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Maize ZmMYB59 inhibits post-germinative shoot and root elongation through ZmGA2ox3/10-mediated gibberellin catabolism.

Gibberellin (GA) promotes seed germination, but sustained or excessive GA signaling after germination can lead to aberrant root and shoot elongation. How GA homeostasis is transcriptionally restrained during post-germinative seedling development remains unclear. Using overexpression and gene-edited maize materials, we demonstrate that ZmMYB59 inhibits root and shoot elongation during post-germinative growth. Integrated RNA-Seq and CUT&Tag analyses identified the GA catabolism genes ZmGA2ox3 and ZmGA2ox10 as candidate direct targets of ZmMYB59. Hormone profiling analysis showed elevated bioactive GA1 and GA4 levels in the scutellum and aleurone layer cells of zmmyb59 mutants. Dual-luciferase assays, electrophoretic mobility shift assays, and ChIP-qPCR further confirmed that ZmMYB59 directly binds AC8 cis-elements in the ZmGA2ox3/10 promoters and activates their transcription. The zmga2ox3/10 double mutant, but neither single mutant, exhibited enhanced root and shoot elongation, accompanied by GA4 accumulation. This phenotype was suppressed by exogenous application of the GA biosynthesis inhibitor uniconazole. Transcriptomic and biochemical analyses further revealed enhanced starch degradation, reduced starch content, and increased soluble sugar accumulation in the double mutant. Taken together, these findings reveal that the ZmMYB59-ZmGA2ox3/10 module restrains GA accumulation and starch mobilization after germination, thereby coordinating reserve utilization with post-germinative root and shoot growth in maize.

Gibberellins

Cloning of two Hsp70 genes and association analysis between SNP haplotypes and high temperature tolerance trait in red swamp crayfish (Procambarus clarkii).

Aquaculture is suffering the challenge from high temperature climate. Two Hsp70 genes, PcHsp70-1 and PcHsp70-2, as key genes involved in the high temperature tolerance of red swamp crayfish (Procambarus clarkii) were identified and cloned in this study. Their molecular features and expression patterns were characterized, revealing the distinct tissue-specific upregulation expression under high temperature stress (33 °C). Two SNPs, PcHsp70-1 (SNP258) and PcHsp70-2 (SNP555) were examined to associate with high temperature tolerance in three populations (n = 675). The genotypes of PcHsp70-1-SNP258 (GA) and PcHsp70-2-SNP555 (TT) were significantly associated with stronger high temperature tolerance. Notably, individuals carrying the haplotype of Hap I (GG + TT) showed a survival rate exceeding 70% under high temperature stress, whereas, the Hap VIII (AA + CT) showed it at 5.2%. RNA interference of PcHsp70-1 resulted in a significant decrease expression of the gene GSH-Px and its encoding protein (glutathione peroxidase) activity, and damage in intestinal tissue under high temperature stress. The transcriptome result revealed that PcHsp70-1 participates in regulation of the pathways related to cytoskeletal construction, immune response, apoptosis, and antioxidant defense. These findings indicate that PcHsp70 genes are crucial for the cellular stress response under high temperature stress. The developed Kompetitive Allele Specific PCR (KASP) markers provide valuable tools for the marker-assisted selection of high temperature tolerant crayfish varieties, supporting the sustainable development of aquaculture under the challenge of global warming.

Animals

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&#x2009;<&#x2009;95%; dDDH&#x2009;<&#x2009;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 -&#x2009;8.8 to -&#x2009;9.0&#xa0;kcal/mol. Daidzein exhibited the highest thermodynamic stability (-&#x2009;9.0&#xa0;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

Genome-Wide Characterization of &#x3b2;-Glucosidase (TaBGLU) Genes in Bread Wheat and Their Expression Under Drought, Cold, and Combined Stress.

Glycoside hydrolase 1 (GH1) &#x3b2;-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

Safe and Stable Germline Transmission of MSTN Mutations in Cattle.

With the global population expected to reach 10 billion by 2050, sustainable livestock production is critical. Gene editing of the myostatin (MSTN) gene represents a promising strategy to enhance muscle growth in cattle. In this study, MSTN-mutated founder (F0) cows were used to generate F1 offspring via ovum pick-up, in&#xa0;vitro fertilization, and embryo transfer. Four F1 calves were born, all confirmed to be heterozygous for the MSTN mutation. Long-term monitoring showed normal growth and no visible health abnormalities. Whole-genome sequencing identified SNPs, INDELs, and structural variants, most with minimal predicted functional effects. Proteomic profiling of Longissimus dorsi muscle quantified 2947 proteins, revealing only subtle expression differences between MSTN-mutated and wild-type cattle. These results demonstrate stable inheritance and confirm that MSTN editing does not disrupt genome integrity or protein expression. Overall, our findings support the safety and utility of MSTN gene editing to improve livestock productivity for future food security.

Animals

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 &#xb1; 0.86 N at week 4; 22.97 &#xb1; 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

A black soybean yoghurt fermented with a reusable probiotic cellulose gel: beneficial effects and metabolic characteristics.

The demand for plant-based yoghurts is continuously increasing. However, achieving stable physicochemical properties and acceptable flavor of the plant-based yoghurts remains challenging. In our previous work, we encapsulated Lactiplantibacillus plantarum (L. plantarum) LCC-605 biofilm into bacterial cellulose (BC), obtaining a LP605@BC gel. LP605@BC gel exhibited excellent harsh-environment resistance abilities and storage stability, and is very suitable as a starter culture. In this work, we used LP605@BC as a starter culture to prepare the fermented plant-based yoghurt (e.g., black soybean yoghurt, BSY-LP605@BC). After fermentation, the inverted nonflowing yoghurt was formed due to the strong interaction between protein and exopolysaccharide (EPS) produced by LCC-605 during fermentation. In addition, the water holding capacity (67.2%) of BSY-LP605@BC was also greatly improved. The viable bacterial counts in BSY-LP605@BC reached 11.2 log CFU/mL after 21&#xa0;days of storage. BSY-LP605@BC showed increased antioxidant, cholesterol-lowering abilities, and hypoglycemic potential compared with the unfermented black soybean milk. Interestingly, LP605@BC could be reused at least 5 times, demonstrating excellent sustainability. Significant metabolomic differences between BSY-LP605@BC and the black soybean milk were observed via untargeted metabolomic analysis, further proving the beneficial effects of BSY-LP605@BC. Overall, our work developed an effective reusable starter culture for preparing the plant-based yoghurt in a sustainable manner, providing a new design direction and form of starter culture.

Yogurt

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

Fasting-refeeding regimes induce compensatory growth and muscle transcriptomic remodeling in juvenile Qihe gibel carp (Carassius gibelio var. Qihe).

Compensatory growth, an important adaptive response in fish, holds considerable potential for improving feeding efficiency in aquaculture. To identify an optimal fasting-refeeding strategy for juvenile Qihe gibel carp (Carassius gibelio var. Qihe) and to clarify the mechanisms underlying the compensatory growth, we divided two-month-old fish into four groups, namely S0 group (continuous feeding for 28&#xa0;days), S2 group (4&#xa0;cycles of 2-day fasting followed by 5-day refeeding), S4 group (fasting for 4&#xa0;days followed by refeeding for 24&#xa0;days), and S8 group (fasting for 8&#xa0;days followed by refeeding for 20&#xa0;days), then growth performance, muscle tissue morphology, biochemical responses, and muscle transcriptomic profiles under different feeding regimes were investigated. After a 28-day aquaculture experiment, fish in the S4 group exhibited significantly greater body length and weight than those in the S0, S2, and S8 groups, indicating over-compensatory growth. Histological analysis further showed that muscle growth in the S4 group was mainly associated with myofiber hyperplasia. Different feeding regimes also induced distinct changes in hepatic antioxidant and metabolic enzyme activities, as well as intestinal digestive enzyme activities. Transcriptome analysis revealed that the forkhead box O (FoxO) signaling pathway was significantly enriched during compensatory growth. Key genes, including serum/glucocorticoid regulated kinase 1 (sgk1) and insulin receptor substrate 1 (irs1), were predicted to play important roles in this process. Overall, these results indicate that fasting for 4&#xa0;days followed by refeeding for 24&#xa0;days (the S4 regime) is the optimal strategy for inducing compensatory growth in juvenile Qihe gibel carp. This study provides new insights into the morphological, physiological, and molecular basis of compensatory growth and offers a scientific foundation for developing efficient and sustainable feeding strategies for this species.

Animals

Dissemination of blaKPC-3-harbouring Klebsiella pneumoniae across ST48 and ST628 in multiple healthcare facilities in the Republic of Korea.

Klebsiella pneumoniae carbapenemase-3 (KPC-3) remains rare in South Korea, where KPC-2 is the dominant carbapenemase, making the repeated detection of a concentrated blaKPC-3 signal over five years notable. We performed genomic analyses of blaKPC-3-harbouring K. pneumoniae from a regional healthcare network. Two chromosomally distinct lineages with concordant capsule loci (ST628/KL15 and ST48/KL62) presented multidrug-resistant phenotypes, and the virulence-associated loci were confined to ST48. Single-nucleotide polymorphism (SNP) analyses revealed near-clonal relatedness within lineages, with 0-38 pairwise SNPs among ST628 isolates and 8 SNPs between the two ST48 isolates. Core-genome multilocus sequence typing (cgMLST) supported this structure, as ST628 isolates were assigned to complex type 19149 with 0-7 allelic differences, and ST48 isolates were assigned to complex type 19150 with 5 allelic differences. These patterns support vertical spread via clonal expansion across multiple facilities. Despite substantial chromosomal separation, most isolates carried the same IncFII(K) plasmid backbone and blaKPC-3, and they were nearly indistinguishable from a plasmid previously reported in South Korea. One isolate carried blaKPC-3 on a distinct multireplicon IncFIB(K)/IncFII(K) plasmid, indicating that the signal was not confined to a single plasmid backbone. In both plasmids, blaKPC-3 was embedded within Tn4401b. These findings indicate that a rare blaKPC-3 genotype can persist regionally through sustained clonal dissemination and that cross-lineage linkage is compatible with past horizontal transfer involving a conserved plasmid. These findings underscore the need for subtype-resolved, regionally coordinated genomic surveillance in connected healthcare networks to detect uncommon carbapenemase variants early.

Klebsiella pneumoniae

Cooperative anaerobic catabolism of chlorinated organic compounds: implications for sustainable bioremediation.

Biodegradation research historically followed a reductionist approach focused on axenic (pure) cultures capable of catabolizing the specific contaminant(s) of interest. While this approach has substantially advanced our understanding of the microbiology, physiology, biochemistry, and genetics of contaminant degradation under laboratory conditions, it does not capture the complexity of natural and engineered environments. During in situ bioremediation, microbiomes are exposed to mixtures of contaminants, and microbial interactions profoundly influence contaminant transformation and fate. In anoxic environments, degradation of chlorinated compounds is often sustained by metabolic cooperation among taxonomically and physiologically distinct microorganisms. Through the exchange of metabolites such as hydrogen, formate, acetate, and other nutrients, microbial populations establish interdependent networks that overcome thermodynamic and physiological constraints, enabling self-sustaining systems of contaminant transformations that would be inefficient or impossible with individual organisms. We highlight examples of microbial interactions that underpin anaerobic catabolism of chlorinated contaminants, including systems resulting in self-sustained anaerobic bioremediation.

Biodegradation, Environmental

Triazole resistance in clinical Aspergillus fumigatus isolates in India, a multicenter surveillance study.

BACKGROUND: Triazole resistance in Aspergillus fumigatus is a global public health concern associated with treatment failure, notably in invasive aspergillosis. However, population-level data on triazole resistance from India remain limited, with most reports originating from single-center studies. METHODS: We conducted a multicenter surveillance study to assess the prevalence of triazole resistance among clinical A. fumigatus isolates across India. Antifungal susceptibility testing was performed using the CLSI broth microdilution method (M38-Ed3), and molecular characterization was conducted on resistant isolates. A total of 518 isolates were analyzed: 115 prospectively collected from 13 tertiary-care hospitals from 2015-2020, and 403 archived isolates obtained from the National Culture Collection of Pathogenic Fungi (1994-2020). RESULTS: The overall pooled prevalence of non-wildtype isolates was 4.1% for itraconazole (95% CI: 2.54-6.17%), 3.9% for posaconazole (95% CI: 2.39-5.94%), while 1.4% were resistant to voriconazole (95% CI: 0.55-2.77%). One multi-azole-resistant isolate from an immunocompromised, mold-active triazole-na&#xef;ve patient carried the TR34/L98H mutation, suggesting environmental acquisition. Prevalence of resistance did not differ significantly across geographic regions or between public and private sector hospitals. Linear regression analysis revealed a significant temporal increase in median MICs of all three licensed triazoles between 1994 and 2020. Approximately 29% of isolates exhibited amphotericin B MICs exceeding the epidemiological cutoff value; however, the clinical significance of this finding remains uncertain. CONCLUSIONS: Azole resistance among clinical A. fumigatus isolates in India remains uncommon (<5%), supporting the continued use of triazoles as first-line therapy. However, the observed temporal increase in triazole MICs underscores the need for sustained national surveillance to detect emerging resistance trends.

Aspergillus fumigatus

Safety and efficacy of recombinant botulinum toxin type A (Eveotox&#xae;) in patients with post-stroke upper limb spasticity: Results from a Phase Ib/II clinical trial.

Upper limb spasticity is a common and disabling complication of stroke. Botulinum toxin type A (BoNT-A) is widely used for focal spasticity treatment, but naturally derived products may present limitations related to immunogenicity and manufacturing variability. Recombinant botulinum toxin type A, produced by genetic engineering without complexing proteins, may provide improved product consistency. This Ib/II study evaluated the safety, tolerability, and preliminary efficacy of recombinant botulinum toxin type A in adults with post-stroke upper limb spasticity. This multicenter, seamless Ib/II clinical study included an open-label dose-escalation Ib phase and a randomized, double-blind, placebo-controlled II phase. Adult patients with post-stroke upper limb spasticity received a single intramuscular injection of recombinant botulinum toxin type A or placebo. The primary endpoint in Phase II was the change from baseline in the Modified Ashworth Scale (MAS) score of the primary target muscle group at Week 4. Secondary endpoints included MAS and Tardieu scale changes in individual muscle groups, Disability Assessment Scale (DAS), Physician's Global Assessment (PGA), and immunogenicity. The Ib phase showed improvements in MAS, DAS, and PGA, indicating an early efficacy signal. In Phase II, recombinant botulinum toxin type A produced a significant reduction in MAS score of the primary target muscle group at Week 4 compared with placebo, with effects sustained through Week 12. At Week 4, the PGA score in the Eveotox&#xae; group showed a statistically significant improvement compared with the placebo group. While MAS and PGA scores showed significant improvement, DAS functional scores did not differ statistically from the placebo group at week 4. The treatment was generally well tolerated, and low incidence of antibodies were observed. Recombinant botulinum toxin type A was safe and effective in reducing post-stroke upper limb spasticity after a single administration. These results support further Phase III clinical evaluation.

Humans

Development, feasibility, acceptability, and preliminary impact of NutriSOS&#xae;: A behavioral mobile app to promote sustainable diets.

The primary objective of this study was to describe the development of the NutriSOS&#xae; app and to evaluate its feasibility and acceptability for its use in the NutriSOS&#xae; Randomized Controlled Trial (RCT) to promote sustainable diets. A secondary objective was to explore preliminary changes in dietary and physical activity behaviors and environmental impact following app use. The NutriSOS&#xae; app integrates personalized dietary advice, educational content, self-monitoring, and social interaction features. A single-arm, pre-post pilot study was conducted in 37 young Mexican adults over four weeks. Feasibility, acceptability, quality, and usability were assessed using online surveys, alongside exploratory changes in dietary and physical activity behaviors, environmental indicators, and their association with perceived behavioral determinants. Feasibility and acceptability were high overall, with favorable responses reaching up to 100% in key components such as the nutritional guide and learning modules, and above 90% for messaging, registration, and design. Greater variability was observed in some sections, particularly the 24-h recall (41-86%). Reductions in red and processed meat and ultra-processed food consumption were observed (from 3 to 1 times/week, p&#xa0;<&#xa0;0.01), with &#x223c;60% decreases in their related environmental footprints (p&#xa0;<&#xa0;0.01) and favorable self-reported behavioral determinants (p&#xa0;<&#xa0;0.0001). Physical activity type and intensity changed (p&#xa0;<&#xa0;0.05). These findings support NutriSOS&#xae; as a feasible and acceptable tool, while highlighting areas for refinement, particularly those related to the time and effort required for data entry, prior to its implementation in the NutriSOS&#xae; RCT, in which its effectiveness will be formally evaluated.

Humans

Sustained cognitive and functional effects of pro-cognitive interventions for bipolar disorder: A systematic review of randomised controlled trials.

A substantial proportion of individuals with bipolar disorder (BD) experience considerable cognitive deficits. Existing systematic reviews have evaluated the efficacy of pro-cognitive interventions in BD, but have not established whether any cognitive benefits translate into functional improvements, with evidence for sustained functional effects remaining limited. A systematic search was conducted on MEDLINE, EMBASE, PsycINFO and Cochrane Library from inception until 21 May 2026. Eligible studies were randomised controlled trials (RCTs) in BD reporting cognitive or functional outcomes at three or more months following a pro-cognitive intervention, or examining the translation of cognitive benefits into improvements in functional outcomes at any timepoint. Seven unique RCTs plus three secondary analyses of these trials (n&#xa0;=&#xa0;615) met the inclusion criteria. Approximately 13% (7/55) of RCTs identified in the search of pro-cognitive interventions in adult BD assessed cognitive or functional outcomes at least 3&#xa0;months after treatment end. Of the seven unique RCTs, most evaluated cognitive remediation (CR; k&#xa0;=&#xa0;4). The average follow-up length was 4&#xa0;months (range: 3-6&#xa0;months). Three of the four RCTs examining CR reported cognitive benefits at 3 to 6&#xa0;months, whereas only one CR RCT found consistent functional effects at 3&#xa0;months. Evidence on the translation of cognitive benefits to functional improvements is scarce and inconsistent. Most trials examining pro-cognitive interventions do not examine whether potential benefits are sustained or whether they translate into improvements in real-world functioning. CR appears to be a promising intervention for achieving durable cognitive gains in BD, although evidence for sustained effects of other interventions is limited.

Humans

Sex Differences in Postoperative Recovery and Mortality After High-Risk Cardiac Surgery: A Propensity Score-Matched Post Hoc Analysis of the SUSTAIN-CSX Trial.

BACKGROUND: Sex-related differences after cardiac surgery remain controversial because women often present with higher baseline risk and complexity than men. We performed a post hoc propensity score-matched analysis of the SUSTAIN-CSX (Sodium Selenite Administration in Cardiac Surgery) trial to evaluate sex differences in mortality, postoperative complications, and recovery after high-risk cardiac surgery. METHODS: Of 1394 trial participants, 1386 had complete data. Women were matched 1:1 to men using nearest-neighbor propensity score matching based on age and European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), with exact matching on surgical category, yielding 327 female-male pairs. Prespecified sensitivity analyses adjusted for frailty, baseline hemoglobin, renal disease, left ventricular ejection fraction, previous myocardial infarction, preoperative medications, and baseline creatinine. RESULTS: In the primary matched analysis, 180-day survival did not differ between women and men (log-rank P=0.086; unadjusted hazard ratio, 1.80 [95% CI, 0.91-3.55]; P=0.091). In descriptive matched comparisons, women had numerically longer intensive care unit stay (median, 3&#x2009;days [quartile 1, quartile 3 (Q1, Q3)=1, 6&#x2009;days] versus 2&#x2009;days [Q1, Q3=1, 5&#x2009;days]) and hospital stay (median, 10&#x2009;days [Q1, Q3=7, 18&#x2009;days] versus 9&#x2009;days [Q1, Q3=6, 16&#x2009;days]; P=0.292), whereas major postoperative complications were similar. In adjusted sensitivity analyses accounting for the matched design and residual imbalance, female sex remained associated with longer intensive care unit stay (adjusted incidence rate ratio [IRR], 1.8 [95% CI, 1.2-2.9]; P=0.009) and hospital stay (adjusted IRR, 1.4 [95% CI, 1.0-1.9]; P=0.031). Mortality sensitivity analyses were model-dependent. CONCLUSIONS: In this propensity score-matched cohort of high-risk cardiac surgery patients, women showed a longer postoperative recovery trajectory in adjusted analyses, whereas mortality findings were sensitive to model specification and should be interpreted cautiously. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002247.

Aged

Sustained effects of auricular point acupressure on chemotherapy-induced neuropathy: a randomized controlled trial follow-up study.

PURPOSE: Chemotherapy-induced neuropathy (CIN) is a persistent condition that impairs function and quality of life. Auricular point acupressure (APA) has shown short-term benefit for CIN, but the durability of these effects after treatment completion is unknown. This study evaluated the sustainability of symptom improvements for 3&#xa0;months following a 4-week APA intervention. METHODS: This prespecified secondary analysis of a randomized wait-list controlled trial compared mobile-supported APA (mAPA) and virtual APA (vAPA) in adults with moderate or greater CIN who received APA during the initial treatment phase (mAPA, n&#x2009;=&#x2009;80; vAPA, n&#x2009;=&#x2009;75). Outcomes at 1, 2, and 3&#xa0;months post-intervention were analyzed using generalized estimating equations with multiple imputation. The primary outcome was CIN severity, measured with an individualized composite outcome (ICO); the secondary outcome was CIN interference. RESULTS: Reductions in CIN severity and interference were maintained throughout follow-up in both groups (all p&#x2009;<&#x2009;.001). ICO scores decreased by 3.10, 3.36, and 3.61 points in mAPA and by 2.88, 2.90, and 3.21 points in vAPA at 1, 2, and 3&#xa0;months, respectively. Benefits were maintained post-treatment, with higher retention in the mAPA group. CONCLUSIONS: Improvements in CIN severity and interference after APA were sustained for up to 3&#xa0;months post-treatment, suggesting a durable benefit as a self-management strategy. Larger studies with longer follow-up and untreated comparison groups are needed. IMPLICATIONS FOR CANCER SURVIVORS: APA may offer survivors a durable, self-administered, nonpharmacologic option for managing CIN well beyond active treatment, without requiring ongoing clinical visits. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT04920097 registered on 3 June 2021.

Acupressure

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5&#x2009;min). Salivary chromogranin A and &#x3b1;-amylase were measured at baseline and 1&#x2009;min post-task. Only VA% and chromogranin A showed significant condition &#xd7; time interactions (p&#x2009;=&#x2009;0.027-0.039). VA% significantly decreased from before to immediately after the task and 1&#x2009;min post-task in both conditions (p&#x2009;&#x2264;&#x2009;0.002), with significantly higher values in the CP condition than in placebo immediately after and 1&#x2009;min post-task (p&#x2009;&#x2264;&#x2009;0.037). Chromogranin A significantly increased from baseline to 1&#x2009;min post-task in the placebo condition (p&#x2009;<&#x2009;0.001) but not in the CP condition (p&#x2009;=&#x2009;0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans