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Cepharanthine (CEP) has excellent anti-SARS-CoV-2 properties, indicating its favorable potential for COVID-19 treatment. However, its application is challenged by its poor dissolubility and oral bioavailability. The present study aimed to improve the bioavailability of CEP by optimizing its solubility and through a pulmonary delivery method, which improved its bioavailability by five times when compared to that through the oral delivery method (68.07% vs. 13.15%). An ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method for quantification of CEP in rat plasma was developed and validated to support the bioavailability and pharmacokinetic studies. In addition, pulmonary fibrosis was recognized as a sequela of COVID-19 infection, warranting further evaluation of the therapeutic potential of CEP on a rat lung fibrosis model. The antifibrotic effect was assessed by analysis of lung index and histopathological examination, detection of transforming growth factor (TGF)-β1, interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and hydroxyproline level in serum or lung tissues. Our data demonstrated that CEP could significantly alleviate bleomycin (BLM)-induced collagen accumulation and inflammation, thereby exerting protective effects against pulmonary fibrosis. Our results provide evidence supporting the hypothesis that pulmonary delivery CEP may be a promising therapy for pulmonary fibrosis associated with COVID-19 infection.

Background In HBV-infected patients, different genotypes of the hepatitis B virus influence liver disease progression and response to antiviral therapy. Moreover, long-term antiviral therapy will eventually select for drug-resistant mutants. Detection of mutations associated to antiviral therapy and HBV genotyping are essential for monitoring treatment of chronic hepatitis B patients. Results In this study, a simple method of partial-S gene sequencing using a common PCR amplification was established for genotyping clinical HBV isolates sensitively, which could detect the drug-resistant mutations successfully at the same time. Conclusions The partial S gene sequencing assay developed in this study has potential for application in HBV genotyping and drug resistant mutation detection. It is simpler and more convenient than traditional S gene sequencing, but has nearly the same sensitivity and specificity when compared to S gene sequencing.

The Pt:SC2H4Ph clusters were synthesized via a modified approach in our previous work. 1 Typically, 0.1 mmol H2PtCl6 and 0.1 mmol phenylethanethiol were added to a 15 mL THF solution. After stirring for 20 min, an aqueous solution of NaBH4 (1.5 mmol) was added. Then, (ratio of thiol/Pt: 1/1) was added, and some black precipitates were immediately formed. Then the precipitates were thoroughly washed with methanol and extracted with CH2Cl2 to give Pt clusters, which are characterized by HR-MS analyses. Generation of single-atom Pt + for the non-oxidative alkane conversionThe Exactive plus EMR MS system (Thermo) is implemented with an ultraviolet laser dissociation module (Scheme S1A), where the charge detector at the back of high-energy collision dissociation (HCD) chamber was removed and an MgF2 window was implemented. The 193 nm laser of 1~2 mJ/pulse (a pulse width of 5 ns), generated by an ArF excimer laser (Gam laser, Orlando, FL, USA), was coaxially introduced into the HCD dissociation chamber though the MgF2 window. The laser beam was focused with a diameter about 2 mm. The Pt clusters were dissolved in an electrospray solution (70 v% CH2Cl2/30 v% methanol) with a concentration of 1 mg/mL. The Pt cluster ions were formed by nanoflow electrospray ionization (nano-ESI) with a spray voltage of 1.5 kV in positive MS mode and the sample injection flowrate was about 300 nL/min. The Pt + cluster ions were transferred into the HCD chamber. The excimer laser was operated in pulsed mode with pulse length of 5 ns and frequency of 3 Hz (with about 300 ms interval between S3/S39 adjacent shots), which was roughly synchronized with the duty cycle of the MS analysis and avoided the photoionization of the conversion intermediates and products.The Pt cluster dissociation-HRMS characterization experiment included following steps (Scheme S1B): the ligand-protected Pt clusters were firstly ionized by nano-ESI and guided into the HCD chamber (no activation energy was applied during the process); then, 5 ns single-shot laser was applied to dissociated the ligand-protected Pt clusters and generate the single-atom Pt cations, which was kept off during conversion and detection to avoid post-activation and ionization of the conversion intermediate and product ions; the Pt + were trapped in the HCD chamber and in-situ reacted with the alkane gas reagents (1 v% alkane gas mixed with 99 v% N2, about 20 mTorr in total; 298 K) for about 100 ms; the conversion intermediate and product ions were transfers to the orbitrap analyser in about 10 ms and characterized with a mass resolution of 140,000 (m/z = 200) before the arrive of next laser shot pulse. HRMS data were collected in a profile mode (continuous mode). 195 Pt + was utilized as the internal standard to calibrate the detected m/z values of alkane conversion species. No collision and activation energy were applied to the Pt + species during the whole alkane conversion process. DFT calculationAll DFT calculations have been performed using Gaussian 16 package 2 . B3LYP functional [3][4] ...