Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

Hepatocellular carcinoma(HCC)has become the second leading cause of cancer-related death worldwide,ranking 6th among all tumors.Due to the lack of obvious early symptoms,most patients are diagnosed in the advanced stage,and the clinical benefits of surgical resection and hepatic artery chemoembolization and radiofrequency ablation are very limited.In recent years,the advent of immune-targeted therapies has revolutionized the systemic and systemic treatment of patients with advanced HCC,however,there is a lack of strong clinical evidence on the safety and efficacy of immune and targeted therapies for special populations,including patients with human immunodeficiency virus(HIV)infection,active autoimmune disease,decompensated cirrhosis(Child B or C),patients with diabetes-associated metabolic syndrome,patients with portal hypertension,vascular invasion,or portal vein thrombosis(PVT),and patients with liver transplantation(LT).This article reviews the current research progress of immune and targeted drugs in special populations.

Objective To explore the mechanism of Baihu Decoction in the treatment of acute lung injury based on network pharmacology and molecular docking technology;To carry out experimental verification.Methods The active components and targets of Baihu Decoction were searched through TCMSP and BATMAN-TCM databases,and human gene searches were conducted in GeneCards,NCBI,and OMIM databases.PPI network construction and GO and KEGG pathway enrichment analysis were conducted to determine the important signaling pathways of Baihu Decoction and acute lung injury.Molecular docking of main active components and core target proteins was performed.The effects of Baihu Decoction on survival rate and inflammatory cytokine content in acute lung injury lethal model mice were observed through animal experiments.Results Totally 211 common targets for Baihu Decoction and acute lung injury were screened,and identified effective components such as quercetin,kaempferol,and stigmasterol,etc.Analysis of KEGG pathway enrichment indicated that Baihu Decoction exerted its pharmacological effects in acute lung injury through a variety of signal pathways,including Toll-like receptor signaling pathway,NOD-like receptor signaling pathway,T cell receptor signaling pathway,and MAPK signaling pathway.Molecular docking results showed that Baihu Decoction had good binding strength with MAPK14,STAT3,JUN,MAPK1,MAPK3,FOS and RELA.The results of animal experiments showed that compared with the model group,the survival rate of mice in the Baihu Decoction group was significantly increased,the degree of pathological injury in the lung tissue was reduced,and serum IL-6,TNF-α contents decreased significantly(P<0.05).Conclusion Baihu Decoction can treat acute lung injury by reducing pathological injury to lung tissue and releasing of inflammatory factors.

China has entered a stage of deep aging. The expanding aging population and subsequently an aging labor force pose significant challenges to China’s social and economic development. European Union (EU) countries have entered the aging phase earlier and to a greater extent. To address the labor shortage and the rising dependency ratio, the EU has implemented a series of policies and measures, including raising retirement age, promoting flexible retirement, enhancing work flexibility, improving welfare for elderly workers, creating age-friendly environments, focusing on occupational health, strengthening knowledge and skills training, and leveraging digital technologies in the workplace. These measures aim to prevent premature exit of elderly workers, better balance their work and life needs, improve occupational health and skills, and enhance overall work efficiency of companies. This review discussed the experience and lessons learned from the EU countries in addressing the aging workforce from the perspectives of occupational health and occupational skills development, aiming to provide rational suggestions to assist China in better adapting the challenges of aging workforce after steadily and orderly advancing the gradual reform of the statutory retirement age, thereby improving the efficiency of the overall workforce and the stability of the labor market, driving the talent dividend of highly educated and skilled middle-aged and elderly employees, and ultimately promoting sustained economic and social development.

Objective To evaluate the effectiveness and safety of Yiyang Pill in preventing and treating cardiovascular adverse reactions in patients with traditional Chinese medicine(TCM)syndrome with qi and yin deficiency and thyroid stimulating hormone(TSH)inhibition after differentiated thyroid cancer(DTC)resection.Methods A randomized,double-blind,placebo-controlled clinical trial was conducted,and 120 patients with TSH inhibition after DTC surgery were enrolled and randomized into two groups in a 1∶1 ratio using SAS 9.4 software generated random tables.The control group received a placebo and TSH suppression therapy,whereas the treatment group received the Yiyang Pill and TSH suppression therapy.The treatment period was 3 months.The incidence of cardiovascular adverse reactions,blood pressure,blood lipids,thyroid function,the dosage of levothyroxine,the efficacy of TCM syndrome,and safety indicators were compared between the two groups.Multivariate Logistic regression was used to analyze the influencing factors of cardiovascular adverse reactions.Results The incidence of cardiovascular adverse reactions in the treatment group was lower than that in the control group(P<0.05),and the efficacy of TCM syndrome treatment was significantly higher than in the control group(P<0.05).The free tetraiodothyronine level in the treatment group was higher than that before treatment(P<0.05),and the systolic and diastolic blood pressure in the control group increased compared to those before treatment(P<0.05).No severe adverse events were observed in either group.Compared with the control group,the cardiovascular incidence in the treatment group was lower,and the cardiovascular incidence in the<100 μg/d group was lower than that in the group with≥100 μg/d before treatment.Conclusion The Yiyang Pill can reduce the incidence of cardiovascular adverse reactions in patients after DTC surgery,effectively improve TCM syndromes,and be safe to use.Yiyang Pill treatment is a protective factor for cardiovascular adverse reactions,and the dosage of levothyroxine≥100 μg/d was a risk factor.

Acute myocardial infarction (AMI) is a prevalent and serious cardiovascular disease characterized by a complex inflammatory response and myocardial tissue remodeling. The early inflammatory response plays a key role in the aftermath of AMI, promoting myocardial injury and repair. At the same time, ventricular remodeling, as a physiological process after AMI, involves myocardial hypertrophy, fibrosis, dilation, and remodeling, which has a profound impact on cardiac function and prognosis. Therefore, it is of great significance to understand the mechanism of action of early inflammation and ventricular remodeling after AMI. In this paper, the mechanism of early inflammation and ventricular remodeling after AMI was systematically reviewed, focusing on the dynamic changes of inflammatory mediators after AMI and the correlation between ventricular remodeling and prognosis, hoping to provide guidance and reference for the prevention, treatment, and prognosis of AMI.

Objective:To investigate the risk factors of pathological complete response(pCR)after neoadjuvant therapy for locally advanced gastric cancer(LAGC)and assess the value of gastric tumor markers for predicting pCR in LAGC patients.Methods:We retrospectively ana-lyzed the clinical and pathological characteristics of 213 patients who underwent radical gastrectomy and gastric tumor marker analysis after neoadjuvant therapy at The Chinse PLA General Hospital First Medical Center,between January 2020 and April 2024(20 and 193 cases in the pCR and non-pCR groups,respectively).The interrelationships among pCR,tumor markers,and clinicopathological features were compared,and independent risk factors for pCR were analyzed.A nomogram was constructed to predict the pCR.Results:Among 213 patients,20(9.4% )achieved pCR.Univariate analysis showed that age(P=0.067),tumor bed diameter(P<0.001),gastrin-17 levels(P=0.005),CA72-4 levels(P=0.073),pepsinogen ratio(P=0.024),and neoadjuvant immunotherapy(P=0.022)were strongly associated with pCR in LAGC pa-tients.Multivariate analysis showed that neoadjuvant immunotherapy,CA72-4 levels<2.5 U/mL,gastrin-17 levels<1.48 pmol/L,and tumor bed diameter<2.85 cm were independent predictive factors for pCR in LAGC patients(P<0.05).These indicators were incorporated into a nomogram prediction model;an receiver operating characteristic curve(ROC)was plotted with an AUC(95% CI)of 0.863(0.785-0.942).The calibration and decision curves suggested that the nomogram was well calibrated and had a good net benefit.Conclusions:Gastric tumor markers can effectively predict pCR after neoadjuvant therapy in LAGC patients.Our nomogram showed a good predictive ability for pCR.Thus,our findings can serve as a useful reference for clinical decision making for LAGC patients.