Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Episodic memory, our ability to recall past experiences, is supported by structures in the medial temporal lobe (MTL) particularly the hippocampus, and its interactions with fronto-parietal brain regions. Understanding how these brain regions coordinate to encode, consolidate, and retrieve episodic memories remains a fundamental question in cognitive neuroscience. Non-invasive brain stimulation (NIBS) methods, especially transcranial magnetic stimulation (TMS), have advanced episodic memory research beyond traditional lesion studies and neuroimaging by enabling causal investigations through targeted magnetic stimulation to specific brain regions. This review begins by delineating the evolving understanding of episodic memory from both psychological and neurobiological perspectives and discusses the brain networks supporting episodic memory processes. Then, we review studies that employed TMS to modulate episodic memory, with the aim of identifying potential cortical regions that could be used as stimulation sites to modulate episodic memory networks. We conclude with the implications and prospects of using NIBS to understand episodic memory mechanisms.
Humans ; Memory, Episodic ; Transcranial Magnetic Stimulation/methods* ; Brain/physiology* ; Nerve Net/physiology* ; Mental Recall/physiology* ; Neural Pathways/physiology*

OBJECTIVE: To assess relationships between cold spells and genitourinary hospitalization risk. METHODS: Hospitalization records for genitourinary system diseases (GUDs) from 16 districts in Beijing (2013-2018) were analyzed. Cold spells were defined based on varying intensity thresholds. A two-stage analytical method was employed: first, generalized linear models assessed district-specific associations between cold spells and hospitalizations; second, random-effects meta-analysis aggregated the district-level results. Subgroup analyses were performed by admission type (emergency vs. outpatient), age, and sex. RESULTS: A total of 271,579 GUD-related hospitalizations were recorded. Cold spells (p1day2，daily mean temperature below the 1 ^st percentiles of the daily mean temperature distribution from January 1, 2013, to December 31, 2018, lasting for two or more consecutive days) were linked to a significant rise in hospitalization risks: 1.43 (95% CI: 1.32-1.56) for all GUDs, 1.35 (95% CI: 1.23-1.49) for urinary system diseases, and 1.46 (95% CI: 1.28-1.67) for renal failure, when compared to non-cold spell days. Emergency admissions showed higher risk increases than outpatient admissions. CONCLUSION Extreme cold spells significantly elevate hospitalization risks for GUDs. This highlights the urgent need for targeted public health interventions to mitigate cold-related health impacts, especially for vulnerable populations.
Humans ; Hospitalization/statistics & numerical data* ; Male ; Female ; Cold Temperature/adverse effects* ; Infant ; Child, Preschool ; Middle Aged ; Adult ; Child ; Aged ; Adolescent ; Young Adult ; Beijing/epidemiology* ; Female Urogenital Diseases/etiology* ; Male Urogenital Diseases/etiology* ; Infant, Newborn ; Risk Factors

The bottom-up construction of artificial cells to mimic signal transduction is of great significance for a deep understanding of the communication networks of complex living systems.The dynamic coupling of signal secretion and response among artificial cells poses an important challenge.In this work,two types of artificial cells were constructed through a bio-artificial hybrid strategy.One was an artificial cell as an AI-2 signal sender(sender),which contained bacteria capable of autonomously synthesizing AI-2 signaling molecules.The other was an artificial cell as an AI-2 signal receiver(receiver),which contained bacteria expressing green fluorescent protein in response to the corresponding AI-2 signal.When the ratio of senders to receivers was 4∶1,the fluorescent signal of the receivers gradually increased over time and reached a plateau at 240 minutes.The artificial cells capable of sending and receiving quorum sensing signaling molecules constructed in this work laid a foundation for the study of complex signal communication within artificial cell populations.

Arson is classified as a violent crime,and often involves accelerants that significantly increase casualties and property damage.These accelerants,typically flammable liquids with low saturated vapor pressure,present volatile characteristic components in fire residues,making evidence preservation critical for accurate forensic analysis.In this study,the preservation performance of AMPAC(American KAPAC polyester sampling bags)and polyethylene(PE)evidence bags were evaluated under simulated field conditions(40 oC)through gas chromatography-mass spectrometry(GC-MS)technique,focusing on background interference,sealing integrity,and cross-contamination.The results demonstrated that AMPAC bags exhibited minimal background interference(C12?C14 alkanes detected after 3?7 days)and effective gasoline sealing,though slight losses of C2?C3 alkylbenzenes and trace cross-contamination were observed.In contrast,PE bags showed significant background hydrocarbons(C15?C19 alkanes)and pronounced gasoline component losses,including C2?C4 alkylbenzenes,naphthalenes,and indenes.Notably,severe cross-contamination of gasoline markers was detected in adjacent blank PE bags,with characteristic components such as C2?C4 alkylbenzenes,naphthalenes,methylnaphthalenes,dimethylnaphthalenes,indenes,indanes,methylindenes,and dimethylindenes identified,indicating substantial cross-contamination issues in PE evidence bags.Microstructural analysis revealed superior sealing in AMPAC bags attributed to their smooth,dense surface morphology compared to PE's rougher,porous structure.This study established a comprehensive evaluation framework for fire residue evidence containers,and found that PE bags were unsuitable for long-term gasoline evidence preservation due to compromised integrity.These findings provided critical references for forensic container selection in fire investigations.

Objective:To investigate the clinical characteristics of pregnancy complicated with Beh?et′s disease, so as to improve the diagnosis and treatment of the disease and improve maternal and neonatal outcomes.Methods:A retrospective analysis was conducted on the clinical data of 10 pregnant women with Beh?et′s disease, who were admitted to Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to June 2024. The maternal and neonatal outcomes were analyzed.Results:The 10 pregnant women with Beh?et′s disease had a mean age of (31.2±5.3) years (range: 25-41 years). Nine were diagnosed before pregnancy and one was diagnosed during the second trimester of pregnancy. The mean age of disease onset was (20.5±6.1) years (range: 10-34 years). Clinical manifestations included oral ulcers, genital ulcers, fever, uveitis, hematochezia, diarrhea, constipation, and skin rash. Nine of them received medication during pregnancy, while one did not. The disease conditions of five women were active during pregnancy and other five remained stable. In terms of delivery mode, five women had vaginal delivery and five delivered by cesarean section. Nine delivered at term and one had preterm delivery. All neonates survived without adverse outcomes.Conclusions:The management of pregnancy complicated with Beh?et′s disease requires a multidisciplinary team approcach. Individualized decisions regarding medication, timing of delivery, and mode of delivery are essential to achieve optimal maternal and fetal outcomes.

How to effectively strengthen mutual supervision and weave a tight protective net against corruption in the medical field between the same-level leadership members in public hospitals, has become an urgent issue to be addressed for public hospitals′ leadership construction. Based on the investigation and research, the authors focused on the problems of " unwilling to supervise, afraid to supervise, unable to supervise and ineffective supervision" that existed between the same-level leadership members in public hospitals. Countermeasures and suggestions were proposed for strengthening mutual supervision between the same-level leadership members from five aspects: consolidating the ideological foundation, focusing on key points, establishing a sound supervision mechanism, purifying the political environment, and improving the evaluation system.

Nonalcoholic steatohepatitis(NASH)is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration,and it plays an important role in the progression of hepatic steatosis.Recent studies have shown that immune homeostasis imbalance between T helper 17(Th17)and regulatory T(Treg)cells are closely associated with the pathological process of NASH.Transforming growth factor-β1(TGF-β1)is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells,and TGF-β1 binds to its receptor and activates the Smad signaling pathway,thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation.This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells,in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.