Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation.

Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4+ T cells was explored in a HAVCR2-/- mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4+ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.

Catalytic Asymmetric Intermolecular [3 + 2] Photocycloaddition of Cyclopropylamines with Electron-Deficient Olefins.

An enantioselective intermolecular [3 + 2] cycloaddition of N-arylcyclopropylamines with 2-aryl acrylates/ketones and cyclic ketone-derived terminal olefins via asymmetric photoredox catalysis is reported. A dual catalyst system involving DPZ and a chiral phosphoric acid is effective for the transformations, leading to a wide array of valuable cyclopentylamines with high yields, ee's, and drs. Among them, elaborate modulation of the ester group of 2-aryl acrylates was shown to be effective in improving reactivity, thereby enabling the success of the transformations.

Asymmetric [3 + 2] photocycloadditions of cyclopropylamines with electron-rich and electron-neutral olefins.

Radical addition to olefins is a common and useful chemical transformation. In the context of offering enantioenriched three-dimensional molecules via such a highly reactive process, chiral hydrogen-bonding (H-bonding) catalysis has been widely used to provide enantiocontrol. The current strategies for operating H-bonding induction are confined to following that are prevalent in ionic-type manifolds. Here, we report a novel protocol towards electron-rich olefins based on converting these species from acting as H-bonding donors to acceptors. It facilitates the first development of asymmetric [3 + 2] photocycloadditions with cyclopropylamines. The method is also effective for electron-neutral olefins, in which the successful construction of all-carbon quaternary stereocentres from 1,1-diaryl ethylenes that feature two structurally similar aryl substituents demonstrates the versatility of this new chiral H-bonding catalytic strategy. Furthermore, the importance of the obtained six kinds of products in pharmaceuticals and asymmetric catalysis underscores the practicability of this work.

Disseminated Coinfection by Mycobacterium fortuitum and Talaromyces marneffei in a Non-HIV Case.

BACKGROUND: Mycobacterium fortuitum is a rapidly growing non-tuberculous mycobacterium (NTM) with weak pathogenicity. Here, we present a rare case of disseminated M. fortuitum and Talaromyces marneffei coinfection in a human immunodeficiency virus (HIV) negative patient. CASE PRESENTATION: A 28-year-old female was admitted to our hospital due to 2 months of swelling of lymph nodes on the right side of her cervix, accompanied by repeated low fever for more than 1 month. Biopsy of the right cervical lymph node and endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) both suggested granulomatous inflammation. The bacterial culture and mycobacteria examination of the lesion as well as HIV antibody test were all negative. Disseminated T. marneffei infection was diagnosed by the quantitative polymerase chain reaction (qPCR) results from the blood showing 1798 copies/ul. In the meantime, treatment with amphotericin B combined with cefoxitin was administered for suspected NTM infection. However, the once-dropped fever recurred and the lymph nodes continued to swell. Metagenomics next-generation sequencing (mNGS) detection of the lymph nodes indicated M. fortuitum. After combination treatment with amphotericin B, voriconazole, linazolamide, and imipenem, the patient's body temperature returned to normal, the lymph node swelling was gradually reduced, and the lung lesion was absorbed. CONCLUSION: We report the first case of an HIV-negative patient diagnosed with disseminated M. fortuitum and T. marneffei coinfection with nonspecific clinical manifestation, in order to heighten awareness of these infections.

Primary salivary gland tumors of the lung: Two cases date report and literature review.

BACKGROUND: Primary salivary gland-type tumors of the lung (PSGTTL) is a rare intrathoracic malignant tumor that accounts for all lungs <1% of tumors. PURPOSE: To introduce two case reports of primary lung salivary gland tumors, and highlight their diagnosis and treatment challenges. CASE REPORT: The first case was a 30-year-old female, who complained of repeated coughing and dyspnea for 1 year and worsening for 2 days. Chest CT and bronchoscopy showed new organisms in the lower part of the trachea, that the bronchus obstruction accounted for 70%. The biopsy histology revealed a adenoid cystic carcinoma. She underwent extensive surgical resection and multiple radiotherapy, and She is recovering well from follow-up. The second case was a 70-year-old man, who complained of intermittent sputum blood for 2 years, worsening hemoptysis and chest tightness for 3 months. The new organisms was found in the upper trachea from Chest CT and bronchoscopy, and histological biopsy was used to diagnose epithelial myoepithelial carcinoma. He underwent twice bronchoscopy thermal ablation treatments. The follow-up is currently in good condition. CONCLUSION: Primary lung salivary gland tumors are considered to be rare malignant tumors in the lungs. Early detection is advocated as late presentation with advanced tumor presents diagnostic and therapeutic challenges.

Hsa_circ_0067997 promotes the progression of gastric cancer by inhibition of miR-515-5p and activation of X chromosome-linked inhibitor of apoptosis (XIAP).

Circular RNAs (circRNAs) have been revealed to play vital roles in modulating gene expression and participate in several pathological responses including gastric cancer (GC). However, the larger numbers of the circRNAs in GC progression remain undetermined. In the present study, four GC related circRNAs expression profiles from the Gene Expression Omnibus (GEO) database were enrolled. We identified hsa_ circRNA_00067997 (circ_0067997) as an oncogene in GC. qRT-PCR was used to validate the expression of circ_0067997 in GC tissues and cell lines. The results revealed that circ_0067997 was upregulated in GC, and high circ_0067997 expression was associated with the poor overall survival rate of GC patients. Knockdown of circ_0067997 significantly reduced cell viability, inhibited colony formation, and attenuated invasive ability, whereas overexpression of circ_0067997 exhibited opposed effects. Circ_0067997 was identified to be a sponge for miR-515-5p directly. Moreover, XIAP was demonstrated to be targeted and regulated by miR-515-5p. In conclusion, circ_0067997 was identified to be an oncogene in GC by regulating miR-515-5p/XIAP axis.

Bioactive alkaloids from the aerial parts of Houttuynia cordata.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata is an important traditional Chinese medicine used in heat-clearing and detoxifying, swelling and discharging pus, promoting diuresis and relieving stranguria which recorded in Pharmacopoeia of the people's Republic of China (2015 Edition). H. cordata has been recorded in the book Bencaogangmu which was written by Shizhen Li for the treatment of pyretic toxicity, carbuncle swelling, haemorrhoids, and rectocele diseases. AIM OF THE STUDY: Phytochemical investigation of the aerial parts of H. cordata and evaluation of their PTP1B inhibitory activities and hepatoprotective activities. MATERIALS AND METHODS: The dried aerial parts of H. cordata were fractionated by liquid-liquid extraction to obtain CHCl3, ethyl acetate, and n-butanolic fractions. The CHCl3 fraction was confirmed active fraction by the bioactivity-guided investigation, which was isolated and purified by chromatographing over silica gel, Sephadex LH-20, MPLC, and preparative HPLC. The chemical structures of the purified compounds were identified by their spectroscopic data and references. RESULTS: Eight new compounds (1-8), together with fourteen known compounds (9-22) were isolated from the aerial parts of H. cordata. The known compounds (9-22) were obtained from this plant for the first time. Among them, some compounds exhibited moderate bioactivities. CONCLUSION: Compounds (1-8) were identified as new alkaloids, and the known alkaloids (9-22) were isolated from this plant for the first time. Compounds 1, 4, 14, and 19 showed significant PTP1B inhibitory activities with IC50 values of 1.254, 2.016, 2.672, and 1.862µm, respectively. Compounds 1, 3, 6, 11, 17, and 20 (10µm) exhibited moderate hepatoprotective activities against D-galactosamine-induced WB-F344 cells damage.

KOtBu-Promoted Oxidation of (Hetero)benzylic Csp3-H to Ketones with Molecular Oxygen.

An efficient and practical (hetero)benzylic sp3 C-H oxidation method has been developed. Notably, this user-friendly protocol employs inexpensive potassium tert-butoxide (KOtBu) as a promoter and proceeds under mild conditions using oxygen as the oxidant. A large variety of oxidation products were prepared in good to excellent yields. The utility of this "green" methodology was further demonstrated by the scale-up preparation of a biologically valued molecule.

Cross-section measurements for (n, 2n) and (n, alpha) reactions on yttrium at neutron energies from 13.5 to 14.6 MeV.

The cross sections for the reactions (89)Y(n, 2n) (88m+g)Y and (89)Y(n, alpha) (86m+g)RB induced by 14MeV neutrons have been measured using the activation technique and a coaxial HPGe gamma-ray detector. Spectroscopically pure Y(2)O(3) powder was used. Fast neutrons were produced by the T(d, n) (4)He reaction. The neutron fluencies were determined using the monitor reaction (93)Nb(n, 2n) (92m)Nb.

Studies on intestinal permeability of cirrhotic patients by analysis lactulose and mannitol in urine with HPLC/RID/MS.

The method for separation and determination of lactulose (L) and mannitol (M) in urine was developed by HPLC with a refractive index detector (RID). The linearity ranged from 5 to 1000 microg/mL for L and M, respectively. Recoveries ranged from 93.1% to 97.1%. The intra- and inter-day relative standard deviations of peak area were between 0.8-1.4% (n=3) and 1.4-3.6% (n=3). The limits of detection were obtained with 1.40 microg/mL for L and 1.65 microg/mL for M. The ratios of L/M in the urine samples for the spontaneous ascitic fluid infection (SAI), sterile ascitic fluid (SA) patients, and healthy volunteers (HV) were determined. The results showed well the correlations among the L/M ratio, intestinal permeability (IP) and the illness status of patients, and also indicated lactulose could improve the IP of SAI patients. The peaks of L and M in chromatograms were identified by electrospray ionization/mass spectrometry (ESI/MS), which ensured the accurate measurement of the ratio L/M. This method presented a rapid, accurate, and practical technique for determining IP in clinical practice and investigating the pathology of hepatocirrhosis.