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Animal studies show aging varies between individuals as well as between organs within an individual 1 – 4 , but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan. We discovered nearly 20% of the population show strongly accelerated age in one organ and 1.7% are multi-organ agers. Accelerated organ aging confers 20–50% higher mortality risk, and organ-specific diseases relate to faster aging of those organs. We find individuals with accelerated heart aging have a 250% increased heart failure risk and accelerated brain and vascular aging predict Alzheimer’s disease (AD) progression independently from and as strongly as plasma pTau-181 (ref. 5 ), the current best blood-based biomarker for AD. Our models link vascular calcification, extracellular matrix alterations and synaptic protein shedding to early cognitive decline. We introduce a simple and interpretable method to study organ aging using plasma proteomics data, predicting diseases and aging effects. Blood plasma protein data was combined with machine learning models for a simple method to determine differences in organ-specific aging; the study provides a basis for the prediction of diseases and aging effects using plasma proteomics.

This research aims to summarize the ultrasound features and pregnancy outcomes of closure of ductus venosus, providing a basis for prenatal consultation and clinical management. A retrospective cohort study was conducted at the Hunan Provincial Maternal and Child Health Care Hospital in China, involving pregnant patients diagnosed with ductus venosus closure between January 2020 and December 2023. Data on maternal age, gestational age, ultrasound findings, timing and method of pregnancy termination, and pregnancy outcomes were collected. Twenty-five pregnant women were diagnosed with ductus venosus closure during the study period. Among them, 12 cases (48%, 12/25) were associated with other abnormalities. Of these, 4 cases (33.33%, 4/12) resulted in live births, while 8 cases (66.67%, 8/12) led to induced labor due to major abnormalities. The remaining 13 cases (52%, 13/25) involved isolated ductus venosus closure, with 1 case (7.69%, 1/13) of intrauterine fetal death and 12 cases (92.31%, 12/13) of successful delivery. The closure of the ductus venosus was primarily characterized by the tramline sign (52%, 13/25) and the cord sign (48%, 12/25) on two-dimensional ultrasound, with no detectable blood flow on Doppler ultrasound imaging. Ductus venosus closure can occur as an isolated finding (52%) or in conjunction with other abnormalities (48%), with cardiac anomalies being the most common. The closure of ductus venosus can occur during the second and third trimesters of pregnancy. The two-dimensional ultrasound showing tramline sign or cord sign, along with the absence of blood flow on Doppler ultrasound imaging, should raise suspicion of closure of ductus venosus.

Ethnopharmacological relevance: Glehnia littoralis (GL) is a well-known traditional Chinese medicine used to clear the lungs and benefit the stomach. Glehnia littoralis polysaccharides (GLPs) constitute one of the primary active ingredients of GL, demonstrating notable biological activities including immunomodulatory, antioxidant activity, and antitumor effects. Aim of the study: This review aims to provide the latest and the most comprehensive information on GLPs, specifically investigating their extraction technologies, isolation and purification methods, structural characteristics, and pharmacological activities of GLPs. It seeks to lay a foundation for further investigating pharmacological activities and application scope and guide the safe clinical practice of GLPs. Materials and methods: PubMed, Google Scholar, Web of Science, Elsevier, China National Knowledge Infrastructure (CNKI), and other online databases were used to collect literature about extraction, isolation, and purification methods, structural characteristics, and pharmacological activities of GLPs published before January 2025. Results: Polysaccharides are the main active ingredient of GL. Currently, 19 types of GLPs have been extracted. Methods of extracting GL include hot water extraction, ultrasound-assisted extraction, and enzyme extraction. The most frequently used method of separation and purification within GLP is column chromatography, often entailing cellulose column chromatography and ion exchange chromatography. GLPs have various pharmacological activities, including immunomodulatory, antioxidant, and antitumor. Conclusions: While GLPs show promising immunomodulatory and antitumor effects, elucidating their structure–activity relationships is essential for advancing our understanding and requires future research.

As coal mining operations extend deeper underground, the importance of refuge chambers as temporary shelters for miners grows given the heightened risk of accidents. The severe geothermal conditions in deep mines present significant challenges to temperature regulation within these chambers, potentially subjecting miners to hazardous heat exposure. The utilization of phase change plates (PCPs) presents a promising approach to improving temperature regulation performance. To systematically investigate the enhancement effects of nano-graphite particles (NGPs) and fin structures on the thermal performance of phase change materials (PCMs), this study conducted thermophysical property tests and temperature-controlled melting experiments to analyze the influence of varying NGP concentrations on the thermal characteristics of PCMs, while observing their melting behavior. Four PCP models were designed: base PCM, PCM with NGPs, plate fin, and pin fin. Based on the enthalpy-porosity method, numerical simulations were performed to systematically evaluate the melting kinetics and temperature regulation performance of each design under extended operation conditions. The findings indicate that while NGP doping markedly increases the thermal conductivity and peak melting temperature of the PCM, it also results in a reduction in latent heat capacity. The NGP-enhanced No. 25 paraffin wax (RT25) PCP reduced the surface temperature by 1.02 °C compared to the base material. During extended operation, the NGP-based model outperformed others, maintaining effective temperature regulation for 149.8 h, 13 h longer than the base PCM and exceeding the standard requirement by 53.8 h. This underscores its notable advantages in thermal management. These advancements offer a valuable reference for the utilization of PCP in refuge chambers, thereby augmenting their temperature regulation capabilities.

The volume-regulated anion channel (VRAC) is formed by LRRC8 proteins and is responsible for the regulatory volume decrease (RVD) after hypotonic cell swelling. Besides chloride, VRAC transports other molecules, for example, immunomodulatory cyclic dinucleotides (CDNs) including 2′3′cGAMP. Here, we identify LRRC8C as a critical component of VRAC in T cells, where its deletion abolishes VRAC currents and RVD. T cells of Lrrc8c−/− mice have increased cell cycle progression, proliferation, survival, Ca2+ influx and cytokine production—a phenotype associated with downmodulation of p53 signaling. Mechanistically, LRRC8C mediates the transport of 2′3′cGAMP in T cells, resulting in STING and p53 activation. Inhibition of STING recapitulates the phenotype of LRRC8C-deficient T cells, whereas overexpression of p53 inhibits their enhanced T cell function. Lrrc8c−/− mice have exacerbated T cell-dependent immune responses, including immunity to influenza A virus infection and experimental autoimmune encephalomyelitis. Our results identify cGAMP uptake through LRRC8C and STING–p53 signaling as a new inhibitory signaling pathway in T cells and adaptive immunity.Concepcion et al. show that the volume-regulated anion channel LRRC8C mediates the transport of cGAMP in T cells, resulting in a noncanonical STING–p53-dependent suppression of Ca2+ influx, T cell proliferation and cytokine production.

Over-accumulation of oxalate in humans may lead to nephrolithiasis and nephrocalcinosis. Humans lack endogenous oxalate degradation pathways (ODP), but intestinal microbes can degrade oxalate using multiple ODPs and protect against its absorption. The exact oxalate-degrading taxa in the human microbiota and their ODP have not been described. We leverage multi-omics data (>3000 samples from >1000 subjects) to show that the human microbiota primarily uses the type II ODP, rather than type I. Furthermore, among the diverse ODP-encoding microbes, an oxalate autotroph, Oxalobacter formigenes , dominates this function transcriptionally. Patients with inflammatory bowel disease (IBD) frequently suffer from disrupted oxalate homeostasis and calcium oxalate nephrolithiasis. We show that the enteric oxalate level is elevated in IBD patients, with highest levels in Crohn’s disease (CD) patients with both ileal and colonic involvement consistent with known nephrolithiasis risk. We show that the microbiota ODP expression is reduced in IBD patients, which may contribute to the disrupted oxalate homeostasis. The specific changes in ODP expression by several important taxa suggest that they play distinct roles in IBD-induced nephrolithiasis risk. Lastly, we colonize mice that are maintained in the gnotobiotic facility with O. formigenes , using either a laboratory isolate or an isolate we cultured from human stools, and observed a significant reduction in host fecal and urine oxalate levels, supporting our in silico prediction of the importance of the microbiome, particularly O. formigenes in host oxalate homeostasis.

Although the intestinal microbiome has been increasingly implicated in autoimmune diseases, much is unknown about its roles in Multiple Sclerosis (MS). Our aim was to compare the microbiome between treatment-naïve MS subjects early in their disease course and controls, and between Caucasian (CA), Hispanic (HA), and African American (AA) MS subjects. From fecal samples, we performed 16S rRNA V4 sequencing and analysis from 45 MS subjects (15 CA, 16 HA, 14 AA) and 44 matched healthy controls, and whole metagenomic shotgun sequencing from 24 MS subjects (all newly diagnosed, treatment-naïve, and steroid-free) and 24 controls. In all three ethnic groups, there was an increased relative abundance of the same single genus, Clostridium , compared to ethnicity-matched controls. Analysis of microbiota networks showed significant changes in the network characteristics between combined MS cohorts and controls, suggesting global differences not restricted to individual taxa. Metagenomic analysis revealed significant enrichment of individual species within Clostridia as well as particular functional pathways in the MS subjects. The increased relative abundance of Clostridia in all three early MS cohorts compared to controls provides candidate taxa for further study as biomarkers or as etiologic agents in MS.

Makeup is widely used in modern society and has a positive effect on perceived attractiveness. However, little is known about the other possible outcomes of makeup use. In this study, we investigated whether makeup enhances a receiver’s emotional experience. Dynamic faces with or without makeup are presented in Experiments 1 and 2. Participants were asked to imagine themselves video chatting with a target person (expresser) with different expressions: neutral, angry, sad, or happy, and then to appraise their own subjective emotional experience. Emotional valence, arousal, and willingness to communicate were also assessed in Experiment 2. The results showed that makeup improved perceived facial attractiveness and increased the willingness to communicate. More importantly, it revealed that wearing makeup could weaken receivers’ negative experiences arising from the angry and sad conditions, which is not the case for the non-makeup condition, but could not affect the happy contagion. Furthermore, incremental changes in the amount of makeup were not accompanied by incremental changes in emotional appraisal (valence and arousal). Overall, we found that makeup may affect emotional contagion and interpersonal communication. Whether the alleviated negative experience due to makeup is adaptive may need further discussion.

Background Primary malignant cardiac tumors are rare in clinic, and surgical resection under cardiopulmonary bypass (CPB) remains the main treatment. The non-physiological perfusion process of CPB leads to contact activation, and the resulting coagulopathy and systemic inflammatory response syndrome (SIRS) are common complications. However, it is difficult to predict the impact of foreign tumor fragments on this pathophysiological process once they enter the bloodstream, making this phenomenon more complex and challenging. Case Presentation We report a case of cardiac intimal sarcoma who developed severe coagulopathy and widespread inflammation after excision of massive right ventricular tumor and replacement of tricuspid valve by median sternotomy under CPB. Although the procedure was expected to cause tumor cell necrosis and precautions were taken, uncontrolled massive postoperative bleeding, persistent fever, abnormally elevated inflammatory markers, and recurrent malignant arrhythmias occurred after surgery. In addition to common factors, the most possible underlying mechanism is contact activation triggered following surgical procedure for intimal sarcoma with CPB. Conclusion Patients with intracardiac malignant tumors are at a high risk for serious contact activation during CPB. Preventive application of comprehensive anti-inflammatory measures such as drugs and adsorptive CPB technology, as well as point-of-care (POC) monitoring of coagulation status will be helpful for individualized guidance and optimization of CPB management, and improvement of patient prognosis.

The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylor i to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but remained stable in controls. Urinary pH increased after antibiotics, but urinary oxalate did not differ between the control and treatment groups. In subjects not on antibiotics, the O. formigenes -positive samples had higher alpha-diversity and significantly differed in Beta-diversity from the O. formigenes -negative samples. Specific taxa varied in abundance in relation to urinary oxalate levels. These studies identified significant antibiotic effects on O. formigenes colonization and urinary electrolytes and showed that overall microbiome structure differed in subjects according to O. formigenes presence. Identifying a consortium of bacterial taxa associated with urinary oxalate may provide clues for the primary prevention of kidney stones in healthy adults.