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The musculoskeletal pain literacy questionnaire (MSK-PLq) - Part 1: Development of a preliminary version through a systematic review and Delphi consensus.

OBJECTIVE: Chronic musculoskeletal (MSK) pain is a leading cause of disability worldwide, and self-management is a first-line approach recommended by international clinical guidelines. Access to evidence-based information that enhances health literacy may support patients' engagement in their self-management and treatment decision-making, potentially reducing disease burden and pain. However, no tool currently exists to assess health literacy specifically in MSK pain. This study aimed to develop and describe the preliminary version of a knowledge-based questionnaire to evaluate MSK pain literacy, the Musculoskeletal Pain-Literacy questionnaire (MSK-PLq). METHODS: A systematic literature review identified existing health literacy instruments and generated a preliminary list of domains. A two-round Delphi study with 22 panellists (19 experts and three people living with chronic MSK pain), followed by consensus meetings, was used to refine domains and items (≥70% agreement). Readability was assessed using the Flesch Reading Ease (FRE) score and three stakeholders were consulted to review the questionnaire for comprehensibility, clarity, and face validity. RESULTS: Six domains were retained (Understand, Access, Appraise, Apply, Digital, Beliefs), comprising 20 items in the preliminary version of MSK-PLq. Readability was acceptable (mean FRE 74, indicating fairly easy reading), and subject feedback supported the questionnaire's clarity and face validity. CONCLUSIONS: The preliminary version of the MSK-PLq is proposed as the first knowledge-based tool to assess functional, interactive, and critical aspects of MSK pain literacy. It may have applications in clinical practice, research, education, and digital health, by informing tailored patient education and supporting self-management strategies, although further psychometric validation is required.

Humans

Climate and soil shape Daqu wheat quality and seed microbiome via rhizosphere taxa and microbial assembly.

The grain quality and seed microbiome of Daqu wheat are fundamental determinants of Daqu fermentation performance; however, the mechanisms by which cultivation environments influence these traits via rhizosphere microbial communities remain unclear. Bacterial and fungal communities across the bulk soil-rhizosphere-seed continuum of three wheat cultivars grown in four ecoregions were characterized using absolute quantitative amplicon sequencing. The rhizosphere microbiome was treated as a central intermediary, while the response variables were seed microbial diversity and grain-quality traits, including starch content, protein content, and grain hardness. Twelve physicochemical properties of soil and 11 climatic factors were integrated into a multidimensional association framework. Environmental conditions exerted stronger influences on both seed quality traits and microbial diversity than cultivar identity. Distinct regional signatures were also evident in rhizosphere microbiomes, with environmental gradients explaining community variation more effectively than geographic distance. Bacterial communities exhibited greater sensitivity to environmental fluctuations than fungi. Mantel analyses identified available nitrogen, precipitation, and atmospheric pressure as significant drivers of core rhizosphere taxa (P&#xa0;<&#xa0;0.05). iCAMP revealed that stochastic processes predominantly governed rhizosphere bacterial assembly, whereas stochastic and deterministic mechanisms jointly shaped fungal assembly. Partial least squares path modeling further uncovered a rhizosphere-mediated environment-seed cascade, wherein sunlight intensity and duration, atmospheric pressure, and soil nitrogen directly or indirectly affected seed wet gluten content, grain hardness, and seed microbial diversity through their influences on rhizosphere microbiota. Rhizosphere bacterial diversity was negatively associated with seed bacterial diversity (path coefficient&#xa0;=&#xa0;-0.118, P&#xa0;<&#xa0;0.05), indicating that rhizosphere communities may shape seed endophytic bacterial assemblages via environmental filtering and competitive interactions. Collectively, these findings elucidate how environments shape the quality and seed microbiomes of Daqu wheat, providing scientific guidance for optimal site selection and the standardized production of high-quality brewing wheat for industrial Baijiu.

Triticum

Pegcetacoplan Delivers Real-World Therapeutic Benefits and Reduces Disease Burden for Patients With Paroxysmal Nocturnal Haemoglobinuria: A Systematic Literature Review of Pegcetacoplan Real-World Clinical and Patient-Reported Outcomes.

AIMS: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired, non-malignant haematological disorder that, if left untreated, can lead to significant morbidity. This systematic literature review (SLR) summarized real-world evidence (RWE) for pegcetacoplan, a complement 3/3b inhibitor (C3i) available since 2021. METHODS: The SLR (PROSPERO-CRD420251043506) followed 2020 PRISMA guidelines and included RW studies of pegcetacoplan (n&#x2009;>&#x2009;1 pts.; English; to April 2025) in adults (age&#x2009;&#x2265;&#x2009;18&#x2009;years) with PNH. RESULTS: Of 409 identified records, 39 qualified, representing 12 distinct studies. Six studies (n&#x2009;=&#x2009;4-39) reported median haemoglobin (Hb) with baseline 8.1-9.6&#x2009;g/dL. Ending median Hb and maximum pegcetacoplan durations were: 12.0&#x2009;g/dL at 12&#x2009;months, 11.1-12.1&#x2009;g/dL at 6&#x2009;months (3 studies), and 11.1&#x2009;g/dL at 3&#x2009;months (1 study). In 4 other studies (n&#x2009;=&#x2009;48-70), ending mean Hb (maximum pegcetacoplan duration) was: 11.3&#x2009;g/dL (7.2&#x2009;months), 11.5&#x2009;g/dL (6.6&#x2009;months), 11.5&#x2009;g/dL (5.9&#x2009;months), and 11.58&#x2009;g/dL (3&#x2009;months). Six studies reported reduced absolute reticulocyte count (ARC; n&#x2009;=&#x2009;4-39) from baseline median 155-301&#x2009;&#xd7;&#x2009;109/L to median 56-106&#x2009;&#xd7;&#x2009;109/L from 14&#x2009;days of pegcetacoplan, maintained to maximum pegcetacoplan of 1-12&#x2009;months. Three studies reported lactate dehydrogenase (LDH; n&#x2009;=&#x2009;4-62); all showed reductions from baseline median 543.0 to 161.7&#x2009;U/L after 3&#x2009;months, and baseline median 299.5-316.0&#x2009;U/L to 193.5-187.0&#x2009;U/L after 6&#x2009;months of pegcetacoplan. In complement 5 inhibitor-na&#xef;ve, LDH reduced from 977.8 to 358.9&#x2009;U/L after 8.4&#x2009;months, and 503.6 to 292.5&#x2009;U/L in C5i-experienced after 7.2&#x2009;months. Three studies (n&#x2009;=&#x2009;4-63) reported reduced LDH from above the upper limit of normal levels. Six studies (n&#x2009;=&#x2009;23-70) reported reduced red blood cell transfusions (RBCt) after maximum pegcetacoplan durations of up to 12&#x2009;months, and median durations of 3.0 and 10.2&#x2009;months. Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale scores in 1 study increased from baseline (mean 28.4) to 38.6 at 3&#x2009;months, 36.3 at 6&#x2009;months, and 34.9 at 9&#x2009;months of pegcetacoplan treatment. Two studies reported FACIT-Fatigue scores of 34.6-40.1 with pegcetacoplan for &#x2265;&#x2009;1&#x2009;month. EQ-5D mean utility scores (0.85-0.94) in 2 studies were comparable to population normative values. On the Short-Form 36 Health Survey, mental and physical component scores were slightly lower than US normative values. CONCLUSIONS: RWE indicates pegcetacoplan is associated with improved haematological outcomes, reduced RBCt dependence and fatigue, and enhanced HRQoL. These findings from real-world studies with diverse cohorts support generalizability and are broadly comparable with clinical trial evidence.

Humans

Comparison of short-term clinical outcomes and patient satisfaction between intraoral scanning and conventional impressions for complete-arch implant prostheses: a pilot RCT.

OBJECTIVE: To compare framework passive fit, subjective evaluations, and short-term clinical outcomes between conventional impressions (CI) and intraoral scanning (IOS) for complete-arch implant-supported fixed dental prostheses (CIFDPs). METHODS: In this randomized controlled trial, 22 patients were allocated to the CI or IOS groups. All participants received a definitive one-piece CIFDP. The primary outcome was framework passive fit, assessed using the Vision and Tactile Score (V&T score), which included framework lift-off, the single-screw test, the full-screw test, smoothness of screw insertion, and radiographic gap assessment. Secondary outcomes included operator evaluation, patient satisfaction using a visual analog scale (VAS), early implant survival, marginal bone loss (MBL), modified Plaque Index (mPII), and complications at the 6-month follow-up. RESULTS: Twenty-two patients were enrolled (CI: n = 11; IOS: n = 11), and one patient in the CI group was lost to follow-up. No statistically significant difference in the V&T score was observed between the CI and IOS groups (4.66 &#xb1; 0.17 vs. 4.65 &#xb1; 0.28; P = 0.93). The operator reported greater nervousness during the CI procedure than during IOS (21.82 &#xb1; 15.69 vs. 8.64 &#xb1; 7.47; P < 0.05). Patients in the CI group reported significantly greater discomfort, including nausea and anxiety, than those in the IOS group (P < 0.05). At the 6-month follow-up, the early implant survival rate was 100% in both groups. No significant differences were found between the groups in MBL (0.09 &#xb1; 0.09 vs. 0.06 &#xb1; 0.10 mm; P = 0.43) or mPII (0.10 &#xb1; 0.12 vs. 0.10 &#xb1; 0.28; P = 0.99). CONCLUSION: IOS and CI achieved comparable short-term clinical outcomes in patients who met the predefined inclusion criteria, including controlled implant number, spacing, and angulation. IOS provided a more favorable experience for both operators and patients. CLINICAL SIGNIFICANCE: In complete-arch implant restorations, intraoral scanning may provide clinical outcomes comparable to those of conventional impressions while improving patient comfort.

Humans

Clinical performance of two lithium disilicate CAD/CAM materials in posterior Class II inlay restorations: A 48-month randomised split-mouth clinical trial.

OBJECTIVES: To compare the clinical performance of Amber Mill (AM) and IPS e.max CAD (EM) lithium disilicate computer-aided design/computer-aided manufacturing (CAD/CAM) materials in posterior Class II inlay restorations and characterise their baseline properties. METHODS: Thirty-four adults received paired AM and EM posterior Class II inlays (68 restorations) in a triple-blind randomised split-mouth trial followed for 48 months. Restorations were evaluated at baseline and annually using revised World Dental Federation (FDI) criteria, with fracture and retention as the primary endpoint. Baseline characterisation included flexural strength, shear bond strength, translucency parameter, and scanning electron microscopy. McNemar, Wilcoxon signed-rank, Friedman, one-way analysis of variance, Tukey post hoc, and inter-rater agreement analyses were used. RESULTS: At 48 months, 18 paired participants were available for primary analysis. Failures occurred in 2 of 18 AM restorations and in 3 of 18 EM restorations, corresponding to success rates of 88.9% and 83.3%, respectively, with no significant between-material difference (McNemar p = 1.000). No catastrophic bulk ceramic fracture was observed. Secondary FDI scores remained mostly within the clinically acceptable range; marginal staining deteriorated over time in both groups (p < .001) without significant between-material differences. Baseline material testing showed significant material- and translucency-dependent differences in flexural strength, shear bond strength, and translucency. CONCLUSIONS: Within the limitations of the 48-month follow-up and the tested Class II inlay indication, AM showed clinical performance comparable to EM. Observed clinical complications were related to retention or marginal/interface behaviour. CLINICAL SIGNIFICANCE: For posterior Class II lithium disilicate CAD/CAM inlays, medium-term complications were mainly retention/interface-related, suggesting adhesive-interface durability may be as important as baseline ceramic strength.

Humans

Beyond Glycaemia: Fear of Hypoglycaemia, Cognition and Functional Mobility After Advanced Hybrid Closed-Loop Therapy in Older Adults With Type 1 Diabetes: A Prespecified Secondary Analysis of a Randomised, Single-Centre Study.

BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged &#x2265;&#x2009;65&#x2009;years with T1D. METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged &#x2265;&#x2009;65&#x2009;years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes. RESULTS: Thirty-one participants were randomised and 29 completed 12&#x2009;months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p&#x2009;=&#x2009;0.008), although this finding did not remain statistically significant after Holm correction (adjusted p&#x2009;=&#x2009;0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p&#x2009;=&#x2009;0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6&#x2009;m; 95% CI: 36.8 to 148.3; p&#x2009;=&#x2009;0.002) and Timed Up and Go performance (-2.27&#x2009;s; 95% CI: -4.28 to -0.27; p&#x2009;=&#x2009;0.028), but not for gait speed (0.27&#x2009;m/s; 95% CI: -0.05 to 0.59; p&#x2009;=&#x2009;0.099). At 12&#x2009;months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up. CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12&#x2009;months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.

Humans

Evaluating Patient Satisfaction and Oral Health Impact Profile-14 (OHIP-14): A Multicenter Crossover Study Comparing Selective Pressure Impression Conventional Dentures with Mucostatic Digital Dentures.

PURPOSE: To compare patient satisfaction and oral health impact between individuals receiving complete dentures made by digital methods and those using conventional techniques. MATERIALS AND METHODS: In this randomized crossover clinical trial, 23 patients aged 40 years and older with completely edentulous arches were enrolled at three treatment centers. Each participant received two sets of complete dentures: one set created using conventional methods (selective pressure impression) and the other through digital techniques (mucostatic digital impression). The order of denture placement was randomized, with each set used for 4 weeks. A trained specialist administered treatments alongside research tools, including a general information questionnaire, a denture satisfaction survey, and the OHIP-14 interview tool. Statistical analysis was conducted using Mann-Whitney U test. RESULTS: Participants with digital dentures reported significantly higher satisfaction regarding treatment duration, comfort, confidence, chewing ability, esthetics, and overall satisfaction compared to those with conventional dentures. There were no significant differences in satisfaction concerning speech and pronunciation. Overall, the oral health impact on quality of life was similar between denture types, but participants indicated improved quality of life while using dentures compared to being edentulous. CONCLUSIONS: Patients with digital dentures exhibited greater satisfaction across various domains compared to those with conventional dentures, despite similar satisfaction levels in speech and pronunciation. The impact on quality of life was comparable between both types, as measured by the OHIP-14.

Humans

Stapled versus hand-sewn intestinal anastomosis in pediatric surgery: A systematic review and meta-analysis.

BACKGROUND: Intestinal anastomosis is a core procedure in pediatric gastrointestinal surgery, performed for conditions such as necrotizing enterocolitis, intestinal atresia, Hirschsprung's disease, and inflammatory bowel disease. Although stapled anastomosis (SA) may improve operative efficiency, its safety and effectiveness compared with hand-sewn anastomosis (HA) in children remain uncertain. This meta-analysis compared clinical outcomes of SA and HA in pediatric patients. METHODS: The study followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251177257). A systematic search of PubMed, Dimensions, and the Cochrane Library was conducted through June 2025. Studies including children under 7 years undergoing intestinal SA or HA were eligible. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using ROB 2 and ROBINS-I tools. Statistical analysis was conducted using Comprehensive Meta-Analysis software (v3) with a random-effects model. RESULTS: Eleven studies involving 903 patients met inclusion criteria, including two randomized controlled trials. Of these, 333 patients underwent SA and 570 underwent HA. SA was associated with significantly shorter operative time (mean difference [MD] = -19.26 min; 95% CI: -24.24 to -14.28; p < 0.001) and earlier initiation of oral feeding (MD = -2.32 days; 95% CI: -3.78 to -0.86; p = 0.002). No significant differences were found in anastomotic leakage, stricture formation, reoperation rate, or length of hospital stay. CONCLUSIONS: Stapled anastomosis appears as safe as hand-sewn techniques in pediatric intestinal surgery while offering shorter operative duration and faster postoperative feeding recovery. Selective use of stapled techniques is supported when anatomically feasible, though further multicenter randomized trials are needed.

Humans

MicroRNAs in Oral Bio-Fluids as Predictive Biomarkers of Orthodontic Tooth Movement: A Systematic Review.

This systematic review was designed to assess scientific evidence of the association of microRNA expression during orthodontic tooth movement through various time points. A systematic review was performed in accordance with the PRISMA checklist. A search strategy was developed in electronic databases including Med Line, Scopus, EBSCO Host and ProQuest Dissertations & Theses Global until June 2025. Eligibility criteria included studies that investigated microRNA expression in saliva/GCF during orthodontic treatment. The risk of bias of the included studies was analysed using the QUADAS-2 and RoB-2 tools. The search retrieved 2800 records, of which nine studies were selected. Minor variations in GCF collection were noted, while stimulated saliva was collected in one study. RT-PCR and the Fluro meter accounted for the majority of miRNA estimation. Thirteen miRNAs were identified as target biomarkers for OTM regulation. Despite the high risk of bias, the evidence from the current systematic review indicates that microRNAs can be considered as potential biomarkers of orthodontic tooth movement in oral biofluids. Trial Registration: Prospero ID-CRD420251153064.

Humans

Interfacial engineering of cobalt tungstate-halloysite nanotube nanocomposite for electrochemical detection of synthetic vanillin in food matrices.

In processed foods and medicine, synthetic vanillin is widely used, although excessive intake poses toxicological risks. Due to the rising usage of synthetic vanillin in food products and associated health hazards, quick, sensitive, and reliable analytical methods are needed to precisely measure vanillin in complex food matrices. This work introduces a CoWO4@F-HNT/GCE nanocomposite as an efficient electrocatalytic modifier for glassy carbon electrodes aimed at trace-level synthetic vanillin detection. Structural and microscopic analyses confirmed phase-pure monoclinic CoWO4, preservation of the tubular aluminosilicate framework, and homogeneous nanoparticle anchoring on F-HNT. Differential pulse voltammetry provided a broad linear range from 0.01 to 372.14&#xa0;&#x3bc;M and a low detection limit of 4.3&#xa0;nM, together with excellent selectivity against common interferents, good cycling stability, and high inter-electrode reproducibility. These characteristics position the CoWO4@F-HNT-modified electrode as a cost-effective and reliable platform for on-site quality control of synthetic vanillin in complex food matrices.

Benzaldehydes

Morphology-engineered NiFe@C nanocages boosting electrochemical quantification of ractopamine in meat samples.

It is essential to acquire efficient electrocatalysts to develop ractopamine (RAC) electrochemical sensors. Herein, we report the synthesis of a series of carbon coated NiFe alloy nanostructures (e.g., NiFe@C nanoparticles, nanocubes and nanocages) using NiFe Prussian blue analogue (PBA) as the precursor. The NiFe@C nanocages exhibited the best electrocatalytic performance for RAC sensing. This is attributed to the embedded NiFe alloy nanoparticles that provide abundant active sites, and the unique nanocage structure facilitates electron transfer pathways while offering a high specific surface area. The resulting sensor achieves a low detection limit (LOD) of 54&#xa0;nM (S/N&#xa0;=&#xa0;3) within a linear range of 0.2-12&#xa0;&#x3bc;M. Moreover, the sensor demonstrates good reproducibility, stability, and excellent long-term stability. Practical applicability was confirmed in meat samples, yielding satisfactory recovery rates ranging from 98% to 108%. A feasible strategy was introduced herein for rational design of metal@carbon electrocatalysts.

Phenethylamines

Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584&#xa0;mM (OXD) and 0.1498&#xa0;mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10&#xa0;ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines

Metal-organic frameworks nanozyme-integrated portable microneedle patch for visual bacterial monitoring in meat.

Foodborne microbial contamination is a major global health concern, with conventional methods often being time-consuming and complex. Herein, we developed a novel portable biosensor by integrating microneedle patch technology and a metal-organic framework (Fe/Cu-NBDC MOF) nanozyme, enabling rapid, on-site, visual detection of bacteria in meat. The sensing system works by encapsulating aptamer-functionalized MOF nanozymes within a hydrogel patch, where their catalytic sites are initially blocked by the aptamer. In the presence of Staphylococcus aureus (S. aureus) as the target, the specific aptamer's binding to bacteria exposes numerous catalytic sites, further activating the chromogenic reaction of the tetramethylbenzidine&#x2011;hydrogen peroxide (TMB-H&#x2082;O&#x2082;) system, enabling visual detection of S. aureus. The biosensor demonstrates a detection limit of 82&#xa0;CFU/mL with excellent specificity to successfully apply to commercial mutton. By integrating sampling, enrichment, and visual detection into a single compact device, this platform offers a practical, efficient solution for rapid on-site screening of foodborne pathogens.

Biosensing Techniques

Preoperative intramuscular testosterone and urethrocutaneous fistula formation after primary hypospadias repair.

INTRODUCTION: Preoperative androgen stimulation is widely used before hypospadias repair to increase penile dimensions and optimise surgical conditions. However, its impact on postoperative complications, particularly urethrocutaneous fistula formation, remains controversial. OBJECTIVE: To evaluate the association between preoperative intramuscular testosterone therapy and urethrocutaneous fistula formation in children undergoing primary hypospadias repair. STUDY DESIGN: This was a retrospective comparative analysis of prospectively collected clinical data from 111 boys undergoing primary hypospadias repair at a single tertiary pediatric urology center. Patients were divided into two groups: those who did not receive hormonal therapy (Group 1, n = 55) and those who received intramuscular testosterone enanthate (2 mg/kg administered 5 and 2 weeks before surgery; Group 2, n = 56). Preoperative penile measurements, operative characteristics, and postoperative complications were compared. The primary outcome was urethrocutaneous fistula formation. The mean follow-up duration was 11.9 months (median 7 months). RESULTS: Preoperative testosterone therapy was associated with significant increases in glans diameter and stretched penile length at the time of surgery. The hormone-treated group had a significantly higher proportion of proximal hypospadias (p = 0.001), underwent more complex urethroplasty procedures, and had longer operative times (p = 0.007). Postoperative edema and local inflammatory changes were more frequently observed in the hormone-treated group. Despite these differences, urethrocutaneous fistula occurred in four patients in each group (7.3% vs 7.1%, p = 0.357), with no statistically significant difference between groups. DISCUSSION: Despite greater baseline anatomical severity and operative complexity in the hormone-treated group, preoperative testosterone administration was not associated with an increased risk of urethrocutaneous fistula. These findings suggest that improved tissue bulk and vascularity may offset the potential adverse effects of transient inflammatory changes. CONCLUSION: Selective preoperative intramuscular testosterone therapy was not associated with increased urethrocutaneous fistula risk and may be considered a reasonable adjunct in appropriately selected patients undergoing primary hypospadias repair. CLINICAL/TRANSLATIONAL APPLICABILITY: These findings provide clinical reassurance that preoperative testosterone can be used selectively in patients with smaller penile dimensions or anticipated technical difficulty without increasing fistula risk, thereby supporting shared decision-making in clinical practice.

Humans

The present and future of nonviral delivery-based genome editing for hereditary hearing loss.

PURPOSE OF REVIEW: This review summarizes nonviral genome-editing delivery platforms for hereditary hearing loss, focusing on lipid nanoparticles (LNPs) and engineered virus-like particles (eVLPs), and discusses their advantages over adeno-associated virus-based delivery, as well as the barriers to clinical translation. RECENT FINDINGS: Recent advances have established LNPs as a clinically advanced nonviral platform, although challenges related to inner ear biodistribution, cell type specificity, endosomal escape, and immunogenicity remain to be addressed. In parallel, eVLPs have undergone substantial technical evolution, progressing from early low efficiency systems to advanced base editor- and prime editor-eVLP architectures that enhance cargo loading and editing efficiency. Extracellular vesicle-based genome editing has also emerged as an additional platform, although issues related to reproducibility, loading efficiency, and scalability remain major hurdles. SUMMARY: Nonviral genome editing platforms expand the therapeutic toolkit for hereditary hearing loss by enabling transient delivery of genome editors with potential safety advantages. Future efforts should focus on characterizing biodistribution and immunogenicity, refining cell type-specific tropism, and establishing scalable manufacturing processes to enable successful clinical translation.

Humans

PdIr bimetallic nanozyme engineered metal-organic frameworks integrated dual-mode sensor toward Stx2 detection in food.

Shiga toxin II (Stx2) has attracted extensive attention due to its toxicity and pathogenicity, making the development of sensitive detection methods urgent. This study constructed a dual-mode sensing platform for the sensitive detection of Stx2 in food. Composite material UIO-66@PdIr with peroxidase-like activity and fluorescent properties was synthesized and combined with cDNA as the signal probe, while aptamer-modified magnetic beads served as the capture probe. Specific binding of Stx2 to the aptamer triggered the release of the signal probe, enabling colorimetric and fluorescence signal readout. The colorimetric mode showed a linear range of 0.05-100&#xa0;ng/mL with an LOD of 0.039&#xa0;ng/mL, and the fluorescence mode exhibited 0.01-1000&#xa0;ng/mL with an LOD of 0.0097&#xa0;ng/mL. Additionally, this method was successfully applied to the detection of Stx2 in food, and the recovery rates were 94.33%&#xa0;&#x223c;&#xa0;102.20%. It indicated that the constructed sensor holds great practical potential for Stx2 detection.

Food Contamination

A MIL-88@Ru-based molecularly imprinted electrochemiluminescence sensor for highly selective and sensitive detection of enrofloxacin residues in animal-derived foods.

Using a metal-organic framework (MOF) - supported Ru(bpy)32+ (MIL-88@Ru) composite luminescent material, this study innovatively adopted electropolymerization to fabricate a molecularly imprinted polymer-based electrochemiluminescent (MIP-ECL) sensor for enrofloxacin (ENR) detection in animal-derived foods. Systematic investigation of the ECL luminescence and ENR's quenching mechanism confirmed that the sensor integrates ECL's high sensitivity and MIP's high specificity, enabling rapid and accurate recognition of ENR. Experimental results show a good linear response in the range of 1&#xa0;nmol/L-20&#xa0;&#x3bc;mol/L (R2&#xa0;=&#xa0;0.99), a limit of detection (LOD) as low as 0.28&#xa0;nmol/L, as well as excellent selectivity and stability. Recoveries of ENR in all investigated matrices ranged from 97.7% to 106.4%, confirming the reliability of the established method. This ECL-MIP coupling strategy provides a new technical approach and application references for the efficient detection of trace pollutants in food safety and environmental monitoring fields.

Enrofloxacin

CAR-T Cell Therapy: Manufacturing Platforms and Clinical Consequences.

Chimeric antigen receptor (CAR) T-cell therapy has transformed hematological cancer care, yet variability in efficacy, durability, and safety cannot be explained solely by antigen selection or patient factors. We propose that manufacturing platforms are active biological determinants of outcome. Viral vectors, used in all licensed products, provide stable genomic integration and durable expression but are limited by cost, cargo capacity, and centralized production. Nonviral strategies, including transposons, CRISPR knock-ins, and messenger RNA delivery, enable faster, less-expensive manufacturing with larger payloads, while introducing distinct safety and persistence profiles. This review presents a three-layer mechanistic framework that reframes manufacturing as biology: integration biology determines genomic risk and transgene stability; clonal fitness shapes persistence, dominance, and exhaustion; and epigenomic imprinting, influenced by gene transfer method, cytokines, and culture stress, preconfigures functional trajectories. Clinical observations link platform choice to immune recovery, where prolonged B-cell aplasia and delayed T-cell reconstitution contribute to infection-related nonrelapse mortality, and hematopoietic reserve at apheresis emerges as a practical predictor. Finally, manufacturing is positioned as the key to democratizing cell therapy. Decentralized, nonviral production aligned with regulatory standards may enable equitable access and transition CAR-T therapy from innovation to sustainable global care.

Humans