Infections caused by Candida species, especially Candida albicans, threaten the public health and create economic burden. Shortage of antifungals and emergence of drug resistance call for new antifungal therapies while natural products were attractive sources for developing new drugs. In our study, fangchinoline, a bis‐benzylisoquinoline alkaloid from Chinese herb Stephania tetrandra S. Moore, exerted antifungal effects on planktonic growth of several Candida species including C. albicans, with MIC no more than 50 μg/mL. In addition, results from microscopic, MTT and XTT reduction assays showed that fangchinoline had inhibitory activities against the multiple virulence factors of C. albicans, such as adhesion, hyphal growth and biofilm formation. Furthermore, this compound could also suppress the metabolic activity of preformed C. albicans biofilms. PI staining, followed by confocal laser scanning microscope (CLSM) analysis showed that fangchinoline can elevate permeability of cell membrane. DCFH‐DA staining suggested its anti‐Candida mechanism also involved overproduction of intracellular ROS, which was further confirmed by N‐acetyl‐cysteine rescue tests. Moreover, fangchinoline showed synergy with three antifungal drugs (amphotericin B, fluconazole and caspofungin), further indicating its potential use in treating C. albicans infections. Therefore, these results indicated that fangchinoline could be a potential candidate for developing anti‐Candida therapies.

TMEM16A is a recently identified calcium-activated chloride channel (CaCC) and its overexpression contributes to tumorigenesis and progression in several human malignancies. However, little is known about expression of TMEM16A and its clinical significance in colorectal cancer (CRC). TMEM16A mRNA expression was determined by quantitative real time-PCR (qRT-PCR) in 67 CRC tissues and 24 para-carcinoma tissues. TMEM16A protein expression was performed by immunohistochemistry in 80 CRC tissues. The correlation between TMEM16A expression and clinicopathological parameters, and known genes and proteins involved in CRC was analyzed. The results showed that TMEM16A mRNA expression was frequently detected in 51 CRC tissues (76%), whereas TMEM16A protein expression was determined at a relatively lower frequency (26%). TMEM16A mRNA expression in tumor tissues was higher than its expression in normal para-carcinoma tissues (P < 0.05). TMEM16A mRNA expression was significantly correlated with TNM stage (p = 0.039) and status of lymph node metastasis (p = 0.047). In addition, there was a strong positive correlation between TMEM16A mRNA expression and MSH2 protein. More importantly, TMEM16A protein expression was positively associated with KRAS mutation, and negatively correlated with mutant p53 protein. Logistic regression analysis demonstrated that TMEM16A mRNA expression was an important independent predictive factor of lymph node metastasis (OR = 16.38, CI: 1.91–140.27, p = 0.01). TMEM16A mRNA and protein expression was not significantly related with patient survival. Our findings provide original evidence demonstrating TMEM16A mRNA expression can be a novel predictive marker of lymph node metastasis and TMEM16A protein expression may be an important regulator of tumor proliferation and metastasis in CRC.

The human opportunistic fungal pathogenCandida albicanscauses a severe health burden while the biofilms formed byC. albicanspresent a kind of infections that are hard to cure, highlighting the pressing need for new antifungal drugs againstC. albicans. This study was to explore the antifungal activities of lycorine hydrochloride (LH) againstC. albicans. The minimal inhibitory concentration (MIC) of LH againstC. albicansSC5314 was 64μM. Below its MIC, LH demonstrated antivirulence property by suppressing adhesion, filamentation, biofilm formation, and development, as well as the production of extracellular phospholipase and exopolymeric substances (EPS). The cytotoxicity of LH against mammalian cells was low, with half maximal inhibitory concentrations (IC₅₀) above 256μM. Moreover, LH showed a synergistic effect with AmB, although its interaction with fluconazole, as well as caspofungin, was indifferent. Thus, our study reports the potential use of LH, alone or in combination with current antifungal drugs, to fightC. albicansinfections.

Colorectal cancer (CRC) metastasis remains a clinically intractable challenge, where the partial epithelial-mesenchymal transition (partial EMT) state is a key driver of metastatic plasticity and treatment resistance. The calcium-activated chloride channel ANO1 (TMEM16A) is frequently overexpressed in epithelial tumors, yet its mechanism in regulating metastasis and partial EMT remains undefined. In this study, we identify ANO1 as a key stabilizer of the partial EMT state. ANO1 was upregulated in CRC tissues and correlated with poor patient survival. Functionally, ANO1 knockdown robustly suppressed CRC cell proliferation, migration, and invasion, and potently induced early apoptosis. Proteomic profiling linked ANO1 depletion to the downregulation of cytoskeletal and adhesion networks. Given the centrality of these processes to EMT, we specifically examined key EMT-associated molecules. Western blot results showed that ANO1 silencing reduced expression of mesenchymal markers (N-cadherin, vimentin, α-SMA) and EMT transcription factors (Zeb1, Snail, Twist), while also downregulating the epithelial marker E-cadherin. Immunofluorescence revealed that ANO1 depletion disrupted a spatially organized hybrid subcellular architecture, and flow cytometry demonstrated that ANO1 knockdown selectively depleted the E-cadherin⁺/vimentin⁺ partial EMT subpopulation. Collectively, these data indicated that ANO1 depletion actively dismantles the organized architecture of the partial EMT state rather than driving a canonical phenotypic reversal. Transcriptomic and integrated multi‑omics analyses further revealed that ANO1 loss induced widespread uncoupling between transcriptional and proteomic regulation, with the mTOR and MAPK pathways enriched among "transcript‑only" changes. Consistently, ANO1 silencing reduced phosphorylation of PI3K, AKT, mTOR, and ERK without altering total protein levels, and pharmacological inhibition of either pathway phenocopied the dissolution of the partial EMT state. In summary, our work delineates a novel mechanism wherein ANO1, acting as an upstream hub, licenses metastatic progression by co‑activating PI3K/AKT/mTOR and ERK signaling to stabilize a plastic, survival‑competent partial EMT state, thereby nominating it as a promising therapeutic target for intercepting CRC dissemination.