Signatures of superconductivity near 80 K in a nickelate under high pressure.

Although high-transition-temperature (high-Tc) superconductivity in cuprates has been known for more than three decades, the underlying mechanism remains unknown1-4. Cuprates are the only unconventional superconductors that exhibit bulk superconductivity with Tc above the liquid-nitrogen boiling temperature of 77 K. Here we observe that high-pressure resistance and mutual inductive magnetic susceptibility measurements showed signatures of superconductivity in single crystals of La3Ni2O7 with maximum Tc of 80 K at pressures between 14.0 GPa and 43.5 GPa. The superconducting phase under high pressure has an orthorhombic structure of Fmmm space group with the [Formula: see text] and [Formula: see text] orbitals of Ni cations strongly mixing with oxygen 2p orbitals. Our density functional theory calculations indicate that the superconductivity emerges coincidently with the metallization of the σ-bonding bands under the Fermi level, consisting of the [Formula: see text] orbitals with the apical oxygen ions connecting the Ni-O bilayers. Thus, our discoveries provide not only important clues for the high-Tc superconductivity in this Ruddlesden-Popper double-layered perovskite nickelates but also a previously unknown family of compounds to investigate the high-Tc superconductivity mechanism.

Record-High T_{c} and Dome-Shaped Superconductivity in a Medium-Entropy Alloy TaNbHfZr under Pressure up to 160 GPa.

Superconductivity has been one of the focal points in medium and high-entropy alloys (MEAs-HEAs) since the discovery of the body-centered cubic (bcc) HEA superconductor in 2014. Until now, the superconducting transition temperature (T_{c}) of most MEA and HEA superconductors has not exceeded 10 K. Here, we report a TaNbHfZr bulk MEA superconductor crystallized in the BCC structure with a T_{c} of 15.3 K which set a new record. During compression, T_{c} follows a dome-shaped curve. It reaches a broad maximum of roughly 15 K at around 70 GPa before decreasing to 9.3 K at 157.2 GPa. First-principles calculations attribute the dome-shaped curve to two competing effects, that is, the enhancement of the logarithmically averaged characteristic phonon frequency ω_{log} and the simultaneous suppression of the electron-phonon coupling constant λ. Thus, TaNbHfZr MEA may have a promising future for studying the underlying quantum physics, as well as developing new applications under extreme conditions.

Monoclinic EuSn_{2}As_{2}: A Novel High-Pressure Network Structure.

The layered crystal of EuSn_{2}As_{2} has a Bi_{2}Te_{3}-type structure in rhombohedral (R3[over ¯]m) symmetry and has been confirmed to be an intrinsic magnetic topological insulator at ambient conditions. Combining ab initio calculations and in situ x-ray diffraction measurements, we identify a new monoclinic EuSn_{2}As_{2} structure in C2/m symmetry above ∼14 GPa. It has a three-dimensional network made up of honeycomblike Sn sheets and zigzag As chains, transformed from the layered EuSn_{2}As_{2} via a two-stage reconstruction mechanism with the connecting of Sn-Sn and As-As atoms successively between the buckled SnAs layers. Its dynamic structural stability has been verified by phonon mode analysis. Electrical resistance measurements reveal an insulator-metal-superconductor transition at low temperature around 5 and 15 GPa, respectively, according to the structural conversion, and the superconductivity with a T_{C} value of ∼4 K is observed up to 30.8 GPa. These results establish a high-pressure EuSn_{2}As_{2} phase with intriguing structural and electronic properties and expand our understandings about the layered magnetic topological insulators.

Saikosaponin-d increases radiation-induced apoptosis of hepatoma cells by promoting autophagy via inhibiting mTOR phosphorylation.

Objective: The aim of this study was to analyze the effects of saikosaponin-d (SSd) on autophagy activity and radiosensitivity of hepatoma cells, and to elucidate its related molecular mechanisms. Methods: The growth of SMMC-7721 and MHCC97L hepatoma cells were detected by clonal formation and survival fraction. Flow cytometry was used to detect the changes of apoptosis of hepatoma cells. The morphological changes of autophagy of hepatoma cells were observed by transmission electron microscopy and were further quantitatively detected by laser confocal microscopy. The expressions of related proteins were detected by Western blotting. Results: SSd can significantly increase the apoptosis of hepatoma cells induced by radiation and inhibit the proliferation of hepatoma cells. The addition of the autophagy inhibitor chloroquine (CQ) or an mTOR agonist (MHY1485), which could reduce the promoting effect of SSd on radiation-induced apoptosis and inhibitory effect on the proliferation of hepatoma cells. Transmission electron microscopy and confocal microscopy results also showed that the number of autophagosomes was significantly higher in the radiation and SSd co-treatment group than in the radiotherapy or SSd alone group; however, the effect of SSd on autophagy in hepatoma cells was decreased after adding MHY1485, siRNA-P53 or AMPK inhibitor (Compound C). Western blot analysis showed that after the addition of SSd, the phosphorylation of mTOR was significantly decreased by radiation, the expression of the autophagy-related proteins LC3-II and Beclin-1 was increased, p62 was decreased, and the expression of cleaved caspase-3 and cleaved PARP was enhanced; this effect of SSd was partially reversed after the addition of MHY1485, siRNA-P53 or Compound C. Conclusions: SSd increases radiation-induced apoptosis of hepatoma cells by promoting autophagy via inhibiting mTOR phosphorylation and providing a possible potential approach for radiosensitization therapy of liver cancer.

Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N,N-Dimethylformamide Dimethyl Acetal.

Aluminum triiodide is harnessed by N,N-dimethylformamide dimethyl acetal (DMF-DMA) for the selective cleavage of ethers via neighboring group participation. Various acid-labile functional groups, including carboxylate, allyl, tert-butyldimethylsilyl (TBS), and tert-butoxycarbonyl (Boc), suffer the conditions intact. The method offers an efficient approach to cleaving catechol monoalkyl ethers and to uncovering phenols from acetal-type protecting groups such as methoxymethyl (MOM), methoxyethoxymethyl (MEM), and tetrahydropyranyl (THP) chemoselectively.

Impact of four lncRNA polymorphisms (rs2151280, rs7763881, rs1136410, and rs3787016) on glioma risk and prognosis: A case-control study.

Long noncoding RNA (lncRNA) polymorphisms are reportedly in connection with tumor susceptibility and prognosis. Glioma is one of the most aggressive and common cancers of the central nervous system. This study aimed to investigate the relationship between four lncRNA variants and glioma susceptibility and prognosis in a Chinese Han population. Sequenom Mass-ARRAY was used to genotype 605 patients with glioma and 1300 cancer-free individuals. Odds ratios or hazard ratios and related 95% confidence intervals were calculated to estimate the correlations. Logistic and Cox regression models, log-rank tests, and Kaplan-Meier curves were used for the statistical analysis. Six inheritance models showed that ANRIL rs2151280 variant genotype (A>G) was related to the susceptibility of glioma, while the other three lncRNAs showed no association. Patients treated with temozolomide or nimustine had better progression-free survival (PFS) and overall survival (OS) than those treated with platinum. Besides, patients aged older than 40 years showed a poorer OS. The Cox multivariate analysis revealed that the rs1136410 GG genotype (A>G) was beneficial for OS and PFS. The Kaplan-Meier analyses indicated that rs1136410 A>G and the rs7763881 A>C were associated with longer OS. ANRIL rs2151280 variant genotype might increase susceptibility of glioma. In addition, PARP1 rs1136410 variant genotype could be beneficial for the overall survival of patients with glioma. More research data are needed to further validate our results.

GSTM1 and GSTT1 null genotype increase the risk of hepatocellular carcinoma: evidence based on 46 studies.

BACKGROUND: It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC. METHODS: We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0). RESULTS: The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18-1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23-1.66) increased the risk of HCC. And GSTM1-GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22-2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22-1.71), GSTT1 null OR = 1.48, 95% CI = (1.25-1.77), GSTM1-GSTT1 null OR = 1.58, 95% CI = (1.19-2.09), while we didn't obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1-GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null. CONCLUSIONS: Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1-GSTM1 dual-null genotypes is more likely to develop HCC.

Effects of SSd combined with radiation on inhibiting SMMC-7721 hepatoma cell growth.

BACKGROUND: The aim of this study was to investigate the effects of Saikosaponin-d (SSd) combined with radiotherapy on SMMC-7721 hepatoma cell lines and its mechanism. MATERIAL/METHODS: SMMC-7721 hepatoma cell lines are selected in our research. With MTT (methylthiazolyldiphenyl-tetrazolium-bromide) method, the effects of SSd and radiation on inhibiting SMMC-7721 cell growth were investigated. We also used transmission electron microscopy (TEM) to observe ultrastructural changes of cells. Colorimetry methods were used to measure content changes of glutathione (GSH) and malondialdehyde (MDA) in cells. RESULTS: Both SSd and radiation inhibited the growth of SMMC-7721 cells. The combination of SSd and radiotherapy had a time-dependent synergistic effect. Radiation caused ultrastructural damage to cells, and the damage was enhanced in combination with SSd. Radiation decreased the GSH content and increased the MDA content in cells, and this effect was suppressed after the intervention of SSd. CONCLUSIONS: SSd can inhibit the growth of SMMC-7721 hepatoma cell lines in vitro. Additionally, it significantly enhances the effects of radiation on inhibiting the growth of SMMC-7721 hepatoma cell lines, and up-regulates the antioxidant level after the radiotherapy. Thus, SSd could be an ideal radiotherapy sensitizer for the treatment of liver cancer.

AlliumDB: a central portal for comparative and functional genomics in Allium.

The genus Allium belongs to the botanical family Amaryllidaceae and includes economically important crops such as onion, garlic, bunching onion, and leek, used as vegetables, spices, and traditional medicines. The large sizes of Allium genomes hamper the genetic dissection of agronomically important traits and molecular breeding. With the growing accumulation of genomic, resequencing, transcriptome, and phenotypic data, the demand for an integrative Allium database is increasing. Here we present a user-friendly database, AlliumDB (https://allium.qau.edu.cn), as a functional genomics hub integrating public and in-house data. The database contains all currently available nuclear and organelle genomes for Allium species, with genes comprehensively annotated based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, orthology, gene families, protein families (Pfam), and non-coding RNA families (Rfam). Transcriptome and variation profiles are integrated into dynamic visualization tools. We took phenotypic photographs and generated trait records for hundreds of Allium germplasms collected worldwide, which are included in the database. We incorporated JBrowse for the visualization of gene structures, RNA sequencing data, and variation data. Analysis tools such as the basic local alignment search tool (BLAST), sequence fetch, enrichment, and motif analyses are available to explore potential gene functions. This database incorporates comprehensive Allium genotypic and phenotypic datasets. As the community assembles new genomes and generates resequencing data for Allium germplasms, the database will be improved and continuously updated with these multi-omics data and comparative genomic studies. We expect the AlliumDB database to become a key resource for the study of Allium crops.

Tunable positions of Weyl nodes via magnetism and pressure in the ferromagnetic Weyl semimetal CeAlSi.

The noncentrosymmetric ferromagnetic Weyl semimetal CeAlSi with simultaneous space-inversion and time-reversal symmetry breaking provides a unique platform for exploring novel topological states. Here, by employing multiple experimental techniques, we demonstrate that ferromagnetism and pressure can serve as efficient parameters to tune the positions of Weyl nodes in CeAlSi. At ambient pressure, a magnetism-facilitated anomalous Hall/Nernst effect (AHE/ANE) is uncovered. Angle-resolved photoemission spectroscopy (ARPES) measurements demonstrated that the Weyl nodes with opposite chirality are moving away from each other upon entering the ferromagnetic phase. Under pressure, by tracing the pressure evolution of AHE and band structure, we demonstrate that pressure could also serve as a pivotal knob to tune the positions of Weyl nodes. Moreover, multiple pressure-induced phase transitions are also revealed. These findings indicate that CeAlSi provides a unique and tunable platform for exploring exotic topological physics and electron correlations, as well as catering to potential applications, such as spintronics.

Flexible Copper Nanowire/Polyvinylidene Fluoride Membranous Composites with a Frequency-Independent Negative Permittivity.

With the increasing popularity of wearable devices, flexible electronics with a negative permittivity property have been widely applied to wearable devices, sensors, and energy storage. In particular, a low-frequency dispersion negative permittivity in a wide frequency range can effectively contribute to the stable working performance of devices. In this work, polyvinylidene fluoride (PVDF) was selected as the flexible matrix, and copper nanowires (CuNWs) were used as the conductive functional filler to prepare a flexible CuNWs/PVDF composite film with a low-frequency dispersion negative permittivity. As the content of CuNWs increased, the conductivity of the resulting composites increased sharply and presented a metal-like behavior. Moreover, the negative permittivity consistent with the Drude model was observed when CuNWs formed a percolative network. Meanwhile, the negative permittivity exhibited a low-frequency dispersion in the whole test frequency range, and the fluctuation of the permittivity spectra was relatively small (-760 to -584) at 20 kHz-1 MHz. The results revealed that the high electron mobility of CuNWs is reasonable for the low-frequency dispersion of negative permittivity. CuNWs/PVDF composite films with a frequency-independent negative permittivity provide a new idea for the development of flexible wearable electronic devices.

Interplay between Charge-Density-Wave, Superconductivity, and Ferromagnetism in CuIr2-xCrxTe4 Chalcogenides.

We report the crystal structure, charge-density-wave (CDW), superconductivity (SC), and ferromagnetism (FM) in CuIr2-xCrxTe4 (0 ≤ x ≤ 2) chalcogenides. Powder x-ray diffraction (PXRD) results reveal that the CuIr2-xCrxTe4 series are distinguished between two structural types and three different regions: (i) layered trigonal structure region, (ii) mixed phase regions, and (iii) spinel structure region. Besides, Cr substitution for Ir site results in rich physical properties including the collapse of CDW, the formation of dome-shaped like SC, and the emergence of magnetism. Cr doping slightly elevates the superconducting critical temperature (Tsc) to its highest Tsc = 2.9 K around x = 0.06. As x increases from 0.3 to 0.4, the ferromagnetic Curie temperature (Tc) increases from 175 to 260 K. However, the Tc remains unchanged in the spinel range of 1.9 ≤ x ≤ 2. This finding provides a comprehensive material platform for investigating the interplay between CDW, SC, and FM multipartite quantum states.

Superconducting dome associated with the suppression and re-emergence of charge density wave states upon sulfur substitution in CuIr2Te4chalcogenides.

We report the path from the charge density wave (CDW)-bearing superconductor CuIr2Te4to the metal insulator transition (MIT)-bearing compound CuIr2S4by chemical alloying with the gradual substitution of S for Te. The evolution of structural and physical properties of the CuIr2Te4-xSx(0 ⩽x⩽ 4) polycrystalline system is systemically examined. The x-ray diffraction (XRD) results imply CuIr2Te4-xSx(0 ⩽x⩽ 0.5) crystallizes in a NiAs defected trigonal structure, whereas it adapts to the cubic spinel structure for 3.6 ⩽x⩽ 4 and it is a mixed phase in the doping range of 0.5

Destabilization of the Charge Density Wave and the Absence of Superconductivity in ScV6Sn6 under High Pressures up to 11 GPa.

RV6Sn6 (R = Sc, Y, or rare earth) is a new family of kagome metals that have a similar vanadium structural motif as AV3Sb5 (A = K, Rb, Cs) compounds. Unlike AV3Sb5, ScV6Sn6 is the only compound among the series of RV6Sn6 that displays a charge density wave (CDW) order at ambient pressure, yet it shows no superconductivity (SC) at low temperatures. Here, we perform a high-pressure transport study on the ScV6Sn6 single crystal to track the evolutions of the CDW transition and to explore possible SC. In contrast to AV3Sb5 compounds, the CDW order of ScV6Sn6 can be suppressed completely by a pressure of about 2.4 GPa, but no SC is detected down to 40 mK at 2.35 GPa and 1.5 K up to 11 GPa. Moreover, we observed that the resistivity anomaly around the CDW transition undergoes an obvious change at ~2.04 GPa before it vanishes completely. The present work highlights a distinct relationship between CDW and SC in ScV6Sn6 in comparison with the well-studied AV3Sb5.

Genistein upregulates cyclin D1 and CDK4 expression and promotes the proliferation of ovarian cancer OVCAR-5 cells.

BACKGROUND: Ovarian epithelial cancer is the leading cause of deaths associated with gynecologic malignancies. Genistein represents a major type of phytoestrogens widely found in foods and herbal medicines. Although multiple epidemiological studies indicated that the consumption of genistein or other isoflavones is associated with a decreased ovarian cancer risk, the cellular effects and underlying mechanisms are not fully understood. This study focuses on the effect of genistein on the proliferation and cell cycle regulation of ovarian cancer cells. METHODS: Ovarian cancer OVCAR-5 cells were treated with genistein in an estrogen-free condition. Cell counting and MTS assays were performed to determine the cell proliferation alterations. Real-time PCR and Western blotting were conducted to examine the expression changes in key cell cycle regulators. RESULTS: Genistein significantly promoted the proliferation and the viability of OVCAR-5 cells. Upon genistein treatment, cellular mRNA and protein expression levels of PCNA, Cyclin D1 and CDK4 were increased, but those of p21 and p27 were decreased. CONCLUSION: In contrary to results of many previous studies, we observed that genistein was able to upregulate the proliferation and G1-S transition of ovarian cancer OVCAR-5 cells. The discrepancy could be caused by diverged experimental conditions and/or different ER expression patterns of cell lines. The findings may provide basic information for in-depth analysis on the role(s) and mechanisms by which genistein confers its effect on ovarian cancer progression.

Linc00963 Promote Cell Proliferation and Tumor Growth in Castration-Resistant Prostate Cancer by Modulating miR-655/TRIM24 Axis.

Previous studies have shown that both long intergenic non-coding RNA 00963 (Linc00963) and tripartite motif containing 24 (TRIM24) are activators of the PI3K/AKT pathway, and both are involved in the carcinogenesis and progression of prostate cancer. However, the regulatory mechanisms between Linc00963 and TRIM24 are still unclear. In this study, we aimed to elucidate the underlying relationship between Linc00963 and TRIM24 in castration-resistant prostate cancer (CRPC). We found that TRIM24, an established oncogene in CRPC, was positively correlated with Linc00963 in prostate cancer tissues. In addition, TRIM24 was positively regulated by Lin00963 in CRPC cells. Mechanistically, TRIM24 was the direct target of microRNA-655 (miR-655) in CRPC cells, and Linc00963 could competitively bind miR-655 and upregulate TRIM24 expression. Using gain- and loss-of- function assays and rescue assays, we identified that miR-655 inhibits TRIM24 expression and cell proliferation and colony forming ability in CRPC, and that Linc00963 promotes TRIM24 expression, cell proliferation, and colony forming ability of CRPC cells by directly suppressing miR-655 expression. We further identified that Linc00963 could promote tumor growth of CRPC cells by inhibiting miR-655 and upregulating TRIM24 axis in vivo. Taken together, our study reveals a new mechanism for the Linc00963/miR-655/TRIM24 competing endogenous RNA (ceRNA) network in accelerating cell proliferation in CRPC in vitro and in vivo, and suggests that Linc00963 could be considered a novel therapeutic target for CRPC.

Association of 13 Occupational Carcinogens in Patients With Cancer, Individually and Collectively, 1990-2017.

Importance: Occupational exposure to carcinogens has been shown to pose a serious disease burden at the global, regional, and national levels. Based on epidemiologic studies and clinical observations, working environment appears to have important effects on the occurrence of human malignant tumors; however, to date, no systematic articles have been published that specifically investigated cancer burden due to occupational exposure in an individual and collective manner. Objective: To estimate the degree of exposure and evaluate the cancer burden attributable to occupational carcinogens (OCs) individually and collectively by sex, age, year, and location. Design, Setting, and Participants: Cross-sectional study including data on 195 countries from the Global Burden of Diseases, Injuries, and Risk Factors Study from January 1, 1990, to December 31, 2017. Data were analyzed from June 24, 2020, to July 20, 2020. Exposures: Thirteen OCs (ie, arsenic, asbestos, benzene, beryllium, cadmium, chromium, diesel engine exhaust, formaldehyde, nickel, polycyclic aromatic hydrocarbons, silica, sulfuric acid, and trichloroethylene). Main Outcomes and Measures: The degree and change patterns of exposure as well as the attributable cancer burden, including deaths and disability-adjusted life years (DALYs), by sex, age, year, and location for 13 OCs. The calculation of the population-attributable fraction was based on past exposure in the population and relative risks. Results: Based on the GBD 2017 study, 13 OCs attributable to 7 cancer types were included. Most summary exposure values for the 13 OCs, particularly those of diesel engine exhaust (35.6% increase; 95% uncertainty interval [UI], 32.4%-38.5%) and trichloroethylene (30.3% increase; 95% UI, 27.3%-33.5%), increased from 1990 to 2017. Only exposure to asbestos decreased by 13.8% (95% UI, -26.7% to 2.2%). In 2017, 319 000 (95% UI, 256 000-382 000) cancer deaths and 6.42 million (95% UI, 5.15 million to 7.76 million) DALYs were associated with OCs combined, accounting for 61.0% (95% UI, 59.6%-62.4%) of the total cancer deaths and 48.3% (46.3% to 50.2%) of the DALYs. Among the 13 OCs, the 3 leading risk factors for cancer burden were asbestos (71.8%), silica (15.4%), and diesel engine exhaust (5.6%). For most OCs, the attributed cancer outcome was tracheal, bronchial, and lung cancer, which accounted for 89.0% of attributable cancer deaths. China (61 644 cancer deaths), the US (42 848), and Japan (20 748) accounted for the largest number of attributable cancer deaths in 2017; for DALYs, China (1.47 million), the US (0.71 million), and India (0.37 million) were the 3 leading countries. Conclusions and Relevance: Results of this study suggest that although OC exposure levels have decreased, the overall cancer burden is continuously increasing.

Long Non-coding RNA SNHG17 Promotes Cell Proliferation and Invasion in Castration-Resistant Prostate Cancer by Targeting the miR-144/CD51 Axis.

Previously, we found that the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) was up-regulated in castration-resistant prostate cancer (CRPC) cells compared to that in hormone sensitive prostate cancer (HSPC) cells. Moreover, we found that CD51 was up-regulated in prostate cancer cells and promoted the carcinogenesis and progression of prostate cancer. However, the regulatory mechanism of SNHG17 and CD51 in the development of CRPC remains unclear. In the current study, we aimed to elucidate the expressions, functions, and underlying mechanism of SNHG17 and CD51 in CRPC. Our results further confirmed that both SNHG17 and CD51 were up-regulated in CRPC tissues and cells. In addition, we found that SNHG17 expression was positively correlated with CD51 expression in prostate cancer. Mechanically, SNHG17 functioned as a competing endogenous RNA (ceRNA) to up-regulate CD51 expression through competitively sponging microRNA-144 (miR-144), and CD51 was identified as a direct downstream target of miR-144 in CRPC. Functionally, down-regulation of SNHG17 or up-regulation of miR-144 inhibited the proliferation, migration, and invasion of CRPC cells, whereas up-regulation of SNHG17 and down-regulation of miR-144 promoted the proliferation, migration and invasion of CRPC cells in vitro and in vivo. Using gain and loss-of function assay and rescue assay, we showed that miR-144 inhibited cell proliferation, migration and invasion by directly inhibiting CD51 expression, and SNHG17 promoted cell proliferation, migration and invasion by directly enhancing CD51 expression in CRPC cells. Taken together, our study reveals the role of the SNHG17/miR-144/CD51 axis in accelerating CRPC cell proliferation and invasion, and suggests that SNHG17 may serve as a novel therapeutic target for CRPC.

miR-499 rs3746444 and miR-196a-2 rs11614913 Are Associated with the Risk of Glioma, but Not the Prognosis.

Previous studies of correlations of microRNA (miR)-499 rs3746444 and miR-196a-2 rs11614913 polymorphisms with glioma risk have yielded inconsistent results. In this study, relationships between these two polymorphisms and glioma risk and survival were evaluated. In total, 605 patients and 1,300 controls were genotyped. rs3746444 increased glioma risk in five genetic models (GA versus AA, odds ratio [OR], 95% confidence interval [CI] = 1.31 [1.05-1.66], p = 0.02; GG versus AA, OR [95% CI] = 10.70 [6.13-18.69], p < 0.0001; GA + GG versus AA, OR [95% CI] = 1.82 [1.47-2.24], p < 0.0001; GG versus AA + GA, OR [95% CI] = 9.99 [5.74-17.40], p < 0.0001; G versus A, OR [95% CI] = 2.18 [1.82-2.60], p < 0.0001). rs11614913 decreased glioma risk in a recessive model (OR [95% CI] = 0.79 [0.64-0.97], p = 0.03). No relationships between either SNP and survival were found. rs3746444 in the miR-499 seed region could affect target recognition. Bioinformatics analyses indicated that miR-499 rs3746444 is involved in various biological processes and pathways, including "cell adhesion molecule binding," "positive regulation of catabolic process," "NF-kappa B pathway," and "PI3K-Akt pathway," by targeting mRNAs. Our results suggested that miR-499 rs3746444 and miR-196a-2 rs11614913 have crucial roles in glioma susceptibility.

Identification of a prognostic immune signature for cervical cancer to predict survival and response to immune checkpoint inhibitors.

Cervical cancer (CC) is a leading cause of cancer-related death in women. Limited studies have investigated whether immune-related genes (IRGs) or tumor immune microenvironment (TIME) could be indicators for CC prognoses. The aim of this study was to develop an improved prognostic signature for CC based on IRGs or TIME to predict survival and response to immune checkpoint inhibitors (ICIs). A prognostic signature was constructed using bioinformatics method and its predictive capability was validated. The mechanisms underlying the signature's predictive capability were explored with CIBERSORT algorithm and mutation analysis. Immunophenoscore (IPS) is validated for ICIs response, and was therefore explored in relation to the signature. A prognostic signature based on 11 IRGs was developed. A multivariate analysis revealed that the 11-IRG signature was an independent prognostic factor for overall survival (OS) and progression-free interval in CC patients. In the 11-IRG signature high-risk group, CD8 T cells and resting mast cells, which are found to associate with better OS in our study, were lower; activated mast cells, associated with poorer OS, were higher, compared with the low-risk group. An IPS analysis suggested that the 11-IRG signature low-risk group, which possessed a higher IPS, represented a more immunogenic phenotype that was more inclined to respond to ICIs. In short, an 11-IRG prognostic signature for predicting CC patients' survival and response to ICIs was firmly established. The predictive capability of this model in CC requires further testing with the goal of better prognostic stratification and treatment management.