{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40797087", "kind": "science-record", "revision": 4, "content_hash": "sha256:0255801004f6e247522ee06fa81956364844871c1223553d98a522e95c9f4eee", "created_at": "2026-11-01T20:30:53Z", "updated_at": "2026-11-01T22:57:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Dehydrotanshinone II A alleviates osteoarthritis via activating PPARγ to inhibit ferroptosis in chondrocytes.", "doi": "10.1038/s41598-025-14896-y", "pmid": "40797087", "authors": ["Wenli Guan", "Fahu Yuan", "Xin Wang"], "journal": "Scientific reports", "year": 2025, "abstract": "Osteoarthritis (OA) is a prevalent chronic degenerative joint disease. Ferroptosis, an iron-dependent form of programmed cell death, has been implicated as a crucial contributor to OA progression. Simiao Powder, a classical traditional Chinese medicine formula, has been widely used in clinical practice to treat inflammatory diseases such as gout and OA. However, its regulatory effects on ferroptosis remain unclear. This study investigates whether Simiao Powder could alleviate OA by regulating ferroptosis and analyzes its underlying mechanisms. We integrated multiple bioinformatics analyses along with in vivo and in vitro experiments to elucidate the mechanism by which DHT IIA treats OA. Potential therapeutic targets of Simiao Powder were identified through the TCMSP and GEO databases, and their potential biological functions were evaluated using GO enrichment, ROC curve analysis, molecular docking, and immune infiltration assessment via CIBERSORTx. OA was induced in SD rats using a high carbohydrate and fat diet, followed by a 16-week intervention with DHT IIA. Histological staining, OARSI scoring, and cartilage thickness measurements were performed. The expression levels of PPARγ, GPX4, and the apoptosis marker TUNEL in rat cartilage were evaluated using immunofluorescence and immunohistochemistry. In an LPS-induced ATDC5 chondrocyte injury model, Western blotting was used to assess the expression of PPARγ, COL2A1, ACSL4, and MMP13. Furthermore, the scTenifoldKnk algorithm was applied to perform a virtual knockout of PPARγ based on the GSE216651 single-cell RNA-seq dataset to explore its downstream regulatory effects. Bioinformatics analysis identified five key genes (CDKN1A, HMOX1, DPP4, GJA1, and PPARγ), among which PPARγ and HMOX1 exhibited strong predictive potential with AUC values > 0.8. Molecular docking analysis revealed that DHT IIA exhibited the lowest binding energy with PPARγ (-8.15 kcal/mol), indicating it as the most likely therapeutic target. In vitro and in vivo experiments demonstrated that DHT IIA significantly upregulated PPARγ expression reduced ACSL4, MMP13 and TUNEL levels, increased COL2A1 and GPX4 expression levels. Meanwhile computer simulated gene knockdown also laterally confirmed that PPARγ is a key gene affecting ferroptosis and OA development. The study confirmed that DHT IIA could improve the articular cartilage structure of OA rats by elevating PPARγ and inhibiting ferroptosis. This study reveals that DHT IIA, the active ingredient of Simiao Powder, may alleviate OA by inhibiting ferroptosis through the activation of PPARγ. These findings provide a new molecular mechanism basis for the treatment of OA by Simiao Powder, as well as scientific support for the subsequent drug development and clinical applications.", "claims": [{"id": "claim-method", "statement": "For data that met the normal distribution and variance chi-square, a one-way ANOVA was performed followed by multiple comparisons using Tukey’s post hoc test. For data that did not meet the assumption of normality, the Kruskal-Wallis H test was used. If significant differences were observed (p < 0.05), pairwise comparisons were performed using Dunn’s test with Bonferroni correction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40797087", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "For data that met the normal distribution and variance chi-square, a one-way ANOVA was performed followed by multiple comparisons using Tukey’s post hoc test. For data that did not meet the assumption of normality, the Kruskal-Wallis H test was used. If significant differences were observed (p < 0.05), pairwise comparisons were performed using Dunn’s test with Bonferroni correction."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used in this study are publicly accessible. The datasets included in this study can be downloaded from the GEO database (GSE98918: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98918; GSE178557: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178557), whose corresponding data are cited in references [18, 19]. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40797087", "locator": "sections[37] \"Data availability\" paragraph 2", "quote": "The datasets used in this study are publicly accessible. The datasets included in this study can be downloaded from the GEO database (GSE98918: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98918; GSE178557: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178557), whose corresponding data are cited in references [18, 19]. Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Bioinformatics analysis identified five key genes (CDKN1A, HMOX1, DPP4, GJA1, and PPARγ), among which PPARγ and HMOX1 exhibited strong predictive potential with AUC values > 0.8.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40797087", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Bioinformatics analysis identified five key genes (CDKN1A, HMOX1, DPP4, GJA1, and PPARγ), among which PPARγ and HMOX1 exhibited strong predictive potential with AUC values > 0.8."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Bioinformatics analysis identified five key genes (CDKN1A, HMOX1, DPP4, GJA1, and PPARγ), among which PPARγ and HMOX1 exhibited strong predictive potential with AUC values > 0.8.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40797087"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE178557"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE178557"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40797087", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-025-14896-y", "sha256": "sha256:29af428334fd4e19f753b005ed5192c9869a2119eea1657810b575378c33774c", "bytes": 60027, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-025-14896-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12343851", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE178557", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178557", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE178557", "version": null, "note": "The datasets used in this study are publicly accessible. The datasets included in this study can be downloaded from the GEO database (GSE98918: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98918; GSE178557: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178557), whose corresponding data are cited in references [18, 19]. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this study are publicly accessible. The datasets included in this study can be downloaded from the GEO database (GSE98918: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98918; GSE178557: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178557), whose corresponding data are cited in references [18, 19]. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5393765", "GSM5393766", "GSM5393767", "GSM5393768", "GSM5393769", "GSM5393770", "GSM5393771", "GSM5393772"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "13497", "taxon": "Homo sapiens", "title": "Microarray identifies differentially expressed mRNAs of cartilages between osteoarthritis (OA) patients and control patients", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE216651", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216651", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE216651", "version": null, "note": "The datasets used in this study are publicly accessible. The datasets included in this study can be downloaded from the GEO database (GSE98918: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98918; GSE178557: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178557), whose corresponding data are cited in references [18, 19]. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this study are publicly accessible. The datasets included in this study can be downloaded from the GEO database (GSE98918: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98918; GSE178557: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178557), whose corresponding data are cited in references [18, 19]. 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No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T03:38:12+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}