Effect of dexmedetomidine infusion on postoperative sleep disturbances in women with breast cancer: A monocentric randomized-controlled double-blind trial.

BACKGROUND: Most women with breast cancer are prone to postoperative sleep disturbances (POSD). Little is known about the differences between sevoflurane and propofol combined with dexmedetomidine on POSD in the same context. We investigated the effect of intra-operative sevoflurane or propofol combined with intravenous dexmedetomidine on the incidence of POSD and postoperative sleep structures. METHODS: A monocentric, randomized-controlled, double-blind trial. Female patients undergoing radical surgery for breast cancer were randomly assigned to receive sevoflurane and placebo, sevoflurane and dexmedetomidine, propofol and placebo, or propofol and dexmedetomidine. Dexmedetomidine was administered at 1.0 µg kg-1 infusion 15 min before induction, then infused at 0.4 µg kg-1 h-1 until the surgical drain started to be placed. The primary outcome was the incidence of POSD within the postoperative first three days (defined as an Athens Insomnia Scale score ≥ 6 points on at least one day of postoperative first three days). The secondary outcome was the duration of sleep structures, collected from the Fitbit Charge 2® smart bracelet (Fitbit, Inc., San Francisco, CA, USA). RESULTS: There were 188 women analyzed with the modified intention-to-treat method. The incidences of POSD in the dexmedetomidine and placebo groups were similar (p = 0.649). In the sevoflurane sedation strategy, dexmedetomidine decreased nocturnal wakefulness on postoperative first day (p = 0.001). In the propofol sedation strategy, dexmedetomidine increased nocturnal deep sleep on postoperative first (p < 0.001) and third (p < 0.001) days. CONCLUSION: Intra-operative infusion of dexmedetomidine had no significant effect on POSD but decreased nocturnal wakefulness in the sevoflurane group and increased nocturnal deep sleep in the propofol group. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR2300070136).

A point mutation in the meiotic crossover formation gene HEI10/TFS2 leads to thermosensitive genic sterility in rice.

Thermosensitive genic female sterility (TGFS) is a promising property to be utilized for hybrid breeding. Here, we identified a rice TGFS line, tfs2, through an ethyl methyl sulfone (EMS) mutagenesis strategy. This line showed sterility under high temperature and became fertile under low temperature. Few seeds were produced when the tfs2 stigma was pollinated, indicating that tfs2 is female sterile. Gene cloning and genetic complementation showed that a point mutation from leucine to phenylalanine in HEI10 (HEI10tfs2), a crossover formation protein, caused the TGFS trait of tfs2. Under high temperature, abnormal univalents were formed, and the chromosomes were unequally segregated during meiosis, similar to the reported meiotic defects in oshei10. Under low temperature, the number of univalents was largely reduced, and the chromosomes segregated equally, suggesting that crossover formation was restored in tfs2. Yeast two-hybrid assays showed that HEI10 interacted with two putative protein degradation-related proteins, RPT4 and SRFP1. Through transient expression in tobacco leaves, HEI10 were found to spontaneously aggregate into dot-like foci in the nucleus under high temperature, but HEI10tfs2 failed to aggregate. In contrast, low temperature promoted HEI10tfs2 aggregation. This result suggests that protein aggregation at the crossover position contributes to the fertility restoration of tfs2 under low temperature. In addition, RPT4 and SRFP1 also aggregated into dot-like foci, and these aggregations depend on the presence of HEI10. These findings reveal a novel mechanism of fertility restoration and facilitate further understanding of HEI10 in meiotic crossover formation.

MDSCs in breast cancer: an important enabler of tumor progression and an emerging therapeutic target.

Women worldwide are more likely to develop breast cancer (BC) than any other type of cancer. The treatment of BC depends on the subtype and stage of the cancer, such as surgery, radiotherapy, chemotherapy, and immunotherapy. Although significant progress has been made in recent years, advanced or metastatic BC presents a poor prognosis, due to drug resistance and recurrences. During embryonic development, myeloid-derived suppressor cells (MDSCs) develop that suppress the immune system. By inhibiting anti-immune effects and promoting non-immune mechanisms such as tumor cell stemness, epithelial-mesenchymal transformation (EMT) and angiogenesis, MDSCs effectively promote tumor growth and metastasis. In various BC models, peripheral tissues, and tumor microenvironments (TME), MDSCs have been found to amplification. Clinical progression or poor prognosis are strongly associated with increased MDSCs. In this review, we describe the activation, recruitment, and differentiation of MDSCs production in BC, the involvement of MDSCs in BC progression, and the clinical characteristics of MDSCs as a potential BC therapy target.

Tannic acid supplementation in the diet of Holstein bulls: Impacts on production performance, physiological and immunological characteristics, and ruminal microbiota.

This study was conducted to evaluate the influences of supplementing tannic acid (TA) at different doses on the production performance, physiological and immunological characteristics, and rumen bacterial microbiome of cattle. Forty-eight Holstein bulls were randomly allocated to four dietary treatments: the control (CON, basal diet), the low-dose TA treatment [TAL, 0.3% dry matter (DM)], the mid-dose TA treatment (TAM, 0.9% DM), and the high-dose TA treatment (TAH, 2.7% DM). This trial consisted of 7 days for adaptation and 90 days for data and sample collection, and samples of blood and rumen fluid were collected on 37, 67, and 97 d, respectively. The average daily gain was unaffected (P > 0.05), whilst the ruminal NH3-N was significantly decreased (P < 0.01) by TA supplementation. The 0.3% TA addition lowered (P < 0.05) the levels of ruminal isobutyrate, valerate, and tumor necrosis factor alpha (TNF-α), and tended to (P < 0.1) increase the gain to feed ratio. The digestibility of DM, organic matter (OM), and crude protein, and percentages of butyrate, isobutyrate, and valerate were lower (P < 0.05), while the acetate proportion and acetate to propionate ratio in both TAM and TAH were higher (P < 0.05) than the CON. Besides, the 0.9% TA inclusion lessened (P < 0.05) the concentrations of glucagon and TNF-α, but enhanced (P < 0.05) the interferon gamma (IFN-γ) level and Simpson index of ruminal bacteria. The 2.7% TA supplementation reduced (P < 0.05) the intake of DM and OM, and levels of malondialdehyde and thyroxine, while elevated (P < 0.05) the Shannon index of the rumen bacterial populations. Moreover, the relative abundances of the phyla Fibrobacteres and Lentisphaerae, the genera Fibrobacter and Bradyrhizobium, and the species Bradyrhizobium sp., Lachnospiraceae bacterium RM29, and Lachnospiraceae bacterium CG57 were highly significantly (q < 0.01) or significantly (q < 0.05) raised by adding 2.7% TA. Results suggested that the TA addition at 0.3% is more suitable for the cattle, based on the general comparison on the impacts of supplementing TA at different doses on all the measured parameters.

Blockade of Nuclear ß-Catenin Signaling via Direct Targeting of RanBP3 with NU2058 Induces Cell Senescence to Suppress Colorectal Tumorigenesis.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world, with high prevalence and low 5-year survival. Most of the CRC patients show excessive activation of the Wnt/ß-catenin pathway which is a vital target for CRC treatment. Based on multiple CRC cell lines with different nuclear expression of ß-catenin, NU2058 is identified from a small molecule library consisting of 280 bioactive compounds and found to selectively inhibit the proliferation of CRC cells with nuclear ß-catenin activation in vitro and in vivo. The translational significance of NU2058 alone or in combination with chemotherapeutic drugs oxaliplatin and irinotecan (SN38) in CRC is demonstrated in orthotopic tumor model and patient-derived xenograft models. By integrating limited proteolysis-small molecule mapping (LiP-SMap) and mass spectrometry (MS), Ran-binding protein 3 (RanBP3) is identified as the direct target of NU2058. The results show that RanBP3 is a tumor suppressor in CRC and is associated with patient survival. Mechanistically, NU2058 increases the interaction of RanBP3 and ß-catenin to promote nuclear export of ß-catenin, which further inhibits transcription of c-Myc and cyclin D1 to induce cell senescence. Collectively, NU2058 may serve as a promising therapeutic agent for CRC patients with selective disruption of pathologic Wnt/ß-catenin signaling.

Catellatospora tritici sp. nov., a novel cellulase-producing actinobacterium isolated from rhizosphere soil of wheat (Triticum aestivum L.) and emended description of the genus Catellatospora.

A Gram-positive, cellulose-degrading actinobacterium, designed strain NEAU-YM18T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) sampled in Langfang, Hebei Province, PR China. The novel strain was characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics confirmed that strain NEAU-YM18T belonged to the genus Catellatospora. Cells of strain NEAU-YM18T were observed to contain meso- and 3-hydroxy-diaminopimelic acids as diagnostic cell-wall amino acids. The acyl type of the cell-wall muramic acid was glycolyl. The whole-cell hydrolysates were xylose, glucose and ribose. The phospholipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major fatty acids were iso-C15 : 0, iso-C16 : 0, C18 : 1 ω9c and summed feature 5 (anteiso-C18 : 0/C18 : 2 ω6,9c). The menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The DNA G+C content was 71.1 %. The results of 16S rRNA gene sequence and phylogenetic analyses indicated that strain NEAU-YM18T was closely related to Catellatospora chokoriensis 2-25(1)T (98.4 % 16S rRNA gene sequence similarity), Catellatospora vulcania NEAU-JM1T (98.3%) and Catellatospora sichuanensis H14505T (98.3 %) and formed a branch with C. sichuanensis H14505T. Furthermore, the whole genome phylogeny of strain NEAU-YM18T showed that the strain formed an independent clade. The digital DNA-DNA hybridization results between NEAU-YM18T and C. chokoriensis 2-25(1)T, C. vulcania NEAU-JM1T and C. sichuanensis H14505T were 25.0, 24.7 and 24.7 %, respectively, and the whole-genome average nucleotide identity values between them were 81.5, 81.4 and 81.4 %, respectively. These genetic results and some phenotypic characteristics could distinguish strain NEAU-YM18T from its reference strains. In addition, genomic analysis confirmed that strain NEAU-YM18T had the potential to decompose cellulose and produce bioactive compounds. Therefore, strain NEAU-YM18T represents a novel species of the genus Catellatospora, for which the name Catellatospora tritici sp. nov. is proposed. The type strain is NEAU-YM18T (=CCTCC AA 2020040T=JCM 33977T).

Nonomuraea aurantiaca sp. nov., a novel cellulase-producing actinobacterium isolated from soil.

A novel cellulase-producing actinobacterium, designated strain NEAU-L178T, was isolated from soil sample collected from Qiqihaer, Heilongjiang Province, PR China. A polyphasic study was carried out to determine the taxonomic status of the strain. On the basis of 16S rRNA gene sequence analysis, strain NEAU-L178T should be classified into the genus Nonomuraea and is closely related to Nonomuraea cavernae SYSU K10005T (99.31 % 16S rRNA gene sequence similarity), Nonomuraea glycinis NEAU-BB2C19T (98.75 %), Nonomuraea guangzhouensis NEAU-ZJ3T (98.75 %) and 'Nonomuraea rhizosphaerae' NEAU-mq18T (98.34 %). The digital DNA-DNA hybridization values between them are 27.1, 26.1, 42.0 and 30.9 %, and the whole-genome average nucleotide identity values between them are 83.1, 82.3, 90.3 and 85.8 %, respectively. The whole-cell hydrolysates contained glucose, ribose, arabinose and madurose. The menaquinones were identified as MK-9(H0), MK-9(H4) and MK-9(H2). The major fatty acids were C16 : 0, iso-C17 : 0 and C17 : 0 10-methyl. The detected polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol and three unidentified phospholipids. The genomic DNA G+C content was 69.7 mol%. In addition, whole-genome analysis indicated that strain NEAU-L178T had the potential to degrade cellulose. Based on the phenotypic, genotypic, chemotaxonomic and phylogenetic data, strain NEAU-L178T can be differentiated from its close phylogenetic relatives and represents a novel species of the genus Nonomuraea, for which the name Nonomuraea aurantiaca sp. nov. is proposed. The type strain is NEAU-L178T (=JCM 34799T=CGMCC 4.7741T).

Inhibition of nuclear deacetylase Sirtuin-1 induces mitochondrial acetylation and calcium overload leading to cell death.

Sirtuin-1 (SIRT1) is a critical nuclear deacetylase that participates in a wide range of biological processes. We hereby employed quantitative acetyl-proteomics to globally reveal the landscape of SIRT1-dependent acetylation in colorectal cancer (CRC) cells stimulated by specific SIRT1 inhibitor Inauhzin (INZ). We strikingly observed that SIRT1 inhibition enhances protein acetylation levels, with the multisite-acetylated proteins (acetyl sites >4/protein) mainly enriched in mitochondria. INZ treatment increases mitochondrial fission and depolarization in CRC cells. The acetylation of mitochondrial proteins promoted by SIRT1 inhibition prevents the recruitment of ubiquitin and LC3 for mitophagic degradation. We then found that, SIRT1 inhibition increases the acetylation of mitochondrial calcium uniporter (MCU) at residue K332, resulting in mitochondrial Ca2+ overload and depolarization, and ultimately CRC apoptosis. Arginine substitution of the K332 (K332R) dramatically decreases the mitochondrial Ca2+ influx, mitochondrial membrane potential loss and ROS burst induced by INZ. This finding uncovers a non-canonical role of SIRT1 in regulating mitochondrial function and implicates a possible way for anticancer intervention through SIRT1 inhibition.

Effect of Systemic Lidocaine on Postoperative Early Recovery Quality in Patients Undergoing Supratentorial Tumor Resection.

Purpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia. Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded. Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P <0.001) in group L (165.5±3.8 vs 173.7±4.7) than those in group C (155.6±4.0 vs 163.2±4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P <0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P <0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality. Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.

Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner.

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

A Novel LOC101927967 Intergenic Region ALK Fusion Identified by NGS and Validated by IHC and FISH in a Patient with Early Stage Adenocarcinoma of Lung.

Anaplastic lymphoma kinase (ALK) gene rearrangement is an essential driver mutation identified in approximately 5% of non-small cell lung cancers (NSCLCs). The results of clinical trials have demonstrated the impressive efficacy of ALK tyrosine kinase inhibitors (ALK-TKIs). Besides the classic EML4-ALK fusions, a growing list of gene fusion partners for ALK in NSCLC have been identified with heterogeneous clinical responses to ALK-TKIs. However, a LOC101927967-ALK fusion has not been reported in NSCLC. Herein, a novel LOC101927967 downstream intergenic region ALK fusion in an early-stage patient with lung adenocarcinoma was first identified by next-generation sequencing (NGS) and verified by immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH), which might provide a treatment option for postoperative recurrence.

New insights into the interplay between long non-coding RNAs and RNA-binding proteins in cancer.

With the development of proteomics and epigenetics, a large number of RNA-binding proteins (RBPs) have been discovered in recent years, and the interaction between long non-coding RNAs (lncRNAs) and RBPs has also received increasing attention. It is extremely important to conduct in-depth research on the lncRNA-RBP interaction network, especially in the context of its role in the occurrence and development of cancer. Increasing evidence has demonstrated that lncRNA-RBP interactions play a vital role in cancer progression; therefore, targeting these interactions could provide new insights for cancer drug discovery. In this review, we discussed how lncRNAs can interact with RBPs to regulate their localization, modification, stability, and activity and discussed the effects of RBPs on the stability, transport, transcription, and localization of lncRNAs. Moreover, we explored the regulation and influence of these interactions on lncRNAs, RBPs, and downstream pathways that are related to cancer development, such as N6-methyladenosine (m6A) modification of lncRNAs. In addition, we discussed how the lncRNA-RBP interaction network regulates cancer cell phenotypes, such as proliferation, apoptosis, metastasis, drug resistance, immunity, tumor environment, and metabolism. Furthermore, we summarized the therapeutic strategies that target the lncRNA-RBP interaction network. Although these treatments are still in the experimental stage and various theories and processes are still being studied, we believe that these strategies may provide new ideas for cancer treatment.

Inhibiting endoplasmic reticulum stress mediated-autophagy enhances the pro-apoptotic effects of resveratrol derivative in colon cancer cells.

Previous studies have demonstrated that endoplasmic reticulum stress (ERS) might play a major role in inducing cellular autophagy and apoptosis in multiple types of cancer. Herein, we observed that trans-3,5,4'-trimethoxystilbene (TMS) exposure facilitated apoptotic cell death and ERS-mediated autophagy in colon cancer SW480 and HCT116 cells. Interestingly, our data demonstrated that ERS was not involved in TMS-induced apoptosis. However, ERS notably induced protective autophagy in SW480 and HCT116 cells. In addition, inhibiting cellular ERS significantly improved the pro-apoptotic effects of TMS. Thus, our results indicated that TMS-mediated autophagy was dependent on ERS, while apoptotic cell death might be induced in the ERS-independent pathway after TMS treatment. Generally, inhibiting ERS-mediated autophagy can enhance the pro-apoptotic effects of TMS. TMS might be a potential therapeutic agent for colon cancer treatment.

Long Noncoding RNA 00472: A Novel Biomarker in Human Diseases.

Long non-coding RNAs (lncRNAs) play important roles in human diseases. They control gene expression levels and influence various biological processes through multiple mechanisms. Functional abnormalities in lncRNAs are strongly associated with occurrence and development of various diseases. LINC00472, which is located on chromosome 6q13, is involved in several human diseases, particularly cancers of the breast, lung, liver, osteosarcoma, bladder, colorectal, ovarian, pancreatic and stomach. Importantly, LINC00472 can be used as a biomarker for breast cancer cell sensitivity to chemotherapeutic regimens, including doxorubicin. LINC00472 is regulated by microRNAs and several signaling pathways. However, the significance of LINC00472 in human diseases has not been clearly established. In this review, we elucidate on the significance of LINC00472 in various human diseases, indicating that LINC00472 may be a diagnostic, prognostic as well as therapeutic target for these diseases.

Advances in targeted therapy for esophageal cancer.

Esophageal cancer (EC) is one of the most lethal cancers in the world, and its morbidity and mortality rates rank among the top ten in China. Currently, surgical resection, radiotherapy and chemotherapy are the primary clinical treatments for esophageal cancer. However, outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional treatments. As a new type of approach, targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer; these include cetuximab and bevacizumab, which target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. In addition, other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously developed. For example, trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), has been approved by the Food and Drug Administration (FDA) as a first-line treatment of HER-2-positive cancer. Moreover, the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma (ESCC). These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer patients. Nevertheless, adverse events, optimal dosages and effective combinations still need further investigation. In this review, we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs, discuss their efficacy and safety, and provide a clinical rationale for precision medicine in esophageal cancer.

Curcumin from Jianghuang (Rhizoma Curcumae Longae) protects against exposure to ultraviolet B by antioxidation and attenuating mitochondrion-dependent apoptosis.

OBJECTIVE: To investigate the protective effect of curcumin extracted from Jianghuang (Rhizoma Curcumae Longae) against ultraviolet B (UVB) and the possible mechanism. METHODS: Effects of curcumin were detected in vivo and in vitro. Morphological changes of white guinea pig skin were assessed by hematoxylin and eosin staining. HaCaT cell proliferation was measured by 3-[4,5-dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium broide (MTT) assays. The cell cycle distribution, apoptotic rate, level of reactive oxygen species (ROS), mitochondrial membrane potential, and intracellullar calcium ion concentration of HaCaT cells were detected by flow cytometry. Antioxidant levels in skin tissues and HaCat cells were measured by biochemical methods. RESULTS: UVB inhibited in vitro cell proliferation by inducing G2/M arrest, increasing ROS, apoptosis, and necrosis, and decreasing B-cell lymphoma-2, and increasing Bax, cytochrome c, and caspase-3 levels. CONCLUSION: Curcumin blocks the effects of UVB by reducing ROS and apoptosis, and reversing UVB-induced changes in the expression of apoptotic proteins. The mitochondrial pathway is involved in curcumin-regulated apoptosis.

Pro-Angiogenic and Pro-Inflammatory Regulation by lncRNA MCM3AP-AS1-Mediated Upregulation of DPP4 in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) represents the most common type of renal cell carcinoma (RCC) in adults, in addition to the worst prognosis among the common epithelial kidney tumors. Inflammation and angiogenesis seem to potentiate tumor growth and metastasis of the malignancy. The current study explored the contributions of the lncRNA MCM3AP-AS1 in tumor-associated inflammation and angiogenesis in ccRCC with a specific focus on its transcriptional regulation and its interactions with transcription factor E2F1 and DPP4. Tumor tissues and matched adjacent non-tumor tissues were collected from 78 ccRCC patients. Methylation-specific PCR and ChIP assays were applied to detect the methylation at the promoter region of MCM3AP-AS1. Dual-luciferase reporter assay, RIP, RNA pull-down, and ChIP assays were employed to confirm the interactions between MCM3AP-AS1, E2F1, and DPP4. Nude mice were subcutaneously xenografted with human ccRCC cells. Cell proliferation was evaluated by CCK-8 assays and EDU staining in ccRCC cells in vitro and by immunohistochemical staining of Ki67 in vivo. Inflammation was examined by detecting the secretion of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6). Pro-angiogenic ability of ccRCC cells was assessed by the co-culture with human umbilical vein endothelial cells (HUVEC) in vitro and by microvessel density (MVD) measurements and angiogenesis in the chicken chorioallantoic membrane. MCM3AP-AS1 was highly-expressed in ccRCC and associated with poor patient survival. Demethylation of MCM3AP-AS1 was noted in ccRCC tissues and cells. Over-expression of MCM3AP-AS1 enhanced cell proliferation, the release of pro-inflammatory cytokines, and the tube formation of HUVECs in cultured human Caki-1 and 786-O cells. MCM3AP-AS1 was shown to enhance the E2F1 enrichment at the DPP4 promoter, to further increase the expression of DPP4. Knockdown of DPP4 could abate pro-angiogenic and pro-inflammatory abilities of MCM3AP-AS1 in ccRCC cells. Pro-angiogenic and pro-inflammatory abilities of MCM3AP-AS1 in vivo were confirmed in mice subcutaneously xenografted with human ccRCC cells. Our findings demonstrate a novel mechanism by which lncRNA MCM3AP-AS1 exerts pro-angiogenic and pro-inflammatory effects, highlighting the potential of MCM3AP-AS1 as a promising target for treating ccRCC.

Glycomyces albidus sp. nov., a novel actinobacterium isolated from rhizosphere soil of wheat (Triticum aestivum L.).

A novel actinobacterium, designated strain NEAU-7082T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) and characterized by using a polyphasic approach. Morphological and chemotaxonomic characteristics confirmed the affiliation of strain NEAU-7082T to the genus Glycomyces. 16S rRNA gene sequence analysis indicated that strain NEAU-7082T belonged to the genus Glycomyces and was closely related to Glycomyces mayteni JCM 16217T (99.0 % 16S rRNA gene sequence similarity), Glycomyces sambucus DSM 45047T (98.4 %), Glycomyces scopariae DSM 44968T (98.3 %), Glycomyces paridis DSM 102295T (98.1 %), Glycomyces artemisiae NBRC 109773T (98.0 %) and Glycomyces dulcitolivorans DSM 105121T (97.9 %). Phylogenetic analysis using the 16S rRNA gene sequence showed that the strain formed a stable clade with G. mayteni JCM 16217T and clustered with G. sambucus DSM 45047T, G. scopariae DSM 44968T, G. artemisiae NBRC 109773T and G. dulcitolivorans DSM 105121T in the genus Glycomyces. The cell wall contained meso-diaminopimelic acid and the whole-cell hydrolysates were glucose and xylose. The polar lipid profile consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), glycolipid (GL), phosphatidylinositol mannoside (PIM) and an unidentified lipid (UL). The menaquinones were MK-11(H4), MK-11 and MK-10. Major fatty acids were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. These chemotaxonomic data substantiated the affiliation of strain NEAU-7082T to the genus Glycomyces. The DNA G+C content was 71.3 mol%. A combination of DNA-DNA hybridization results and some phenotypic characteristics demonstrated that strain NEAU-7082T could be distinguished from its closest relatives. Therefore, strain NEAU-7082T is considered to represent a novel species of the genus Glycomyces, for which the name Glycomyces albidus sp. nov. is proposed. The type strain is NEAU-7082T (=CCTCC AA 2019045T=JCM 33458T).

The discovery, design and synthesis of potent agonists of adenylyl cyclase type 2 by virtual screening combining biological evaluation.

Adenylate cyclases (ACs), play a critical role in the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP). Studies have indicated that adenylyl cyclase type 2 (AC2) is potential drug target for many diseases, however, up to now, there is no AC2-selective agonist reported. In this research, docking-based virtual screening with the combination of cell-based biological assays have been performed for discovering novel potent and selective AC2 agonists. Virtual screening disclosed a novel hit compound 8 as an AC2 agonist with EC50 value of 8.10 µM on recombinant human hAC2 + HEK293 cells. The SAR (structure activity relationship) based on the derivatives of compound 8 was further explored on recombinant AC2 cells and compound 73 was found to be the most active agonist with the EC50 of 90 nM, which is 160-fold more potent than the reported agonist Forskolin and could selectively activate AC2 to inhibit the expression of Interleukin-6. The discovery of a new class of AC2-selective agonists would provide a novel chemical probe to study the physiological function of AC2.

The diagnostic performance of PET/CT scans for the detection of para-aortic metastatic lymph nodes in patients with cervical cancer: A meta-analysis.

OBJECTIVE: We performed a meta-analysis to evaluate the diagnostic value of positron emission tomography/computed tomography (PET/CT) in the detection of para-aortic lymph node metastasis in cervical cancer. METHODS: We searched the PubMed, Embase, Web of Science, Cochrane Library, Chinese Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang and VIP databases in all languages from their inception to September 2018. Stat15.0 software was used to obtain pooled estimates of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) as well as a summary receiver operating characteristic (SROC) curves. Deek's funnel plot was used to assess publication bias. QUADAS-2 was used to evaluate the quality of the studies. The protocol for this meta-analysis is registered in PROSPERO (CRD42019115330). RESULTS: We obtained 14 studies, and the pooled estimates for sensitivity and specificity of PET/CT were 0.71 (95% confidence interval (CI) = 0.54-0.83) and 0.97 (95% CI = 0.93-0.98), respectively. Pooled PLR and NLR were 21.53 and 0.30, respectively. The diagnostic odds ratio (DOR) was70.59, and the area under the curve (AUC) was 0.95. CONCLUSION: PET/CT is an effective and important imaging method for the diagnosis of para-aortic lymph node metastasis in early cervical cancer.