements in the Barthel Index (mean difference = 16.60, 95% confidence interval: 10.51-22.68) and the Functional Independence Measure (mean difference = 17.41, 95% confidence interval: 10.83-23.98). In conclusion, adjunctive hyperbaric oxygen therapy appears to improve motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury compared to conventional treatments alone. However, due to methodological limitations and potential publication bias in the included studies, these findings should be interpreted with caution, and further high-quality, multi-center randomized controlled trials are warranted.

Humans↗

PubMed2026

The value of international collaborations for supporting neuroanesthesia practice, education, and research in resource-constrained settings.

PURPOSE OF REVIEW: Neuroanesthesia practice in low- and middle-income countries is constrained by workforce shortages, limited infrastructure, and variability in clinical practice. Growing global interest in collaboration makes it timely to evaluate how international partnerships can address these gaps and improve equity in care, education, and research. RECENT FINDINGS: Recent literature highlights substantial variability in neuroanesthesia practice and limited access to context-appropriate guidelines and advanced technologies. International collaborations, including training partnerships, scholarship programs, and research networks, have improved knowledge exchange, workforce development, and the adoption of standardized practices. Evidence suggests that specialized training is associated with improved clinical outcomes. However, persistent inequities in research participation, authorship, and leadership, as well as concerns regarding sustainability and 'parachute research', remain. SUMMARY: International collaboration is a key strategy for advancing neuroanesthesia in resource-constrained settings. Sustainable, equitable partnerships that prioritize local ownership, capacity building, and contextual adaptation are essential to improving clinical practice, strengthening education, and enhancing global research representation.

Humans↗