Objective To explore an artificial intelligence (AI)-based method for automated hand hygiene monitoring and to compare the effectiveness of three algorithms (UniFormerV2, TDN, C3D) in recognizing hand hygiene steps in surgical settings, thereby aiding hospital infection control. Methods From April to October 2024, we non-invasively collected 641 video recordings of healthcare staff performing hand hygiene at four-bay scrub sinks in two tertiary hospitals using overhead HD cameras. The dataset was annotated by five trained experts for model training and validation. Results Following training on 385 samples, internal validation (n=119) showed the C3D model achieved 81% accuracy, 87% recall, and an 83% F1-score. The TDN model achieved 93%, 91%, and 92% for the same metrics. The UniFormerV2 model outperformed both, with an accuracy, recall, and F1-score of 93%—an improvement of over 10 percentage points compared to traditional CNNs (TDN, C3D). It also achieved an 84% accuracy in external validation, demonstrating strong generalization. Conclusion The UniFormerV2 model is more accurate than CNN-based models for hand hygiene step recognition and shows robust performance in external validation. It presents a viable tool for healthcare facilities to enhance hand hygiene management, ultimately improving medical quality and patient safety.

To improve the targeted therapeutic effect of magnolol (Mag) on neuroblastoma, Mag-loaded mitochondria-targeting immunoliposomes modified by datuximab (aGD2) and triphenylphosphine (TPP) (Mag/aGD2-T-ILN) were prepared, and their physicochemical properties, targeting characteristics and anti-tumor activity were evaluated. Physico-chemical properties showed that the surface of Mag/aGD2-T-ILN was smooth and spherical, with good dispersibility. The particle sizes, PDI and Zeta potentials of Mag/aGD2-T-ILN were measured to be (136.5 ± 5.1) nm, 0.184 ± 0.010 and (27.5 ± 3.6) mV, respectively. Mag/aGD2-T-ILN could release the drug continuously and slowly, and maintain good stability at 4 ℃. Cytotoxicity test exhibited that the IC50 of 2-ME/aGD2-T-ILN was (4.07 ± 0.48) µmol/L, and compared with free Mag, the toxicity of Mag/aGD2-T-ILN to SH-SY5Y cells increased by 6.4 times. Cellular binding and uptake assays suggested that Rho-aGD2-T-ILN could specifically target GD2-positive tumor cells and then further reach their mitochondria. Therapeutic efficacy indicated that Mag/aGD2-T-ILN could better suppress the growth of SH-SY5Y tumor cells in the body with lower toxicity and less side-effects. The results demonstrated that the Mag/aGD2-T-ILN nanoparticles system could achieve intracellular endocytosis through specific binding of antibodies and antigens between the carrier and the surface of tumor cells and electrostatic interaction, then effectively delivered and released the drugs into mitochondria by crossing the mitochondrial phospholipid membrane through TPP, and thus achieving mitochondria-targeting therapy of Mag/aGD2-T-ILN. Through the construction of this active targeting delivery system, the clinical application value of datuximab and Mag is improved, providing a novel approach for the clinical treatment of neuroblastoma.

Background As a traditional labor-intensive industry, the wooden furniture manufacturing sector has been facing significant occupational health hazards, notably noise exposure. Objective To understand the current status of occupational health management and workplace noise monitoring in the wooden furniture manufacturing industry in Foshan City of Guangzhou Province over the past five years (2020−2024), to clarify the exposure level of occupational noise hazards in this industry, the implementation of prevention and control measures, and their dynamic changing trends, and to provid a reference basis for formulating and optimizing targeted occupational health supervision strategies. Methods By judgment sampling method, 381 wooden furniture manufacturing enterprises in Foshan City from 2020 to 2024 were selected. Through document review, on-site investigation, and on-site testing, the basic information of the enterprise, key indicators of occupational health management (declaration of projects with occupational disease hazards, occupational health training, the setting and effect of occupational disease prevention facilities, the allocation and use of personal protective equipment, occupational health examinations, etc.) and monitoring data of noise intensity in the workplace were systematically collected. Descriptive statistical analysis was adopted to present the characteristics of enterprises and various indicators, and trend tests were used for dynamic changes of occupational health management indicators and noise intensity monitoring results between each year. Results Among the 381 enterprises, small and micro enterprises accounted for 94.0% (358/381), the overall occupational hazard exposure rate of workers was 56.7% (15199/26798), and the noise exposure rate was 45.6% (12221/26798). The report rate of projects with occupational disease hazards was 100%, the occupational health training rate of exposed workers was 69.6%, the setting rate and effectiveness rate of noise prevention facilities were 24.9% and 95.8% respectively, the distribution rate and effective wearing rate of noise protection earplugs/earmuffs were 77.6% and 87.1% respectively, and the rate of occupational health examinations for noise-exposed workers and the abnormal rate were 55.4% and 2.5% respectively. The trend analysis results showed that the rates of occupational health training, setting and effectiveness of noise prevention facilities, distribution and effective wearing of noise protection earplugs/earmuffs, occupational health examinations for noise-exposed workers, and abnormal health examination results all showed an overall upward trend (P values were all<0.05). The proportion of workplace noise intensity greater than 85 dB(A) and the rate of noise exceeding standards at work positions both showed an overall upward trend (P values were both<0.01). Conclusion During the period from 2020 to 2024, the occupational health management in the wooden furniture manufacturing industry in Foshan City has achieved certain positive progress, particularly in areas such as the installation of protective facilities, the use of personal protective equipment, and the implementation of occupational health examinations. However, workplace noise hazards have not been effectively controlled. Moving forward, regulatory efforts must consolidate existing management achievements while strengthening mandatory requirements and support for the technical transformation of high-noise processes and the widespread adoption of noise reduction facilities. This approach is essential to fundamentally curb occupational noise hazards.

To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*