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SMYD3 is a chromatin modifier that facilitates the trimethylation of histone 3 lysine 4 (H3K4) to induce diverse biological activities. We have provided a brief demonstration of the anti-aging effect of ZYZ-384, a newly developed inhibitor targeting SMYD3. In order to validate the anti-senescence effect of ZYZ-384, we utilized angiotensin II to induce senescence in two types of human endothelial cells (HMEC-1) and mouse endothelial cells (SVEC4-10), creating cellular models for senescence. Additionally, we employed D-galactose-induced subacute senescence animal models as well as natural senescence animal models. At the cellular level, we assessed proliferation capacity and intracellular markers associated with aging. Aging markers, SASP and differential metabolites were evaluated at an organismal level using animal models. Compared to senescent cells or animals, ZYZ-384 application significantly inhibited levels of aging markers in both senescent cell and senescent animal models while promoting cell proliferation. Furthermore, it suppressed expression of SMYD3 and H3K4me3 along with over expression of HSP 90 and NF-κB. Our study demonstrates that ZYZ-384 is an effective inhibitor targeting SMYD3 which can effectively delay aging.

Purpose Social adaptability is essential for healthy aging. This study examines how Contracted Family Doctor Services (CFDS) affect social adaptability in rural Chinese middle-aged and older adults, assessing the mediating role of regular health management (RHM). Methods and materials Using national cross-sectional data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), we analyzed 13,895 community-dwelling adults. We employed generalized linear models (GLM), mediation analysis, and an instrumental variable-based control function approach (IV-CFA) to evaluate causality and control for confounding. Results Research demonstrated that CFDS participation was significantly associated with enhanced social adaptability ( β = 0.204, p < 0.01). RHM partially mediated this relationship, explaining 29.5% of the total effect. Heterogeneity analyses indicated significant associations between CFDS and social adaptability for adults aged 45-60 years ( β = 0.250, p < 0.01) and males ( β = 0.308, p < 0.01), whereas no significant effects were observed among adults ≥60 years or females. Conclusions CFDS significantly enhances social adaptability among rural middle-aged and older adults, broadening primary care's impact beyond biomedical domains. RHM mediates 29.5% of this effect. The benefits were particularly pronounced among younger individuals and male subgroups. To sustain CFDS effectiveness, China should maintain 1-3% annual coverage growth while implementing targeted measures: combating social isolation in older adults, screening for perimenopausal comorbidities among women, and strengthening intergenerational care support programs.

In this research, we explored the synthesis optimization of the silica-based quaternized adsorption material (SG-VTS-VPQ) and its adsorption behavior for Pu(IV). By optimizing the synthesis process, the grafting amount of 4-vinylpyridine reached 1.25 mmol·g−1. According to the analysis of NMR and XPS, the quaternization rate of pyridine groups reached 91.13%. In the adsorption experiments, the thermodynamic experiment results show that the adsorption of Pu(IV) by SG-VTS-VPQ is more in line with the Langmuir adsorption model and the adsorption type is a typical chemical adsorption; the kinetic results show that adsorption process is more in line with the pseudo first-order kinetic model, and the larger specific surface area of SG-VTS-VPQ plays an important role in the adsorption. The results of the adsorption mechanism show that the adsorption of Pu(IV) by SG-VTS-VPQ is mainly complex anion Pu(NO3)62− and Pu(NO3)5−. This research provides in-depth and detailed ideas for the surface modification and application of porous silica gel, and at the same time provides a new way to develop the direction of the analysis of pretreatment materials in the spent fuel reprocessing field.

Objective : For patients with chronic diseases requiring long-term use of medications who are quarantined at home, the management of medication therapy during the COVID-19 pandemic is a problem that pharmacists urgently need to discuss and solve. The study aims to establish and launch a telepharmacy framework to implement pharmaceutical care during the COVID-19 pandemic. Methods : To establish a remote pharmacy service model based on a medication consultation service platform under the official account of the “Beijing Pharmacists Association” on the social software WeChat app, obtain the medication consultation records from February 28 to April 27, 2020, during the worst period of the epidemic in China, and to perform a statistical analysis of the information about the patients seeking consultation, consultation process, content and follow-up results. Results : The medication consultation service system and telepharmacy service model based on social software were established in February 2020. The “Cloud Pharmacy Care” platform had 1,432 views and 66 followers and completed 39 counseling cases in 2 months. Counseling was available for patients of all ages. Of the 39 cases, 82.05% of patients were young and middle-aged. During the COVID-19 pandemic, the long-term medication usage problems of patients with chronic disease were effectively addressed using “Cloud Pharmacy Care”. In the consultation, 35 cases (89.7%) were related to the use of medicines or health products, and 4 cases (10.3%) involved disease state management and the use of supplements. The top five drug-related issues included the selection of medications, the dosage and usage of drugs, medications for special populations, medication therapy management of chronic diseases, and adverse drug reactions. All consultations were completed within 4 h, with a positive review rate of 97.4%. Conclusion : During the COVID-19 pandemic, a remote pharmacy service “Cloud Pharmacy Care” based on the social software WeChat app was quickly constructed and applied to solve the medication-related problems of patients and the public during home quarantining. The significance of the study lies in the timely and interactive consultation model helps to carry out medication therapy management for chronically ill patients and improves patients’ medication compliance, improves medical quality, and plays a positive role in promoting the popularization of safe medication knowledge.

Prior attempts at forming theoretical predictions regarding the quality of binary odor mixtures have failed to find any consistent predictor for overshadowing of one component in a binary mixture by the other. We test here the hypothesis that trigeminality contributes to overshadowing effects in binary mixture perception. Most odorants stimulate the trigeminal nerve in the nasal sensory epithelium. In the current study we test rats’ ability to detect component odorants in four binary odor sets chosen for their relative trigeminality. We predicted that the difference in trigeminal intensity would predict the degree of overshadowing by boosting or suppressing perceptual intensity of these odorants during learning or during mixture perception. We used a two-alternative choice (TAC) task in which rats were trained to recognize the two components of each mixture and tested on a range of mixtures of the two without reinforcement. We found that even though odorant concentrations were adjusted to balance volatility, all odor sets produced asymmetric psychometric curves. Odor pairs with the greatest difference in trigeminality showed overshadowing by the odorant with weaker trigeminal properties. Odor sets with more evenly matched trigeminal properties also showed asymmetry that was not predicted by either small differences in volatility or trigeminality. Thus, trigeminal properties may influence overshadowing in odor mixtures, but other factors are also likely involved. These mixed results further support the need to test each odor mixture to determine its odor quality and underscore recent results at the level of olfactory receptor neurons that show massive and unpredictable inhibition among odorants in complex mixtures.

Background Acute myeloid leukemia can develop as myoblasts infiltrate into organs and tissues anywhere other than the bone marrow, which called extramedullary infiltration (EMI), indicating a poor prognosis. Circular RNAs (circRNAs) are a novel class of non-coding RNAs that feature covalently closed continuous loops, suggesting their potential as micro RNA (miRNA) “sponges” that can participate in biological processes and pathogenesis. However, investigations on circRNAs in EMI were conducted rarely. In this study, the overall alterations of circRNAs and their regulatory network between EMI and non-EMI AML were delineated. Methods CircRNA and whole genome microarrays derived from EMI and non-EMI AML bone marrow mononuclear cells were carried out. Functional analysis was performed via Gene Ontology and KEGG test methods. The speculated functional roles of circRNAs were based on mRNAs and predicted miRNAs that played intermediate roles. Integrated bioinformatic analysis was conducted to further characterize the circRNA/miRNA/mRNA regulatory network and identify the functions of distinct circRNAs. The Cancer Genome Atlas (TCGA) data were acquired to evaluate the poor prognosis of distinct target genes of circRNAs. Reverse transcription-quantitative polymerase chain reaction was conducted to identify the expression of has_circRNA_0004520. Connectivity map (CMap) analysis was further performed to predict potential therapeutic agents for EMI. Results 253 circRNAs and 663 genes were upregulated and 259 circRNAs and 838 genes were downregulated in EMI compared to non-EMI AML samples. GO pathways were enriched in progress including cell adhesion (GO:0030155; GO:0007155), migration (GO:0016477; GO:0030334), signal transduction (GO:0009966; GO:0007165) and cell–cell communication. Overlapping circRNAs envolved in pathways related to regulate cell–cell crosstalk, 17 circRNAs were chosen based on their putative roles. 7 target genes of 17 circRNAs (LRRK1, PLXNB2, OLFML2A, LYPD5, APOL3, ZNF511, and ASB2) indicated a poor prognosis, while overexpression of PAPLN and NRXN3 indicated a better one based on data from TCGA. LY-294002, trichostatin A and SB-202190 were identified as therapeutic candidates for EMI by the CMap analysis. Conclusion Taken together, this study reveals the overall alterations of circRNA and mRNA involved in EMI and suggests potential circRNAs may act as biomarkers and targets for early diagnosis and treatment of EMI.

To compare efficacy and safety of laparoscopicnephrectomy (LN) versus open nephrectomy (ON) in the management of autosomal dominant polycystic kidney disease (ADPKD), we conducted a systematic review and meta-analysis. A systematic search of the electronic databases PubMed, Scopus, and the Cochrane Library was performed up to October 2014. This systematic review was performed based on observational comparative studies that assessed the two techniques. The weighted mean difference (WMD) and risk ratio (RR), with their corresponding 95% confidence interval (CI), were calculated to compare continuous and dichotomous variables, respectively. Seven studies were identified, including 195 cases (118 LN/77 ON). Although LN was associated with longer operative time (WMD 30.236, 95%CI 14.541 -45.932, P<0.001) and the specimen might not have been resected as heavy as the ON group (WMD -986.516, 95%CI -1883.24--89.795, P = 0.031), patients in this group might benefit from a shorter length of hospital stay (WMD -3.576, 95%CI 4.976--2.176, P <0.001), less estimated blood loss (WMD -180.245, 95%CI -317.939--42.556, P = 0.010), and lower need of transfusion (RR 0.345, 95%CI 0.183-0.650, P = 0.001). The LN group also had less overall complications (RR 0.545, 95%CI 0.329-0.903, P = 0.018). The need of narcotic analgesics between the two groups might have no significant difference (WMD -54.66, 95%CI -129.76-20.44, P = 0.154). LN for giant symptomatic ADPKD was feasible, safe and efficacious. Morbidity was significantly reduced compared with the open approach. For an experienced laparoscopist, LN might be a better alternative.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by providing durable responses and a favorable safety profile, ushering in a new era of tumor immunotherapy. However, immune-related adverse events (irAEs) remain a significant clinical challenge. Among these, gastrointestinal irAEs, especially immune-related colitis (ir-colitis), can lead to serious complications if not promptly recognized and managed. Here, we present a case of grade 3 ir-colitis induced by the programmed cell death protein 1 (PD-1) inhibitor sintilimab in a 68-year-old woman with endometrial cancer. The patient developed severe acute diarrhea following ICI administration, which progressed despite initial antidiarrheal and antimicrobial treatments. A multidisciplinary team (MDT) involving gastroenterologists, oncologists, a pathologist, and a clinical pharmacist confirmed the diagnosis and implemented high-dose corticosteroid therapy, yielding significant clinical improvement. Importantly, this report highlights the mechanistic link between PD-1 blockade and ir-colitis pathogenesis, focusing on the dysregulation of the mucosal immune environment and its role in triggering colonic injury. In addition to the case description, we provide a comprehensive review of the literature and clinical guidelines, discussing risk factors, diagnostic approaches, therapeutic strategies, and long-term monitoring. By integrating insights from pharmacology, immunology, and clinical practice, this work emphasizes the importance of early detection, patient education, and MDT collaboration for optimizing therapeutic outcomes and advancing the understanding of ir-colitis in the context of ICI therapy.

Objectives: This bibliometric analysis investigates recent research trends in biologics and small molecules for treating inflammatory bowel disease (IBD) based on literature from the past decade. Methods: This cross-sectional study involved analyzing data retrieved from the Web of Science Core Collection (WoSCC) database to examine the evolution and thematic trends of biological agents and small-molecular drugs for IBD conducted between 1 January 2014, and 20 September 2024. VOSviewer software was utilized to assess co-authorship, co-occurrence, co-citation, and network visualization, followed by a further discussion on significant sub-themes. Results: From 2014 to 20 September 2024, the annual number of global publications increased by 23%, reflecting an acceleration in research activity. The journal “Inflammatory Bowel Diseases” published the highest number of manuscripts (579 publications) and garnered the most citations (13,632 citations), followed by the “Journal of Crohn’s & Colitis” (480 publications) and “Alimentary Pharmacology & Therapeutics” (250 publications). The United States led in productivity with 1943 publications and 66,320 citations, with UC San Diego (291) and authors Sandborn and Vermeire (180) topping the list. The co-occurrence cluster analysis of the top 100 keywords resulted in the formation of six distinct clusters: Disease Mechanisms, Drug Development, Surgical Interventions, Therapeutic Drug Monitoring (TDM), Immunological Targets, and Emerging Therapies. Burst terms (TNF-α inhibitors, JAK inhibitors, and trough-level optimization) highlight trends toward personalized biologics and small-molecule regimens. Conclusions: The bibliometric analysis indicates that IBD therapeutic research and clinical applications focus on biologics and small molecules, with research trends leaning toward precise therapy conversion or the combination in non-responders. Future work will assess monotherapy, the combination, and conversion therapies and investigate new drugs targeting inflammatory pathways.

One of the central questions of neuroethology is how specialized brain areas communicate to form dynamic networks that support complex cognitive and behavioral processes. Developmental song learning in the male zebra finch songbird (Taeniopygia guttata) provides a unique window into the complex interplay among sensory, sensorimotor, and motor network nodes. The foundation of a young male's song structure is the sensory memory he forms during interactions with an adult \"tutor.\" However, even in the absence of tutoring, juveniles produce a song-like behavior. Thus, by controlling a juvenile male's tutor exposure, we can examine how tutor experience affects distributed neural networks and how network properties predict behavior. Here, we used longitudinal, resting-state fMRI (rs-fMRI) functional connectivity (FC) and song analyses to examine known nodes of the song network, and to allow discovery of additional areas functionally related to song learning. We present three major novel findings. First, tutor deprivation significantly reduced the global FC strength of the caudomedial nidopallium (NCM) subregion of the auditory forebrain required for sensory song learning. Second, tutor deprivation resulted in reduced FC between NCM and cerebellar lobule VI, a region analogous to areas that regulate limbic, social, and language functions in humans. Third, NCM FC strength predicted song stereotypy and mediated the relationship between tutoring and stereotypy, thus completing the link between experience, neural network properties, and complex learned behavior.