Synthesis and Biological Evaluation of 3-(Pyridine-3-yl)-2-Oxazolidinone Derivatives as Antibacterial Agents

In this research, a series of 3-(pyridine-3-yl)-2-oxazolidinone derivatives was designed, synthesized, and evaluated for in vitro antibacterial activity, which included bacteriostatic, morphological, kinetic studies, and molecular docking. The results demonstrated that compounds 21b, 21d, 21e and 21f exhibited strong antibacterial activity similar to that of linezolid toward five Gram-positive bacteria. After observing the effect of the drug on the morphology and growth dynamics of the bacteria, the possible modes of action were predicted by molecular docking. Furthermore, the antibiofilm activity and the potential drug resistance assay was proceeded. These compounds exhibited universal antibiofilm activity and compound 21d showed significant concentration-dependent inhibition of biofilm formation. Compound 21d also showed a stable effect on S. pneumoniae (ATCC 49619) with less drug resistance growth for 15 days, which is much longer than that of linezolid. Overall, these results can be used to guide further exploration of novel antimicrobial agents

Exploring Mirror Twin Higgs Cosmology with Present and Future Weak Lensing Surveys

We explore the potential of precision cosmological data to study non-minimal dark sectors by updating the cosmological constraint on the mirror twin Higgs model (MTH). The MTH model addresses the Higgs little hierarchy problem by introducing dark sector particles. In this work, we perform a Bayesian global analysis that includes the latest cosmic shear measurement from the DES three-year survey and the Planck CMB and BAO data. In the early Universe, the mirror baryon and mirror radiation behave as dark matter and dark radiation, and their presence modifies the Universe's expansion history. Additionally, the scattering between mirror baryon and photon generates the dark acoustic oscillation process, suppressing the matter power spectrum from the cosmic shear measurement. We demonstrate how current data constrain these corrections to the $\Lambda$CDM cosmology and find that for a viable solution to the little hierarchy problem, the proportion of MTH dark matter cannot exceed about $30\%$ of the total dark matter density, unless the temperature of twin photon is less than $30\%$ of that of the standard model photon. While the MTH model is presently not a superior solution to the observed $H_0$ tension compared to the $\Lambda$CDM+$\Delta N_{\rm eff}$ model, we demonstrate that it has the potential to alleviate both the $H_0$ and $S_8$ tensions, especially if the $S_8$ tension persists in the future and approaches the result reported by the Planck SZ (2013) analysis. In this case, the MTH model can relax the tensions while satisfying the DES power spectrum constraint up to $k \lesssim 10~h\rm {Mpc}^{-1}$. If the MTH model is indeed accountable for the $S_8$ and $H_0$ tensions, we show that the future China Space Station Telescope (CSST) can determine the twin baryon abundance with a $10\%$ level precision.Comment: 32 pages, 12 figures, 4 table

ErbB2 and p38γ MAPK Mediate Alcohol-Induced Increase in Breast Cancer Stem Cells and Metastasis

Background: Both epidemiological and experimental studies suggest that excessive alcohol exposure increases the risk for breast cancer and enhances metastasis/recurrence. We have previously demonstrated that alcohol enhanced the migration/invasion of breast cancer cells and cancer cells overexpressing ErbB2/HER2 were more sensitive to alcohol exposure. However, the underlying mechanisms remain unclear. This study was designed to investigate the mechanisms underlying alcohol-enhanced aggressiveness of breast cancer. Cancer stem cells (CSCs) play a critical role in cancer metastasis and recurrence. Methods: We evaluated the effect of chronic alcohol exposure on mammary tumor development/metastasis in MMTV-neu transgenic mice and investigated the cell signaling in response to alcohol exposure in breast cancer cells overexpressing ErbB2/HER2. Results and discussion: Chronic alcohol exposure increased breast cancer stem cell-like CSC population and enhanced the lung and colon metastasis in MMTV-neu transgenic mice. Alcohol exposure caused a drastic increase in CSC population and mammosphere formation in breast cancer cells overexpressing ErbB2/HER2. Alcohol exposure stimulated the phosphorylation of p38γ MAPK (p-p38γ) which was co-localized with phosphorylated ErbB2 and CSCs in the mammary tumor tissues. In vitro results confirmed that alcohol activated ErbB2/HER2 and selectively increased p-p38γ MAPK as well as the interaction between p38γ MAPK and its substrate, SAP97. However, alcohol did not affect the expression/phosphorylation of p38α/β MAPKs. In breast cancer cell lines, high expression of ErbB2 and p-p38γ MAPK was generally correlated with more CSC population. Blocking ErbB2 signaling abolished heregulin β1- and alcohol-stimulated p-p38γ MAPK and its association with SAP97. More importantly, p38γ MAPK siRNA significantly inhibited an alcohol-induced increase in CSC population, mammosphere formation and migration/invasion of breast cancer cells overexpressing ErbB2. Conclusions: p38γ MAPK is downstream of ErbB2 and plays an important role in alcohol-enhanced aggressiveness of breast cancer. Therefore, in addition to ErbB2/HER2, p38γ MAPK may be a potential target for the treatment of alcohol-enhanced cancer aggressiveness

Human Angiostrongyliasis Outbreak in Dali, China

Angiostrongyliasis, caused by the rat lungworm Angiostrongylus cantonensis, is a potentially fatal food-borne disease. It is endemic in parts of Southeast Asia, the Pacific Islands, Australia, and the Caribbean. Outbreaks have become increasingly common in China due to the spread of efficient intermediate host snails, most notably Pomacea canaliculata. However, infections are difficult to detect since the disease has a rather long incubation period and few diagnostic clinical symptoms. Reliable diagnostic tests are not widely available. The described angiostrongyliasis epidemic in Dali, China lasted for eight months. Only 11 of a total of 33 suspected patients were clinically confirmed based on a set of diagnostic criteria. Our results demonstrate that the rapid and correct diagnosis of the index patient is crucial to adequately respond to an epidemic, and a set of standardized diagnostic procedures is needed to guide clinicians. Integrated control and management measures including health education, clinical guidelines and a hospital-based surveillance system, should be implemented in areas where snails are a popular food item

First-principles study of the O2 and Cl2 molecules adsorption on the pristine and doped boron nitride nanotubes

The adsorptions of the oxygen (O2) and chlorine (Cl2) on pristine and impurity X atom (X=C, Al, Si, Ca, Mn, Fe, Co, Ni, Cu or Ge) doped (10,0) and (6,6) boron nitride nanotubes (BNNTs) have been theoretically studied using first-principles approach based on density functional theory (DFT). Comparing with the formation energy, the distance between gas molecule and X atoms, the Bader charge transfer and the elevation of dopant atom, we find that the O2 or Cl2 molecule undergoes weakly physical adsorption on the pristine (10,0) and (6,6) BNNTs, and the Al, Si and Mn atoms are suitable dopants to modify BNNTs to enhance the reactivity of tube to gas molecule. This work reveals that the sensitivity of BNNT-based chemical gas sensors for O2 and Cl2 can be drastically improved by introducing appropriate dopant, and Al, Si and Mn doped BNNTs can be used as O2 and Cl2 gas sensor manufacturing raw materials.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author