Exosomal miR-4516 derived from ovarian cancer stem cells enhanced cisplatin tolerance in ovarian cancer by inhibiting GAS7.

Ovarian cancer (OC) is a devastating disease for women, with chemotherapy resistance taking the lead. Cisplatin has been the first-line therapy for OC for a long time. However, the resistance of OC to cisplatin is an important impediment to its efficacy. Mounting studies showed that ovarian cancer stem cells (OCSCs) affected chemotherapy resistance by secreting exosomes. MicroRNAs (miRNAs) play important roles in exosomes secreted by OCSCs. Here, through the analysis of GEO database (GSE107155) combined with RT-qPCR of OC-related cells/clinical tissues, it was found that hsa-miR-4516 (miR-4516) was significantly up-regulated in OCSCs. Then, OCSCs-derived exosomes were isolated and identified, and it was observed the influence of exosomes on the chemoresistance in SKOV3/cisplatin (SKOV3/DDP) cells. These results manifested that OCSCs-mediated exosomes facilitated the chemoresistance of SKOV3/DDP cells by delivering miR-4516 into them. Growth arrest-specific 7 (GAS7), a downstream target of miR-4516, was determined by bioinformatics prediction combined with molecular biological detection. Next, we up-regulated GAS7 expression and discovered that the promotion of chemoresistance in SKOV3/DDP cells by OCSCs-derived exosomes was significantly impaired. Finally, the mice tumor model of SKOV3/DDP cells was built to estimate the effect of GAS7 over-expression on OC growth. The results showed that GAS7 inhibited the chemoresistance of OC in vivo. In conclusion, our experiments suggested that OCSCs-derived exosomes enhanced OC cisplatin resistance by suppressing GAS7 through the delivery of miR-4516. This study provides a possible target for the treatment of OC DDP resistance.

M6A-mediated hsa_circ_0061179 inhibits DNA damage in ovarian cancer cells via miR-143-3p/TIMELESS.

Ovarian cancer (OC) is among the most common and deadly solid malignancies in women. Despite many advances in OC research, the incidence of OC continues to rise, and its pathogenesis remains largely unknown. Herein, we elucidated the function of hsa_circ_0061179 in OC. The levels of hsa_circ_0061179, miR-143-3p, TIMELESS, and DNA damage repair-related proteins in OC or normal ovarian tissues and cells were measured using real-time quantitative polymerase chain reaction and immunoblotting. The biological effects of hsa_circ_0061179 and miR-143-3p on proliferation, clone formation, DNA damage, and apoptosis of OC cells were detected by the cell counting kit-8 assay, 5-methylethyl-2'-deoxyuridine, flow cytometry, the comet assay, and immunofluorescence staining combined with the confocal microscopy. The interaction among hsa_circ_0061179, miR-143-3p, and TIMELESS was validated by the luciferase reporter assay. Mice tumor xenograft models were used to evaluate the influence of hsa_circ_0061179 on OC growth in vivo. We found that human OC biospecimens expressed higher levels of hsa_circ_0061179 and lower levels of miR-143-3p. Hsa_circ_0061179 was found to bind with miR-143-3p, which directly targets TIMELESS. Hsa_circ_0061179 knockdown or miR-143-3p overexpression suppressed the proliferation and clone formation of OC cells and increased DNA damage and apoptosis of OC cells via the miR-143-3p/TIMELESS axis. Furthermore, we demonstrated that METTL3 could direct the formation of has_circ_0061179 through a specific m6A modification site. YTHDC1 facilitated the cytoplasmic transfer of has_circ_0061179 by directly binding to the modified m6A site. Our findings suggest that hsa_circ_0061179 acts as the sponge of miR-143-3p to activate TIMELESS signaling and inhibits DNA damage and apoptosis in OC cells.

Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer.

Ovarian cancer (OC) is the most lethal gynecological tumor, characterized by its insidious and frequently recurring metastatic progression. Owing to limited early screening methods, over 70% of OC cases are diagnosed at advanced stages, typically stage III or IV. Recently, N6-methyladenosine (m6A) modification has emerged as a hotspot of epigenetic research, representing a significant endogenous RNA modification in higher eukaryotes. Numerous studies have reported that m6A-related regulatory factors play pivotal roles in tumor development through diverse mechanisms. Moreover, recent studies have indicated the aberrant expression of multiple regulatory factors in OC. Therefore, this paper comprehensively reviews research advancements concerning m6A in OC, aiming to elucidate the regulatory mechanism of m6A-associated regulators on pivotal aspects, such as proliferation, invasion, metastasis, and drug resistance, in OC. Furthermore, it discusses the potential of m6A-associated regulators as early diagnostic markers and therapeutic targets, thus contributing to the diagnosis and treatment of OC.

Ovarian cancer (OC) presents a formidable challenge in the medical field, often detected at advanced stages, necessitating urgent exploration of diagnostic and therapeutic avenues. This review delves into the intricate role of N6-methyladenosine (m6A) RNA modification in OC, a dynamic epigenetic process increasingly recognized for its regulatory role in cancer biology. Highlighting recent advancements, the review sheds light on how m6A-related factors influence crucial aspects of OC progression, including tumor growth, metastasis, and resistance to treatment. Specifically, m6A methyltransferases, binding proteins, and demethylases exert multifaceted effects on OC progression, influencing the expression of pivotal oncogenes and tumor suppressors. While promising, translating these insights into effective therapies requires further investigation. By comprehensively understanding the influence of m6A on OC, there lies hope for developing improved diagnostic techniques and novel treatment strategies to combat this complex disease.

Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment.

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness of immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance the antitumor immune response of the cervical cancer through gas-amplified metalloimmunotherapy with dual activation of pyroptosis and STING pathway. The bioactive MCSP exhibited the ability to rapidly release Ca2+, Mn2+, and H2S in response to the tumor microenvironment. H2S disrupted the calcium buffer system of cancer cells by interfering with the oxidative phosphorylation pathway, leading to calcium overload-triggered pyroptosis. On the other hand, H2S-mediated mitochondrial dysfunction further promoted the release of mitochondrial DNA (mtDNA), enhancing the activation effect of Mn2+ on the cGAS-STING signaling axis and thereby activating immunosuppressed dendritic cells. The released H2S acted as an important synergist between Mn2+ and Ca2+ by modulating dual signaling mechanisms to bridge innate and adaptive immune responses. The combination of MCSP NPs and PD-1 immunotherapy achieved synergistic antitumor effects and effectively inhibited tumor growth. This study reveals the potential collaboration between H2S gas therapy and metalloimmunotherapy and provides an idea for the design of nanoimmunomodulators for rational regulation of the immunosuppressive tumor microenvironment.

Current data and future perspectives on DNA methylation in ovarian cancer (Review).

Ovarian cancer (OC) represents the most prevalent malignancy of the female reproductive system. Its distinguishing features include a high aggressiveness, substantial morbidity and mortality, and a lack of apparent symptoms, which collectively pose significant challenges for early detection. Given that aberrant DNA methylation events leading to altered gene expression are characteristic of numerous tumor types, there has been extensive research into epigenetic mechanisms, particularly DNA methylation, in human cancers. In the context of OC, DNA methylation is often associated with the regulation of critical genes, such as BRCA1/2 and Ras­association domain family 1A. Methylation modifications within the promoter regions of these genes not only contribute to the pathogenesis of OC, but also induce medication resistance and influence the prognosis of patients with OC. As such, a more in­depth understanding of DNA methylation underpinning carcinogenesis could potentially facilitate the development of more effective therapeutic approaches for this intricate disease. The present review focuses on classical tumor suppressor genes, oncogenes, signaling pathways and associated microRNAs in an aim to elucidate the influence of DNA methylation on the development and progression of OC. The advantages and limitations of employing DNA methylation in the diagnosis, treatment and prevention of OC are also discussed. On the whole, the present literature review indicates that the DNA methylation of specific genes could potentially serve as a prognostic biomarker for OC and a therapeutic target for personalized treatment strategies. Further investigations in this field may yield more efficacious diagnostic and therapeutic alternatives for patients with OC.

Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients.

Background: Genome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germline mutations in CHEK1 are rarely reported. Case presentation: In this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in KRAS, PPP2R1A, and PIK3R1. Importantly, her paired peripheral blood cells harbored a germline CHEK1 mutation, CHEK1 exon 6 c.613 + 2T>C, which was also found in her father. Unfortunately, the CHEK1 status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the CHEK1 gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation. Conclusion: This case highlights a rare germline CHEK1 mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.

Prognostic value of tumor­associated CD177+ neutrophils in lung adenocarcinoma.

The aim of the present study was to detect CD177+ neutrophils in tumor tissues and analyze their association with the clinical characteristics and prognosis of patients with lung adenocarcinoma (LUAD). Immunohistochemistry was used to detect CD177+ neutrophils in tumors and adjacent tissues of 16 patients with LUAD who underwent curative surgical resection. A total of 120 patients with LUAD were recruited, and their clinical data were collected; survival follow-up was performed. CD177+ neutrophils in tumor tissues were detected via immunohistochemistry, and the association between CD177+ neutrophils and clinical characteristics was analyzed. The density of CD177+ neutrophils in tumor tissues and adjacent tissues of patients with LUAD was analyzed using t-test, and the association between CD177+ neutrophils and clinical characteristics was analyzed through the Chi-square test. Survival was calculated using the Kaplan-Meier survival rate curve. Finally, the association between these indicators and the survival of LUAD patients was evaluated using Cox regression analysis. CD177+ neutrophil infiltration was significantly higher in LUAD tumor tissues, and the high density of CD177+ neutrophils was associated with the clinical characteristics of TNM stage, tumor differentiation and poor progression-free and overall survival in LUAD. In conclusion, tumor-associated CD177+ neutrophils associated with malignant progression and poor prognosis may be independent and unfavorable prognostic biomarkers for LUAD.

A novel SIK2 inhibitor SIC-19 exhibits synthetic lethality with PARP inhibitors in ovarian cancer.

PURPOSE: Ovarian cancer patients with HR proficiency (HRP) have had limited benefits from PARP inhibitor treatment, highlighting the need for improved therapeutic strategies. In this study, we developed a novel SIK2 inhibitor, SIC-19, and investigated its potential to enhance the sensitivity and expand the clinical utility of PARP inhibitors in ovarian cancer. METHODS: The SIK2 protein was modeled using a Molecular Operating Environment (MOE), and the most favorable model was selected based on a GBVI/WSA dG scoring function. The Chembridge Compound Library was screened, and the top 20 candidate compounds were tested for their interaction with SIK2 and downstream substrates, AKT-pS473 and MYLK-pS343. SIC-19 emerged as the most promising drug candidate and was further evaluated using multiple assays. RESULTS: SIC-19 exhibited selective and potent inhibition of SIK2, leading to its degradation through the ubiquitination pathway. The IC50 of SIC-19 correlated inversely with endogenous SIK2 expression in ovarian cancer cell lines. Treatment with SIC-19 significantly inhibited cancer cell growth and sensitized cells to PARP inhibitors in vitro, as well as in ovarian cancer organoids and xenograft models. Mechanistically, SIK2 knockdown and SIC-19 treatment reduced RAD50 phosphorylation at Ser635, prevented nuclear translocation of RAD50, disrupted nuclear filament assembly, and impaired DNA homologous recombination repair, ultimately inducing apoptosis. These findings highlight the crucial role of SIK2 in the DNA HR repair pathway and demonstrate the significant PARP inhibitor sensitization achieved by SIC-19 in ovarian cancer. CONCLUSIONS: SIC-19, a novel SIK2 inhibitor, effectively inhibits tumor cell growth in ovarian cancer by interfering with RAD50-mediated DNA HR repair. Furthermore, SIC-19 enhances the efficacy of PARP inhibitors, providing a promising therapeutic strategy to improve outcomes for ovarian cancer patients.

Eco-friendly management of Meloidogyne incognita in cadmium-contaminated soil by using nematophagous fungus Purpureocillium lavendulum YMF1.683: Efficacy and mechanism.

Root-knot nematodes (RKNs) are distributed globally, including in agricultural fields contaminated by heavy metals (HM), and can cause serious crop damages. Having a method that could control RKNs in HM-contaminated soil while limit HM accumulation in crops could provide significant benefits to both farmers and consumers. In this study, we showed that the nematophagous fungus Purpureocillium lavendulum YMF1.683 exhibited a high nematocidal activity against the RKN Meloidogyne incognita and a high tolerance to CdCl2. Comparing to the P. lavendulum YMF1.838 which showed low tolerance to Cd2+, strain YMF1.683 effectively suppressed M. incognita infection and significantly reduced the Cd2+ uptake in tomato root and fruit in soils contaminated by 100 mg/kg Cd2+. Transcriptome analyses and validation of gene expression by RT-PCR revealed that the mechanisms contributed to high Cd-resistance in YMF1.683 mainly included activating autophagy pathway, increasing exosome secretion of Cd2+, and activating antioxidation systems. The exosomal secretory inhibitor GW4869 reduced the tolerance of YMF1.683 to Cd2+, which firstly demonstrated that fungal exosome was involved in HM tolerance. The up-regulation of glutathione synthesis pathway, increasing enzyme activities of both catalase and superoxide dismutase also played important roles in Cd2+ tolerance of YMF1.683. In Cd2+-contaminated soil, YMF1.683 limited Cd2+-uptake in tomato by up-regulating the genes of ABCC family in favor of HM sequestration in plant, and down-regulating the genes of ZIP, HMA, NRAMP, YSL families associated with HM absorption, transport, and uptake in plant. Our results demonstrated that YMF1.683 could be a promising bio-agent in eco-friendly management of M. incognita in Cd2+ contaminated soils.

Ultrasonographic diagnosis of ovarian tumors through the deep convolutional neural network.

OBJECTIVES: The objective of this study was to develop and validate an ovarian tumor ultrasonographic diagnostic model based on deep convolutional neural networks (DCNN) and compare its diagnostic performance with that of human experts. MATERIAL AND METHODS: We collected 486 ultrasound images of 192 women with malignant ovarian tumors and 617 ultrasound images of 213 women with benign ovarian tumors, all confirmed by pathological examination. The image dataset was split into a training set and a validation set according to a 7:3 ratio. We selected 5 DCNNs to develop our model: MobileNet, Xception, Inception, ResNet and DenseNet. We compared the performance of the five models through the area under the curve (AUC), sensitivity, specificity, and accuracy. We then randomly selected 200 images from the validation set as the test set. We asked three expert radiologists to diagnose the images to compare the performance of radiologists and the DCNN model. RESULTS: In the validation set, AUC of DenseNet was 0.997 while AUC was 0.988 of ResNet, 0.987 of Inception, 0.968 of Xception and 0.836 of MobileNet. In the test set, the accuracy was 0.975 with the DenseNet model versus 0.825 (p < 0.0001) with the radiologists, and sensitivity was 0.975 versus 0.700 (p < 0.0001), and specificity was 0.975 versus 0.908 (p < 0.001). CONCLUSIONS: DensNet performed better than other DCNNs and expert radiologists in identifying malignant ovarian tumors from benign ovarian tumors based on ultrasound images, a finding that needs to be further explored in clinical trials.

Efficacy observation and prognosis analysis of EGFR-TKIs alone versus EGFR-TKIs plus chemotherapy in advanced lung adenocarcinoma with EGFR Exon 19 Deletion, Exon 21 L858R mutation: A historical cohort study.

The aim of this study was to investigate the clinical efficacy and determine the prognostic value of Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) alone versus EGFR-TKIs plus chemotherapy for the treatment of advanced lung adenocarcinoma with EGFR Exon 19 Deletion(19Del), Exon 21 L858R (L858R) mutation. The demographic and clinical characteristics of 110 newly diagnosed metastatic lung adenocarcinoma patients with the EGFR 19Del, L858R mutation from June 2016 to October 2018 were retrospectively analyzed. Total remission rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and patient 1-year/2-year survival between EGFR-TKIs combined with first-line platinum-containing double-drug chemotherapy (Observation) group and an EGFR-TKIs alone (Control) group were evaluated and analyzed. For lung adenocarcinoma patients with the EGFR 19Del, L858R mutation, the Observation group had a better ORR (81.4% vs 52.2%), mPFS (12.0 vs 9 months), and 2-year survival (72.1% vs 52.2%) than the Control group, and the differences were statistically significant (P < .05), but DCR (95.3% vs 88.1%) and 1-year survival (90.7% vs 83.6%) were not significantly different between the groups (P > .05). For lung adenocarcinoma with the EGFR 19Del mutation, the Observation group showed a better ORR (81.8% vs 54.3%), and mPFS (14.5 vs 11.0 months) than the Control group, and the differences were statistically significant (P < .05), but DCR (95.5% vs 91.4%), 1-year survival (90.9% vs 85.7%), and 2-year survival (72.7% vs 60.0%) were not significantly different (P > .05). For lung adenocarcinoma with the EGFR L858R mutation, the Observation group showed a better ORR (81.0% vs 50.0%), mPFS (12.0 vs 9.0 months), and 2-year survival (71.4% vs 43.8%) than the Control group (P < .05), but DCR (95.2% vs 84.4%) and 1-year survival (90.5% vs 81.3%) were not significantly different (P > .05). Compared to EGFR-TKIs alone, EGFR-TKIs combined with chemotherapy improved ORR and mPFS in cases of advanced lung adenocarcinoma with EGFR 19Del, L858R mutation. In particular, patients with the EGFR L858R mutation showed a long-term survival benefit trend. EGFR-TKIs combined chemotherapy may therefore be a viable treatment method for delaying targeted drug resistance.

In Situ-Formed Fibrin Hydrogel Scaffold Loaded With Human Umbilical Cord Mesenchymal Stem Cells Promotes Skin Wound Healing.

Healing of full-thickness skin wounds remains a major challenge. Recently, human umbilical cord mesenchymal stem cells (hUC-MSCs) were shown to possess an extraordinary potential to promote skin repair in clinical settings. However, their low survival rate after transplantation limits their therapeutic efficiency in treating full-thickness skin wounds. Hydrogels are considered an ideal cell transplantation vector owing to their three-dimensional mesh structure, good biosafety, and biodegradation. The objective of this study was to investigate the skin wound healing effect of a fibrin hydrogel scaffold loaded with hUC-MSCs. We found that the fibrin hydrogel had a three-dimensional mesh structure and low cytotoxicity and could prolong the time of cell survival in the peri-wound area. The number of green fluorescent protein (GFP)-labeled hUC-MSCs was higher in the full-thickness skin wound of mice treated with hydrogel-hUC-MSCs than those of mice treated with cell monotherapy. In addition, the combination therapy between the hydrogel and hUC-MSCs speed up wound closure, its wound healing rate was significantly higher than those of phosphate-buffered saline (PBS) therapy, hydrogel monotherapy, and hUC-MSCs monotherapy. Furthermore, the results showed that the combination therapy between hydrogel and hUC-MSCs increased keratin 10 and keratin 14 immunofluorescence staining, and upregulated the relative gene expressions of epidermal growth factor (EGF), transforming growth factor-ß1 (TGF-ß1), and vascular endothelial growth factor A (VEGFA), promoting epithelial regeneration and angiogenesis. In conclusion, the fibrin hydrogel scaffold provides a relatively stable sterile environment for cell adhesion, proliferation, and migration, and prolongs cell survival at the wound site. The hydrogel-hUC-MSCs combination therapy promotes wound closure, re-epithelialization, and neovascularization. It exhibits a remarkable therapeutic effect, being more effective than the monotherapy with hUC-MSCs or hydrogel.

Nocardiopsis changdeensis sp. nov., an endophytic actinomycete isolated from the roots of Eucommia ulmoides Oliv.

Strain Mg02T was isolated from roots of Eucommia ulmoides Oliv. collected from Changde City, Hunan Province, China. Strain Mg02T, which exhibited distinct chemotaxonomic characteristics of the genus Nocardiopsis: cell-wall chemotype III/C, i.e., meso-diaminopimelic acid as diagnostic amino acid in whole-cell hydrolysates and menaquinone MK-10 with variable degrees of saturation in the side chain as the predominant isoprenoid quinone, was investigated by a polyphasic approach to determine their taxonomic position. Sequence analysis of the 16S rRNA gene indicated that strain Mg02T is affiliated to the genus Nocardiopsis, having highest sequence similarity to Nocardiopsis flavescens CGMCC 4.5723T (99.1%) and <98.7% to other species of the genus Nocardiopsis with validly published names. Phylogenetic analysis of 16S rRNA gene indicated strain Mg02T formed a separate evolutionary clade, suggesting that it could be a novel Nocardiopsis species. Phylogenomic analysis showed that strain Mg02T was closely related to N. flavescens CGMCC 4.5723T and distinct from the latter according to the clustering patterns. The Average Nucleotide Identity and digital DNA-DNA hybridization values between strain Mg02T and N. flavescens CGMCC 4.5723T were far below the species-level thresholds. Based on phenotypic, phylogenetic and chemotaxonomic characteristics, we think that strain Mg02T should represent a novel Nocardiopsis species, for which the name Nocardiopsis changdeensis sp. nov. is proposed. The type strain is Mg02T (=MCCC 1K06174T = JCM 34709T).

Hsa_circ_0001445 works as a cancer suppressor via miR-576-5p/SFRP1 axis regulation in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) has high mortality and morbidity. Circular RNA (circRNA) can deeply impact the tumor occurrence and growth. The pathogenic activity of one particular circRNA, hsa_circ_0001445 (hcR1445), in OC remains unclear and was therefore analyzed in this study. METHODS: Human OC tissue specimens and cell lines (SKOV3, HO8910, and OVCAR8) were used to examine the levels of hcR1445 and the microRNA miR-576-5p using polymerase chain reaction. The 5-ethynyl-2'-deoxyuridine, flow cytometry, cellular scratch test, CCK-8, and Transwell migration assays were used to examine the biological activities of hcR1445 and miR-576-5p on cell apoptosis, invasion, migration, and proliferation in OC cells. Protein expression of WNT/ß-catenin and secreted frizzled-related protein 1 (SFRP1) were tested using Western blot analysis. The potential interactions of miR-576-5p/SFRP1 and hcR1445/miR-576-5p were evaluated using a dual-luciferase report assay. The effect of hcR1445 on OC growth and metastasis was further determined using an OC tumor xenograft model in vivo. RESULTS: hcR1445 level was declined in OC cells and tissues. hcR1445 reduced cellular invasion, proliferation, and migration by blocking the ability of miR-576-5p to upregulate SFRP1 expression and consequently prohibit WNT/ß-catenin signal transduction. hcR1445 upregulation suppressed OC growth, development, and intraperitoneal metastasis in vivo. CONCLUSION: hcR1445 acts an antioncogene by targeting the miR-576-5p/SFRP1 axis and blocking OC progression and development. Thus, hcR1445 may be employed as an indicator or a possible therapeutic target in OC patients.

Role of tumor-associated neutrophils in lung cancer (Review).

Lung cancer is the most common malignancy and the leading cause of cancer mortality worldwide; therefore, it is very important to understand the mechanism of its occurrence and progression. It has reported that inflammation is linked to the incidence of various malignancies. Neutrophils not only participate in the inflammatory response, but are also involved in the composition of the tumor microenvironment. Tumor-associated neutrophils (TANs) are infiltrating neutrophils in tumors that directly promote tumor development and progression. Moreover, they regulate the immune microenvironment and affect the therapeutic efficacy and prognosis of lung cancer. In the present review, the role of TANs in lung cancer development/progression and the underlying molecular signaling are evaluated, as well as the possibility of TANs as a potential therapeutic target for lung cancer intervention.

Nocardiopsis akebiae sp. nov., a novel endophytic actinomycete isolated from fruits of Akebia trifoliata.

A novel actinobacterium, designated strain HDS12T, was isolated from fruits collected from Changde city located in the northwest of Hunan Province, China and characterized using a polyphasic approach. The 16S rRNA gene sequence analysis indicated that strain HDS12T belonged to the genus Nocardiopsis, and had highest similarities to N. dassonvillei subsp. dassonvillei CGMCC 4.1231T (99.79%), N. deserti H13T (99.73%), N. alborubida NBRC 13392T (99.66%), N. dassonvillei subsp. crassaminis D1T (99.64%), N. synnemataformans DSM 44143T (99.45%), N. lucentensis DSM 44048T (99.04%), N. aegyptia DSM 44442T (98.90%), N. flavescens CGMCC 4.5723T (98.76%), N. alba DSM 43377T (98.69%) and N. halotolerans DSM 44410T (98.63%), respectively. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain HDS12T formed an independent subclade, suggesting that strain HDS12T could belong to a potential novel species. Phylogenomic analysis demonstrated that strain HDS12T was closely related to N. dassonvillei subsp. dassonvillei CGMCC 4.1231T and N. dassonvillei subsp. crassaminis D1T. However, the average nucleotide identity value and the digital DNA-DNA hybridization value between them were well below 95-96% and 70% cut-off point recommended for delineating species. Based on its phenotypic and chemotaxonomic characteristics, strain HDS12T (= MCCC 1K06173T = JCM 34708T) represents the type strain of a novel species, for which the name Nocardiopsis akebiae sp. nov. is proposed.

tRNA-derived fragment tRF-Glu49 inhibits cell proliferation, migration and invasion in cervical cancer by targeting FGL1.

A transfer RNA (tRNA)-derived fragment (tRF) was found to be a new possible biological marker and target in carcinoma therapy. However, the effect exerted by tRFs on cervical carcinoma remains unclear. In the present study, the potential tumor suppressor gene tRF-Glu49 was identified in cervical carcinoma through tRF and tiRNA microarray investigation. A reverse transcription-quantitative PCR assay then demonstrated that tRF-Glu49 was downregulated in the cervical carcinoma tissue. Further clinicopathological analysis proved that tRF-Glu49 was associated with less aggressive clinical features and improved prognosis. Cell Counting Kit-8 tests, Transwell and Matrigel tests, and xCELLigence system tests revealed that tRF-Glu49 inhibited cervical cell proliferation, migration and invasion processes. Mechanistic investigation revealed that tRF-Glu49 directly regulated the oncogene, fibrinogen-like protein-1 (FGL1). In general, according to the result achieved in the present study, tRF-Glu49 can modulate cervical cell proliferation, migration, and invasion processes through the target process for FGL1, and tRF-Glu49 is likely to be a possible prognostic biological marker in patients with cervical carcinoma.

Streptomyces akebiae sp. nov., a novel actinomycete isolated from rhizosphere soil of Akebia trifoliate.

A novel actinomycete strain, designated as MG28T, was isolated from rhizosphere soil of Akebia trifoliate. The taxonomic position of the strain was investigated by using a polyphasic approach. BLAST search of the full-length 16S rRNA gene sequence of strain MG28T indicated it represented a member of the genus Streptomyces, and displayed 99.03%, 98.90%, 98.90%, 98.89%, 98.83% and less than 98.70% sequence similarities with S. phaeolivaceus GY16T, S. deccanensis KCTC 19241T, S. europaeiscabiei KACC 20186T, S. fructofermentans CGMCC 4.1593T, S. scabiei NRRL B-16523T and other species of the genus Streptomyces with validly published names, respectively. Phylogenomic analysis indicated that strain MG28T was closely related to Streptomyces deccanensis KCTC 19241T. However, the average nucleotide identity values and the digital DNA-DNA hybridization values between them indicated that strain MG28T represented a distinct species. Furthermore, strain MG28T was also distinctly differentiated from strain KCTC 19241T by morphological, physiological and biochemical characteristics. Therefore, strain MG28T (= MCCC 1K06895T = JCM 34922T) represents a novel species of the genus Streptomyces, for which the name Streptomyces akebiae sp. nov. is proposed.

Function, quality-of-life and complications after sacrospinous ligament fixation using an antegrade reusable suturing device (ARSD-Ney) at 6 and 12 months: a retrospective cohort study.

Background: Pelvic organ prolapse (POP) is a common pathology in the female population. Sacrospinous ligament fixation (SSLF) is one of the traditional transvaginal procedures for POP and high sacrospinous ligament fixation (h-SSLF) optimizes it using an antegrade reusable suturing device (ARSD-Ney). Previous studies on h-SSLF have focused on the correction of anatomical positions, with less assessment of patients' function, quality of life and complications. In this study, we evaluated post-operative complications, function, and quality-of-life after h-SSLF to confirm the safety and effectiveness of it. Methods: This was a retrospective cohort study that included 71 patients between 2018 and 2021: 50 patients for h-SSLF and 21 patients for laparoscopic sacrocolpopexy (LSC) according to patient age and background, POP-Q stage, patient preference, and so on. A clinical evaluation took place before surgery and was repeated at 6 and 12 months postoperatively. Intra- and post-operative complications and anatomical results were recorded. Patients completed self-administered questionnaires for functional pelvic problems [Pelvic Floor Disability Index-20 (PFDI-20)], quality of life [Pelvic Floor Impact Questionnaire-7 (PFIQ-7)], and sexual function [Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12)] at each medical visit. Results: Patients in both h-SSLF and LSC groups were similar in terms of demographic characteristics except for surgery time (86.04±28.70 vs. 153.19±54.88, P<0.05), postoperative indwelling catheter time (3.88±1.65 vs. 4.90±1.84, P<0.05), and hospital stay (8.94±2.38 vs. 10.57±2.06, P<0.05). There were no statistically significant differences between the 2 groups in scores of PFDI-20, PFIQ-7, and PISQ-12 at pre- and post-operative 6 and 12 months (P>0.05). Functional pelvic problems (PFDI-20 scores) and their impact on patients' quality of life (PFIQ-7 scores) significantly improved at 6 and 12 months postoperatively (P<0.05). Improvements in sexual activity were noted at 6 and 12 months postoperatively (P<0.05). Conclusions: This retrospective cohort study confirmed the positive results of h-SSLF in terms of improvement in function and quality of life following treatment for pelvic organ prolapse.