搜索结果：Research synthesis methods

Diabetic peripheral neuropathy (DPN) is a common and disabling condition for which no disease-modifying therapies are available. Glycemic and metabolic drivers do not fully explain why only a subset of individuals with diabetes develop DPN, and genetic contributors remain poorly defined. We aimed to perform a multi-population genome-wide association study (GWAS) of DPN to highlight potential new etiological pathways and therapeutic targets. We performed a multi-population GWAS of neuropathy in people with and without diabetes using the VA Million Veteran Program and UK Biobank, followed by replication in the All of Us Research Program (AoU), and gene-based and gene-set analyses to identify implicated pathways. Causal relationships between circulating serine levels and DPN were further tested using two-sample Mendelian randomization. To further evaluate pathogenic potential, we analyzed rare, high-impact variants in GWAS-implicated genes among individuals with unresolved inherited neuropathies using the GENESIS platform. Among individuals with type 2 diabetes, we identified seven genome-wide significant loci (p<5&#xd7;10 -8 ): PHGDH and PSPH (key serine-synthesis genes), TEAD1, CYP4F11, LARGE1, FTO , and COBLL1 . No loci were significant in individuals without diabetes or with type 1 diabetes. Four loci ( PHGDH, TEAD1, FTO and CYP4F11) replicated in AoU ( p <0.05). Mendelian randomization demonstrated that higher genetically predicted serine levels were associated with lower DPN risk, consistent with a causal role of serine metabolism in disease pathogenesis. Rare-variant burden analyses revealed associations of predicted deleterious variants with inherited neuropathy case status in PHGDH (odds ratio [OR] 12.7 [95% CI 7.9, 20.4]), PSPH (OR 8.5 [7.2, 10.2]), PHKG1 (OR 4.8 [3.7, 6.3]), and LARGE1 (OR 0.007 [0.0004, 0.1]). Convergent genetic evidence across common and rare variation implicates serine synthesis as a key pathway in DPN. These findings link diabetic and inherited neuropathies through a shared metabolic mechanism, identifying serine metabolism as a potential therapeutic target. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by MVP000 and by awards MVP009/MVP037 I01-BX005831 and MVP051. S.R. is supported by VA award I01-BX006417. V.F. is supported by NIH award 1K23DK118202-01A1, S.Z. is supported by the CMT Association, CMT Research Foundation, All of US Research Program (3OT2OD037907), and NIH (1R21HG013397, 5R01NS072248). J.E.B.R. is supported by VA awards BX002046, CX001532, the CU Diabetes Research Center award DK11607, and the Ludeman Center. L.S.P. is supported in part by VA awards CSP #2008, I01 CX001899, I01 CX001737, and I01 BX005831; NIH awards R01 DK127083, R03 AI133172, R21 AI156161, U01 DK098246, UL1 TR002378; and a Cystic Fibrosis Foundation award PHILLI12A0. L.VdV. was supported by the Peripheral Nerve Society Laura Feltri Basic Research Fellowship.

As a significant representative of monoterpenoid indole alkaloids (MIAs) and 1,1-disubstituted tetrahydro-&#x3b2;-carboline (TH&#x3b2;C) alkaloids, Arborisidine, since its discovery in 2016 by Kam and coworkers, has emerged as a focal molecule in the field of total synthesis due to its unique pentacyclic cage-like skeleton and the quaternary carbon center at C(16). Multiple research groups have conducted in-depth investigations into its total synthesis and successfully developed novel synthetic strategies. These studies have not only advanced the total synthesis and structural modification of this class of MIA natural products but also provided scientific approaches for structure-activity relationship (SAR) studies. Furthermore, with the rapid advancement of synthetic biology, investigations into the biosynthetic pathways of these alkaloids have not only offered innovative synthetic strategies for chemical synthesis but also delivered precise tools for structure-directed modification, thereby significantly accelerating structure-based drug design (SBDD). Based on this background, this review summarizes the recent advances in the total synthesis and biosynthetic studies of arborisidine, aiming to provide scientific insights for the synthesis of other family members through comparative analysis of diverse synthetic strategies, as well as to offer methodological support for drug design based on this structural framework.

Research misconduct poses a significant threat to the integrity of evidence synthesis. Although Cochrane reviews are known for rigorous methodological standards, the potential inclusion of studies authored by researchers with substantial retractions records raises concerns about the reliability of their conclusions. This study aims to (a) quantify the extent to which Cochrane reviews include or cite papers authored by researchers with at least 24 retractions (as listed in the Retraction Watch Leaderboard),and (b) examine whether sensitivity analyses were performed and identify the stated reasons for excluding those studies from the reviews. The Retraction Watch database was used to identify researchers with 24 or more retractions in the database. This was done with custom code in Stata, created to identify individuals with&#x2009;>&#x2009;24 entries. Data on Cochrane's systematic reviews that included or referenced the studies by authors with 24 or more retraction records was collected. For reviews where these studies were excluded, the stated reasons for exclusion were recorded. We also assessed the frequency and nature of sensitivity analyses conducted to account for potential bias from problematic studies. Of 9,323 Cochrane Reviews, 81(0.9%)included or cited at least one potentially fraudulent study. 57(0.6%) of these reviews referenced and 32(0.3%) included such studies in meta-analyses. In cases where such studies were excluded, the justification was typically unrelated to trustworthiness. Of the 32 reviews that include potentially fraudulent studies, only a minority of reviews (19%, 6 out of 32) conducted sensitivity analyses after paper exclusions, primarily due to retracted papers, with only one analysis conducted in response to potential fraudulent studies. The inclusion or insufficient handling of studies by highly retracted researchers in Cochrane reviews without sensitivity analysis highlights the concerns regarding the integrity and reliability of evidence used to guide clinical practice. This study underscores the need for formal mechanisms to assess author trustworthiness, recommends transparency in handling these studies, and calls for sensitivity analyses to be mandatory.

The structure of N-linked glycans regulates protein folding, stability, conformation, and fundamental cellular functions. However, current biosynthesis methods yield heterogeneous glycoforms, and chemical total synthesis is prohibitively step-intensive, significantly hindering functional studies of glycan structure-function relationships, preventing detailed studies of the functions of N-glycans on proteins. To overcome these limitations, a novel, streamlined strategy for the direct single-step synthesis of glycoproteins with structurally defined N-glycans has been developed. This method utilizes visible-light-mediated photoredox catalysis in phosphate-buffered saline (PBS) to enable the straightforward addition of N-glycosyl carbamoyl radicals, generated from N-glycosyl-1,4-dihydropyridines (DHPs), to the dehydroalanine (Dha) double bond on proteins. Under mild conditions, this radical addition provides direct access to well-defined N-linked glycoproteins, such as small ubiquitin-related modifier 2 (SUMO2), phosphate-transport protein (PstS), interleukin-1 alpha (IL-1&#x3b1;), and &#x3b2;-lactoglobulin with two disulfide bonds. This streamlined approach promises accessible, well-defined glycoproteins for high-throughput structure-function studies.

Multiple long-term conditions (MLTC) represent a growing global public health challenge, yet research is hindered by inconsistent outcomes across health-care settings and populations. Although several core outcome sets (COS) have been developed, important gaps remain in their coverage, inclusivity, and measurement validity. This overview of reviews summarised outcomes reported in systematic reviews of MLTC research to identify existing domains, describe how measurement instruments were addressed, and highlight areas requiring standardisation. We conducted a prospectively registered overview of reviews (PROSPERO CRD420251005152), following PRISMA, PRIOR, and SWiM guidelines. Eligible reviews included adults or children with MLTC-defined as the coexistence of two or more chronic conditions-and reported on outcome measures or COS relevant to this population. Five databases (MEDLINE, CINAHL, Scopus, Cochrane Library, COMET (Core Outcome Measures in Effectiveness Trials)) were searched from inception to April 2025. Two reviewers independently screened, extracted data, and appraised quality using the Joanna Briggs Institute checklist. A narrative synthesis mapped outcomes by domain (clinical, patient-reported, service/system, engagement/experience), care setting, and population subgroup. From 6331 records, 10 reviews met inclusion criteria, encompassing 709 primary studies. Four developed COS, and six mapped outcomes without proposing COS. Quality of life and health-care utilisation were most consistently reported; treatment burden, patient engagement, and child outcomes were infrequently assessed. Existing COS advanced standardisation but remained limited in stakeholder diversity, geographic scope, and specification of measurement instruments, with only one including low- and middle-income countries. Greater inclusivity, validation, and global applicability are needed to operationalise agreed domains and improve comparability across MLTC research.

Open-access intensive care unit policies prioritize family integration. However, these guidelines may not fully account for the physical and psychological demands placed on surrogate decision-makers. Continuous, unregulated family presence is associated with physical exhaustion and cognitive fatigue. This burden may negatively affect the decisional capacity these policies intend to support. This study aimed to evaluate the evidence regarding the psychological burden on intensive care unit surrogates and to construct a resilience framework based on the Conservation of Resources theory. This systematic narrative synthesis (Resilience Ecosystem for Surrogate Titration, Overload Recovery, and Engagement) combined the methodological rigor of systematic identification, utilizing structured database searches, dual screening, and standardized quality appraisal, with narrative thematic analysis. A multi-database search (PubMed, Scopus, Web of Science) identified relevant literature published through February 2026. After quality appraisal, data from 35 articles were analyzed using thematic synthesis and mapped onto the Conservation of Resources framework. Findings suggest that current evaluation metrics often equate visitation duration with quality of care, which may not account for the physiological limits of surrogates. The synthesis identifies "Compulsive Hyper-engagement," a state of cognitive fatigue associated with continuous, unstructured visitation. To address this, the framework proposes the Clinical Titration of Family Presence, which uses structured rest periods ("Restorative Dosing") to regulate the intensity of family engagement. Furthermore, a Pan-Dimensional Matrix for Surrogate Resilience is introduced. This matrix categorizes protective interventions across five dimensions: physiological infrastructure, cognitive support, psycho-spiritual frameworks, social architecture, and technological connectivity. The synthesized evidence identifies a plausible risk that unrestricted intensive care unit visitation without structural support may contribute to surrogate exhaustion. To preserve decisional capacity, clinical practice may benefit from shifting toward actively structuring family resilience. Implementing the Clinical Titration of Presence suggests providing scheduled rest intervals. This approach aims to reduce surrogate guilt and support their role as capable partners in shared decision-making. Not applicable. (As a narrative synthesis, prospective registration is not required; however, an internal methodological protocol was followed).

Enzymatic polymer synthesis emerges as a sustainable alternative to chemical methods, operating under mild and environmentally benign conditions. Integrating enantioselective synthesis with polymerisation enables the use of nonpolymerisable and prochiral molecules as monomers for biodegradable plastics. Here, the scale-up of a biocatalytic asymmetric reduction of &#x3b2;-ketoesters into enantiomerically pure &#x3b2;-hydroxy esters is presented. These &#x3b2;-hydroxy esters are readily polymerised to macromolecular polyesters by lipases under bulk conditions. By pairing immobilised ketoreductases with immobilised lipases of compatible enantioselectivity, either R- or S-stereoregular poly(3-hydroxybutanoate) was obtained, achieving 30-40% monomer conversion and molecular weights around 650&#x202f;&#x202f;Da. The resulting stereoregular polymers have no detectable crystalline domains due to their low molecular weight. This approach expands sustainable routes to biodegradable materials and enables future development of continuous biocatalytic processes.

The clinician-patient relationship is a vital component of therapeutic success in disorders of gut-brain interaction (DGBI), recently codified as the foundational "Level 1" psychosocial care within the Rome V biopsychosocial framework. This systematic review aimed to identify evidence-based methods for building and maintaining effective clinician-patient relationships in adult DGBI care. Following the PRISMA 2020 and Synthesis Without Meta-analysis (SWiM) guidelines, we searched PubMed, Cochrane CENTRAL, and Ichushi Web for studies published through January 2026. Quality assessment was performed using AMSTAR 2 and RoB 2/ROBINS-I tools, facilitated by a human-AI collaborative verification process. Twelve studies (four systematic reviews and eight primary studies) were identified. Narrative synthesis revealed that "augmented encounters," characterized by empathy, warmth, and active listening improved clinical outcomes, including symptom severity and quality of life, particularly in irritable bowel syndrome. Strategic communication providing a confident positive diagnosis and psychoeducation regarding the gut-brain axis (rather than a diagnosis of exclusion) was found to be superior for enhancing treatment adherence in functional dyspepsia. Furthermore, multidisciplinary care models (spanning from provider-delivered self-management education to fully integrated Level 3 gastropsychology) and the use of non-deceptive placebos optimized the therapeutic context. The review also identified potential cultural moderators, hypothesizing that disease-centered reassurance might play a distinct role in certain East Asian clinical settings compared to Western contexts, though this warrants further investigation. This review structurally organized multiple relational tools, highlighting their fundamental role in DGBI management. Although current evidence is heterogeneous and partly relies on indirect findings, these promising supportive strategies conceptually align with Rome V psychosocial care. Further high-quality, direct clinical studies are needed to clarify which relational strategies are most effective for specific DGBI populations and clinical contexts. CRD420251126617.

Glycoproteins often exist in nature as heterogeneous glycoforms, making it difficult to obtain pure homogeneous samples for studying the roles of specific N-glycans within a glycoprotein. Despite various chemical and enzymatic methods developed for the synthesis of N-glycans, access to highly diverse N-glycans remains a challenge. Herein, we report a concise strategy for the synthesis of multiantennary N-glycans from designed common core structures with phosphate and sulfate protecting groups, which can be selectively deprotected by respective phosphatase and sulfatase, thereby enabling enzymatic elongation to install a desired glycan chain at a specific antenna. We also explored the directing effect of galactose sulfation for enzymatic fucosylation of the neighboring GlcNAc, further expanding the structural diversity of multiantennary N-glycans. Starting from sulfate and phosphate-terminated core structures, this synthetic strategy in aqueous solution provides an efficient and practical route for the enzymatic assembly of a diverse array of complex N-glycans for biological study.

In this research, we present the successful synthesis of benzimidazolium salts (2a-e) and their corresponding selenium-NHC adducts (3a-e), achieved with satisfactory yields ranging from 75% to 88%, and characterized using spectroscopic techniques, including NMR, FTIR, and mass spectrometry analysis. This work is the first to evaluate the antimicrobial activities and molecular docking studies of these novel compounds, shedding light on the limited enhancement provided by selenium incorporation and providing valuable insights into their enzyme inhibition mechanisms. The antimicrobial and antifungal activities of these compounds were evaluated against various bacterial and yeast strains using disk diffusion and minimum inhibitory concentration (MIC) methods. Benzimidazolium salts, particularly 2d and 2e, demonstrated superior antimicrobial efficacy against Staphylococcus aureus with inhibition zones of 26.73 mm and 18.10 mm and MIC values of 1.56 &#x3bc;g/mL, and against Candida albicans with inhibition zones of 18.10 mm and MIC values of 25 &#x3bc;g/mL and 12.5 &#x3bc;g/mL respectively, significantly outperforming the reference agents Ampicillin (15.33 mm inhibition zone; MIC: 25 &#x3bc;g/mL for S. aureus) and Caspofungin (14.30 mm inhibition zone; MIC: 25 &#x3bc;g/mL for C. albicans). Additionally, compounds 2d and 2e exhibited better activity against Escherichia coli with MIC values of 12.5 &#x3bc;g/mL compared to Ampicillin (25 &#x3bc;g/mL). Conversely, selenium-NHC compounds exhibited moderate to weak activity, with inhibition zones ranging from 8.35 to 11.93 mm and MIC values ranging from 100 to 800 &#x3bc;g/mL, and did not outperform the reference agents. To elucidate the potential mechanism of action, molecular docking studies were performed on compound 2d and its derivative 3d against three key bacterial enzymes&#xe5f8;DNA gyrase, dihydrofolate reductase (DHFR), and tyrosyl-tRNA synthetase (TyrRS)&#xe5f8;in addition to the fungal sterol 14-&#x3b1;-demethylase (CYP51) to assess possible antifungal interactions. The results revealed strong binding affinities for both bacterial and fungal enzymes. The compounds interact with crucial amino acids in the enzyme active sites, mirroring the interactions of native ligands. However, the presence of selenium in complex 3d did not enhance its inhibitory activity significantly compared to the salt 2d. The findings highlight the potential of benzimidazolium salts, particularly 2d and 2e, as promising therapeutic agents for microbial infections, with selenium incorporation offering limited enhancement in activity.

Fast-growing Vibrio natriegens is now recognized as a next-generation chassis for synthetic biology and biotechnology; however, its low transformation efficiency, limited gene editing methods and high fermentation cost are still the main challenges hampering its industrial application. In this study, we established an efficient electroporation transformation and dual-plasmid CRISPR-Cas9 editing system in V. natriegens. Subsequently, the heterologous ergothioneine biosynthetic pathway involving the combination of the superstrong PL lacO1 promoter and weak RBS7 was constructed in V. natriegens. Multiple genes encoding genes involved in byproduct formation and adenosine triphosphate (ATP) degradation were consecutively deleted, while several key genes involved in the S-adenosylmethionine (SAM) cycle and the ATP synthesis pathway were overexpressed to increase ergothioneine production. Finally, fed-batch fermentation was performed using low-cost sucrose as the sole carbon source under high-salinity, non-sterile conditions, resulting in an ergothioneine titer of 1.2&#xa0;g/L in a 2-L bioreactor. This study not only provides the first successful example of the ergothioneine biosynthesis with engineered V. natriegens strains but also establishes an efficient and economic platform in which V. natriegens is used to produce other high-value compounds.

The integration of Large Language Models into medical diagnosis represents an emerging field with the potential to support diagnostic workflows across diverse clinical settings. However, the trends and evolutionary trajectory of LLM-assisted diagnostic research remain insufficiently understood. This bibliometric review aims to map the global research landscape, identify key research clusters, and analyze the development trajectory of LLM technologies in medical diagnosis, with an emphasis on descriptive synthesis rather than formal evaluation. A bibliometric analysis was conducted on relevant publications retrieved from the Web of Science Core Collection, covering the period from Q1 2023 to Q1 2025. The extracted data were processed and visualized using Excel, ArcGIS, VOSviewer, CiteSpace, and Pajek. The analyses included publication trends, influential authors and institutions, collaboration networks, and research cluster mapping. A total of 650 publications were included in the analysis. Research output increased markedly from Q1 2023 onward, rising from 2 publications to 148 by Q1 2025, corresponding to an average quarterly growth rate of 71.25%. The United States (273 publications), China (135 publications), and Germany (65 publications) emerged as the leading contributing countries. The three most productive institutions were all based in the United States: Harvard University (26 publications), Stanford University (26 publications), and the Icahn School of Medicine at Mount Sinai (20 publications). Keyword co-occurrence analysis identified 10 core clusters, with a modularity Q value of 0.8231 and a silhouette S value of 0.9412, indicating a highly coherent clustering structure and strong internal consistency. The development of LLM technologies has substantially influenced the research landscape of medical diagnostics. As this field continues to evolve, it is crucial to refine model performance, integrate multimodal data, and address ethical considerations. Future research should focus on optimizing LLMs for specific clinical applications and evaluating their implementation in real-world healthcare settings.

High-performance nanocatalysts are pivotal for advancing clean energy technologies such as fuel cells; however, conventional fabrication methods are often limited by complex procedures and the difficulty of precisely controlling active sites. Laser solid-phase synthesis (LSPS), characterized by its rapid, clean, and controllable nature, presents a promising avenue for catalyst preparation. Here, we report a strategy combining laser-induced graphene with LSPS to construct semi-encapsulated palladium nanoparticles (Pd NPs) on three-dimensional porous laser-induced graphene supports. The resulting catalysts exhibit enhanced catalytic activity and superior stability toward the ethanol oxidation reaction (EOR), retaining over 90% of their initial activity after 2500 accelerated durability test (ADT) cycles. Mechanistic insights from coupled FEM-MD simulations reveal that the laser-induced non-equilibrium thermal field is pivotal in forming a semi-encapsulated architecture. This work provides a new paradigm for the rational design of stable Pd-based EOR catalysts and demonstrates their potential for use in direct ethanol fuel cells (DEFCs).

Alexithymia, characterized by difficulties in identifying and describing emotions, affects ~10% of the general population. Prevalence is substantially higher in individuals with neurodevelopmental disorders. To systematically map existing research on alexithymia across Down syndrome, autism spectrum disorder, and dual diagnosis populations, synthesize current knowledge, and identify critical research gaps informing future investigation priorities. Following Arksey and O'Malley's framework and PRISMA-ScR guidelines, searches were conducted across MEDLINE, PsycINFO, EMBASE, CINAHL, and Cochrane databases from inception to December 2024. Studies examining alexithymia, emotional processing, or emotional awareness in DS, ASD, or DS-ASD populations underwent selection and narrative synthesis employing thematic analysis. Database searches yielded 2,847 records, of which 55 studies met inclusion criteria spanning 1994-2024. Literature demonstrates research imbalances, with extensive evidence on ASD contrasted with minimal investigation on DS and the absence of research on dual diagnoses. Six major themes emerged: prevalence disparities with ASD populations showing 49.9% weighted mean prevalence vs. unestablished DS rates; assessment limitations with current tools lacking intellectual disability validation; intervention approaches demonstrating moderate effectiveness (d = 0.65) in limited populations; neurobiological correlates implicating emotion processing networks; developmental trajectory gaps across the lifespan; and clinical implications for therapeutic engagement and quality of life. Seven research gaps were identified, including the absence of validated assessment tools for populations with intellectual disabilities and the lack of longitudinal developmental studies. Current evidence reveals research imbalances with extensive ASD literature contrasting with the absence of DS research, limiting understanding and evidence-based practice. The lack of dual diagnosis investigation represents a gap affecting 16-18% of individuals with DS. Priorities include developing assessment methodologies for intellectual disability populations, establishing DS alexithymia prevalence, and investigating population-specific intervention approaches to optimize therapeutic outcomes and quality of life across the neurodevelopmental spectrum. https://doi.org/10.17605/OSF.IO/K8UEC, identifier: OSF.IO/K8UEC.

Healthcare professionals including physicians, nurses, and speech-language pathologists (SLPs), audiologists, dentists, and others have occupations with high voice demand and have an increased risk for voice disorders. This review synthesizes prevalence estimates, symptom profiles, and diagnoses across three professions, and data were unavailable for two others. A systematic search of MEDLINE (Ovid), PubMed, and EMBASE identified observational studies reporting the prevalence and types of voice disorders among the target groups, following PRISMA guidelines. The review identified 4598 records, with 984 duplicates removed, yielding 3614 unique studies screened. Ultimately, 20 studies met the inclusion criteria, primarily employing cross-sectional designs across various regions. No relevant studies reporting on audiologists and dentists were identified. The prevalence of voice complaints varied significantly: among physicians and medical students, the 12-month prevalence of self-reported voice issues was 53%, while the average Voice Handicap Index (VHI-10) score was approximately 3.8. For nurses, point and 12-month estimates ranged from 9% to 37%, often averaging around 30%. SLPs and SLP students reported higher prevalence rates of 33% to 77% for chronic voice problems, with vocal fatigue affecting up to 71% of students. Clinician-diagnosed laryngeal pathologies were less frequent, at 5.1% in one cohort, with common diagnoses including reflux laryngitis and vocal fold nodules. Identified risk factors included high vocal load, extended work hours, and unfavorable working conditions. The variability in definitions and measurement approaches hindered comparability across studies. Voice disorders and voice-related symptoms are reported commonly among physicians, nurses, and SLPs, with subjective complaints far exceeding clinician-diagnosed pathology. Data are not available for audiologists and dentists. Methodological heterogeneity and predominance of self-reported measures constrain prevalence estimates. Standardized definitions combined subjective/objective assessment, and longitudinal research is needed to characterize voice burden better and to establish prevention and workplace interventions.

Intervertebral disc (IVD) degeneration remains the leading cause of low back pain worldwide. Regenerative therapies focused on restoring extracellular matrix (ECM) composition and disc height often overlook the IVD microenvironment, which remains to be fully characterized. This study first aims to profile the microenvironment of human nucleus pulposus (NP) tissue across degeneration grades from discectomy procedures, quantifying glucose, oxygen, pH, lactate, osmolarity, and 13 cytokines (TNF, IL-1&#x3b2;, IL-6, MMP-3, &#x3b2;-NGF, BNDF, IL-10, TIMP-1, -2, -3, FGF, and ADAMTS4 and 5). Profiling within the same samples enabled correlation analysis between all parameters. Second, this study investigated how clinically relevant microenvironmental conditions influence NP cell matrix synthesis and metabolic activity. Microenvironmental profiling: NP tissue was obtained via informed consent from patients undergoing discectomy. pH was measured using a fiber optic microsensor. Oxygen was quantified using Image-iT green hypoxia reagent. Glucose and lactate were quantified via colorimetric assays, and osmolarity was measured using a vapor pressure osmometer. Cytokines were analyzed by multiplex and enzyme-linked immunosorbent assay (ELISA). Cellular response: NP cells were formed into microtissues and primed with TGF-&#x3b2;3 for 7&#x2009;days, followed by 14&#x2009;days of clinically relevant microenvironmental insult with different combinations of glucose and pH or cytokine exposure and pH. Cell viability, DNA, GAG, collagen, and metabolic rates were assessed. Across a broad donor cohort, microenvironmental parameters, cytokine concentrations, and ECM were maintained with increasing degeneration grades, despite notable donor variability. NP microtissues demonstrated resilience across clinically relevant ranges of glucose, pH, and cytokine exposure. This study establishes experimentally defined microenvironmental ranges that are representative of the human NP microenvironment and supported by donor-specific in silico modeling. It further demonstrates that human NP cells within a native matrix are not highly sensitive to clinically relevant changes in microenvironmental conditions, an important consideration for cell-based regenerative strategies.

Inflammatory bowel disease (IBD) is recognized as a prototypical disorder of brain-gut interaction. Although neuroimaging research in this field has advanced rapidly in recent years, the findings remain fragmented across multiple disciplines, and a systematic integration of the literature is lacking. This study presents the first integrated bibliometric analysis and literature review to map the landscape and evolving trends of neuroimaging research in IBD over the past two decades and to identify the knowledge base and research frontiers. We conducted a systematic search of the Web of Science Core Collection and Scopus databases for IBD-related neuroimaging literature published between January 2000 and January 2026. Following the PRISMA guidelines, two independent reviewers screened titles, abstracts, and full texts. A total of 175 articles met the inclusion criteria. Data were extracted on study characteristics, neuroimaging modalities, and clinical findings. For the synthesis, we employed a dual approach: (1) a bibliometric analysis using VOSviewer, Biblioshiny, and CiteSpace to map publication trends, collaboration networks, and research hotspots; and (2) a structured literature review across five predefined dimensions: technical modalities, brain region-symptom associations, subtype differences, mechanistic pathways, and clinical translation. The systematic search and selection process identified 175 articles for final synthesis. The field has entered a phase of rapid expansion since 2021, with China and the United States as core contributing countries. Emerging frontiers include the "brain-gut axis" and the "default mode network." The literature synthesis indicates that: (1) brain alterations are predominantly localized within an emotional and interoceptive network (anterior cingulate cortex, insula, and amygdala), with abnormalities generally associated with abdominal pain, anxiety, and depression; and (2) Crohn's disease and ulcerative colitis appear to exhibit distinguishable neuroimaging phenotypes, though direct comparative studies remain limited. This study systematically clarifies the knowledge structure of the IBD neuroimaging field, demonstrates that the available neuroimaging evidence is consistent with the brain-gut axis as a central theoretical framework, and identifies subtype-specific neural characteristics. Future efforts should prioritize large-sample multicenter validation, longitudinal designs capable of testing mechanistic hypotheses, and multimodal data integration to transition the field from descriptive observations toward clinically meaningful applications,though substantial barriers-including small sample sizes, methodological heterogeneity, and lack of standardization-must first be overcome.

Cervical cancer, a common type of cancer with gynecological malignant tumors, poses a serious threat to women's health. Despite significant advances in cancer treatment, there is still a lack of effective early detection methods, and many therapeutic approaches suffer from low specificity and adverse side effects. Therefore, there is an urgent need to explore efficient diagnostic methods and targeted treatments with strong specificity and high efficacy. The Materials of Institute Lavoisier (MIL) family of materials possesses favorable porosity, large specific surface area, high drug-loading capacity, tunable pore sizes, and superior chemical stability. Notably, their satisfactory biocompatibility has further promoted their widespread research in cancer diagnosis and targeted therapy. Inspired by this, this review summarizes recent developments in the application of MIL materials in cervical cancer diagnosis and treatment. Primarily, the properties, structures, and synthesis methods of MIL materials, including MIL-100, MIL-101, MIL-88, and MIL-53, are introduced. Then, the application of MIL materials in the diagnosis of cervical cancer is discussed. MIL-based nanoplatforms for chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), photodynamic therapy (PDT), and related combination therapies in cervical cancer treatment are reviewed. Finally, the challenges encountered in applying MIL materials in cervical cancer treatment are summarized, and prospects for their future development are provided.

Community nurses play a pivotal role in palliative care but face barriers in managing complex symptoms, such as fragmented knowledge and a lack of community-tailored evidence-based guidance, impairing clinical efficiency. The aim of this study was to develop and evaluate a knowledge graph-based question-answering system for symptom management in community palliative care. A three-phase codesign study guided by the Knowledge-to-Action framework was conducted. Phase 1 (Knowledge Creation): A Symptom Management Knowledge Base (Knowledge Product I) was developed through a codesign process involving a multidisciplinary expert panel. This panel adapted a knowledge base created by researchers through systematic evidence synthesis, employing FAME criteria for contextual adaptation. Phase 2 (Action Cycle: Implementation): A semantically structured knowledge graph (Knowledge Product II) was constructed via automated extraction by software developers, followed by manual verification by researchers. Based on this graph, a question-answering system was created and implemented as a WeChat mini-program, resulting in a practical KG-QA system (Knowledge Product III). Phase 3 (Action Cycle: Evaluation): The system's acceptability, usability, and perceived usefulness and ease of use were assessed among experts and community nurses during a two-week evaluation period using the Clinical Nursing Information System Effectiveness Evaluation Scale and the Post-Study System Usability Questionnaire, which is grounded in the Technology Acceptance Model. The knowledge base comprises 225 evidence items for nine symptoms; the knowledge graph integrates ten entity types, 11 relationship categories, 442 entities and 668 relationships, with the system supporting four query interfaces and three search methods. The evaluations demonstrated high perceived usefulness and ease of use, with strong scores for acceptability (102.25&#x2009;&#xb1;&#x2009;16.21; 110.56&#x2009;&#xb1;&#x2009;9.90) and usability (2.47&#x2009;&#xb1;&#x2009;1.98; 2.23&#x2009;&#xb1;&#x2009;1.93). The question-answering system bridges the evidence-practice gap via a nursing-process paradigm, offering a potentially scalable model that aligns with national policies pending further validation. However, these findings are based on a small&#x2011;scale, single&#x2011;region, short&#x2011;term evaluation relying largely on subjective measures. Future research should explore its long-term clinical outcomes and cross-setting scalability.