Biofilms produced by Candida albicans (C. albicans) are intrinsically resistant to fungicidal agents, which are a main cause of the pathogenesis of catheter infections. Several lines of evidence have demonstrated that calcineurin inhibitor FK506 or cyclosporine A (CsA) can remarkably enhance the antifungal activity of fluconazole (FLC) against biofilm-producing C. albicans strain infections. The aim of present study is thus to interrogate the mechanism underpinning the synergistic effect of FLC and calcineurin inhibitors. Twenty four clinical C. albicans strains isolated from bloodstream showed a distinct capacity of biofilm formation. A combination of calcineurin inhibitor CsA and FLC exhibited a dose-dependent synergistic antifungal effect on the growth and biofilm formation of C. albicans isolates as determined by a XTT assay and fluorescent microscopy assay. The synergistic effect was accompanied with a significantly down-regulated expression of adhesion-related genes ALS3, hypha-related genes HWP1, ABC transporter drug-resistant genes CDR1 and MDR1, and FLC targeting gene, encoding sterol 14alpha-demethylase (ERG11) in clinical C. albicans isolates. Furthermore, an addition of CsA significantly reduced the cellular surface hydrophobicity but increased intracellular calcium concentration as determined by a flow cytometry assay (p < 0.05). The results presented in this report demonstrated that the synergistic effect of CsA and FLC on inhibited C. albicans biofilm formation and enhanced susceptibility to FLC was in part through a mechanism involved in suppressing the expression of biofilm related and drug-resistant genes, and reducing cellular surface hydrophobicity, as well as evoking intracellular calcium concentration.

The objective of this study was to explore the molecular epidemiology and the genetic support of clinical multidrug resistant (MDR) Acinetobacter baumannii (A. baumannii) isolates in an ICU ward of a comprehensive hospital. A total of 102 non-duplicate drug-resistant A. baumannii isolates were identified and 93 (91.1%) of them were MDR strains. Molecular analysis demonstrated that carbapenemase genes bla_OXA-23 and bla_OXA-51 were presented in all 93 MDR isolates (100%), but other carbapenemase genes, including bla_OXA-24, bla_OXA-58, bla_IMP-1, bla_IMP-4, bla_SIM, and bla_VIM genes were completely absent in all isolates. In addition, genes of AdeABC efflux system were detected in 88.2% (90/102) isolates. Interestingly, an addition to efflux pump inhibitor, reserpine could significantly enhance the susceptibility of MDR isolates to moxifloxacin, cefotaxime, and imipenem (p < 0.01). Clonal relationship analysis further grouped these clinical drug-resistant isolates into nine clusters, and the MDR strains were mainly in clusters A, B, C, and D, which include 16, 13, 25, and 15 isolates, respectively. This study demonstrated that clinical isolates carrying carbapenemase-encoding genes bla_OXA-23 and AdeABC efflux pump genes are the main prevalent MDR A. baumannii, and the co-expression of oxacillinase and efflux pump proteins are thus considered to be the important reason for the prevalence of this organism in the ICU of this hospital.

Sensitive and selective detection of cancer biomarkers is crucial for early diagnosis and treatment of cancer, one of the most dangerous diseases in the world. Metal-organic frameworks (MOFs), a class of hybrid porous materials fabricated through the assembly of metal ions/clusters and organic ligands, have attracted increasing attention in the sensing of cancer biomarkers, due to the advantages of adjustable size, high porosity, large surface area and ease of modification. MOFs have been utilized to not only fabricate active sensing interfaces but also arouse a variety of measurable signals. Several representative analytical technologies have been applied in MOF-based biosensing strategies to ensure high detection sensitivity toward cancer biomarkers, such as fluorescence, electrochemistry, electrochemiluminescence, photochemistry and colorimetric methods. In this review, we summarized recent advances on MOFs-based biosensing strategies for the detection of cancer biomarkers in recent three years based on the categories of metal nodes, and aimed to provide valuable references for the development of innovative biosensing platform for the purpose of clinical diagnosis.

Lanatoside C (LanaC), a cardiac glycoside, has been reported to possess therapeutic potential in acute intestinal inflammation; however, its in vivo effects on ulcerative colitis (UC) remain incompletely understood. In this study, we demonstrated that LanaC effectively attenuates DSS-induced colitis in mice by reducing inflammation, mitigating epithelial damage, and preserving barrier integrity. Mechanistically, LanaC treatment was associated with reduced macrophage infiltration in the colon and spleen, suppression of pro-inflammatory M1 macrophage markers, and enhancement of M2-associated markers. In vitro, LanaC inhibited LPS-induced M1 polarization and pro-inflammatory cytokine production in BMDMs, while promoting IL-4-driven M2 polarization and anti-inflammatory cytokine expression. These effects were accompanied by attenuation of STAT1/STAT3 signaling and enhancement of STAT6 activation, suggesting a selective reprogramming of macrophage responses. Collectively, these findings reveal that LanaC alleviates DSS-induced colitis, at least in part, through regulating macrophage infiltration and repolarization supporting its potential as a macrophage-targeted therapeutic candidate in UC.

Background: Adolescent lower respiratory infections (LRIs) are one of the major public health problems worldwide. Utilizing data from Global Burden of Disease 2021 (GBD 2021), this study aimed to investigate the trends and distribution characteristics of the burden of LRIs among children and adolescents from global to local levels, as well as to assess inequalities in disease burden. Unlike previous GBD reports, our analysis provides unprecedented subnational resolution across 953 global locations, uncovering local inequalities often masked in national-level estimates. Methods: We conducted an extensive analysis of the impact of LRIs across 953 global regions. This investigation included various metrics, including prevalence, incidence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs). Additionally, we performed an inequality analysis and a frontier analysis pertinent to the sociodemographic index (SDI). Results: From 1990 to 2021, the incidence rate among adolescents decreased by 55.8%, and the DALYs rate decreased by 76.7%. Mortality rates decreased from 127.7 (95% uncertainty interval [UI]: 110.9 to 149.7) in 1980 to 21.2 (95% UI: 17.5 to 25.5) in 2021. In 2021, there were still 1.8 million adolescents worldwide suffering from LRIs. Among 652 local administrative regions, Mandera in Kenya had the highest incidence rate at 7,743.6 (95% UI: 6,876.8–8,715.6), and Sokoto in Nigeria had the highest DALYs rate at 16,663.3 (95% UI: 11,825.8–22,776.3). Since 1990, the global burden of LRIs among adolescents has significantly decreased, but regional disparities remain significant. From 1990 to 2021, the slope index of inequality (SII) for incidence rates and DALYs rates decreased by 56.8% and 81.5%, respectively, with higher disease burdens in low- and low- middle-SDI regions. In 2021, only 14.2% reached the incidence rate frontier level, and 15.2% reached the DALYs rate frontier level. Conclusions: Substantial progress has been made in reducing the burden of LRIs, but the burden remains heavy, particularly in low- and low- middle SDI regions. Trend analysis provides scientific evidence for international aid and policy-making to address inequalities.