Passively Broadband Tunable Dual Circular Dichroism via Bound States in the Continuum in Topological Chiral Metasurface.

Dynamic control for a strong circular dichroism (CD) response is essential in engineering applications such as polarization manipulation, sensing, and imaging. Here, we propose and experimentally demonstrate a broadband tunable dual CD response via bound states in the continuum (BICs) in two-dimensional topologically protected metasurfaces composed of all-dielectric Si chiral grating structures that generate a pair of mixed and degenerated BIC mode and circular dichroic mode (CDM) as an additional degree of freedom in CD manipulation. It is found that a singular CD peak of nearly 100% at 1.6 µm can be achieved by CDM when BIC is hidden under normal incidence, while the CD peak can be split into two in which peak wavelengths can be precisely and linearly tuned over a bandwidth of 180 nm by the incident angle when the BIC mode is excited under oblique incidence. Additionally, dynamic modulation of output polarization states from linear to circular can be arbitrarily achieved at the split CD peaks by controlling the incident angle when asymmetry perturbations on chiral gratings are introduced due to the decoupling of various polarization states at Γ point by BIC to different positions in K space. The proposed chiral grating metasurface exhibits unique angle-sensitive tunable CD spectral characteristics, making it ideal for hyperspectral and spin-selective wavefront shaping, and holds significant promise in various applications such as optical security, angle sensors, chiral lasers, nonlinear filters, and other active chiral optical devices.

Novel oxazolidinones harbor potent in vitro activity against the clinical isolates of multidrug-resistant Mycobacterium tuberculosis in China.

Objective: To investigate the in vitro activities of five oxazolidinones in parallel against the reference strains of different mycobacterial species and clinical isolates of Mycobacterium tuberculosis (Mtb), and shed light on the differences in the efficacy of these homolog drugs. Materials and methods: The minimum inhibitory concentrations (MICs) of linezolid, tedizolid, sutezolid, delpazolid, and contezolid against 16 mycobacterial reference strains and 69 M. tuberculosis clinical isolates, including 17 drug-susceptible isolates and 52 multidrug-resistant (MDR) isolates, were determined by microplate alamarBlue assay (MABA). The intracellular killing activities of contezolid and linezolid against Mtb H37Rv were compared. In addition, mutations in the linezolid resistance-related genes (rplC, rplD, and 23S rRNA) of the Mtb clinical isolates were also analyzed. Results: Tedizolid exhibited the strongest inhibitory activities against the reference strains of both rapidly growing mycobacteria (RGM) and slowly growing mycobacteria (SGM), among the tested oxazolidinones. In contrast, sutezolid only manifested potent activity against reference strains of SGM. Linezolid, delpazolid, and contezolid were less active against the non-tuberculous mycobacterial references. For the Mtb clinical isolates, the antimicrobial action was ranked as: sutezolid > tedizolid > contezolid and linezolid > delpazolid, whereas no difference between drug-sensitive and multiple drug-resistant isolates was observed. Notably, contezolid demonstrated obviously superior intracellular antimicrobial activity than linezolid. Few strains harbored mutations in rrl gene or rplD genes, although these strains had drug susceptible profiles to linezolid. Conclusion: Different oxazolidinones can have discrepant antimicrobial activity against different mycobacterial species, or have different manifestations out of cell or in cell. Understanding these differences would be helpful in choosing the appropriate drug in clinical practice.

Trends and Species Diversity of Non-tuberculous Mycobacteria Isolated From Respiratory Samples in Northern China, 2014-2021.

Background: Pulmonary non-tuberculous mycobacteria (NTM) infection has become a public health concern in China and around the world. The objective of this study was to describe the longitudinal changes in the frequency and diversity of NTM in northern China. Methods: We retrospectively analyzed data on mycobacterium species in Beijing Chest Hospital from January 2014 to December 2021. The isolates were identified to species level by targeted DNA sequencing. Results: After excluding duplicates, 1,755 NTM strains were analyzed, which were from 27 provinces in China over 8 years. Among all mycobacteria, the proportion of NTM increased each year, from 4.24% in 2014 to 12.68% in 2021. Overall, 39 different NTM species were identified, including 23 slow growing mycobacteria (SGM) and 16 rapid growing mycobacteria (RGM). The most common species were M. intracellulare (51.62%), M. abscessus (22.22%), M. kansasii (8.32%), M. avium (7.75%) and M. fortuitum (2.05%). The number of NTM species identified also increased each year from 9 in 2014 to 26 in 2021. Most species showed stable isolation rates over the years; however, the proportion of M. avium increased from 3.85 to 10.42% during the study period. Besides, 81 non-mycobacteria strains, including Gordonia (21 isolates), Nocardia (19 isolates) and Tsukamurella (17 isolates), etc., were also discovered. Conclusion: The proportion of NTM and species diversity increased considerably in northern China from 2014 to 2021. M. intracellulare was the most common NTM isolated among respiratory specimens, followed by M. abscessus and M. kansasii. Rare NTM species and non-mycobacteria pathogens also need attention.

In vitro activity of fidaxomicin against nontuberculosis mycobacteria.

Introduction. Nontuberculous mycobacteria (NTM) infections are increasing worldwide and are relatively resistant to many of the first- and second-line drugs to treat tuberculosis. Macrolide antibiotics, such as clarithromycin and azithromycin, are the key drugs for treating NTM infections. Fidaxomicin is a macrolide antibiotic that is widely used in treating Clostridium difficle (C.difficile) infections, and has high in vitro activity against Mycobacterium tuberculosis especially multidrug-resistant tuberculosis (MDR-TB) and has no cross-resistance with rifampicin.Hypothesis. Fidaxomicin may have in vitro activity against NTM strains.Aim. To find that whether the macrolide antibiotic fidaxomicin has in vitro activity against NTM strains.Methodology. Fidaxomicin used in this study was firstly tested on C. difficile reference strains and has shown to be effective and workable. And then 28 rapidly growing mycobacteria (RGM), 12 slowly growing mycobacteria (SGM) reference strains and 103 NTM clinical isolates were tested by the microplate-based AlamarBlue assay (MABA) method to determine the MICs. Fidaxomicin, rifampicin and clarithromycin were tested against M. abcessus complex subspecies 14 M. abscessus and 5 M. massiliense strains for inducible resistance determination.Results. In total, 21 out of 28 RGM and 9 of 12 SGM reference strains have the MICs of fidaxomicin at or below 1 µg ml-1. Fidaxomicin also showed low MIC values for some clinical isolates including M. abscessus complex, M. avium complex, M. fortuitum, M. kansasii and M. parascrofulaceum. Fidaxomicin also has no inducible macrolide resistance in M. abscessus complex in comparison with clarithromycin.Conclusion. Fidaxomicin has high in vitro activity against most of the NTM reference strains and some prevalent NTM clinical isolates. This promising finding warrants further investigation on the actions of fidaxomicn in vivo and as a potential antibiotic for NTM treatment.

Extremely high levels of central nervous system involvement in miliary tuberculosis.

BACKGROUND: Miliary tuberculosis (TB) is one of the severest manifestations of TB that can be lethal when concomitant with the central nervous system (CNS) involvement. Bacteriological, biochemical and radiological methods for find CNS comorbidity in miliary TB was evaluated in this study. METHODS: Consecutive miliary TB adults were retrospectively enrolled from two designated TB hospitals in China. The capacities of examinations of cerebrospinal fluid (CSF), cerebral computed tomography (CT) and magnetic resonance imaging (MRI) for diagnosis of CNS involvement were assessed. RESULTS: Assessment of CNS involvement with a lumbar puncture and/or neuroimaging was undertaken in 282 out of 392 of acute miliary TB. Of these 282 patients, 87.59% (247/282) had CNS involvement. Cerebral contrast-enhanced MRI (96.05%, 170/177) and MRI (93.15%, 204/219) yielded significantly higher sensitivities over CSF examination (71.92%, 146/203, P < 0.001) and CT (34.69%, 17/49, P < 0.001). The sensitivity of CSF examination was superior to CT scan (P < 0.001). Although 59.65% (134/225) miliary TB patients acquired bacteriological evidence with sputum examination, the positivity was only 8.82% (21/238) for CSF examination by conventional and molecular tests. CONCLUSION: Almost all miliary TB had CNS involvement and MRI demonstrated outstanding potential over other methods. Therefore, a routinely screening of CNS TB should be strongly suggested in miliary TB and MRI could be used as the initial approach in resources rich settings.

Protein engineering for crystallization of the GTPase Sar1 that regulates ER vesicle budding.

Sar1 is an important and unique GTPase that regulates vesicle budding from the ER membrane. An effort to crystallize full-length hamster Sar1 was unsuccessful owing to the aggregation of Sar1 in solution as indicated by dynamic light-scattering measurements. It was presumed that a patch of hydrophobic residues in the N-terminal region of Sar1 was responsible for the aggregation. To attempt to improve protein crystallizability, the N-terminal residues of Sar1 were progressively truncated and the solution behavior of the resulting Sar1 variants was monitored by dynamic light scattering. Truncation of the first nine residues from the N-terminus led to a Sar1 variant that is monodisperse in solution. This well behaved Sar1 variant yielded crystals in just a few days that were ultimately refined to diffraction quality.