Exploring the regulatory role of lncRNA in cancer immunity.

Imbalanced immune homeostasis in cancer microenvironment is a hallmark of cancer. Increasing evidence demonstrated that long non-coding RNAs (lncRNAs) have emerged as key regulatory molecules in directly blocking the cancer immunity cycle, apart from activating negative regulatory pathways for restraining tumor immunity. lncRNAs reshape the tumor microenvironment via the recruitment and activation of innate and adaptive lymphoid cells. In this review, we summarized the versatile mechanisms of lncRNAs implicated in cancer immunity cycle, including the inhibition of antitumor T cell activation, blockade of effector T cell recruitment, disruption of T cell homing, recruitment of immunosuppressive cells, and inducing an imbalance between antitumor effector cells (cytotoxic T lymphocytes, M1 macrophages, and T helper type 1 cells) versus immunosuppressive cells (M2 macrophages, T helper type 2 cells, myeloid derived suppressor cells, and regulatory T cells) that infiltrate in the tumor. As such, we would highlight the potential of lncRNAs as novel targets for immunotherapy.

[Clinical observation on acupuncture for symptom burden in gastric cancer patients undergoing adjuvant chemotherapy after gastrectomy].

OBJECTIVE: To observe the efficacy of acupuncture on symptom burden in patients with gastric cancer during adjuvant chemotherapy after gastrectomy. METHODS: A total of 58 patients were randomized into a high-dose acupuncture group (19 cases, 5 cases dropped off), a low-dose acupuncture group (20 cases, 6 cases dropped off) and a control group (19 cases, 2 cases dropped off). Conventional chemotherapy and antiemetic treatment were adopted in the control group. On the basis of the treatment in the control group, acupuncture was applied 7 times each chemotherapy cycle for totally 21 times in the high-dose acupuncture group, and 3 times each chemotherapy cycle for totally 9 times in the low-dose acupuncture group. Baihui (GV 20), Zusanli (ST 36), Neiguan (PC 6), etc. were selected in the two acupuncture groups, as well as back-shu points selected by the meridian heat sensing technique. Electroacupuncture was connected to ipsilateral Zusanli (ST 36) and Neiguan (PC 6), with continuous wave, 2 Hz in frequency for 20 min. The Edmonton symptom assessment system (ESAS) score was observed on day 1-7, 14, and 21 of each cycle of chemotherapy respectively in the 3 groups. RESULTS: The symptom burden was worst within 7 days of each cycle of chemotherapy in the 3 groups. After the 3rd chemotherapy cycle, the total score of ESAS in the low-dose acupuncture group was lower than the control group (P<0.05), the total score and the scores of feeling of non-well being, pain and shortness of breath of ESAS in the acupuncture group (the high-dose acupuncture group combined with the low-dose acupuncture group) were lower than the control group (P<0.05). CONCLUSION: Acupuncture shows promising effect in controlling symptom burden during adjuvant chemotherapy in gastric cancer patients after gastrectomy.

Nrf2 dictates the neuronal survival and differentiation of embryonic zebrafish harboring compromised alanyl-tRNA synthetase.

tRNA synthetase deficiency leads to unfolded protein responses in neuronal disorders; however, its function in embryonic neurogenesis remains unclear. This study identified an aars1cq71/cq71 mutant zebrafish allele that showed increased neuronal apoptosis and compromised neurogenesis. aars1 transcripts were highly expressed in primary neural progenitor cells, and their aberration resulted in protein overloading and activated Perk. nfe2l2b, a paralog of mammalian Nfe2l2, which encodes Nrf2, is a pivotal executor of Perk signaling that regulates neuronal phenotypes in aars1cq71/cq71 mutants. Interference of nfe2l2b in nfe2l2bΔ1/Δ1 mutants did not affect global larval development. However, aars1cq71/cq71;nfe2l2bΔ1/Δ1 mutant embryos exhibited increased neuronal cell survival and neurogenesis compared with their aars1cq71/cq71 siblings. nfe2l2b was harnessed by Perk at two levels. Its transcript was regulated by Chop, an implementer of Perk. It was also phosphorylated by Perk. Both pathways synergistically assured the nuclear functions of nfe2l2b to control cell survival by targeting p53. Our study extends the understanding of tRNA synthetase in neurogenesis and implies that Nrf2 is a cue to mitigate neurodegenerative pathogenesis.

Acupuncture for Quality of Life in Gastric Cancer Patients Undergoing Adjuvant Chemotherapy.

CONTEXT: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. OBJECTIVES: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. METHODS: In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. RESULTS: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). CONCLUSION: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

Specific Gene Co-variation Acts Better Than Number of Concomitant Altered Genes in Predicting EGFR-TKI Efficacy in Non-small-cell Lung Cancer.

BACKGROUND: There occurs huge heterogeneity in clinical outcomes for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The purpose of this study was to indicate genetic biomarkers predicting primary resistance of EGFR-TKIs in these patients. PATIENTS AND METHODS: Using a next-generation sequencing panel with 168 cancer-related genes, matched tumor biopsy and plasma samples before treatments from patients with NSCLC were analyzed. Patients taking EGFR-TKIs were followed-up with imaging examination. Correlation of co-alterative genes with progression-free survival (PFS) was analyzed. RESULTS: Of the 48 patients treated with EGFR-TKIs, 46 (95.83%) had at least 1 genetic co-variant beyond EGFR mutation. Multivariate analysis indicated that RB1, PIK3CA, and ERBB2 co-alterations, rather than number of co-alterative genes, were independently associated with poorer PFS. Grouping patients by specific gene status showed best likelihood ratio χ2, Akaike information criterion, and Harrell concordance index. The median PFS for patients in group A (less genetic co-variations and wild specific genes), group B (more genetic co-variations and wild specific genes), group C (less genetic co-variations and altered specific genes), and group D (more genetic co-variations and altered specific genes) were 10.4, 9.13 (vs. group A; P = .3112), 6.33 (vs. group B; P = .0465), and 3.90 (vs. group C; P = .0309) months, respectively. CONCLUSIONS: This study revealed a high concomitant genetic alteration rate in patients with EGFR-mutated NSCLC. Specific gene variants were more important than number of altered genes in predicting poor PFS, and may help select patients needing new treatment strategies.

Relationship between degree of breast MRI background parenchymal enhancement and breast cancer subtype. / ä¹³è ºMRIèƒŒæ™¯å®žè´¨å¼ºåŒ–ç¨‹åº¦ä¸Žä¹³è ºç™Œåˆ†å­åˆ†åž‹çš„å ³ç³».

OBJECTIVES: To observe the distribution of magnetic resonance imaging (MRI) breast parenchymal enhancement (BPE) among different breast cancer subtypes and to explore the relationship between the BPE and the breast cancer tumor type. METHODS: A total of 150 consecutive patients with breast cancer underwent breast dynamic enhanced scanning image. According to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) and Ki-67, the molecular subtypes were classified into Luminal-A, Luminal-B, HER-2 over- expression, and triple-negative breast cancer. The BPE of the whole breast was evaluated and categorized as minimal, mild, moderate, or marked according to the breast imaging reporting and data system (BI-RADS). The relationship between the distribution of BPE and the breast cancer subtypes was analyzed. RESULTS: In patients with mild BPE, the incidence of Luminal-B breast cancer was significantly increased, and there were statistical differences among the Luminal-B and the luminal-A, the HER-2 over-expressed type, and the triple-negative type (all P<0.01). In the marked BPE patients, the proportion of triple negative breast cancer was the highest, and there was statistical difference among the triple-negative type and the Luminal-A, the Luminal-B, and the HER-2 over-expression types (all P<0.05). CONCLUSIONS: The BPE can be served as an additional risk stratification index in the targeted screening of breast cancer type, which can offer reference value in the clinical diagnose and individualized treatment.

Facile Approach for Synthesizing High-Performance MnO/C Electrodes from Rice Husk.

Pyrolysis is an effective way to convert biomass into biofuel while obtaining highly porous active carbon materials. In this study, a facile approach, involving hydrothermal and pyrolysis steps, is described for preparing hybrid metal oxide nanoparticle-embedded porous hard carbon matrices (MnO/C) from the biowaste rice husk and organometallic precursors. It was found that the pyrolysis/calcination temperature had a strong influence over the microstructure, especially over the porosity, but also over the carbon content and crystallinity of the nanocomposites; hence, the electrical properties can be controlled. Galvanostatic measurements showed that the nanocomposite obtained at 600 °C exhibited the highest charge/discharge capacity and best stability, delivering an initial discharge capacity of 1104 mA·h·g-1 at a current density of 200 mA·g-1, and retaining a value of 830 mA·h·g-1 after 200 cycles, suggesting excellent cycle stability. A discharge capacity of 581 mA·h·g-1 was obtained even at a current density as high as 2400 mA·g-1, demonstrating superb rate capability. This outstanding electrochemical performance, ascribed to high electrochemical activity of the embedded MnO nanoparticles enhanced by electrical conductivity provided through the high surface area of the active porous carbon support, is discussed in relation to the microstructure of the nanocomposite.

Hierarchical ZnO Superstructures: Nanoflake-Decorated Nanonail Arrays.

By using metallic Zn powders as zinc source, we synthesized unusual hierarchical ZnO superstructures, nanoflake-decorated nanonail arrays, on a large scale via a simple low-temperature thermal evaporation method. The hierarchical superstructures were characterized by using X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, high resolution transmission electron microscopy as well as selected area electron diffraction. Studies found that both the ZnO nanonails and the decorated ZnO nanoflakes are single-crystals, with the preferred growth orientations along the (001) direction. The possible formation mechanism for the interesting hierarchical superstructures has been discussed. It was found that the deposition of indium films on a Si substrate and the heterogeneous nucleation of ZnO nanoflakes on the main ZnO nanonails play key roles in the fabrication of ZnO superstructures. Moreover, these special hierarchical superstructures showed much strong and complicated photoluminescent emissions in the visible region.

Experimental and numerical characterization of floc morphology: role of changing hydraulic retention time under flocculation mechanisms.

The formation, breakage, and re-growth of flocs were investigated by using modified flocculation tests and numerical simulation to explore the evolution of floc morphology for different hydraulic retention times. The shorter the aggregation time was, the smaller the flocs produced for the same hydraulic conditions were. Another interesting discovery was that broken flocs that formed in shorter aggregation time had the capacity to completely recover, whereas those formed in a longer amount of time had rather worse reversibility of broken flocs. With the addition of the maximum motion step in the representative two-dimensional diffusion-limited aggregation (DLA) model, there was a transition for flocs from isotropic to anisotropic as the maximum motion step increased. The strength of flocs was mainly affected by the distribution of particles near the aggregated core rather than distant particles. A simplified breakage model, which found that broken flocs provided more chances for diffused particles to access the inner parts of flocs and to be uniformly packed around the aggregated core, was first proposed. Moreover, an important result showed that the floc fragments formed with a larger value of the maximum motion step had more growing sites than did those with a smaller msa value, which was a benefit of following the re-forming procedure.

Synthesis of phenothiazines via ligand-free CuI-catalyzed cascade C-S and C-N coupling of aryl ortho-dihalides and ortho-aminobenzenethiols.

A ligand-free CuI-catalyzed cascade C-S and C-N cross coupling of (hetero)aryl ortho-dihalides and ortho-aminobenzenethiols has been developed, and various phenothiazines were synthesized with excellent regioselectivity. A possible mechanism is proposed for the cascade coupling.

Dichlorido[tris-(benzimidazol-2-ylmeth-yl)amine]-indium(III) chloride ethanol solvate dihydrate.

In the title complex, [InCl(2)(C(24)H(21)N(7))]Cl·C(2)H(5)OH·2H(2)O, the In(III) ion is coordinated by four N atoms from the tris-(benz-imidazol-2-ylmeth-yl)amine (NTB) ligand and two Cl atoms in a distorted octa-hedral environment. In the crystal structure, inter-molecular N-H⋯O, O-H⋯O, O-H⋯Cl and weak C-H⋯Cl hydrogen bonds connect the cations, anions and solvent mol-ecules into a three-dimensional network. The ethanol solvent mol-ecule is disordered over two sites with refined occupancies of 0.54 (2) and 0.46 (2).

8-Quinolyl 5-(dimethyl-amino)-naphthalene-1-sulfonate.

In the title compound, C(21)H(18)N(2)O(3)S, the dihedral angle between the naphthalene and quinoline ring systems is 55.53 (2)°, and the torsion angle involving the connecting C-S-O-C atoms is 87.60 (3)°. In the crystal structure, weak inter-molecular C-H⋯O hydrogen bonds connect mol-ecules into chains along [100] and there are π-π stacking inter-actions between pairs of chains with a centroid-centroid distance of 3.5485 (15) Å.

[N,N,N',N'-Tetra-kis(benzimidazol-2-yl-meth-yl)ethane-1,2-diamine]copper(II) sulfate monohydrate.

In the title compound, [Cu(C(34)H(32)N(10))]SO(4)·H(2)O, the Cu(II) ion is coordinated by six N atoms of a hexa-dentate N,N,N',N'-tetra-kis(benzimidazol-2-ylmeth-yl)ethane-1,2-diamine (EDTB) ligand, in a distorted octa-hedral environment. In the crystal structure, inter-molecular N-H⋯O and weak C-H⋯O hydrogen bonds connect the cations, anions and water mol-ecules into a three-dimensional network. The O atoms of the anion are disordered over two sites with refined occupancies of 0.711 (2) and 0.289 (2).

5-(Dimethyl-ammonio)naphthalene-1-sulfonate dihydrate.

There are two formula units in the asymmetric unit of the title compound, C(12)H(13)NO(3)S·2H(2)O. In the crystal structure, mol-ecules are linked by inter-molecular O-H⋯O, N-H⋯O and weak C-H⋯O hydrogen bonds, forming a three-dimensional network.

[N,N,N',N'-Tetra-kis(benzimidazol-2-yl-meth-yl)cyclo-hexane-1,2-diamine]-nickel(II) dinitrate dihydrate.

In the title compound, [Ni(C(38)H(38)N(10))](NO(3))(2)·2H(2)O, the Ni(II) ion is located on a crystallographic twofold rotation axis and is in a distorted octa-hedral coordination environment. The crystal structure is stablized by inter-molecular N-H⋯O and C-H⋯O hydrogen bonds, and weak C-H⋯π inter-actions. The O atoms of the unique nitrate ion are disordered over two sites with occupancies of 0.63 (1) and 0.37 (1). In addition, the O atom of the unique solvent water mol-ecule is disorded over two sites with equal occupancies.