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Rosmarinic acid (RosA), a hydrophilic phenolic compound found in various plants, has several biological effects such as anti-inflammatory and anti-apoptosis activities. However, its potential impact on chronic obstructive pulmonary disease (COPD) and its underlying mechanism has not been investigated. In this study, we explored the potential therapeutic effects and mechanism of RosA on COPD airway inflammation and alveolar epithelial apoptosis in vivo and in vitro . Our data suggested that RosA may be a therapeutic candidate for COPD with low toxicity. The corresponding mechanism lies in its anti-inflammatory effect on macrophage and bronchial epithelial cells, as well as protective effect on lung epithelial apoptosis via the jointly cross-target spleen tyrosine kinase (Syk).

Background: Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD)., Methods: We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes., Results: By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33 , and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD., Conclusion: This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33 , and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Fan, Xie, Wang, Li, Liu, Wang, Yu, Zou, Gao, Zhang, Hao, Feng, Yang, Wang, Fu, Bao and Duan.)

Lycium Barbarum Polysaccharides (LBP) can benefit lipid parameters such as total cholesterol, triglyceride, and high-density lipoprotein levels and upregulate the level of Firmicutes , increase the diversity of gut microbiota and reduce metabolic disorders, finally relieving weight gain of obese rats. But it cannot reverse the outcome of obesity. Over 30 differential metabolites and four pathways are altered by LBP.

The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8 + T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting., (© 2024. The Author(s).)

Objective: To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis. Methods: A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ (2) test. The inter-group comparison was performed using continuous variables, a t -test, one-way analysis of variance (ANOVA), or a nonparametric test. Results: There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP ( OR =1.32, 95% CI : 1.12-1.56, P =0.001). Patients combined with EGV ( OR =3.09, 95% CI : 2.63-3.65, P <0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism ( P <0.001). Patients with PBC ( OR =0.64, 95% CI : 0.50-0.82, P <0.001) and PSC ( OR =0.23, 95% CI : 0.06-0.65, P =0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients ( P <0.001), and the lower proportion of hypersplenism in combined PSC patients ( P =0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures ( P <0.05), but a lower rate of liver biopsy ( P <0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without ( P =0.004). Conclusion: TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.

Introduction: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines., Research Design and Methods: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications., Results: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m 2 , HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m 2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes., Conclusions: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events., Trial Registration Number: NCT04049149., Competing Interests: Competing interests: JCNC and RCWM hold patents for using genetic markers to predict diabetes and its complications for personalized care. JCNC, RCWM and CL are cofounders of a start-up biotech company partially supported by the Technology Start-up Support Scheme for Universities (TSSSU) of the Hong Kong Government Innovation and Technology Commission., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3-90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The multivariate fractional polynomial regression (MFPR) emerged as the preferred algorithm, optimised with non-linear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3000 study participants. This model can inform about the biological and behavioural implications of deviations from typical age-related neuroanatomical changes and support future study designs. The model and scripts described here are freely available through CentileBrain., Competing Interests: Declaration of interests SSH is supported by the US National Institutes of Health (NIH)'s National Institute of Mental Health (T32MH122394) and received a travel award from the Society of Biological Psychiatry to attend the annual meeting in 2023. HB declares an institutional grant from the Australian National Health and Medical Research Council; has received compensation for being on an advisory board or a consultant to Biogen, Eisai, Eli Lilly, Roche, and Skin2Neuron; payment for being on the Cranbrook Care Medical Advisory Board; and honoraria for being on the Montefiore Homes Clinical Advisory Board. RMB and HEHP declare partial funding through the Geestkracht programme of the Dutch Health Research Council (Zon-Mw, grant No 10–000–1001) and matching funds from participating pharmaceutical companies (ie, Lundbeck, AstraZeneca, Eli Lilly, and Janssen Cilag), universities (Academic Psychiatric Centre of the Academic Medical Center, University Medical Center Groningen, Maastricht University Medical Centre, and University Medical Center Utrecht), and mental health care organisations (GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord, Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht, Parnassia psycho-medical center The Hague, GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET GGZ, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem, Altrecht, and GGZ Centraal and Delta); and received funding from Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO 51·02·061 to HEHP, NWO 51·02·062 to DIB, NWO–NIHC Programs of excellence 433–09–220 to HEHP, NWO-MagW 480–04–004 to DIB, and NWO/SPI 56–464–14192 to DIB), FP7 Ideas: European Research Council (ERC-230374 to DIB), and Universiteit Utrecht (High Potential Grant to HEHP). RB declares funding by the NIH's National Institute on Aging (R01AG067420); received compensation for being on the scientific advisory board from Alkermes and Cognito Therapeutics with no conflict to the present work; received honoraria from academic institutions for talks (all under $1000) and $1000 for speaking at a Massachusetts General Hospital and Harvard Medical School course; received travel fees for services to attend the annual meeting from the Simons Foundation; serves as a Director on the Simons Foundation Collaborative Initiative on Aging; is a paid scientific advisory board member for philanthropic grants for The Foundation for OCD Research and the Klarman Family Foundation. BF has received educational speaking fees from Medice. DG reports funding from the NIH. UD is funded through the German Research Foundation (DFG; DA 1151/9–1, DA 1151/10–1, DA 1151/11–1). GS declares funding from the European Commission, DFG, and National Science Foundation of China. CKT has received grants from the Research Council of Norway and the Norwegian Regional Health Authority, unrelated to the current work. HW reports funding from the German Research Foundation (WA 1539/11–1). NJ reports funding from the NIH and compensation from the International Neuropsychological Society. PMT declares a grant from the NIH and travel funded by NIH grants. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)