A novel lung cancer stem cell extracellular vesicles lncRNA ROLLCSC modulate non-stemness cancer cell plasticity through miR-5623-3p and miR-217-5p targeting lipid metabolism.

BACKGROUND: The high mortality rate of lung cancer is largely attributed to metastasis. Lung cancer stem cells (CSC) are conducive to cancer heterogeneity. Long noncoding RNAs are known to participate in various biological processes regulating the development of lung cancer. However, characterization of the role and mechanisms of lncRNA in lung cancer metastasis remains a challenge. RESULTS: We demonstrate that ROLLCSC, a highly expressed lncRNA in LLC-SDs, promotes the metastasis of the low metastatic LLCs both in vitro and in vivo. ROLLCSC can be transferred from LLC-SD to LLC through encapsulation in extracellular vesicles (EVs), ultimately leading to the enhancement of the metastatic phenotype of LLCs. Mechanistically, we demonstrate that the pro-metastatic activity of ROLLCSC is achieved through its function as a competing endogenous RNA (ceRNA) of miR-5623-3p and miR-217-5p to stimulate lipid metabolism. CONCLUSION: In this study, we have characterized ROLLCSC, a novel lncRNA, as a pivotal regulator in the metastasis of lung cancer, highlighting its potential as a therapeutic target. Specifically, we show that ROLLCSC is encapsulated by the EVs of LLC-SDs and transmitted to the LLCs, where it acts as a ceRNA of miR-5623-3p and miR-217-5p to stimulate lipid metabolism and ultimately augments metastatic colonization of LLCs.

Novel lncRNA Gm33149 modulates metastatic heterogeneity in melanoma by regulating the miR-5623-3p/Wnt axis via exosomal transfer.

The high mortality rate associated with melanoma primarily results from metastasis and recurrence. However, the precise mechanisms driving these processes remain poorly understood. Intercellular communication between cancer cells and non-cancer cells significantly influences the tumor microenvironment and plays a crucial role in metastasis. Therefore, our current study aims to investigate the role and mechanism of long non-coding RNAs (lncRNAs) in regulating the interaction between melanoma cancer stem cells (CSCs) and non-CSCs during the metastatic colonization process. This study has characterized a novel lncRNA called Gm33149. Importantly, we provide evidence for the first time that Gm33149, originating from highly metastatic melanoma stem cells (OL-SD), can be packaged into exosomes and transferred to low-metastatic nonstem cells (OL). Once internalized by OL cells, Gm33149 exerts its function through a competitive endogenous RNA mechanism (ceRNA) involving miR-5623-3p. Specifically, Gm33149 competitively binds to miR-5623-3p, thereby activating the Wnt signaling pathway and promoting the acquisition of a more aggressive metastatic phenotype by OL cells. In summary, our findings suggest that targeting lncRNA Gm33149 within extracellular vesicles could potentially serve as a therapeutic strategy for the treatment of metastatic melanoma. Schematic representation of the mechanisms underlying the pro-metastatic activity of lncRNA Gm33149 mediated by exosomal transfer. The figure illustrates the key mechanisms involved in the pro-metastatic activity of lncRNA Gm33149 through exosomal transfer. Melanoma stem cells (OLSD) release exosomes containing lncRNA Gm33149. These exosomes are taken up by non-stem melanoma cells (OL), delivering lncRNA Gm33149 to the recipient cells. Within OL cells, lncRNA Gm33149 functions as a competitive endogenous RNA (ceRNA), sequestering miR-5623-3p. This sequestration prevents miR-5623-3p from binding to its target genes, thereby activating the Wnt signaling pathway. The activated Wnt signaling pathway enhances the migration, invasion, and metastatic colonization capabilities of OL cells. The transfer of lncRNA Gm33149 via exosomes contributes to OL cells acquiring "metastatic competency" while promoting their metastatic colonization. These findings underscore the importance of lncRNA Gm33149 in intercellular communication and the metastatic progression of melanoma.

The effects of different repair methods for a posterior root tear of the lateral meniscus on the biomechanics of the knee: a finite element analysis.

PURPOSE: To explore the impact of different repair methods for a lateral meniscus posterior root tear on the biomechanics of the knee joint using finite element analysis. METHODS: Finite element models of a healthy knee were established on the basis of MRI data from a volunteer using Mimics software, and the validity of the models was tested. The changes in the contact mechanics and kinematics of these finite element models under different repair approaches were then analyzed and compared. RESULTS: The normal meniscus had the maximum joint contact area, the minimum contact pressure, and the minimum contact stress. When total meniscectomy of the lateral meniscus was performed, the lateral compartment had the minimum joint contact area, the maximum contact pressure and the maximum contact stress. When complete avulsions of the posterior root of the lateral meniscus occurred, the maximum values of contact pressure and contact stress were between those of an intact meniscus and those of a meniscus treated with total meniscectomy. Lateral meniscal root attachment reconstruction by the single-stitch and double-stitch techniques resulted in a significant decrease in joint contact pressure and contact stress, leading to values comparable to those of a normal knee joint, and the double-stitch technique performed better than the single-stitch technique. CONCLUSIONS: Repair surgery for lateral meniscal posterior root avulsions can effectively restore the contact mechanics and kinematics of the knee joint, and the double-stitch technique can result in better clinical outcomes than the single-stitch technique.

Long-term oncologic outcomes of liver resection for hepatocellular carcinoma in adolescents and young adults: A multicenter study from a hepatitis B virus-endemic area.

BACKGROUND: Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection. METHODS: From a Chinese multicenter database, patients were categorized as AYA (aged 13-39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR. RESULTS: Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age (<40 years) was independently associated with poorer TTR. CONCLUSIONS: Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.

[Clinical Significance of Minimal Residual Disease Monitoring by Multi-parameter Flow Cytometry before Allogeneic Hematopoietic Stem Cell Transplantation for Prognosis of Acute Leukemia Patients].

OBJECTIVE: To investigate the clinical significance of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia. METHODS: 81 cases of patients with AL treated with allo-HSCT in Department of Hematology, the First Affiliated Hospital of Chongqing Medical University form July 2015 to July 2018 was selected and retorspectively analyed. of which 79 patients were in CR and two patients were in non-CR. The CR group was further divided into two groups of MRD+ and MRD- based on the MRD level prior to HSCT. RESULTS: Among 81 patients, there were statistically significant differences in the three-year overall survival(OS) (CR 82.2%: NCR 0%), cumulative relapse incidence(RI) (CR 17.7%; NCR 100%) and leukemia-free survival rate(LFS) (CR 42.3%: NCR 0%) between CR and NCR group(P<0.05). Among 79 CR patients, MRD was negative in 30 patients while positive in 49 patients, there was significant differences in the three-year overall survival between MRD- and MRD+ group. The results of univariate analysis showed that the MRD+ group showed lower LFS compared with that of MRD- group （10.5% vs 36.2%）(P＜0.001，95%CI). CONCLUSION: MRD- patients shows longer LFS as compared with that of MRD+ patients, therefore, MRD monitoring by MFC before allo-HSCT is very important for the prognosis of the AL patients.

Differentiation of CD45­/CD31+ lung side population cells into endothelial and smooth muscle cells in vitro.

Side population (SP) cells are a small subpopulation of cells found in many mammalian tissues and organs, identified by their capacity to efflux Hoechst 33342 dye. They are enriched for stem/progenitor cell activity. SP cells isolated from the adult mouse lung can be separated into a CD45+ subset (bone marrow­derived) and a CD45­ subset that can be subdivided into CD31­ and CD31+ subpopulations. CD45­/CD31­ lung SP (LSP) cells are known to be mesenchymal stem cells. However, CD45­/CD31+ LSP cells are not fully characterized. In the present study, it was found that CD45­/CD31+ LSP cells were able to form colonies. Based on the expression of vascular endothelial growth factor receptor 2 (VEGFR2), these cells were separated into VEGFR2­ and VEGFR2+ cells. The CD45­/CD31+/VEGFR2­ LSP cells expressed genes characteristic of smooth muscle and endothelial progenitors, and were able to differentiate into smooth muscle and endothelial cells in vitro. The CD45­/CD31+/VEGFR2+ LSP cells expressed genes characteristic of endothelial progenitors and gave rise to endothelial cells, although not smooth muscle, in vitro. The data demonstrate that CD45­/CD31+/VEGFR2­ LSP cells differentiated into CD45­/CD31+/VEGFR2+ LSP cells and then endothelial cells, indicating that CD45­/CD31+/VEGFR2+ LSP cells are likely to be derived from CD45­/CD31+/VEGFR2­ LSP cells. Taken together, the results suggest that CD45­/CD31+ LSP cells can be separated into CD45­/CD31+/VEGFR2­ LSP cells, which may be progenitors of endothelial and smooth muscle, whereas CD45­/CD31+/VEGFR2+ LSP cells may serve as late commitment endothelial progenitors in the adult mouse lung.

Successful second allogeneic stem-cell transplantation from the same sibling donor for a patient with recurrent hepatosplenic gamma-delta (γ/δ) T-cell lymphoma: A case report.

RATIONALE: Hepatosplenic T-cell lymphoma (HSTCL) is a rare but aggressive type of peripheral T-cell lymphoma (PTCL). There is an urgent need for effective treatment due to the poor prognosis of HSTCL. Here, for the 1st time we describe the rare successful case of HSTCL who relapsed after a previous allogeneic stem-cell transplantation (allo-SCT), achieved remission with the second allo-SCT from the same donor. PATIENT CONCERNS: A 24-year-old male, presented with a 2-week history of fever, drenching night sweats and nonquantified weight loss. DIAGNOSES: Laboratory studies, flow cytometry of immunophenotyped, and physical examination results strongly suggested hepatosplenic γ/δ T-cell lymphoma, stage IVB. INTERVENTIONS: We proceeded to an allo-SCT with a human leukocyte antigen (HLA) identical sibling donor. The bone marrow examination and fluorescent in situ hybridization were observed for complete donor chimerism of bone marrow cells on day 34. On day 157 after the initial allo-SCT, the bone marrow examination revealed the relapse of the sinusoidal infiltration with lymphoma cells. Considering the disease persistence, we conducted the second allo-SCT from the same HLA-identical sibling donor immediately. OUTCOMES: Bone marrow examination indicated hematologic recovery without residual lymphoma cells. LESSONS: Our encouraging outcome suggests that the latter allo-SCT needs to be considered early for patients with disease recurrence, and it also demonstrates that graft-vs-lymphoma conferred by allo-SCT may play an essential role on HSTCL treatment. Furthermore, detecting related genes at diagnosis may have prognostic implications and guidance value for personal chemotherapy program.

Two Likely Auto-Tetraploidization Events Shaped Kiwifruit Genome and Contributed to Establishment of the Actinidiaceae Family.

The genome of kiwifruit (Actinidia chinensis) was sequenced previously, the first in the Actinidiaceae family. It was shown to have been affected by polyploidization events, the nature of which has been elusive. Here, we performed a reanalysis of the genome and found clear evidence of 2 tetraploidization events, with one occurring ∼50-57 million years ago (Mya) and the other ∼18-20 Mya. Two subgenomes produced by each event have been under balanced fractionation. Moreover, genes were revealed to express in a balanced way between duplicated copies of chromosomes. Besides, lowered evolutionary rates of kiwifruit genes were observed. These findings could be explained by the likely auto-tetraploidization nature of the polyploidization events. Besides, we found that polyploidy contributed to the expansion of key functional genes, e.g., vitamin C biosynthesis genes. The present work also provided an important comparative genomics resource in the Actinidiaceae and related families.

[Variation Characteristics and Health Risk Assessment of BTEX in the Atmosphere of Northern Suburb of Nanjing].

BTEX concentrations were determined by GC5000 online gas chromatography in the atmosphere of the north suburb of Nanjing in March 2013 to February 2014, using the EPA human exposure analysis evaluation method for benzene series compounds of volatile organic compounds (VOCs) in health risk assessment. The results showed that the total amount of BTEX showed the variation characteristics of spring > winter > autumn > summer. BTEX concentration was higher in the periods of 07:00-10:00 and 17:00-20:00, and the lowest was detected between 13:00-15:00; At the weekend, the concentration of BTEX was higher than on the working day. The sources of BTEX included traffic sources, industrial sources and solvent evaporation. The HQ of BTEX in all four seasons showed the order of benzene > xylene > ethylbenzene > toluene, and the HQ risk values were within the safety range in all analysis periods. The distribution of R value was winter > autumn > spring > summer, and R was higher than the safety threshold for all the analyses, indicating the existence of carcinogenic risk.

Assessment of Clinical Effect of Perioperative Comprehensive Nursing Intervention Pattern in 23G Minimally Invasive Vitreous Surgery.

BACKGROUND: We observed the clinical effects of comprehensive nursing intervention pattern in 23G minimally invasive vitreous surgery according to the comprehensive nursing intervention table developed by our hospital, which would supply a basis for its clinical application. METHODS: In this prospective study, we followed 120 patients undergoing 23G minimally invasive vitreous surgery from Xuzhou First People's Hospital from February 2013 to February 2015 and divided them into control and observation groups by a random number table (60 patients in each group). A regular nursing pattern was adopted for the control group, and a comprehensive nursing intervention pattern was adopted for the observation group. After that, a comparative analysis was made to identify the differences between the clinical effects of the two groups. RESULTS: Scores of cognition ratio, patient compliance and comfort level of patients in the observation group were higher than those of the control group were, and there was significant difference between the groups (P< 0.05). Complication incidence of the observation group is significantly lower than that of the control group (P<0.05). CONCLUSION: The comprehensive nursing intervention pattern developed by our hospital can improve clinical effects notably, which is of application value .We recommend it to be applied in eye diseases.

Helical growth of aluminum nitride: new insights into its growth habit from nanostructures to single crystals.

By understanding the growth mechanism of nanomaterials, the morphological features of nanostructures can be rationally controlled, thereby achieving the desired physical properties for specific applications. Herein, the growth habits of aluminum nitride (AlN) nanostructures and single crystals synthesized by an ultrahigh-temperature, catalyst-free, physical vapor transport process were investigated by transmission electron microscopy. The detailed structural characterizations strongly suggested that the growth of AlN nanostructures including AlN nanowires and nanohelixes follow a sequential and periodic rotation in the growth direction, which is independent of the size and shape of the material. Based on these experimental observations, an helical growth mechanism that may originate from the coeffect of the polar-surface and dislocation-driven growth is proposed, which offers a new insight into the related growth kinetics of low-dimensional AlN structures and will enable the rational design and synthesis of novel AlN nanostructures. Further, with the increase of temperature, the growth process of AlN grains followed the helical growth model.

Overexpression Nanog activates pluripotent genes in porcine fetal fibroblasts and nuclear transfer embryos.

Nanog as an important transcription factor plays a pivotal role in maintaining pluripotency and in reprogramming the epigenome of somatic cells. Its ability to function on committed somatic cells and embryos has been well defined in mouse and human, but rarely in pig. To better understand Nanog's function on reprogramming in porcine fetal fibroblast (PFF) and nuclear transfer (NT) embryo, we cloned porcine Nanog CDS and constructed pcDNA3.1 (+)/Nanog and pEGFP-C1/Nanog overexpression vectors and transfected them into PFFs. We studied the cell biological changes and the expression of Nanog, Oct4, Sox2, Klf4, C-myc, and Sall4 in transfected PFFs. We also detected the development potential of the cloned embryos harboring Nanog stably overexpressed fibroblasts and the expression of Oct4, Sox2, and both endogenous and exogenous Nanog in these embryos. The results showed that transient overexpression Nanog in PFF could activate the expression of Oct4 (5-fold), C-myc (2-fold), and Sall4 (5-fold) in somatic cells, but they could not be maintained during G418 selection. In NT embryos, although Nanog overexpression did not have a significant effect on blastocyst development rate and blastocyst cell number, it could significantly activate the expression of endogenous Nanog, Oct4, Sox2 to 160-fold, 93-fold, and 182-fold, respectively (P < 0.05). Our results demonstrate that Nanog could interact with and activate other pluripotent genes both in PFFs and embryos.