Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease.

Regulatory T (Treg) cells and T helper type 17 (Th17) cells play important roles in adaptive immune responses, antagonizing each other in immune disorders. Th17/Treg balance is critical to maintaining the immune homeostasis of human bodies and is tightly regulated under healthy conditions. The transcription factors that are required for driving Th17 and Treg cell lineages differentiation respectively, RORγt and FOXP3 are tightly regulated under different tissue microenvironment, especially the transcriptional induction, posttranslational modifications, and dynamic enzymatic cofactors binding. The imbalance caused by alteration of the quantity or properties of RORγt+ Th17 or FOXP3+ Treg can contribute to inflammatory disorders in humans. Restoring Th17/Treg balance by modifying the enzymatic activities of RORγt and FOXP3 binding partners may be therapeutically applied to treat severe immune disorders. In this review, we focus on the transcriptional and posttranslational regulations of Th17/Treg balance, immune disorders caused by Th17/Treg imbalance, and new therapeutic strategies for restoring immune homeostasis.

Spatially modulated snapshot computed tomographic polarization imaging spectrometer.

Herein, a spatially modulated snapshot computed tomographic polarization imaging spectrometer (SMSCTPIS) is proposed. This instrument can obtain spatial, intensity, and polarization information of different wavelengths of a target simultaneously. It can also alleviate certain limitations of the spatially modulated snapshot imaging polarimeter (SMSIP) based on a Savart polarizer, which cannot obtain information of different wavelengths in a single measurement. Further, it can also mitigate the need to frequently replace the filters of SMSIPs for different detection wavelengths. The paper introduces the structure and principle of the SMCTPIS first, followed by experiments confirming its accuracy. Finally, the experimental results are analyzed, and conclusions are drawn.

Spatially modulated snapshot imaging polarimeter using two Savart polariscopes.

We present a spatially modulated snapshot imaging polarimeter using two Savart polariscopes (SMSIPTS). Not only can it avoid alignment angle errors and additional phase errors of a half-wave plate (HWP), it can also avoid changing the HWP frequently when we want the target polarization state at different wavelengths and can increase some channel bandwidth to improve image quality, compared with a spatially modulated snapshot imaging polarimeter (SMSIP). The alignment angle error and additional phase errors of SMSIP and the optical layout and principle of SMSIPTS are derived first. The full Stokes polarization images can be obtained by processing the interferogram. Based on SMSIPTS, we determine the filtering method by simulation. We proved the feasibility of SMSIPTS, and the effect of SMSIPTS and SMSIP on reconstruction is compared by simulation. Last, we experimentally verified the feasibility of the theory of SMSIPTS.

Evaluation of a High-Intensity Green Fluorescent Protein Fluorophage Method for Drug- Resistance Diagnosis in Tuberculosis for Isoniazid, Rifampin, and Streptomycin.

A novel method for detecting drug resistance in Mycobacterium tuberculosis using mycobacteriophage Φ (2) GFP10 was evaluated with clinical isolates. The phage facilitates microscopic fluorescence detection due to the high expression of green fluorescence protein which also simplifies the operative protocol as well. A total of 128 clinical isolates were tested by the phage assay for isoniazid (INH), rifampin (RIF), and streptomycin (STR) resistance while conventional drug susceptibility test, by MGIT960, was used as reference. The sensitivities of Φ (2) GFP10 assay for INH, RIF, and STR resistance detection were 100, 98.2, and 89.3%, respectively while their specificities were 85.1, 98.6, and 95.8%, respectively. The agreement between phage and conventional assay for detecting INH, RIF, and STR resistance was 92.2, 98.4, and 93.0%, respectively. The Φ (2) GFP10-phage results could be available in 2 days for RIF and STR, while it takes 3 days for INH, with an estimated cost of less than $2 to test all the three antibiotics. The Φ (2) GFP10-phage method has the potential to be a valuable, rapid and economical screening method for detecting drug-resistant tuberculosis.

Pyrazinamide resistance among multidrug-resistant tuberculosis clinical isolates in a national referral center of China and its correlations with pncA, rpsA, and panD gene mutations.

Our study was aimed to identify the phenotypic and genotypic pyrazinamide (PZA) resistance features among multidrug-resistant (MDR) isolates in a national tuberculosis (TB) referral center of China. PZA susceptibility test was performed for a total of 142 MDR-TB clinical isolates using the MGIT 960 PZA kits, and the pncA, rpsA, and panD genes were sequenced. Extensively drug-resistant (XDR) and pre-XDR strains had higher PZA resistance rate than that of MDR strains which were still sensitive to fluoroquinolone and aminoglycoside (42.9%, 24/56) (χ(2)=8.922, P=0.012). No panD mutation was detected among the PZA resistant strains with wild-type pncA and rpsA genes. Our study indicates that PZA-resistant frequency increases with TB drug resistance level; pncA, rpsA, and panD mutations had strong, low, and no correlation with PZA resistance, and rapid molecular assay will facilitate the timely identification of the PZA-sensitive MDR-TB.

Transmitted Extended-Spectrum Extensively Drug-Resistant Tuberculosis in Beijing, China, with Discordant Whole-Genome Sequencing Analysis Results.

Drug resistance to tuberculosis remains a major public health threat. Here, we report two cases of extended-spectrum extensively drug-resistant (XXDR) tuberculosis showing resistance to most first- and second-line agents. The results of a correlation of whole-genome sequencing (WGS) and phenotypic testing were discordant, suggesting that overreliance on WGS may miss clinically relevant resistance in extensively drug-resistant disease.

The Clinical Features and Bacteriological Characterizations of Bone and Joint Tuberculosis in China.

Bone and Joint tuberculosis (BJTB) constitutes about 10% of total extra-pulmonary TB cases. Since the BJTB is a paucibacillary condition, there has been no systematic study on the bacterial characterization, especially the epidemiological feature. Here we collected the mycobacterial clinical isolates, analyzed the clinical features and the bacteriological characteristics from 113 BJTB cases reported in China. The mean age of the cases was 40.33 years while most of the patients fell into the 20-29 year age group; local pain was the most common onset symptom of BJTB cases; mean time from symptom onset to BJTB diagnosis was 13.16 months. 31 isolates were defined as drug resistant, including 15 multidrug resistant (MDR) and 2 extensively drug resistant (XDR) isolates according to the drug susceptibility test outcomes; after spoligotyping, 87.6% (99/113) isolates were categorized as Beijing family. In contrast to the isolates from pulmonary tuberculosis patients, here the MIRU-VNTR assay did not find anything significant. A prolonged time span for BJTB diagnosis highlights the requirement of paying further attention to BJTB infection in China. This study provides essential insights into the demographic and microbial characteristics of BJTB cases in China.

Xpert MTB/RIF and GenoType MTBDRplus assays for the rapid diagnosis of bone and joint tuberculosis.

BACKGROUND: Bone and joint tuberculosis (BJTB) constitutes about 10-20% of the extrapulmonary tuberculosis (EPTB) cases in China. The GenoType MTBDRplus assay (MTBDR) has been endorsed by the World Health Organization (WHO) for the diagnosis of pulmonary TB (PTB), while the Xpert MTB/RIF assay (Xpert) has also been endorsed by the WHO for the diagnosis of both PTB and EPTB. The diagnostic utility of these two techniques for BJTB was investigated prospectively. METHODS: Sixty pus specimens were obtained from orthopedic patients. Smear, culture, Xpert, and MTBDR assays were performed for each specimen, and MGIT 960-based drug susceptibility testing (DST) was conducted for all of the isolates recovered. The diagnostic efficiency of Xpert and MTBDR was evaluated on the basis of bacteriological examination and the composite reference standard (CRS). RESULTS: Fifty of the 60 patients were considered to have BJTB according to the CRS. The sensitivities of smear, culture, Xpert, and MTBDR were 26% (13/50), 48% (24/50), 82% (41/50), and 72% (36/50) respectively, while the specificities of all of the tests were 100% (10/10). Xpert was 100% concordant with MGIT 960-based DST for the detection of rifampicin resistance. MTBDR had a sensitivity of 83.3% and a specificity of 100% for the detection of rifampicin resistance and a sensitivity of 85.7% and specificity of 100% for the detection of isoniazid resistance. CONCLUSION: With their high sensitivities, short turnaround times, and ability to diagnose TB and detect drug resistance simultaneously, both Xpert and MTBDR are feasible as diagnostic tools for BJTB in clinical practice.