Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Preoperative CT radiomics of esophageal squamous cell carcinoma and lymph node to predict nodal disease with a high diagnostic capability.

PURPOSE: To develop CT radiomics models of resectable esophageal squamous cell carcinoma (ESCC) and lymph node (LN) to preoperatively identify LN+. MATERIALS AND METHODS: 299 consecutive patients with ESCC were enrolled in the study, 140 of whom were LN+ and 159 were LN-. Of the 299 patients, 249 (from the same hospital) were randomly divided into a training cohort (n = 174) and a test cohort (n = 75). The remaining 50 patients, from a second hospital, were assigned to an external validation cohort. In the training cohort, preoperative contrast-enhanced CT radiomics features of ESCC and LN were extracted, then integrated with clinical features to develop three models: ESCC, LN and combined. The performance of these models was assessed using area under receiver operating characteristic curve (AUC), and F-1 score, which were validated in both the test cohort and external validation cohort. RESULTS: An ESCC model was developed for the training cohort utilizing the 8 tumor radiomics features, and an LN model was constructed using 9 nodal radiomics features. A combined model was constructed using both ESCC and LN extracted features, in addition to cT stage and LN+ distribution. This combined model had the highest predictive ability among the three models in the training cohort (AUC = 0.948, F1-score = 0.878). The predictive ability was validated in both the test and external validation cohorts (AUC = 0.885 and 0.867, F1-score = 0.816 and 0.773, respectively). CONCLUSION: To preoperatively determine LN+, the combined model is superior to models of ESCC and LN alone.

Extraction and characterization of anti-virus anthraquinones from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220.

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.

Perceived Stress Mediating the Association Between Mindfulness and Resilience Among Registered Nurses.

Purpose: Resilience continues to be an important concept in the nursing profession due to its significant role in personal healthcare, patients' healthcare, and leadership. The present study examined the mediating role of perceived stress in the association between mindfulness and resilience among registered nurses in order to understand their importance among those in the Taiwanese nursing profession. Materials and Methods: Between October and November 2021, a total of 816 registered nurses participated in a cross-sectional survey including psychometric measures assessing perceived stress (Chinese Perceived Stress Scale-10), mindfulness (Chinese Mindful Attention Awareness Scale), and resilience (Chinese Questionnaire of Resilience). Results: Results indicated that perceived stress mediated the association between mindfulness and resilience (standardized coefficient = 0.251, p<0.001), although there was no significant association between mindfulness and resilience (standardized coefficient = 0.042, p=0.16). This suggests that perceived stress may function as both distress and eustress because mindfulness was not directly associated with resilience but indirectly via perceived stress. Conclusion: Nurses and their administrators should focus on different ways of coping with stress so that they become more resilient in facing other stressors. Future studies may be conducted to examine the mediating role of perceived stress in the association between other coping strategies and resilience among registered nurses.

In Situ Buildup of Zinc Anode Protection Films with Natural Protein Additives for High-Performance Zinc Battery Cycling.

The uncontrolled growth of dendrites and serious side reactions, such as hydrogen evolution and corrosion, significantly hinder the industrial application and development of aqueous zinc-ion batteries (ZIBs). This article presents ovalbumin (OVA) as a multifunctional electrolyte additive for aqueous ZIBs. Experimental characterizations and theoretical calculations reveal that the OVA additive can replace the solvated sheath of recombinant hydrated Zn2+ through the coordination water, preferentially adsorb on the surface of the Zn anode, and construct a high-quality self-healing protective film. Notably, the OVA-based protective film with strong Zn2+ affinity will promote uniform Zn deposition and inhibit side reactions. As a result, Zn||Zn symmetrical batteries in ZnSO4 electrolytes containing OVA achieve a cycle life exceeding 2200 h. Zn||Cu batteries and Zn||MnO2 (2 A g-1) full batteries show excellent cycling stability for 2500 cycles, demonstrating promising application prospects. This study provides insights into utilizing natural protein molecules to modulate the kinetics of Zn2+ diffusion and enhance the stability of the anode interface.

ADAM17 Confers Temozolomide Resistance in Human Glioblastoma Cells and miR-145 Regulates Its Expression.

Glioblastoma (GBM) is a malignant brain tumor, commonly treated with temozolomide (TMZ). Upregulation of A disintegrin and metalloproteinases (ADAMs) is correlated to malignancy; however, whether ADAMs modulate TMZ sensitivity in GBM cells remains unclear. To explore the role of ADAMs in TMZ resistance, we analyzed changes in ADAM expression following TMZ treatment using RNA sequencing and noted that ADAM17 was markedly upregulated. Hence, we established TMZ-resistant cell lines to elucidate the role of ADAM17. Furthermore, we evaluated the impact of ADAM17 knockdown on TMZ sensitivity in vitro and in vivo. Moreover, we predicted microRNAs upstream of ADAM17 and transfected miRNA mimics into cells to verify their effects on TMZ sensitivity. Additionally, the clinical significance of ADAM17 and miRNAs in GBM was analyzed. ADAM17 was upregulated in GBM cells under serum starvation and TMZ treatment and was overexpressed in TMZ-resistant cells. In in vitro and in vivo models, ADAM17 knockdown conferred greater TMZ sensitivity. miR-145 overexpression suppressed ADAM17 and sensitized cells to TMZ. ADAM17 upregulation and miR-145 downregulation in clinical specimens are associated with disease progression and poor prognosis. Thus, miR-145 enhances TMZ sensitivity by inhibiting ADAM17. These findings offer insights into the development of therapeutic approaches to overcome TMZ resistance.

C-Alkylated flavonoids from the whole plants of Desmodium caudatum and their anti-TMV activity.

BACKGROUND: Natural products are important sources of biopesticides to control plant virus, and flavonoids are identified as promising anti-tobacco mosaic virus (TMV) agents. Since Desmodium caudatum is a rich source of flavonoids, this study focuses on the discovery of the new anti-TMV active flavonoids from D. caudatum and their possible mode of action. RESULTS: Three new (compounds 1-3) and nine known (compounds 4-12) C-alkylated flavonoids were isolated from D. caudatum. To the best of our knowledge, the framework of 1-3 was reported in natural products for the first time. In addition, 1-3, 5, and 6 showed notable anti-TMV activity with inhibition rates in the range of 35.8-64.3% at a concentration of 50 µg/mL, and these rates are higher than that of positive control (with inhibition rates of 34.6% ± 2.8). In addition, the structure-activity relationship study revealed that the (pyrrol-2-yl)methyl moiety on flavone can significantly increases the activity. This result is helpful to find new anti-TMV inhibitors. CONCLUSION: C-Alkylated flavonoids showed potent activities against TMV with multiple modes of actions. The increase of defense-related enzyme activities, up-regulate the expression of defense related genes, down-regulate the expression of Hsp70 protein by inhibiting the related Hsp genes that are involved in tobacco resistance to TMV. By the actions mentioned earlier, the infection of TMV was influenced, thereby achieving the effects of control of TMV. The successful isolation of the earlier-mentioned flavonoids provide the new source of biopesticides to TMV proliferation, and also contribute to the utilization of D. caudatum. © 2023 Society of Chemical Industry.

Aspergillus Niger Derived Wrinkle-Like Carbon as Superior Electrode for Advanced Vanadium Redox Flow Batteries.

The scarcity of high electrocatalysis composite electrode materials has long been suppressing the redox reaction of V(II)/V(III) and V(IV)/V(V) couples in high performance vanadium redox flow batteries (VRFBs). Herein, through ingeniously regulating the growth of Aspergillus Niger, a wrinkle-like carbon (WLC) material that possesses edge-rich carbon, abundant heteroatoms, and nature wrinkle-like structure is obtained, which is subsequently successfully introduced and uniform dispersed on the surface of carbon fiber of graphite felt (GF). This composite electrode presents a lower overpotential and higher charge transfer ability, as the codoped multiheteroatoms increase the electrocatalysis activity and the wrinkled structure affords more abundant reaction area for vanadium ions in the electrolyte when compared with the pristine GF electrode, which is also supported by the density functional theory (DFT) calculations. Hence, the assembled battery using WLC electrodes achieves a high energy efficiency of 74.5% for 300 cycles at a high current density of 200 mA cm-2 , as well as the highest current density of 450 mA cm-2 . The WLC material not only uncovers huge potential in promoting the application of VRFBs, but also offers referential solution to synthesis microorganism-based high-performance electrode in other energy storage systems.

Molecular targets of metformin against ovarian cancer based on network pharmacology.

The objective of this study was to analyze potential targets of metformin against ovarian cancer (OC) through network pharmacology. Pharmacodynamic targets of metformin were predicted using the Bioinformatics Analysis Tool for the molecular mechanism of traditional Chinese medicine (BATMAN), Drugbank, PharmMapper, SwissTargetPrediction, and TargetNet databases. R was utilized to analyze the gene expression of OC tissues, normal/adjacent noncancerous tissues, and screen differentially expressed genes (DEGs) in the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) + Genotype-Tissue Expression (GTEx) datasets. STRING 11.0 was utilized to explore the protein-protein interaction (PPI) of metformin target genes differentially expressed in OC. Cytoscape 3.8.0 was used to construct the network and screen the core targets. Additionally, gene ontology (GO) annotation and enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for the common targets of metformin and OC through the DAVID 6.8 database. A total of 95 potential common targets of metformin and OC were identified from the intersection of 255 potential pharmacodynamic targets of metformin and 10,463 genes associated with OC. Furthermore, 10 core targets were screened from the PPI network [e.g., interleukin (IL) 1B, KCNC1, ESR1, HTR2C, MAOB, GRIN2A, F2, GRIA2, APOE, PTPRC]. In addition, it was shown in GO enrichment analysis that the common targets were mainly associated with biological processes (i.e., response to stimuli or chemical, cellular processes, and transmembrane transport), cellular components (i.e., plasma membrane, cell junction, and cell projection), and molecular functions (i.e., binding, channel activities, transmembrane transporter activity, and signaling receptor activities). Furthermore, it was indicated by KEGG pathway analysis that the common targets were enriched in metabolic pathways. The critical molecular targets and molecular pathways of metformin against OC were preliminarily determined by bioinformatics-based network pharmacology analysis, providing a basis, and reference for further experimental studies.

Dielectrics and possible ferroelectricity in diol/glycerol covalently grafted kaolinites.

Kaolinite possesses a structure with asymmetrically layered 1 : 1 dioctahedral aluminum silicate, and this structural property provides a useful platform for creating new cost-efficient functional materials that require noncentrosymmetric crystal packing. In this study, we prepared three covalently grafted kaolinites of propanediol (PD)/butanediol (BD)/glycerol (GL) by forming Al-O-C bonds between the OH groups of PD/BD/GL and the surface of kaolinite (K). Three covalently grafted kaolinites (K-PD, K-BD and K-GL) were characterized by X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and microanalysis for C, H and N elements. The test of K-PD, K-BD and K-GL stirred with water at ambient conditions for 3 days demonstrated these hybrids showing extra high chemical stability to water. The dielectric spectra of three hybrids show two-step dielectric relaxation in the range of 1-107 Hz, and the P-E measurements revealed the existence of ferroelectricity at room temperature with the spontaneous polarization, the remanent polarization and the coercive field of ∼0.014 µC cm-2, ∼0.008 µC cm-2 and ∼0.426 kV cm-1 for K-PD, ∼0.017 µC cm-2, ∼0.011 µC cm-2 and ∼0.645 kV cm-1 for K-BD, and ∼0.018 µC cm-2, ∼0.011 µC cm-2 and ∼0.141 kV cm-1 for K-GL, respectively.

Combinations of liver lobe and spleen volumes obtained on magnetic resonance imaging to predict esophagogastric variceal bleeding in hepatitis B-related cirrhotic patients: A prospective cohort study.

To evaluate whether combinations of liver lobe and spleen volumes obtained on magnetic resonance imaging (MRI) could predict esophagogastric variceal bleeding (EVB) in hepatitis B-related cirrhotic patients. Ninety-six consecutive patients with hepatitis B-related cirrhosis underwent upper abdominal contrast-enhanced MRI within 1 week after initial hospitalization, and grouped based on outcomes of EVB during the 2 years' follow-up after being discharged. Total liver volume (TLV), spleen volume (SV) and 4 liver lobe volumes including right lobe volume (RV), left medial lobe volume (LMV), left lateral lobe volume (LLV), and caudate lobe volume (CV) were measured on MRI. Percentages of individual liver lobe volumes in TLV (including RV/TLV, LMV/TLV, LLV/TLV, and CV/TLV), ratios of SV to individual liver lobe volumes (including SV/RV, SV/LMV, SV/LLV, and SV/CV), and SV/TLV were statistically analyzed to predict EVB. Patients with EVB had lower RV than without EVB (P value = .001), whereas no differences in LMV, LLV, CV, and TLV were found (P values >.05 for all). Among percentages of individual liver lobe volumes in TLV, RV/TLV was lower whereas LMV/TLV and LLV/TLV were greater in patients with EVB than without EVB (P values <.05 for all). SV, ratios of SV to individual liver lobe volumes, and SV/TLV in patients with EVB were larger than without EVB (P values <.05 for all). Among parameters with difference between patients with and without EVB, SV/RV could best predict EVB with an area under receiver operating characteristic curve of 0.84. SV/RV could best predict EVB in hepatitis B-related cirrhotic patients.

UPANets: Learning from the Universal Pixel Attention Neworks.

With the successful development in computer vision, building a deep convolutional neural network (CNNs) has been mainstream, considering the character of shared parameters in a convolutional layer. Stacking convolutional layers into a deep structure improves performance, but over-stacking also ramps up the needed resources for GPUs. Seeing another surge of Transformers in computer vision, the issue has aroused severely. A resource-hungry model is hardly implemented for limited hardware or single-customers-based GPU. Therefore, this work focuses on these concerns and proposes an efficient but robust backbone, which equips with channel and spatial direction attentions, so the attentions help to expand receptive fields in shallow convolutional layers and pass the information to every layer. An attention-boosted network based on already efficient CNNs, Universal Pixel Attention Networks (UPANets), is proposed. Through a series of experiments, UPANets fulfil the purposes of learning global information with less needed resources and outshine many existing SOTAs in CIFAR-{10, 100}.

The role of demographic factors, mindfulness and perceived stress in resilience among nurses: A cross sectional study.

AIM: To examine the role of demographic factors, mindfulness, and perceived stress on resilience among nurses. BACKGROUND: Resilience is an important attribute in the nursing profession although factors affecting it are very diverse. Knowing these factors may help in enhancing nurses' resilience and their subsequent quality healthcare delivery. METHOD: Utilizing a cross-sectional descriptive survey, a convenience sample was recruited to answer questions assessing resilience, perceived stress, and mindfulness in Taiwan between October and November 2021. Independent t-tests, one-way analyses of variance (ANOVAs) and hierarchical regression were used to analyse the data. RESULTS: A total of 816 nurses participated in the study. Postgraduate degree nurses had lower perceived stress (p = .006) and higher resilience (p = .003) compared with their college and undergraduate counterparts. Nurses working in internal medicine had significantly higher levels of perceived stress (p = .006) and lower levels of mindfulness (p = .005) compared with those in other departments. Single nurses had significantly higher levels of mindfulness (p = .04) but lower levels of resilience (p = .049) than those who were married. Educational level, perceived stress, and mindfulness were all factors that influenced nurses' resilience. CONCLUSION: Higher educational levels, perceived stress, and mindfulness appear to influence nurses' resilience. Nurses should therefore be encouraged to upgrade themselves academically, attend refresher courses, and learn adaptive coping strategies. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital authorities should help nurses deal with stressful issues and offer career development opportunities to update, upgrade, and enhance their skillsets in the profession.

[Application of RUNX2 gene over expression vector modified exosomes from BMSC combined with calcium carbonate scaffold system in bone defect].

OBJECTIVE: To investigate the effect of RUNX2 gene overexpression vector modified exosomes derived from bone marrow mesenchymal stem cells (BMSCs) combined with calcium carbonate scaffold system in bone defect. METHODS: Rabbit BMSCs were used as the research object, and BMSCs were identified by flow cytometry. Construct RUNX2 gene overexpression vector, transfect BMSCs with lentivirus, and collect exosomes by ultracentrifugation. The morphology of exosomes was observed by transmission electron microscope, the expression of exosome marker CD63 was detected by Western blot, and the calcium carbonate scaffold was constructed by three chamber parallel automatic temperature control reaction system. According to whether the RUNX2 gene overexpression vector was transfected or not, the complex of BMSCs and calcium carbonate scaffold was divided into three groups, namely BMSCs group, RUNX2 overexpression group and exosome group. The osteogenic differentiation of BMSCs was detected by oil red O staining and RT-PCR. There were 9 clean adult healthy male New Zealand white rabbits, aged (12.97±1.21) months, with a body weight of (19.3±3.6) kg, with 3 rabbits in each group. The animal model of skull defect was constructed by surgical method, and the repair of bone defect was evaluated by imaging, he staining and Masson staining. RESULTS: The results of flow cytometry showed that the expression of CD29 protein, CD44 protein, CD11b protein and CD45 protein on the surface of BMSCs were 99.5%, 100%, 0.1% and 0.1%, respectively. Transmission electron microscopy showed that the exosomes were bilayer vesicles with a diameter of 50 to 150 nm. Western blot showed that the molecular marker CD63 of exosomes was positive. Oil red O staining showed that the osteogenic differentiation of BMSCs in exosome group was significantly higher than that in RUNX2 overexpression group and BMSCs group. The results of RT-PCR showed that the relative expressions of RUNX2, BMP-2 and ALP mRNA in BMSCs in exosome group were significantly higher than those in RUNX2 overexpression group and BMSCs group (P<0.05). The imaging results showed that the repair effect of skull defect in exosome group was better than that in RUNX2 overexpression group. HE staining and Masson staining showed that the repair effect of skull defect in exosome group was better than that in RUNX2 overexpression group (P<0.05). MSCs in exosome group was significantly higher than that in RUNX2 overexpression group and BMSCs group. The results of RT-PCR showed that the relative expressions of RUNX2, BMP-2 and ALP mRNA in BMSCs in exosome group were significantly higher than those in RUNX2 overexpression group and BMSCs group(P<0.05). The imaging results showed that the repair effect of skull defect in exosome group was better than that in RUNX2 overexpression group. HE staining and Masson staining showed that the repair effect of skull defect in exosome group was better than that in RUNX2 overexpression group(P<0.05). CONCLUSION: Compared with RUNX2 gene overexpression vector transfection, extraction of exosomes directly can promote the differentiation of BMSCs into osteoblasts more efficiently, and the combination with calcium carbonate scaffold can better promote the healing of bone defects. So as to provide new ideas and methods for the clinical treatment of bone defects.

Propofol induces apoptosis and ameliorates 5­fluorouracil resistance in OSCC cells by reducing the expression and secretion of amphiregulin.

Among the different types of oral cancer, >90% of cases are oral squamous cell carcinoma (OSCC). 5­fluorouracil (5­FU) is a commonly used treatment for OSCC, but cells typically display resistance to the drug. Propofol, an intravenous anesthetic agent, exhibits certain anticancer effects, including the inhibition of cancer cell proliferation, migration and invasion. Secreted proteins, such as growth factors and cytokines are involved in cancer development and progression, but the effect of propofol on secreted proteins in OSCC is not completely understood. An MTT assay, flow cytometry and western blotting were performed to determine the anticancer effects of propofol. The secretion profile of OSCC was determined using an antibody array, and clinical importance was assessed using the Gene Expression Profiling Interactive Analysis database. The results were verified by performing reverse transcription­quantitative PCR (RT­qPCR) and western blotting. 5­FU­resistant cells were established to determine the role of the gene of interest in drug resistance. The results demonstrated that propofol decreased cell viability and promoted cell apoptosis. The antibody array results showed that propofol attenuated the secretion of multiple growth factors. The bioinformatics results indicated that amphiregulin (AREG) was expressed at significantly higher levels in cancer tissues, which was also related to poor prognosis. The results of RT­qPCR and western blotting revealed that propofol decreased AREG expression. Pretreatment with exogenous recombinant AREG increased EGFR activation and conferred propofol resistance. Moreover, the results indicated that the expression and activation of AREG was also related to 5­FU resistance, but propofol ameliorated 5­FU drug resistance. Therefore, the present study suggested that propofol combination therapy may serve as an effective treatment strategy for OSCC.

[Lentivirus mediated siRNA hsa-circ-0000885 transfection of BMSCs and osteoclast co-culture system on cell differentiation, proliferation and apoptosis].

OBJECTIVE: To explore the effects of siRNA hsa-circ-0000885 modified bone marrow mesenchymal stem cells (BMSCs) on osteogenic differentiation, cell proliferation and apoptosis in order to provide new ideas and methods for the clinical treatment of osteoporosis (OP). METHODS: From September 2018 to February 2020, 13 patients with osteoporosis admitted to our hospital were selected as the research objects, including 11 females and 2 males, with an age of (65.45±10.77) years old. After obtaining the informed consent of patients, peripheral blood tissues were extracted. Then the expression level of cir-cRNA in peripheral blood mononuclear cells(PBMC) was detected by circ RNA chip. The expression of circ RNA was silenced by siRNA technology. The BMSCs were transfected with lentivirus. According to the siRNA interference plasmid hsa-circ-0000885, the cells were divided into the blank group, the empty vector group and the siRNA interference group. After 72 hours of treatment, the cell cycle was detected by flow cytometry, the apoptosis level was detected by AV-PI kit, and the osteogenic differentiation ability of BMSCs was detected by ALP staining. RESULTS: The expression of hsa-circ-0000885 in PBMC of patients with osteoporosis was significantly higher than that of healthy controls (t=2.119, P<0.05). ALP staining showed that siR-NA hsa-circ-0000885 could promote the osteogenic differentiation of BMSCs, which was obviously too much in the blank group and blank plasmid group (F=9.132, q=2.995, 2.897;P=0.009, 0.012<0.05). The results of CCK-8 showed that siRNA hsa-circ-0000885 could promote the proliferation of BMSCs, which was significantly higher than that of the blank group and blank plasmid group (F=9.881, q=2.457, 2.904;P=0.032, 0.016<0.05). The results of AV-PI showed that the apoptosis rate of siRNA interference group was significantly lower than that of blank group and blank plasmid group(F=10.208;q=2.885, 3.001; P=0.019, 0.011<0.05). CONCLUSION: The lentivirus mediated siRNA hsa-circ-0000885 plasmid transfected into BMSCs and osteoclast co culture system can promote cell proliferation, inhibit apoptosis and promote osteogenic differentiation of BMSCs, which can be used as a potential therapeutic target for OP patients.

Tumor Stage-Based Gross Tumor Volume of Resectable Esophageal Squamous Cell Carcinoma Measured on CT: Association With Early Recurrence After Esophagectomy.

OBJECTIVE: To investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy. MATERIALS AND METHODS: Two hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen's Kappa tests were used to evaluate the performances of the previous ROC predictive models. RESULTS: ER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P-values < 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533-7.459] and 1.222 (95% CI: 1.125-1.327), respectively (all P-values < 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT1-4a, cT2, and cT3 (all P-values < 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT1-4a, cT2, and cT3 with Cohen k of 0.696 (95% CI, 0.498-0.894), 0.733 (95% CI, 0.386-1.080), and 0.862 (95% CI, 0.603-1.121), respectively. CONCLUSION: GTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER.

Contrast-enhanced CT radiomics features to predict recurrence of locally advanced oesophageal squamous cell cancer within 2 years after trimodal therapy: A case-control study.

ABSTRACT: Radiomics transforms the medical images into high-dimensional quantitative features and provides potential information about tumor phenotypes and heterogeneity. We conducted a retrospective analysis to explore and validate radiomics model based on contrast-enhanced computed tomography (CECT) to predict recurrence of locally advanced oesophageal squamous cell cancer (SCC) within 2 years after trimodal therapy. This study collected CECT and clinical data of consecutive 220 patients with pathology-confirmed locally advanced oesophageal SCC (154 in the training cohort and 66 in the validation cohort). Univariate statistical test and the least absolute shrinkage and selection operator method were performed to select the optimal radiomics features. Logistic regression was conducted to build radiomics model, clinical model, and combined model of both the radiomics and clinical features. Predictive performance was judged by the area under receiver operating characteristics curve (AUC), accuracy, and F1-score in the training and validation cohorts. Ten optimal radiomics features and/or 7 clinical features were selected to build radiomics model, clinical model, and the combined model. The integrated model of radiomics and clinical features was superior to radiomics model or clinical model in predicting recurrence of locally advanced oesophageal SCC within 2 years in the training (AUC: 0.879 vs 0.815 or 0.763; accuracy: 0.844 vs 0.773 or 0.740; and F1-score: 0.886 vs 0.839 or 0.815, respectively) and validation (AUC: 0.857 vs 0.720 or 0.750; accuracy: 0.788 vs 0.700 or 0.697; and F1-score: 0.851 vs 0.800 or 0.787, respectively) cohorts. The combined model of radiomics and clinical features shows better performance than the radiomics or clinical model to predict the recurrence of locally advanced oesophageal SCC within 2 years after trimodal therapy.

Application of contrast-enhanced CT radiomics in prediction of early recurrence of locally advanced oesophageal squamous cell carcinoma after trimodal therapy.

BACKGROUND: Early recurrence of oesophageal squamous cell carcinoma (SCC) is defined as recurrence after surgery within 1 year, and appears as local recurrence, distant recurrence, and lymph node positive and disseminated recurrence. Contrast-enhanced computed tomography (CECT) is recommended for diagnosis of primary tumor and initial staging of oesophageal SCC, but it cannot be used to predict early recurrence. It is reported that radiomics can help predict preoperative stages of oesophageal SCC, lymph node metastasis before operation, and 3-year overall survival of oesophageal SCC patients following chemoradiotherapy by extracting high-throughput quantitative features from CT images. This study aimed to develop models based on CT radiomics and clinical features of oesophageal SCC to predict early recurrence of locally advanced cancer. METHODS: We collected electronic medical records and image data of 197 patients with confirmed locally advanced oesophageal SCC. These patients were randomly allocated to 137 patients in the training cohort and 60 in the test cohort. 352 radiomics features were extracted by delineating region-of-interest (ROI) around the lesion on CECT images and clinical signature was generated by medical records. The radiomics model, clinical model, the combined model of radiomics and clinical features were developed by radiomics features and/or clinical characteristics. Predicting performance of the three models was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1 score. RESULTS: Eleven radiomics features and/or six clinical signatures were selected to build prediction models related to recurrence of locally advanced oesophageal SCC after trimodal therapy. The AUC of integration of radiomics and clinical models was better than that of radiomics or clinical model for the training cohort (0.821 versus 0.754 or 0.679, respectively) and for the validation cohort (0.809 versus 0.646 or 0.658, respectively). Integrated model of radiomics and clinical features showed good performance in predicting early recurrence of locally advanced oesophageal SCC for both the training and validation cohorts (accuracy = 0.730 and 0.733, and F-1score = 0.730 and 0.778, respectively). CONCLUSIONS: The integrated model of CECT radiomics and clinical features may be a potential imaging biomarker to predict early recurrence of locally advanced oesophageal SCC after trimodal therapy.

Elevated XRCC5 expression level can promote temozolomide resistance and predict poor prognosis in glioblastoma.

Drug resistance and disease recurrence are important contributors for the poor prognosis of glioblastoma multiforme (GBM). Temozolomide (TMZ), the standard chemotherapy for GBM treatment, can methylate DNA and cause the formation of double-strand breaks (DSBs). X-ray repair cross complementing 5 (XRCC5), also known as Ku80 or Ku86, is required for the repair of DSBs. The present study identified novel determinants that sensitize cells to TMZ, using an array-based short hairpin (sh)RNA library. Then, cBioportal, Oncomine, and R2 databases were used to analyze the association between gene expression levels and clinical characteristics. Subsequently, lentiviral shRNA or pCMV was used to knockdown or overexpress the gene of interest, and the effects on TMZ sensitivity were determined using a MTT assay and western blot analysis. TMZ-resistant cells were also established and were used in in vitro and in vivo experiments to analyze the role of the gene of interest in TMZ resistance. The results indicated that XRCC5 was effective in enhancing TMZ cytotoxicity. The results from the bioinformatics analysis revealed that XRCC5 mRNA expression levels were associated with clinical deterioration and lower overall survival rates. In addition, XRCC5 knockdown could significantly increase TMZ sensitivity in GBM cells, while XRCC5 overexpression caused the cancer cells to be resistant to TMZ. Both the in vivo and in vitro experiments showed that TMZ treatment could induce expression of XRCC5 in TMZ-resistant cells. Taken together these findings suggested that XRCC5 could be a promising target for GBM treatment and could also be used as a diagnostic marker for refractory GBM.