The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection.

Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine (CCL23 and CXCL5) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.

Multimodality Endoscopic Approach for Benign Central Airway Stenosis in Pediatric Tuberculosis: A Case Report.

More children are benefitting from the wide application of bronchoscopy as interventional therapy to complications with airway involvement. We present the case of an 11-year-old boy with tracheobronchial tuberculosis complicated by severe obstruction in the left main bronchus. Early interventional endoscopic balloon dilation and cryoablation were adopted as adjunct therapy to his anti-tuberculosis treatment and had shown satisfying treatment outcomes.

How Does the Change of Information Source Affect Residents' Risk Attitudes?

Using data from the China Family Panel Studies (CFPS), this paper investigates the effects of Internet use on residents' risk attitudes. Both Generalized Ordered Logit Model and Logit model are used to identify the effects of Internet use. The results reveal an association between Internet use and increases in both subjective and objective risk preferences that remains even after we adjust for possible endogeneity. The heterogeneity analysis also reveals that these impacts are different among groups with different reasons for Internet use and different personal characteristics. Our study expands the research on the effects of Internet on people's concepts from the micro perspective and suggests that while promoting the application of information technology we should also pay attention to the individual characteristics of residents so that we can better share the "digital dividend" brought by the popularization of information technology in the whole society.

LncRNA CCAT1 is overexpressed in tuberculosis patients and predicts their survival.

INTRODUCTION: LncRNA CCAT1 promotes inflammatory responses, which contribute to tuberculosis. Therefore, CCAT1 may participate in tuberculosis. Therefore, we analyzed the involvement of CCAT1 in tuberculosis. METHODS: Plasma samples were donated by a total of 200 patients with newly developed tuberculosis (N-TB), 102 patients with recurrent tuberculosis (R-TB), and 102 healthy controls on the day of admission. Plasma samples were also collected from N-TB and R-TB patients every month after the initiation of treatment for a total of 6 months. CCAT1 expression in these samples was detected by quantitative reverse transcription polymerase chain reaction. Levels of IFN-γ, IL-1ß, iNOS, TNF-α, and IL-10 in plasma were determined by enzyme-linked immunosorbent assay. N-TB and R-TB patients were monitored for 2 months to analyze their survival. RESULTS: On the day of admission, the highest levels of CCAT1, IFN-γ, IL-1ß, iNOS, and TNF-α were detected in N-TB patients, followed by R-TB patients and controls, while the lowest levels of plasma IL-10 were detected in N-TB patients, followed by R-TB patients and controls. Across R-TB and N-TB patients, CCAT1 was inversely correlated with IL-10 but not closely correlated with other inflammatory factors. During the treatment, plasma CCAT1 levels decreased in both N-TB and R-TB patients. High CCAT1 levels were closely correlated with high mortality rates of both N-TB and R-TB patients. CONCLUSION: CCAT1 is overexpressed in tuberculosis patients and predicts their survival. Its function in tuberculosis may be related to IL-10.

Performance optimization of multi-plane light conversion (MPLC) mode multiplexer by error tolerance analysis.

The linear polarized (LP) mode multiplexer based on the inverse designed multi-plane light conversion (MPLC) has the advantages of low insertion loss and low mode crosstalk. However, the multiplexer also requires the fabrication and alignment accuracy in experiments, which have not been systematically analyzed. Here, we perform the error tolerance analysis of the MPLC and summarize the design rules for the LP mode multiplexer/demultiplexer. The error tolerances in the fabrication process and experimental demonstration are greatly released with proper parameters of the input/output optical beam waist, the pitch of optical beam array, and the propagation distances between the phase plane. To proof this design rule, we experimentally demonstrate the LP mode multiplexer generating LP01, LP11a, LP11b, LP21 modes and coupling to the few mode fiber, with the insertion loss lower than -5 dB. The LP modes are demultiplexed by MPLC, with the crosstalk of different mode groups lower than -10 dB. LP modes carrying 10 Gbit/s on-off keying signals transmit in a 5 km few mode fiber. The measured bit error rates (BER) curves of the LP01, LP11a, LP21 modes have the power penalties lower than 12 dB.

Pharmacokinetic studies of the recombinant chicken interferon-α in broiler chickens.

In this study, 24 male and female broiler chickens at 30-day-old were divided into three groups with 8 animals in each group. The animals were administered with recombinant chicken interferon-α (rChIFN-α) at a dose of 1.0 × 106 IU/kg intravenously, intramuscularly or subcutaneously, respectively. Serum samples were collected at different time points post administration, and the titers of rChIFN-α in the blood were determined by cytopathic effect inhibition assay. The results showed that the pharmacokinetic characteristics of rChIFN-α by intramuscular injection and subcutaneous injection were fitted to one compartment open model, and the Tmax was 3.21 ± 0.79 hr and 3.95 ± 0.85 hr, respectively, and the elimination half-life (T1/2) was 6.20 ± 2.77 hr and 5.03 ± 3.70 hr, respectively. In contrast, the pharmacokinetics of rChIFN-α via intravenous injection was in line with the open model of two-compartment and was eliminated in the first order, and the elimination half-life (T1/2) was 4.61 ± 0.84 hr. In addition, compared with those in the intravenous group and the subcutaneous group, the bioavailability of rChIFN-α in the intramuscular group was 82.80%. In conclusion, rChIFN-α was rapidly absorbed and slowly eliminated after intramuscular administration of single dose of rChIFN-α aqueous formulations. Thus, rChIFN-α can be used as a commonly-used therapeutic agent.

An updated patent therapeutic agents targeting MMPs.

The traditional consensus that matrix metalloproteinases (MMPs) has correlation with various pathological and physiological processes led to the exploitation of a vast number of natural or synthetic broad-spectrum MMP inhibitors (MMPIs) for the prophylaxis or treatment of various MMP-related disorders, such as autoimmune, inflammatory, cardiovascular, neurodegenerative, respiratory diseases, and malignant cancer as well. Yet the unsatisfactory preclinical and/or clinical results motivated further investigation of the physiological roles of certain MMP subtypes. Despite the intricate and complicated MMP functions in normal physiology and disease pathology, the effort of designing specific inhibitors that can selectively target certain MMP family members for individualized therapy is ongoing and remains an arduous task. Success will rely on continued insight into the biological roles of these multifaced proteases. In our previous effort, we summarized various MMPIs that have entered preclinical or clinical trials as well as the patents in regard to MMPIs (Recent Pat Anticancer Drug Discov. 2010; 5(2): 109-41). In our on-going review, to illustrate the major challenges in MMP validation as druggable targets, we highlighted the physiological and pathological roles of representative MMPs, with an emphasis on description of the newly emerging MMPI-based patents, in particular, the inhibitors containing sulfonamide or sulfone motif. By analyzing the structural characteristics and selectivity profiles of these supplementary inhibitors, we hereby described their pharmaceutical application, and also expanded the strategies for potent MMPI design.

Recent advances in the development of MMPIs and APNIs based on the pyrrolidine platforms.

Pyrrolidine scaffold has been widely used to design a variety of N-heterocyclic derivatives towards various targets. Amongst them, matrix metalloproteins (MMPs) and aminopeptidase N (APN) represent two kinds of important metalloproteinase targets which have been proved to be tightly related to tumor proliferation, invasion, metastasis and angiogenesis. As a result, their respective inhibitors, namely MMP inhibitors (MMPIs) and APN inhibitors (APNIs), have been systematically studied in our group for many years. Recent advances in the elucidation of MMPIs and APNIs based on the pyrrolidine platforms are briefly reviewed in this paper.

Novel aminopeptidase N inhibitors derived from antineoplaston AS2-5 (Part I).

Overexpression of zinc-dependent metalloproteinase, aminopeptidase N (APN/CD13), is considered to be involved in the process of tumor invasion and metastasis. Herein we describe the synthesis and in vitro enzymatic inhibition assay of antineoplaston AS2-5 scaffold peptidomimetic compounds. The results demonstrated that most of these L-iso-glutamine derivatives displayed selective inhibitory activity against APN as compared with MMP-2, with IC(50) values in the micromole range. The structure-activity relationships were also briefly discussed.

Strategies to overcome or circumvent P-glycoprotein mediated multidrug resistance.

Cancer patients who receive chemotherapy often experience intrinsic or acquired resistance to a broad spectrum of chemotherapeutic agents. The phenomenon, termed multidrug resistance (MDR), is often associated with the over-expression of P-glycoprotein, a transmembrane protein pump, which can enhance efflux of a various chemicals structurally unrelated at the expense of ATP depletion, resulting in decrease of the intracellular cytotoxic drug accumulation. The MDR has been a big threaten to the human health and the war fight for it continues. Although several other mechanisms for MDR are elucidated in recent years, considerable efforts attempting to inverse MDR are involved in exploring P-glycoprotein modulators and suppressing P-glycoprotein expression. In this review, we will report on the recent advances in various strategies for overcoming or circumventing MDR mediated by P-glycoprotein.