MoS2 nanosheets supported on anodic aluminum oxide membrane: An effective interface for label-free electrochemical detection of microRNA.

The interesting adsorption affinity of two-dimensional nanosheets to single stranded over double stranded nucleic acids have stimulated the exploration of these materials in biosensing. Herein, MoS2 nanosheets decorated anodic aluminum oxide (AAO) membrane was simply prepared by suction filtration. The MoS2/AAO hybrid membrane was initially applied to the electrochemical detection of microRNA using let-7a as the model. When let-7a was incubated with its complementary DNA, double stranded DNA-RNA formed and which displayed weak adsorption capability to the hybrid membrane. And thus the steric effect combining the electrostatic repulsion of the backbone phosphate of nucleic acids for [Fe(CN)6]3- transport across the hybrid membrane varied with the concentration of let-7a. In this way, a label-free electrochemical detection method for microRNA was established by monitoring the change of the redox current of [Fe(CN)6]3-. To further improve the detection sensitivity of the method, we proposed two separate strategies focusing on the amplification of the target-induced steric hindrance with DNA nanostructure and the magnification of the electrode sensitivity for [Fe(CN)6]3- by electrode modification. By using the two strategies, the hybrid membrane based-detection method exhibited broad linear range, low detection limit and good selectivity as well as reproducibility. Therefore, this study provided a proof-of-concept for the application of two-dimensional material to nucleic acids detection.

Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer.

Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main component of the tumor microenvironment, regulated DNA damage response of NSCLC cells following irradiation and clarify the involved mechanisms. We found CAFs inhibited irradiation-induced DNA damage while promoted DNA repair of NSCLC cells and caused cell cycle arrest in the radioresistant S phase. CAFs have the ability of up-regulating and stabilizing c-Myc, leading to the transcription activation of HK2 kinase, a key rate-limiting enzyme in glycolysis by activating Wnt/ß-catenin pathway. Attenuation of glycolysis significantly reversed the effect of CAFs on DNA damage response of NSCLC cells. By high-throughput screening of human cytokines/chemokines array, we found CAFs-secreted midkine led to the promotion of glycolysis by activating Wnt/ß-catenin pathway in NSCLC cells. In vivo, CAFs caused the radioresistance of NSCLC cells also by promoting the glycolysis in a ß-catenin signaling-dependent manner. These findings may provide novel strategies for reversing the radioresistance of NSCLC cells.

Combining bioinspired nanochannels with ferrocene doped MoS2 nanoplates: Application to ratiometric electrochemical detection of let-7a.

Sensitive and accurate detection of tumor suppressor genes is vastly important to the related therapeutic research. Herein, a ratiometric electrochemical method for let-7a detection was established by integrating a ferrocene (Fc) doped MoS2 nanoplates modified electrode into the nanochannels-based biosensing platform. The ratiometric signal was developed by the redox current of methylene blue (MB) which reflects the target recognition occurred into the nanochannels and the redox current of Fc which corrects the slight signal deviation caused by some analyte-independent factors. And thus, the ratio of peak current of MB and Fc (IMB/IFc) measured at differential pulse voltammogram varied precisely with the increment of the concentration of let-7a incubated in the bioinspired nanochannels. The strategy of spherical DNAzyme induced deposition in nanochannels was utilized to further amplify the signal. Under optimal conditions, a wide linear dynamic range of 50 aM to 10 pM spanning five orders of magnitude was obtained. The developed electrochemical method, with attomole level of detection limit, was successfully applied to the determination of let-7a in human serum and tumor cells. The study not only offers a new route for reliable nucleic acid detection, but also provides an excellent opportunity to extend the application of the two-dimensional transition-metal dichalcogenides.

Liver fibrosis therapy based on biomimetic nanoparticles which deplete activated hepatic stellate cells.

Liver fibrosis is one of the most common liver diseases with substantial morbidity and mortality. However, effective therapy for liver fibrosis is still lacking. Considering the key fibrogenic role of activated hepatic stellate cells (aHSCs), here we reported a strategy to deplete aHSCs by inducing apoptosis as well as quiescence. Therefore, we engineered biomimetic all-trans retinoic acid (ATRA) loaded PLGA nanoparticles (NPs). HSC (LX2 cells) membranes, presenting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were coated on the surface of the nanoparticles, while the clinically approved agent ATRA with anti-fibrosis ability was encapsulated in the inner core. The biomimetic coating of TRAIL-expressing HSC membranes does not only provide homologous targeting to HSCs, but also effectively triggers apoptosis of aHSCs. ATRA could induce quiescence of activated fibroblasts. While TM-NPs (i.e. membrane coated NPs without ATRA) and ATRA/NPs (i.e. non-coated NPs loaded with ATRA) only showed the ability to induce apoptosis and decrease the α-SMA expression in aHSCs, respectively, TM-ATRA/NPs induced both apoptosis and quiescence in aHSCs, ultimately leading to improved fibrosis amelioration in both carbon tetrachloride-induced and methionine and choline deficient L-amino acid diet induced liver fibrosis mouse models. We conclude that biomimetic TM-ATRA/NPs may provide a novel strategy for effective antifibrosis therapy.

Cancer-associated fibroblasts: An emerging target against esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. More than 70% of ESCC patients are diagnosed at the intermediate or advanced stage. Concurrent chemoradiotherapy is the standard treatment regimen for patients with advanced ESCC. However, ESCC patients show a poor 5-year survival rate of around 20%. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and control tumor initiation and progression. CAFs create a pro-survival and immunosuppressive microenvironment by crosstalk with cancer cells. Moreover, CAFs lead the collective invasion of cancer cells of the epithelial phenotype by remodeling the extracellular matrix. In this review, we highlight the impact of CAFs on ESCC, including induction of chemo- and radio-resistance, migration, invasion, and immune escape. The origin of CAFs and the influence of ESCC cells on CAF activation are also described. Furthermore, we highlight the clinical prospects and future trends of CAFs-targeted therapies in ESCC. A better understanding of the molecular biology of CAFs may contribute to the development of novel anti-ESCC strategies.

LncRNAs link cancer stemness to therapy resistance.

Cancer stem cells (CSCs) are a cellular subpopulation accelerating cancer cell growth, invasion and metastasis and survival. After chemoradiotherapy, CSCs are enriched because of their survival advantages and lead to tumor relapse and metastasis. Elimination of CSCs is critically important for the radical treatment of human cancers. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides and have no protein-coding potential. Aberrant expressions of lncRNAs are associated with human diseases including cancer. LncRNAs function as cancer biomarkers, prognostic factors and therapeutic targets. They induce cancer stemness by chromatin modification, transcriptional regulation or post-transcriptional regulation of target genes as a sponge or through assembling a scaffold complex. Several factors caused aberrant expressions of lncRNAs in CSCs such as genes mutations, epigenetic alteration and environmental stimuli. Targeting of lncRNAs has been demonstrated to significantly reverse the chemoradioresistance of CSCs. In this review, we have summarized the progress of studies regarding lncRNAs-mediated therapy resistance of CSCs and clarified the molecular mechanisms. Furthermore, we have for the first time analyzed the influences of lncRNAs on cell metabolism and emphasized the effect of tumor microenvironment on lncRNAs functions in CSCs. Overall, the thorough understanding of the association of lncRNAs and CSCs would contribute to the reversal of therapy resistance.

Cancer-associated fibroblasts in non-small cell lung cancer: Recent advances and future perspectives.

Non-small cell lung cancer (NSCLC) constitutes the majority of lung cancer, which is the leading cause of cancer-related deaths in the world. Nearly 70% of NSCLC patients were diagnosed at advanced stage with only 15% of five-year survival rate. Cancer-associated fibroblasts (CAFs) are the major component of tumor microenvironment and account for almost 70% of the cells in tumor tissues. By the crosstalk with cancer cells, CAFs reprogrammed cancer cell metabolism, remodeled extracellular matrix (ECM) and created a supportive niche for cancer stem cells. CAFs lead collective invasion of tumor cells and shape tumor immune microenvironment, promoting tumor metastasis and immune escape. In this review, we have summarized the progress of studies regarding CAFs influences on NSCLC in recent five years from the aspects of cell growth, metabolism, therapy resistance, invasion and metastasis and immune suppression. We have discussed the involved mechanisms and implications for the development of anti-NSCLC therapies. The current strategies of CAFs targeting and elimination have also been generalized. Only better understanding of the molecular biology of CAFs may contribute to the development of novel anti-NSCLC strategies.

The mechanisms and reversal strategies of tumor radioresistance in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of most lethal malignancies with high aggressive potential in the world. Radiotherapy is used as one curative treatment modality for ESCC patients. Due to radioresistance, the 5-year survival rates of patients after radiotherapy is less than 20%. Tumor radioresistance is very complex and heterogeneous. Cancer-associated fibroblasts (CAFs), as one major component of tumor microenvironment (TME), play critical roles in regulating tumor radioresponse through multiple mechanisms and are increasingly considered as important anti-cancer targets. Cancer stemness, which renders cancer cells to be extremely resistant to conventional therapies, is involved in ESCC radioresistance due to the activation of Wnt/ß-catenin, Notch, Hedgehog and Hippo (HH) pathways, or the induction of epithelial-mesenchymal transition (EMT), hypoxia and autophagy. Non-protein-coding RNAs (ncRNAs), which account for more than 90% of the genome, are involved in esophageal cancer initiation and progression through regulating the activation or inactivation of downstream signaling pathways and the expressions of target genes. Herein, we mainly reviewed the role of CAFs, cancer stemness, non-coding RNAs as well as others in the development of radioresistance and clarify the involved mechanisms. Furthermore, we summarized the potential strategies which were reported to reverse radioresistance in ESCC. Together, this review gives a systematic coverage of radioresistance mechanisms and reversal strategies and contributes to better understanding of tumor radioresistance for the exploitation of novel intervention strategies in ESCC.

[Dendritic cell tumor vaccine assisted by Tiaohengfang polysaccharides enhances immune function of S180 tumor-bearing mice and inhibits tumor growth].

Objective To investigate the immunotherapeutic effect and mechanism of dendritic cell (DC) vaccine assisted by Tiaohengfang polysaccharides (ThPP) in S180 tumor-bearing mice. Methods Mouse bone marrow-derived cells were cultured in vitro and mature DCs were obtained with the assistance of cytokines and ThPP. The expression of CD80 and CD86 of DCs induced by ThPP was examined, and S180 tumor cells were used as antigens to stimulate dendritic cells to become dendritic cell tumor vaccine. Tumor-bearing models were established in mice by S180 tumor cells inoculated into the armpit of the left forelimb, and the mice were randomly divided into four groups according to body mass, namely tumor-bearing blank group, positive control group (cyclophosphamide), dendritic cell vaccine group adjuvanted by ThPP and TNF-α. The tumor-bearing mice were treated on the 5th and 10th days after inoculation of tumor cells. The tumor-bearing mice were killed on the 12th day and the tumor inhibition was observed by the tumor mass detection. At the same time, peritoneal macrophages were isolated and cultured, and the expression of CD11b and IL-12 were measured by immunohistochemistry. The levels of serum IL-12 and TNF-α in the mice were detected by ELISA. The survival time of the other four groups of tumor-bearing mice was observed after treatment with the same method. Results The expression of CD80 and CD86 in the TNF-α group and ThPP group were higher than those in the blank control group, and the ThPP group was more significant. The tumor inhibition rate and survival extension period of ThPP, TNF-α and positive groups were significantly higher than those of the model blank group. The levels of serum IL-12 and TNF-α in the ThPP group were higher than those in the positive cyclophosphamide group and model black group. There was no significant difference between the ThPP group and TNF-α group. The expression of CD11b in the macrophages of ThPP group was lower than that in the model blank group and positive group, while the expression of IL-12 in the macrophages of ThPP group was higher than that in the model blank group and positive group, without significant difference compared with TNF-α group. Conclusion ThPP-adjuvanted DC tumor vaccine can inhibit tumor growth and prolong survival time of S180 tumor-bearing mice, which is related to promoting the maturation of DCs and increasing the secretion of IL-12 and TNF-α.

Single-cell RNA-seq of esophageal squamous cell carcinoma cell line with fractionated irradiation reveals radioresistant gene expression patterns.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) cells are heterogeneous, easily develop radioresistance, and recur. Single-cell RNA-seq (scRNA-seq) is a next-generation sequencing method that can delineate diverse gene expression profiles of individual cells and mining their heterogeneous behaviors in response to irradiation. Our aim was using scRNA-seq to describe the difference between parental cells and cells that acquired radioresistance, and to investigate the dynamic changes of the transcriptome of cells in response to FIR. RESULTS: We sequenced ESCC cell lines KYSE180 with and without fractionated irradiation (FIR). A total of 218 scRNA-seq libraries were obtained from 88 cells exposed to 12 Gy (KYSE-180-12 Gy), 89 exposed to 30 Gy (KYSE-180-30 Gy), and 41 parental KYSE-180 cells not exposed to FIR. Dynamic gene expression patterns were determined by comprehensive consideration of genes and pathways. Biological experiments showed that KYSE-180 cells became radioresistant after FIR. PCA analysis of scRNA-seq data showed KYSE-180, KYSE-180-12 Gy and KYSE-180-30 Gy cells were discrete away from each other. Two sub-populations found in KYSE-180-12 Gy and only one remained in KYSE-180-30 Gy. This sub-population genes exposure to FIR through 12 Gy to 30 Gy were relevant to the PI3K-AKT pathway, pathways evading apoptosis, tumor cell migration, metastasis, or invasion pathways, and cell differentiation and proliferation pathways. We validated DEGs, such as CFLAR, LAMA5, ITGA6, ITGB4, and SDC4 genes, in these five pathways as radioresistant genes in bulk cell RNA-seq data from ESCC tissue of a ESCC patient treated with radiotherapy and from KYSE-150 cell lines. CONCLUSIONS: Our results delineated the divergent gene expression patterns of individual ESCC cells exposure to FIR, and displayed genes and pathways related to development of radioresistance.

Sub-region based radiomics analysis for survival prediction in oesophageal tumours treated by definitive concurrent chemoradiotherapy.

BACKGROUND: Evaluating clinical outcome prior to concurrent chemoradiotherapy remains challenging for oesophageal squamous cell carcinoma (OSCC) as traditional prognostic markers are assessed at the completion of treatment. Herein, we investigated the potential of using sub-region radiomics as a novel tumour biomarker in predicting overall survival of OSCC patients treated by concurrent chemoradiotherapy. METHODS: Independent patient cohorts from two hospitals were included for training (n = 87) and validation (n = 46). Radiomics features were extracted from sub-regions clustered from patients' tumour regions using K-means method. The LASSO regression for 'Cox' method was used for feature selection. The survival prediction model was constructed based on the sub-region radiomics features using the Cox proportional hazards model. The clinical and biological significance of radiomics features were assessed by correlation analysis of clinical characteristics and copy number alterations(CNAs) in the validation dataset. FINDINGS: The overall survival prediction model combining with seven sub-regional radiomics features was constructed. The C-indexes of the proposed model were 0.729 (0.656-0.801, 95% CI) and 0.705 (0.628-0.782, 95%CI) in the training and validation cohorts, respectively. The 3-year survival receiver operating characteristic (ROC) curve showed an area under the ROC curve of 0.811 (0.670-0.952, 95%CI) in training and 0.805 (0.638-0.973, 95%CI) in validation. The correlation analysis showed a significant correlation between radiomics features and CNAs. INTERPRETATION: The proposed sub-regional radiomics model could predict the overall survival risk for patients with OSCC treated by definitive concurrent chemoradiotherapy. FUND: This work was supported by the Zhejiang Provincial Foundation for Natural Sciences, National Natural Science Foundation of China.

Ultrasensitive Electrochemical Immunoassay Based on Cargo Release from Nanosized PbS Colloidosomes.

Colloidosome is a novel nanostructure composed of millions of colloid particles. In this work, nanosized PbS colloidosomes were initially prepared and applied as nanoprobes for an ultrasensitive immunoassay. The colloidosomes were simply prepared in mild conditions by assembling the elementary approximately 8 nm PbS nanoparticles at the water-in-oil interface of emulsion droplets. To enhance the rigidity and biocompatibility of the colloidosomes, interfacial polymer was introduced by utilizing self-polymerization of dopamine. By treating with dilute nitric acid, a bursting release of lead ions from the colloidosomes occurred and the lead ions can be detected easily by anodic stripping voltammetry. In this way, a colloidosome-based electrochemical immunoassay was developed by using the nanosized PbS colloidosomes as electroactive labels. The proposed method featured a linear calibration range from 10 fg·mL-1 to 100 ng·mL-1 with a low detection limit of 3.4 fg·mL-1 for the detection of human epididymis protein 4. This work introduced a new member for the family of colloidosomes and offered a novel perspective for the rational implementation of various colloidosomes for novel low-abundance cancer biomarkers analysis.

Cancer-associated Fibroblast-promoted LncRNA DNM3OS Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma.

PURPOSE: Our study aimed to investigate whether CAF (cancer-associated fibroblasts) were involved in long noncoding RNAs (lncRNA)-regulated radioresponse in esophageal squamous cell carcinoma (ESCC).Experimental Design: By use of lncRNAs PCR array, 38 lncRNAs were screened in esophageal cancer cells and in normal esophageal epithelial cells Het-1A. LncRNA DNM3OS was detected in tumor tissues of patients with ESCC and in matched normal esophageal epithelial tissues by qRT-PCR analysis and in situ hybridization assay. The association of DNM3OS and tumor radioresistance was investigated in vitro and in vivo. The influences of DNM3OS on DNA damage response (DDR) was investigated by Western blotting, immunofluorescence imaging, and comet assay. The mechanisms by which CAFs promoted DNM3OS expression was investigated by kinase inhibitors' screening, luciferase assay, and chromatin immunoprecipitation. RESULTS: Among the 38 lncRNAs tested, DNM3OS was found to have a much higher expression level in esophageal cancer cells than in Het-1A. In tumor tissues of 16 patients with ESCC, the expression level of DNM3OS showed an average increase of 6.3429-fold compared with that in matched normal tissues. DNM3OS conferred significant radioresistance in vitro and in vivo by regulating DDR. CAFs promoted the expression of DNM3OS with a 39.2554-fold and 38.3163-fold increase in KYSE-30 and KYSE-140, respectively. CAFs promoted the expression of DNM3OS in a PDGFß/PDGFRß/FOXO1 signaling pathway-dependent manner. FOXO1, a transcription factor downstream of PDGFß/PDGFRß signaling pathway, initiated the transcription of DNM3OS by binding to DNM3OS promoter. CONCLUSIONS: Our study highlighted CAF-promoted DNM3OS as an attractive target to reverse tumor radioresistance in ESCC.

Effect of smartphone application assisted medical service on follow-up adherence improvement in pediatric cataract patients.

PURPOSE: To evaluate the potential of the smartphone application assisted medical service to increase patient compliance in attendance of follow-up after pediatric cataract treatment. METHODS: This prospective study enrolled a total of 163 pediatric cataract patients with uneventful surgery. According to their follow-up intervention method, patients were divided into the smartphone application assisted medical service group (WeChat group, 75 patients) or control group (88 patients). Attendance at five follow-up appointments after surgery was recorded. The percentage of patients that attend each follow-up appointment and the compliance of refractive correction were assessed. RESULTS: Although no significant difference was observed in the first appointment comparing the two groups (98.7% vs. 94.3%, p = 0.293), the attendance rates at the other appointments of the WeChat group were significantly higher than the control group (second: 98.7% vs. 89.8%, third: 97.3% vs. 83%, fourth: 93.3% vs. 78.4%, fifth: 80% vs. 56.8%, total: 93.6% vs. 80.5%, respectively). Compared with the control group, the odd ratios for adherence improvement were 4.4 for males (95% confidence index [CI] 2.54-7.65), 4.75 for patients more than 2 years old (95% CI 2.41-9.36), 4.19 for intraocular lens implantation (2.29-7.66), 6.93 for unilateral cataract (2.9-16.52), 4.87 for undeveloped cities (2.74-8.65), and 3.49 for cities far away (2.04-5.96), with all the p < 0.0001. CONCLUSIONS: This study demonstrates that the use of smartphone application assisted medical service can significantly improve follow-up attendance after pediatric cataract treatment.

[Blockade of TLR4/NF-κB pathway promotes the inflammation of Acinetobacter baumannii-infected rats].

Objective To explore the effects of TLR4 on Acinetobacter baumannii (A. baumannii) infection in a rat model. Methods Healthy male SD rats were divided into normal control group, TAK-242 treated group, A. baumannii treated group, TAK-242 and A. baumannii combined treatment group. Rats of TAK-242-treated group were prepared by caudal vein injection of TAK-242 (1 mg/kg). A. baumannii were isolated from intensive care unit (ICU) and the freshly grown bacteria (1×108 CFU/mL) were prepared. Each normal or TAK-242-treated rat was inoculated with 50 µL A. baumannii through trachea. The bronchoalveolar lavage fluid (BALF) and blood were collected at 72 hours after inoculation. The histopathology of lung was evaluated by HE staining. TNF-α and IL-6 were detected by ELISA. The level of phosphorylated NF-κBp65 (p-NF-κBp65) in peripheral blood mononuclear cells (PBMCs) was detected by Western blot analysis. Results A. baumannii were eliminated within 72 hours in normal rats, whereas bacteria continued to replicate rapidly in the lungs of TAK-242 A. baumannii treated group. The pulmonary inflammatory was more severe than the normal rats. The levels of TNF-α and IL-6 increased markedly after the infection. However, the levels of TNF-α and IL-6 in the TAK-242 combined with A. baumannii treated group were lower than those in the A. baumannii treated group. The level of p-NF-κBp65 increased significantly in the PBMCs of the normal rats 72 hours after infected with A. baumannii, but increased slightly in the TAK-242 combined with A. baumannii treated group. Conclusion TLR4/NF-κB pathway plays an important role in the process of A. baumannii infection, and TLR4 can be used as a target molecule in the treatment of A. baumannii infection.

[Activation of platelet activating factor receptor by Acinetobacter baumannii results in oxidative stress and apoptosis in human bronchial epithelial cells].

Objective To investigate the effect of platelet activating factor receptor (PAFR) on human bronchial epithelial (HBE) cells infected by Acinetobacter baumannii (A. baumannii). Methods HBE cells were divided into control group, ginkgolide B (GB) group, A. baumannii infected group, A. baumannii infection and inhibitor group. HBE cells were infected with low dose (1×103 CFU/mL), medium dose (1×105 CFU/mL) and high dose (1×107 CFU/mL) A. baumannii separated from clinical samples. The PAFR activity was blocked by the 10 µmol/L GB. The expression of PAFR was detected using Western blotting in HBE cells. The proliferation ability of HBE cells was detected using CCK-8 assay. The oxidative stress level was evaluated by superoxide dismutase (SOD) and malondialdehyde(MDA) kits. Apoptosis of HBE cells was observed by annexin V-FITC-V/PI staining. The phosphorylation level of PAFR and its downstream molecule JAK1/STAT1 in HBE cells were examined by Western blot analysis. Results Compared with the control group, the expression of PAFR increased significantly in A. baumannii infected group. A. baumannii infection could decrease cell vitality, but increase intracellular oxidative stress, apoptosis, and JAK1/STAT1 phosphorylation. Conclusion PAFR is an important mediator molecule for A. baumannii infection in HBE cells, and PAFR/JAK1/STAT1 signaling pathway plays an important role in the pulmonary infection of A. baumannii.

Burn wound healing potential of a polysaccharide from Sanguisorba officinalis L. in mice.

Sanguisorba officinalis L. is widely used in China to treat various wounds, particularly burns. The present study was carried to evaluate the healing efficacy of a purified polysaccharide (SOP) from the roots of S. officinalis L. on burn wound models in mice. The results indicated that oral administration of SOP (50 and 200mg/kg) significantly stimulated wound contraction and reduced epithelialization time as compared to control group, which might be mediated by promoting collagen synthesis as evidenced by an increase of hydroxyproline content. Elevation of IL-1ß and VEGF content was also observed in mice following SOP treatment, which in turn facilitate epithelization and angiogenesis. Besides, histopathological examination of the wound tissues in the SOP-treated animals showed collagen deposition and epidermal formation. It may be concluded that the enhancement of burn wound healing by SOP might be due to promotional collagen synthesis and angiogenesis during skin wound repair as a result of the stimulation of hydroxyproline, IL-1ß and VEGF production. The excellent wound-healing activities of SOP provide a scientific rationale for the development of plant-based product in the management of wounds.

Single-cell Transcriptome Analyses Reveal Molecular Signals to Intrinsic and Acquired Paclitaxel Resistance in Esophageal Squamous Cancer Cells.

Paclitaxel is widely used in the combination chemotherapy for many cancers including esophageal squamous cell carcinoma (ESCC). However, the paclitaxel resistance occurs frequently in treating ESCC and the mechanism is not fully understood yet. The heterogeneity of gene expression within the drug-resistant cancer cells may be one of the major factors contributing to its resistance. In the present study, we successfully induced paclitaxel resistance in ESCC cell line KYSE-30 through low dose and long-term treatment of paclitaxel. Gene expression profiles were measured utilizing population RNA-seq and single-cell RNA-seq (scRNA-seq). 37 single cells from KYSE-30 cells and 73 single cells from paclitaxel resistant KYSE-30 cells (Taxol-R) were subjected to scRNA-seq. Weighted gene co-expression network analysis (WGCNA) of scRNA-seq data revealed two major subpopulations in both KYSE-30 and Taxol-R cancer cells. Two subpopulations based on the KRT19 expression levels in KYSE-30 cells exhibited different paclitaxel sensitivity, suggesting the existence of an intrinsic paclitaxel resistance in KYSE-30 cells. In addition, the Taxol-R cells that acquired the resistance to paclitaxel through induction were characterized with higher expressions of proteasomes but a lower expression of HIF-1 signaling genes. Furthermore, we showed that carfilzomib (CFZ), a proteasome inhibitor, could attenuate the paclitaxel resistance in Taxol-R cancer cells through activating the HIF-1 signaling. Our new finding may pave a way leading to an improvement in the treatment on cancers including ESCC by combining CFZ with paclitaxel as a novel approach for cancer therapy.

Sustained accuracy improvement in intraocular lens power calculation with the application of quality control circle.

Accurate intraocular lens (IOL) power calculation is always a challenge in ophthalmology, and unoptimized process may lead to inaccurate refractive outcomes. Quality control circle (QCC) has shown its success in many fields as a process management tool. However, its efficacy in ophthalmology remains unclear. Here we utilized the QCC method to optimize the process and evaluate its efficacy in improving the accuracy of IOL power calculation. After the QCC application, the percentage of eyes with achieved refractive outcomes within 0.5 diopter significantly increased from 63.2% to 80.8% calculated by Haigis formula and 59.2% to 75.8% by SRK/T formula in patients with normal axial length (AL) (22 mm ≤ AL < 26 mm). Although there were no statistically significant differences in patients with long AL by the two formulas (p = 0.886 and 0.726), we achieved an accuracy of 75% with the application of the PhacoOptics software, which was significantly higher than that using the other two formulas (p < 0.001). Our findings indicated that QCC optimized and standardized the process of IOL power calculation, thus improved the accuracy of IOL power calculation in patients who underwent cataract surgery.