Hydrogen-rich solution alleviates acute radiation pneumonitis by regulating oxidative stress and macrophages polarization.

This study was aimed to investigate the effect of hydrogen-rich solution (HRS) on acute radiation pneumonitis (ARP) in rats. The ARP model was induced by X-ray irradiation. Histopathological changes were assessed using HE and Masson stains. Inflammatory cytokines were detected by ELISA. Immunohistochemistry and flow cytometry were performed to quantify macrophage (CD68) levels and the M2/M1 ratio. Western blot analysis, RT-qPCR, ELISA and flow cytometry were used to evaluate mitochondrial oxidative stress injury indicators. Immunofluorescence double staining was performed to colocalize CD68/LC3B and p-AMPK-α/CD68. The relative expression of proteins associated with autophagy activation and the adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway were detected by western blotting. ARP decreased body weight, increased the lung coefficient, collagen deposition and macrophage infiltration and promoted M1 polarization in rats. After HRS treatment, pathological damage was alleviated, and M1 polarization was inhibited. Furthermore, HRS treatment reversed the ARP-induced high levels of mitochondrial oxidative stress injury and autophagy inhibition. Importantly, the phosphorylation of AMPK-α was inhibited, the phosphorylation of mTOR and ULK1 was activated in ARP rats and this effect was reversed by HRS treatment. HRS inhibited M1 polarization and alleviated oxidative stress to activate autophagy in ARP rats by regulating the AMPK/mTOR/ULK1 signaling pathway.

Circular RNA circ_0096041 promotes osteosarcoma cell proliferation and migration via sponging miR-556-5p and regulating LIN28A expression.

Strategies targeting lin-28 homolog A (LIN28A) for the treatment of osteosarcoma are limited, even though salient findings have illustrated the crucial role of LIN28A in bone deformities and cancer. In the present study, we proved circ_0096041, one of the circular RNAs (circRNAs) with significant upregulated expression in osteosarcoma, to be notably engaged in the progression of osteosarcoma. We elucidated that osteosarcoma patients with highly expressed circ_0096041 had relatively worse prognoses. We determined that circ_0096041 potentially sponge miR-556-5p using the Circular RNA Interactome database. Meanwhile, we proved circ_0096041 was associated with miR-556-5p. Furthermore, we determined that miR-556-5p was targeted by LIN28A directly, evidenced by in silico analysis using the miRWALK tool and in vitro analysis. Functionally, our experimental setting aimed to explore the function of circ_0096041/miR-556-5p/LIN28A axis in vitro and in vivo. Our findings demonstrated that circ_0096041 boosted the proliferation and migration of osteosarcoma via LIN28A/miR-556-5p axis. In vivo models were further established to estimate the metastasis promoted by circ_0096041. This research elucidated the enhanced osteosarcoma progression by circ_0096041 and its potential mechanism, which provided innovative targets for osteosarcoma treatment.

Two genes encoded by mulberry crinkle leaf virus (MCLV): The V4 gene enhances viral replication, and the V5 gene is needed for MCLV infection in Nicotiana benthamiana.

Mulberry crinkle leaf virus (MCLV) is a member of the genus Mulcrilevirus, family Geminiviridae. The expression and functions of the V4 and V5 genes encoded by the MCLV genome remain unknown. Here, we confirmed the expression of V4 and V5 by analyzing the V4 and V5 mRNAs and the promoter activity of individual ORFs upstream sequences. The functions of V4 and V5 were investigated by constructing Agrobacterium-mediated infectious clones of wild-type MCLV variant П (MCLV vII), MCLVwt and MCLV vП mutants, such as MCLVmV4 (start codon of V4 ORF mutated), MCLVdV4 (5'-end partial deletion of V4 ORF sequence) and MCLVmV5 (V5 ORF start codon mutated). Although MCLVwt, MCLVmV4, and MCLVdV4 could infect natural host mulberry and experimental tomato plants systematically, the replication of the MCLVmV4 and MCLVdV4 genomes was obviously reduced compared to MCLVwt in both mulberry and tomato plants. MCLV vП expressing V5 could infect Nicotiana benthamiana plants systematically, but MCLVmV5 could not, implying that V5 is needed for MCLV vП to infect N. benthamiana plants. Taken together, V4 is involved in replication of the MCLV genome in host plants, and V5 potentially might extend the host range. Our findings lay a foundation for in-depth insight into the functions of MCLV-encoded proteins and provide a novel perspective for the subsequent study of MCLV-host plant interactions.

Unveiling human origins of replication using deep learning: accurate prediction and comprehensive analysis.

Accurate identification of replication origins (ORIs) is crucial for a comprehensive investigation into the progression of human cell growth and cancer therapy. Here, we proposed a computational approach Ori-FinderH, which can efficiently and precisely predict the human ORIs of various lengths by combining the Z-curve method with deep learning approach. Compared with existing methods, Ori-FinderH exhibits superior performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.9616 for K562 cell line in 10-fold cross-validation. In addition, we also established a cross-cell-line predictive model, which yielded a further improved AUC of 0.9706. The model was subsequently employed as a fitness function to support genetic algorithm for generating artificial ORIs. Sequence analysis through iORI-Euk revealed that a vast majority of the created sequences, specifically 98% or more, incorporate at least one ORI for three cell lines (Hela, MCF7 and K562). This innovative approach could provide more efficient, accurate and comprehensive information for experimental investigation, thereby further advancing the development of this field.

Erratum: Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4: Erratum.

[This corrects the article DOI: 10.7150/jca.39760.].

Chaetoglobosin E inhibits tumor growth and promotes the anti-tumor efficacy of cytotoxic drugs in esophageal squamous cell carcinoma by targeting PLK1.

Background: Currently, there is no satisfactory treatment available for esophageal squamous cell carcinoma (ESCC), and thus, there is a pressing need to develop effective drugs. Chaetoglobosin E, a cytochalasan alkaloid derived from metabolites of Chaetomium madrasense 375, is a chaetoglobosin with intense anti-tumor activity. Therefore, revealing its anti-tumor mechanism for the application of cytochalasans is crucial. Methods: The cytotoxic effect of chaetoglobosin E and cisplatin on esophageal cancer KYSE-30, KYSE-150, and TE-1 cells was detected using cell viability or colony formation assays. The cell cycle, apoptosis, autophagy, invasion, and metastasis were assayed by flow cytometry or western blot. The potential target of chaetoglobosin E was assayed by RNA sequencing (RNA-seq) and large loop prediction software analysis and was assessed by western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of its target on cell pyroptosis was assayed using overexpression and silence experiments. Results: Chaetoglobosin E significantly inhibited the proliferation of KYSE-30, KYSE-150, and TE-1 cells, especially KYSE-30 cells. Our results showed that chaetoglobosin E induced the G2/M phase arrest of KYSE-30 cells, followed by the down-regulation of cyclinB1, CDC2, and p-CDC2, and up-regulation of p21. Moreover, chaetoglobosin E also decreased the anti-apoptotic protein expression of Bcl-2, increased apoptotic expression of Bax, increased autophagy protein expressions of beclin1 and LC3, decreased invasion and metastasis protein expression of E-cadherin, and increased expression of vimentin. The RNA-seq and large loop prediction software analysis results indicated that its potential target might be polo-like kinase 1 (PLK1). Moreover, results also showed that chaetoglobosin E can reverse the PLK1 overexpression plasmid-induced up-regulation of the PLK1 protein. Furthermore, we found that chaetoglobosin E induced pyroptosis via the activation of the gasdermin E (GSDME) protein. Further studies showed that the high expression of PLK1 inactivated the GSDME protein, while the knockdown of PLK1 expression activated the GSDME protein, indicating that chaetoglobosin E induced cell pyroptosis by inhibiting PLK1. Conclusions: This study suggested that chaetoglobosin E may be a novel lead compound to the treatment of ESCC patients by targeting PLK1, and elucidated for the first time that PLK1 was involved in a new pyroptosis mechanism.

Electrically switchable structural colors based on liquid-crystal-overlaid aluminum anisotropic nanoaperture arrays.

Actively tunable or reconfigurable structural colors are highly promising in future development for high resolution imaging and displaying applications. To this end, we demonstrate switchable structural colors covering the entire visible range by integrating aluminum nanoaperture arrays with nematic liquid crystals. The geometrically anisotropic design of the nanoapertures provides strong polarization-dependent coloration. By overlaying a nematic liquid crystal layer, we further demonstrate switchable ability of the structural colors by either changing the polarization of the incident light or applying an external voltage. The switchable structural colors have a fast response time of 28 ms at a driving voltage of 6.5 V. Furthermore, colorful patterns are demonstrated by coding the colors with various dimensions of nanoaperture arrays with dual switching modes. Our proposed technique in this work provides a dual-mode switchable structural colors, which is highly promising for polarimetric displays, imaging sensors, and visual cryptography.

Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence: A multicenter retrospective study.

Background: Early recurrence is common after surgical resection (SR) for hepatocellular carcinoma (HCC) with high risk of recurrence and is associated with poor prognosis. The combinations of lenvatinib (LEN), anti-PD-1 antibodies (PD-1) and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. It is unknown whether triple therapy for neoadjuvant treatment of resectable HCC with high risk of recurrence is effective. This article aimed to compare the outcomes of surgery alone and neoadjuvant combination treatment with triple therapy before SR in patients with HCC with high risk of recurrence. Methods: A retrospective study was conducted on patients diagnosed with HCC with high risk of recurrence who received treatment with or without triple therapy. The records of 24 patients in the triple therapy group and 76 patients in the surgery-alone group were analyzed. Propensity score matching (PSM) was performed to minimize the influence of potential confounders. Results: One hundred patients were enrolled. In the triple therapy group, 8 (33.3%) and 12 (50.0%) patients had complete and partial responses, respectively, as assessed by an investigator. Before PSM, the overall survival (OS) rates for the triple therapy group at 6, 12, 18, and 24 months were 100.0%, 100.0%, 100.0%, and 85.7%, respectively, compared with corresponding 92.1%, 73.7%, 53.9%, and 48.7% for the surgery-alone group (P<0.001). The disease-free survival (DFS) rates were 82.2%, 66.95%, 48.8%, and 48.8% for the triple therapy and 41.92%, 28.34%, 27.05%, and 22.99% for the surgery-alone group (P=0.003). After PSM, DFS and OS were significantly longer in the triple therapy group than in the surgery-alone group (DFS, p=0.019; OS, p=0.003). Conclusions: Neoadjuvant combination treatment before SR had a high rate of tumor response and provided significantly better postoperative survival outcomes than surgery alone in patients with HCC with high risk of recurrence.

B cell subsets were associated with prognosis in elderly patients with community acquired pneumonia.

BACKGROUND: The role of B cell subsets remained to be elucidated in a variety of immune diseases, though which was used as an effective biomarker for anti-inflammatory or antiviral response. This study aimed to evaluate the early changes of B cell subtypes distribution in elderly patients with community acquired pneumonia (CAP), as well as the association between B cell subtypes and prognosis. METHODS: This prospective study included elderly patients with CAP, severe CAP (sCAP) and healthy elderly subjects between April 2016 and March 2018. Flow cytometry was used to detect CD3, CD20, HLA-DR, CD24, CD27, CD38, IgM, and IgD. CD20+ B cells were further divided into naïve B cells (Bn), IgM/D+ memory B cells (IgM+ Bm), switched B cells (SwB), and transitional B cells (Btr). RESULTS: A total of 22 healthy controls, 87 patients with CAP and 58 patients with sCAP were included in the study. Compared to CAP, sCAP was characterized by significantly lower absolute number of B cells, Bn and Btr, significantly lower Btr and Bn subset percentage, while percentage of IgM+ Bm was significantly higher. Heat map showed Bn and Btr on day 3 and day 7 was negatively correlated with activated partial prothrombin time (APTT), international normalized ratio (INR), sequential organ failure assessment score (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II). After 28-day follow-up, Btr percentage in survival group was significantly higher. Receiver operator characteristic (ROC) curve analysis found that Btr count showed sensitivity of 48.6% and specificity of 87.0% for predicting the 28-day survival, with an area under the ROC curves of 0.689 (p = 0.019). CONCLUSIONS: Severity and prognosis of CAP in elderly people is accompanied by changes in the B cell subsets. Btr subsets could play prognostic role for a short-term mortality of elderly CAP patients.

Microstructure Evolution and Formation of Gradient Structures in Single Crystal Nickel-Based Superalloy by Surface Mechanical Creep-Feed Grinding Treatment.

Gradient structures have been created in single crystal nickel-based superalloys (SX alloys) via surface mechanical creep-feed grinding treatment (SMCGT). It has been found that these gradient structures are mainly composed of nano-sized grains, sub-micron-sized grains, dislocation structures, and the matrix material of single crystals along the depth from the treated surface. In addition, the evolution of such structures is found to be dominated by the dislocation movements which run through both γ channels and γ' precipitates, subdividing the two types of microstructures into various dislocation structures, and eventually introducing the refined grains into the surface layer. Furthermore, the evolution process of gradient structures primarily originates from the mechanical effect between abrasive grits and workpiece material, owing to the large grinding force (up to 529 N) and low grinding temperature (less than 150 °C) during the unique creep-feed grinding treatment in the present investigation. Due to the typical grain refinement, the hardness of the nanostructures exhibits the largest value of around 10 GPa in the surface layer, approximately 26% higher than that of the matrix material. This study further enhances the understanding of the microstructure-property relationship of SX alloys subjected to creep-feed grinding treatment and contributes to achievement of high-performance components.

Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study.

BACKGROUND: Lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) exerted promising effects on unresectable hepatocellular carcinoma (uHCC). We assessed the safety and clinical efficacy of triple therapy [LEN+PD-1+transcatheter arterial chemoembolization (TACE)] in uHCC. METHODS: uHCC patients with an ECOG PS score of 0-1 and Child-Pugh class A who underwent triple therapy were included. The primary endpoint was objective response rate (ORR) based on mRECIST. Secondary endpoints were conversion rate to liver resection and treatment-related adverse events. RESULTS: Between November 2018 and December 2020, 62 uHCC patients who underwent triple therapy at four major cancer centers in China were analyzed, including 35 in BCLC-C, 21 in BCLC-B, and 6 in BCLC-A. With a median follow-up of 12.2 months (range, 7.6-33.3 months), the investigator and blinded independent central review-assessed ORR were 80.6% and 77.4%, respectively. A total of 33 patients (53.2%) reached the standard of conversion to resectable HCC and 29 patients underwent resection. The median interval between start of triple therapy and resection was 123 days (range, 55-372 days). Pathological complete response and major pathological response were observed in 16 and 24 patients, respectively. Median overall survival and progression-free survival were not reached. Treatment-related adverse events occurred in 74.2% of the patients (grade ≥3, 14.5%; grade ≥4, 4.8%). CONCLUSION: Combination of LEN, PD-1 and TACE showed a high rate of tumor response and convert resection in uHCC patients, with manageable toxicity.

[Expression and Significance of Shh Signaling Pathway in Bone Marrow CD34+ Cells of Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia with Myelodysplasia-Related Changes].

OBJECTIVE: To study the expression of Shh singaling related gene, including Shh, Ptch1, Smo and Gli1 in bone marrow CD34+ cells of patients with myelodysplastic syndrome(MDS) and acute myeloid leukemia with myelodysplasia-related changes(AML-MRC), and to explore their clinical significance. METHODS: The count of CD34+ cells in bone marrow was detected by flow cytometry in 53 patients with MDS and 30 patients with AML-MRC. Magnetic beads were used to separate CD34+ cells. The expression of Shh, Ptch1,Smo and Gli1 on CD34+ cells was detected by qRT-PCR, the effect of the 4 gene expression on prognosis of patients in MDS and AML-MRC group was compared, 25 patients with iron-deficiency anemia were used as controls. RESULTS: The expression levels of Shh, Smo and Gli1 of patients in MDS and AML-MRC group were significantly higher than those in control group (P＜0.05), moreover increased with disease progression(P<0.05). The expression of Ptch1 was not statistically significantly different between 3 groups（P＞0.05）. In comparison of prognosis, the expression of Smo and Gli1 in the patients of relatively high risk groups and AML-MRC groups were significantly increased (P<0.05). The median overall survival time of patients in MDS and AML-MRC groups was 12（7.5，16.5） and 6（3.0，9.0） months (P=0.000) respectively. The median survival time of MDS and AML-MRC patients with high expression of Smo and Gli1 was significantly shorter than that of MDS and AML-MRC patients with low expression of Smo and Gli1(P<0.05). CONCLUSION: Shh signaling pathway in the patients with MDS is activated, which is involved in the progress and prognosis of MDS.

[Analysis of Transfusion Therapy Effectiveness in Patients with Myelodysplastic Syndrome].

OBJECTIVE: To investigate the transfusion effectiveness of suspended leucocyte depleted red blood cells (sld RBC) and fresh and irradiated apheresis platelets (fia Plt) in patients with myelodysplastic syndromes (MDS), and to explore the causes and mechanisms of ineffective platelet transfusion in patients with MDS. METHODS: Clinical data of 37 patients with confirmed MDS (WHO standard) such as the sex, age, Hb levels, Plt count, hemorrhage and coagulation functions, TEG and so on, were retrospectively analyzed. RESULTS: Among the 37 patients, 15 patients (40.5%) received only sld RBC transfusion, 9 patients (24.3%) received only fia Plt transfusion, and 13 patients (35.1%) received both transfusion. Among the 15 patients with only red blood cell transfusion, 3 patients were ineffective and the ineffectual transfusion rate was 20.0%. Among the 9 patients with only received platelet transfusion, 5 patients were ineffective and the ineffectual transfusion rate was 55.6%, there were significant statistical differences between the two groups (P﹤0.01). The red blood cell transfusion ineffective were 3 patients (23.1%) , the platelet transfusion ineffective were 8 patients (61.5%) and the both transfusion ineffective were 2 patients (15.4%) among the patients both transfusion . The positive rate of platelet antibody in MDS patients with ineffective platelet transfusion was 23.1%. Compared with the normal control group, Human P selectin (P-SelectinCD62P) (P＜0.001) and human anti-thrombin 3 antibody (AT-III Ab) (P＜0.001) significantly increased and human tissue factor pathway inhibitor (TFPI) significantly decreased (P＜0.05) in MDS patients with ineffective platelet transfusion. CONCLUSION: In the process of component transfusion for MDS patients, compared with the transfusion of red blood cells, the inefficiencies of platelet transfusion significantly increased, mainly due to the disorder of blood coagulation and the generation of platelet antibodies in MDS patients with ineffective platelet transfusion. Compared with the normal control group, human P selectin and human anti-thrombin 3 antibody significantly increase and human tissue factor pathway inhibitor significantly decreases in MDS patients with ineffective platelet transfusion. Human P selectin, human anti-thrombin 3 antibody and human tissue factor pathway inhibitor in molecular markers and fibrinolytic markers can be used as indicators of platelet transfusion time and efficiency in patients with MDS.

[Effect of Sonic Hedgehog Signal Pathway Inhibitor Jervine on Myelodysplastic Syndromes MUTZ-1 Cells].

OBJECTIVE: To study the effect of SMO inhibitor (Jervine) on proliferation, apoptosis and cell cycle of MDS cell line MUTZ-1, and its mechanism. METHODS: The effect of different concentrations Jervine on proliferation of MUTZ-1 cells was detected by CCK-8 method. Apoptosis and cell cycle of MUTZ-1 cells were detected by flow cytometry. Western blot was used to detect the changes of Shh signaling pathway effecting proteins BCL2 and CyclinD1. The expression levels of Smo and Gli1 gene were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). RESULTS: Jervine inhibited MUTZ-1 cell proliferation in a concentration dependent manner (24 h, r=-0.977), the apoptosis rate of MUTZ-1 cells increased with the enhancement of concentration of Jervine in MUTZ-1 cells (P＜0.001), the cell proportion of G1 phase increased and the cell number of S phase decreased with enhancement of concentration (P＜0.001). The result of RT-qPCR and Western blot showed that the expression of Smo, Gli1 mRNA and BCL2, CyclinD1 proteins decreased (P＜0.05). CONCLUSION: SMO inhibitor can effectively inhibit the growth of MDS cell line MUTZ-1 improve the cell apoptosis and induce cell cycle arrest. Its action mechanism may be related with dowm-regulating the expression of BCL2 and CyclinD1.

Increased Th17 activation and gut microbiota diversity are associated with pembrolizumab-triggered tuberculosis.

INTRODUCTION: A hypersensitivity response akin to immune reconstitution inflammatory syndrome (IRIS) has been proposed as a mechanism responsible for anti-PD-1 therapy-induced tuberculosis. IRIS is associated with enhanced activation of IL-17A-expressing CD4 + T cells (Th17). Gut microbiota is thought to be linked to pulmonary inflammation through the gut-lung axis. MATERIALS AND METHODS: We used ImmuCellAI to investigate the T cell population in lung cancer and tuberculosis samples. Then, we applied flow cytometry to monitor the expression levels of the Th17 cell activation marker CD38 in the peripheral blood of a patient experiencing adverse events, including tuberculosis, in response to pembrolizumab. The gut microbiome was examined by 16S rRNA sequencing to examine the alterations caused by pembrolizumab. RESULTS: The percentage of Th17 cells was increased in both lung cancer and tuberculosis. FACS analysis showed that pembrolizumab induced substantial CD38 expression in Th17 cells. The patient's fecal samples showed that the diversity of the gut microbiota was significantly increased in response to the pembrolizumab cycle. One enriched genus was Prevotella, which has previously been linked to lung inflammation and Th17 immune activation. DISCUSSION: The observed Th17 activation in our patient was consistent with a role of Th17-mediated IRIS in pembrolizumab-triggered tuberculosis. Pembrolizumab might trigger airway inflammation with a Th17 phenotype through microbiota interactions in the gut-lung axis.

Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4.

Lung cancer is a type of malignant tumor with high morbidity and mortality. Due to its complicated etiology and clinical manifestations, no significant therapeutic advance has been made. Lung squamous cell carcinoma (LSCC) is the most common type of lung cancer. To combat this disease, novel therapeutic targets are badly requirement. ASPM (Abnormal spindle-like microcephaly-associated protein) is involved in multiple cellular or developmental processes, such as neurogenesis and brain growth. ASPM is also reported widely expressed in multiple tumor tissues and involved in the development and progression of several cancers including lung cancer. However, the potential role on ASPM on LSCC is still unclear. In this study, we reported that ASPM was related to the poor prognosis of patients with lung squamous cell carcinoma. Our results further showed that ASPM depletion dramatically inhibited the proliferation of LSCC cells, consistent with the obviously decreased of cyclin D1(CCND1) and cyclin dependent kinases 4 (CDK4) expression. In vivo assays further confirmed ASPM ablation markedly blocked tumor growth in vivo compared with control. In addition, a co-expression was found between ASPM and CDK4 in human tumor tissues. Taken together, our data provides strong evidence that ASPM promotes lung squamous cell carcinoma proliferation in vitro and in vivo, and indicates its potential role as a LSCC therapeutic target.

Linearly Polarized Emission from Shear-Induced Nematic Phase Upconversion Nanorods.

Lanthanide-doped particles exhibit unique polarization-dependent luminescence due to the anisotropic crystalline local symmetry surrounding the emitter. Precise control of the orientation of particles shows great significance for exploiting the luminescent polarization and their potential applications. Here, we demonstrated a facile polypropylene-aided shear-driven method to obtain large-scale orientationally ordered upconversion nanorods, showing a liquid-crystalline nematic phase. Upconversion nanorods with low aspect ratios were well-aligned with the crystalline c-axis along the shearing direction using monodispersed colloid nanorods as the nanoink. The order parameter of aligned upconversion nanorods can reach up to 0.95. The nematic upconversion nanorods demonstrated strong polarization-dependent luminescence with the high degrees of polarization of the 4F9/2 sublevels at 657 and 661 nm being 0.47 and 0.59, respectively. Taking advantage of these mesoscopic well-aligned upconversion nanorods, their peculiar polarized emissions are potentially useful for some interdisciplinary applications such as polarization-sensitive bioprobes and anticounterfeiting.

Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis.

A newly identified lncRNA designated as RP11-284P20.2 has been identified to be up-regulated in hepatocellular carcinoma (HCC), but its role in HCC remain poorly understood. Quantitative PCR and immunocytochemical analysis were performed using the HCC tissues to identify the potential interaction partners of RP11-284P20.2. Moreover, RP11-284P20.2 was knocked down in HCC cell lines, HepG2 and SMMC7721, to investigate the influence of this lncRNA on cell growth properties. Additionally, RNA fluorescence in situ hybridization and immunofluorescence, RNA immunoprecipitation, and RNA pull-down assays were performed to determine the interaction of RP11-284P20.2 with c-met mRNA and eukaryotic translation initiation factor 3b (EIF3b). Silencing RP11-284P20.2 inhibited cell viability, migration, invasion, and colony formation, and increased apoptosis. Overexpression of c-met abolished these effects of RP11-284P20.2 in HCC cells. Histopathological examination showed that HCC tissues with high RP11-284P20.2 expression had higher c-met protein level than that in HCC tissues with low RP11-284P20.2 expression. However, there was no positive correlation between the expression levels of RP11-284P20.2 and c-met mRNA. RP11-284P20.2 knockdown led to a decease in c-met protein expression level, but did not affect the c-met mRNA expression level. These data suggest that RP11-284P20.2 regulates c-met protein expression level, which is independent of c-Met mRNA expression level. It was also confirmed that RP11-284P20.2 has high affinity toward both c-met mRNA and EIF3b protein, and hence RP11-284P20.2 probably recruits EIF3b protein to c-met mRNA and further facilitates its translation. RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis.

Durable response to pulsatile icotinib for central nervous system metastases from EGFR-mutated non-small cell lung cancer: A case report.

BACKGROUND: Central nervous system (CNS) metastases are a catastrophic complication of non-small cell lung cancer (NSCLC), including brain and leptomeningeal carcinomatosis, and are always accompanied by a poor prognosis. Despite the continuous development of existing treatments, the therapy of CNS metastases remains challenging. CASE SUMMARY: We report a patient who was definitively diagnosed with brain and leptomeningeal metastases from NSCLC with a targeted mutation in epidermal growth factor receptor (EGFR). A standard dosage of icotinib (125 mg three times daily) was implemented but ineffective. CNS lesions developed despite stable systemic control, so pulsatile icotinib (1125 mg every 3 d) was administered. This new strategy for administration has lasted 25 mo so far, and resulted in complete remission of neurological symptoms, almost vanished lesions, and longer survival with no notable side effects. CONCLUSION: This is the first successful example of pulsatile icotinib for treating isolated CNS progression from EGFR mutation-positive NSCLC, providing a new alternative for the local treatment of CNS metastases.

Morusalones A-D, Diels-Alder Adducts with 6/7/6/6/6/6 Hexacyclic Ring Systems as Potential PTP1B Inhibitors from Cell Cultures of Morus alba.

Morusalones A-D (1-4), a new class of Diels-Alder adducts featuring unprecedented 6/7/6/6/6/6 hexacyclic core skeletons with a unique bridged cycloheptenone ring, were isolated from Morus alba cell cultures. The biosyntheses for 1-4 were proposed through an unusual Diels-Alder cycloaddition with quinostilbenes as dienophiles and prenyl 2-phenylbenzofuran as a diene to yield the typical methylhexene unit and a rare intramolecular nucleophilic addition to form the cycloheptenone ring. Compounds 1-4 exhibited protein tyrosine phosphatase 1B inhibitory activity.