The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2.The analysis of mutant nucleic acid (NA) variants can provide crucial clinical and biological insights for many diseases. Yet, existing analysis techniques are generally constrained by nonspecific "noise" signals from excessive wildtype background sequences, especially under rapid isothermal multiplexed target amplification conditions. Herein, the molecular hybridization chemistry between NA bases is manipulated to suppress noise signals and achieve ultraselective multiplexed detection of cancer gene fusion NA variants. Firstly, modified locked NA (LNA) bases are rationally introduced into oligonucleotide sequences as designed "locker probes" for high affinity hybridization to wildtype sequences, leading to enrichment of mutant variants for multiplexed isothermal amplification. Secondly, locker probes are coupled with a customized "proximity-programmed" (SERS) readout which allows precise control of hybridization-based plasmonic signaling to specifically detect multiple target amplicons within a single reaction. Moreover, the use of triple bond Raman reporters endows NA noise signal-free quantification in the Raman silent region (≈1800-2600 cm-1 ). With this dual molecular hybridization-based strategy, ultraselective multiplexed detection of gene fusion NA variants in cancer cellular models is actualized with successful noise suppression of native wildtype sequences. The distinct benefits of isothermal NA amplification and SERS multiplexing ability are simultaneously harnessed.Colorectal cancer (CRC) is the third most common cancer worldwide. Even if 5-fluorouracil (5-FU) is used as the first-line chemotherapeutic drug, responsiveness is only 20-30%. Acquired resistance to 5-FU contributes to both poor patient prognosis and relapse, emphasizing the need to identify biomarkers. Sortilin, a vacuolar protein sorting 10 protein (Vps10p), implicated in protein trafficking, is over expressed in CRC cell lines cultured 72 hours in presence of 5-FU. This overexpression was also observed in 5-FU-resistant cells derived from these cell lines as well as in CRC primary cultures (or patients derived cell lines). A significantly higher expression of sortilin was observed in vivo, in 5-FU-treated tumours engrafted in Nude mice, as compared with non-treated tumour. A study of transcriptional regulation allowed identifying a decrease in ATF3 expression, as an explanation of sortilin overexpression following 5-FU treatment. In silico analysis revealed SORT1 expression correlation with poor prognosis. Moreover, sortilin expression was found to be positively correlated with CRC tumour grades. Collectively, our findings identify sortilin as a potential biomarker of 5-FU resistance associated with poor clinical outcomes and aggressiveness in CRC. As a new prognostic factor, sortilin expression could be used to fight against CRC.
  Understanding local perceptions of mental health in different cultures and contexts is crucial for designing and implementing appropriate mental healthcare services.
 
  This qualitative study was conducted to investigate local perceptions of mental health in two highly populated provincial districts in Iran. Data were collected using the free list technique and interviews. A two-phase training workshop was held with the research team at a local health center, followed by a pilot study with the participation of six subjects. All the interviews were audio-recorded, transcribed, and then analyzed by the third and fourth authors in DEDOOSE.
 
  A total of 30 individuals (20 in the free list and 10 as key informants in the interviews) took part in the study. Based on the study findings and the key informants' ideas, mental health problems were categorized into three categories of depression, anxiety, and obsessive-compulsive disorder (OCD).
 
  Mental health problems appear to be expressed in different ways and with different symptoms in different cultures, and there is a distinct need for examining mental disorders in each culture and nationality separately using culturally appropriate tools for disease screening.
 Mental health problems appear to be expressed in different ways and with different symptoms in different cultures, and there is a distinct need for examining mental disorders in each culture and nationality separately using culturally appropriate tools for disease screening.Nanoparticles have been widely used in detection and killing of bacteria; however, targeting bacteria is still challenging. Delicate design of nanoparticles is required for simultaneous targeting, detection, and therapeutic functions.  https://www.selleckchem.com/products/gsk963.html  Here the use of Au/MnFe2 O4 (Au/MFO) Janus nanoparticles to target Gram-positive bacteria via metabolic labeling is reported and realize integrated self-reporting and thermal killing of bacteria. In these nanoparticles, the Au component is functionalized with tetrazine to target trans-cyclooctene group anchored on bacterial cell wall by metabolic incorporation of d-amino acids, and the MFO part exhibits peroxidase activity, enabling self-reporting of bacteria before treatment. The spatial separation of targeting and reporting functions avoids the deterioration of catalytic activity after surface modification. Also important is that MFO facilitates magnetic separation and magnetic heating, leading to easy enrichment and magnetic thermal therapy of labeled bacteria. This method demonstrates that metabolic labeling with d-amino acids is a promising strategy to specifically target and kill Gram-positive bacteria.