The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.

C-Reactive protein(CRP)is an important acute-phase response protein,which is widely used in the assessment of inflammation and cardiovascular disease risk,and acts as a pathogenic factor directly involved in the disease process of certain conditions.Therefore,developing immunosuppressants targeting CRP or investigating its pathogenic mechanisms is of significant importance.Most B-cell epitopes are conformational epitopes,and studying conformational epitopes is typically challenging.To date,no methods have been reported for mapping the conformational epitopes of CRP in solution.In this study,a rapid strategy was developed for studying conformational epitopes by combining hydrogen/deuterium exchange mass spectrometry(HDX-MS)with multiparametric prediction of B-cell epitopes and protein secondary structure analysis.This approach was successfully applied to the binding sites and allosteric targets of the 115 kDa full pentameric CRP and the clinically used monoclonal antibody(mAb)5A8.The results showed that the amino acid residues 84-103,138-146,and 165-173 together form the potential conformational epitopes for mAb 5A8 on CRP,while the amino acid residues 21-32 and 175-178 were identified as potential allosteric targets.The discovery of the mAb 5A8 binding sites and allosteric targets was crucial for improving clinical diagnostic capabilities.Experimental results demonstrated that this workflow allowed rapid conformational epitope mapping of CRP under near-physiological conditions,with advantages such as high speed,high sensitivity,and high throughput.

Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

Objective:To investigate the relationship between the level of angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) in the uterine fluid and the thickness of endometrium in infertile women with chronic endometritis.Methods:A case-control study was conducted to select 122 patients who underwent hysteroscopy and endometrial tissue biopsy at Assisted Reproduction Center, Taiyuan Central Hospital due to infertility from March 2023 to January 2024 as the study subjects. According to the results of hysteroscopy and endometrial tissue biopsy, the patients were divided into 52 cases in the infertility group with normal endometrium (NE infertility group) and the chronic endometritis combined with infertility group (CE infertility group) with 70 cases. Enzyme-linked immunosorbent assay was used to detect the level of AT1-AA in uterine fluid of the two groups. General clinical data, AT1-AA absorbance value of uterine fluid and uterine related indexes of the two groups were analyzed, and the correlations between AT1-AA level and the variation of indexes were analyzed.Results:Gravidity (median: 1 vs 1; Z=7.029, P=0.030) and parity (median: 0 vs 0; Z=12.258, P=0.002) in CE infertility group were higher than those in NE infertility group. There was AT1-AA in the uterine fluid, and the level of AT1-AA in CE infertility group was significantly higher than that in NE infertility group (median: 2.07 vs 1.44; Z=3.099, P=0.029). The endometrial thickness of CE infertility group was lower than that of NE infertility group (median: 6.0 vs 7.0 mm; Z=-2.179, P=0.029), and there were no statistical differences in other indexes between the two groups (all P>0.05). Further correlation analysis showed that there were no correlation between the level of AT1-AA in uterine fluid and parity, endometrial thickness, gravidity in NE infertility group (all P>0.05). However, the level of AT1-AA in uterine fluid of CE infertility group was positively correlated with parity (Spearman′s r=0.339, P=0.004), and negatively correlated with endometrial thickness (Spearman′s r=-0.499, P<0.001), but not correlated with gravidity ( P>0.05). Conclusions:AT1-AA is present in the uterine fluid of infertile women. The elevated level of AT1-AA in uterine fluid of infertile women with CE is related to the thinning of the endometrium.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

Aim To explore the action mechanism of isoquercitrin(IQ)in ameliorating anxiety based on network pharmacology,cellular transcriptomics,molecu-lar docking and animal experiments.Methods The common targets of anxiety disorders and IQ were ob-tained by using relevant databases.The protein-protein interaction network,the biological function and signa-ling pathway enrichment analysis were conducted by u-sing the common targets.Primary hippocampal neurons were cultured in vitro,and corticosterone was added to induce neurons to establish a corticosterone injury mod-el.IQ treatment was added to the culture system,and transcriptomics was used to screen for differentially ex-pressed genes and enrich for differentially expressed pathways.Subsequently,the results were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Possible targets and signaling pathways for IQ treatment on anxiety were speculated and screened u-sing network pharmacology,transcriptomics and molec-ular docking.The anxiety rat model was constructed,and the anxiety state of rats was evaluated after IQ in-tervention,and the protein expression level of hippo-campus was detected to verify the relevant mechanism.Results Network pharmacology,cellular transcrip-tome,and molecular docking analyses revealed that the key mechanism of IQ for anxiety may be related to the BDKRB2/PI3K/Akt signaling pathway.Animal exper-iments showed that IQ was effective in improving anxie-ty behaviour and learning memory ability in rats.IQ increased the movement distance and residence time in the central area of the open field,the time and number percentage of entries into the open arm in the elevated plus maze,and the spontaneous alternations score in the Y maze in rats,and significantly elevated protein expression of BDKRB2,PI3K,Akt and decreased pro-tein expression of NF-κB in the hippocampus.Conclu-sions Isoquercitrin can effectively treat anxiety,and the mechanism of action may be related to the regula-tion of BDKRB2/PI3K/Akt signaling pathway in hip-pocampus.