Search

To compare the efficacy and safety of focused ultrasound (FUS) therapy and cryotherapy for cervical squamous intraepithelial lesion (SIL).In this retrospective study, data pertaining to women treated for cervical SIL with FUS therapy or cryotherapy at the Second Affiliated Hospital of Chongqing Medical University between 21 April 2018 and 31 August 2020 were obtained. The patients were followed up after 3-6 and 6-12 months. The proportions of women with no evidence of disease, recurrent disease, clearance of the human papillomavirus (HPV) and adverse effects or complications were determined.Of the 250 women with complete data who were included in the study, 144 and 106 received FUS therapy and cryotherapy, respectively. Overall, FUS therapy was observed to be more effective than cryotherapy (91.7 vs. 79.2%,The results of this study suggest that FUS therapy is superior to cryotherapy in the treatment of cervical LSIL.

To investigate the safety, efficacy, and the immune responses of focused ultrasound in cervical intraepithelial neoplasia (CIN).Patients with biopsy-confirmed CIN were recruited for focused ultrasound treatment and asked to return during 3-6 and 6-12 months post-treatment to receive cervical cytology, high-risk human papilloma virus (HPV) detection, and colposcopy. The effective rate was evaluated within 3-6 months, whereas the recurrence rate was evaluated within 6-12 months. Cervicovaginal lavage and cervical tissue were sampled before and 3-6 months after treatment. The expression of interferon gamma (IFN-γ), endoplasmic reticulum aminopeptidase 1 (ERAP1), human leucocyte antigen I (HLA-I), cluster of differentiation 4 (CD4), and cluster of differentiation 8 (CD8) in the cervical tissue were observed by immunohistochemistry. Immunoglobulin A (IgA) and interleukin 10 (IL-10) levels in the cervicovaginal lavage were detected by enzyme-linked immunosorbent assay. Comparisons were made in immune analyte levels before and after treatment.We analyzed the results of 154 patients. The effective rate at 3-6 months was 96.8%. The recurrence rate at 6-12 months was 2.0%. The eradication rate of HPV was 72.4% at 3-6 months and 81.0% at 6-12 months. No serious adverse reactions and complications were observed. After treatment, a higher expression of ERAP1 was observed (Focused ultrasound is an effective and safe therapy for treating CIN, which could improve the local immune milieu of the cervix to some extent.

PDF file - 9027K, Supplemental Table 1 and supplemental Figures 1-3 Supplemental Table 1. MEK functional activation gene signature qRT-PCR results Supplemental Figure 1. For individual growth curve plots: Upper left panel: Control; Upper right panel: AZD6244 100 mg/kg BID x 5/SID x 2 for six consecutive weeks; lower left panel: AZD6244 75 mg/kg BID x 5/SID x 2 for six consecutive weeks; Lower right panel100 mg/kg SID for six consecutive weeks. Tumors A5 and B4 (arrowed) were selected for further transplant to select for selumetinib resistance in vivo. Supplemental Figure 2. Representative immunostaining of BT-40 and derivative xenografts using the VE1 antibody that recognizes BRAFV600E.Tumor samples were fixed and stained as described in a Materials and Methods and read 'blinded' (DC). Panels at the bottom were stained simultaneously and demonstrate intensity of staining for patient derived brain tumors. Supplemental Figure 3. qRT-�PCR to detect IL6 receptor alpha was performed using human-specific primers on snap-�frozen control tumor tissue as described in Supplemental Table 1.

Purpose: The BT-40 low-grade childhood astrocytoma xenograft model expresses mutated BRAFV600E and is highly sensitive to the MEK inhibitor selumetinib (AZD6244). In this study, we developed and characterized selumetinib resistance and explored approaches to circumventing the mechanisms of acquired resistance.Experimental Design: BT-40 xenografts were selected in vivo for selumetinib resistance. Resistant tumors were obtained and characterized, as were tumors that reverted to sensitivity. Characterization included expression profiling, assessment of MEK signature and compensatory pathways, MEK inhibition, BRAF expression, and cytokine levels. Combination treatment of BT-40/AZD–resistant tumors with the MEK inhibitor and a STAT3 inhibitor (LLL12) was assessed.Results: Resistance was unstable, tumors reverting to selumetinib sensitivity when passaged in untreated mice, and MEK was equally inhibited in sensitive and resistant tumors by selumetinib. Drug resistance was associated with an enhanced MEK signature and increased interleukin (IL)-6 and IL-8 expression. Selumetinib treatment induced phosphorylation of STAT3 (Y705) only in resistant xenografts, and similar results were observed in BRAFV600E astrocytic cell lines intrinsically resistant to selumetinib. Treatment of BT-40–resistant tumors with selumetinib or LLL12 had no significant effect, whereas combined treatment induced complete regressions of BT-40/AZD–resistant xenografts.Conclusions: Resistance to selumetinib selected in vivo in BT-40 tumor xenografts was unstable. In resistant tumors, selumetinib activated STAT3, and combined treatment with selumetinib and LLL12 induced complete responses in resistant BT-40 tumors. These results suggest dual targeting BRAF (V600E) signaling and STAT3 signaling may be effective in selumetinib-resistant tumors or may retard or prevent onset of resistance. Clin Cancer Res; 19(24); 6716–29. ©2013 AACR.

PurposeTo investigate the clinical factors affecting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC).MethodsClinical data of 124 LARC patients treated with nCRT and surgery in the fourth Hospital of Hebei Medical University from 2014 to 2019 were retrospectively analyzed. In this study, univariate analysis and logistic dichotomous multivariate regression analysis were used to study the clinical factors affecting pCR, and the receiver operator characteristic curve (ROC) analysis was used to further verify the accuracy of partial indexes in predicting pCR.ResultsOf the 124 enrolled patients, 19 patients (15.32%) achieved pCR. Univariate analysis showed that the number of cycles of consolidation chemotherapy, serum carcino-embryonic antigen (CEA) level before treatment, MRI longitudinal length of tumor, and extramural vascular invasion (EMVI) were statistically correlated with pCR. ROC analysis of the longitudinal length of tumor measured by MRI showed that the area under the curve (AUC) value, sensitivity and specificity were 0.735, 89.47% and 48.57% respectively, and the optimal cut-off value was 5.5cm. The ROC analysis showed that the AUC value, sensitivity and specificity of pCR prediction using CEA were 0.741, 63.16% and 90.48%, respectively, and the optimal cut-off value was 3.1ng/ml. Multivariate results showed that the number of cycles of consolidation chemotherapy, serum CEA level before treatment, and EMVI were independent predictors of pCR.ConclusionThe number of cycles of consolidation chemotherapy, serum CEA level before treatment, and EMVI may be important determinants of LARC patients to reach pCR after nCRT.

A 26-year-old woman with pulmonary metastasis of thyroid cancer underwent a total thyroidectomy and cervical lymph node dissection followed by 2 courses of 131I therapy. The posttherapeutic whole-body scan after the second dose of 131I therapy showed diffuse tracer uptake in both lungs. Besides this, there is a local abnormal radiotracer uptake in the left axillary region. SPECT/CT images localized this abnormal radioactivity in a subcutaneous, oval-shaped, approximately 2.2-cm slightly hyperdense lesion, which was pathologically confirmed as an epidermal cyst.

Cetaceans (whales, dolphins, and porpoises) have undergone a radical transformation from the typical terrestrial mammalian body plan to a streamlined body, while exhibiting dramatic interspecific size differences. However, the molecular mechanisms underlying the diversification of cetacean body size are largely unknown. Here, by using genomic and phenotypic data for 22 cetaceans, we performed phylogenetic genome-body size analysis and explored the genetic basis of the high diversity of body size in cetaceans. A functional enrichment analysis showed that body size-related genes in cetaceans are enriched in pathways associated with immunity, cell growth, and metabolism, suggesting that they contributed to body size diversification. Genes showing correlated evolution with body size were mainly involved in immune surveillance, tumor suppression function, and development of hypertumors. The role of these genes in tumor control resolves Peto's paradox (i.e., the lack of a correspondence between an expansion in body size and, thereby, cell number and an increased cancer incidence). Our results provide novel insights into the evolution of substantial body size variation in cetaceans.

To evaluate the predictive value ofFrom January 2016 to March 2020, 52 LARC patients who underwentTumor response assessment showed that 13 of 52 patients received good response (GR), including 9 cases with pathological complete regression (pCR) and 4 cases with near-pathological complete regression (near-pCR). We also found that the maximum standard uptake value after nCRT (post-SUVmax), the response index (RI), the mean standard uptake values after nCRT (post-SUVmean), and the ratio of tumor SUVmean to liver SUVmean after nCRT (post-Ratio), were correlated with GR and pCR. Among these parameters, post-SUVmax and RI had a near-strong correlation with pCR (rFor LARC patients, the analysis of imaging parameters such as post-SUVmax and RI, which can reflect the changes of

Mammals have evolved different tooth phenotypes that are hypothesized to be associated with feeding habits. However, the genetic basis for the linkage has not been well explored. In this study, we investigated 13 tooth-related genes, including seven enamel-related genes (AMELX, AMBN, ENAM, AMTN, ODAM, KLK4 and MMP20) and six dentin-related genes (DSPP, COL1A1, DMP1, IBSP, MEPE and SPP1), from 63 mammals to determine their evolutionary history. Our results showed that different evolutionary histories have evolved among divergent feeding habits in mammals. There was stronger positive selection for eight genes (ENAM, AMTN, ODAM, KLK4, DSPP, DMP1, COL1A1, MEPE) in herbivore lineages. In addition, AMELX, AMBN, ENAM, AMTN, MMP20 and COL1A1 underwent accelerated evolution in herbivores. While relatively strong positive selection was detected in IBSP, SPP1, and DSPP, accelerated evolution was only detected for MEPE and SPP1 genes among the carnivorous lineages. We found positive selection on AMBN and ENAM genes for omnivorous primates in the catarrhini clade. Interestingly, a significantly positive association between the evolutionary rate of ENAM, ODAM, KLK4, MMP20 and the average enamel thickness was found in primates. Additionally, we found molecular convergence in some amino acid sites of tooth-related genes among the lineages whose feeding habit are similar. The positive selection of related genes might promote the formation and bio-mineralization of tooth enamel and dentin, which would make the tooth structure stronger. Our results revealed that mammalian tooth-related genes have experienced variable evolutionary histories, which provide some new insights into the molecular basis of dietary adaptation in mammals.

Background Biochar is an important material for remediation of Cd in contaminated paddy soils. However, different biochars have variable effects on bioavailability of Cd while single biochar cannot properly amend immobilized Cd. Co-production of biochar from peanut shells and maize straw at different mass mixing ratios (1:0, 1:1, 1:2, 1:3). The characteristics, properties and effects of co-pyrolysis biochars on amendments of Cd polluted paddy soil was evaluated. Results Our research revealed that yield, ash, elemental contents and specific surface area of co-pyrolysis biochars have variable amendment effects compared with single biochar. The co-pyrolysis biochars have produced rich oxygen-containing functional groups and crystal structure, especially 1P3M (co-pyrolysis biochar produced from peanut shell and maize straw in mass ratios of 1:3). The addition of biochar has significantly enhanced pH and EC value, however, content of available Cd during incubation was significantly reduced compared with control treatment. The efficiency of biochars have reduced available Cd in order of 1P3M > M > 1P1M > 1P2M > 2P1M > 3P1M > P after incubation. The 1P3M was most effective in reducing CaCl2-extractable Cd concentration up to 43.97%. The BCR sequential extraction method has produced lowest exchangeable fraction Cd content and highest residual fraction Cd content in 1P3M among all biochar amended treatments. Conclusions It is concluded that 1P3M has a much greater potential to decreased the bioavailability of Cd in contaminated paddy soil. And 1P3M was highly effective for transporting Cd from soluble form to less toxic stable forms in polluted paddy soils. Graphical Abstract

The interaction of non-kinase transmembrane glycoprotein CD44 with ligands including hyaluronic acid (HA) is closely related to the occurrence and development of tumors. Changes in CD44 glycosylation can regulate its binding to HA, Siglec-15, fibronectin, TM4SF5, PRG4, FGF2, collagen and podoplanin and activate or inhibit c-Src/STAT3/Twist1/Bmi1, PI3K/AKT/mTOR, ERK/NF-κB/NANOG and other signaling pathways, thereby having a profound impact on the tumor microenvironment and tumor cell fate. However, the glycosylation of CD44 is complex and largely unknown, and the current understanding of how CD44 glycosylation affects tumors is limited. These issues must be addressed before targeted CD44 glycosylation can be applied to treat human cancers.

Integrons play important roles in the dissemination of antimicrobial resistant genes among bacteria. Class 2 integrons usually has an internal stop codon, TAA, in integrase genes (intI2), leading to a truncated integrase, IntI2*. However, a few class 2 integrons with a natural full-length integrase have been reported. In this study, the sequences of natural full-length intI2 were extracted from INTEGRALL database and analyzed. A total of 236 sequences of intI2 were retrieved from INTEGRALL database, only seven of which were natural full-length intI2 genes and could be divided into five types according to their coding amino acid sequence. Quantitative real-time PCR was used to detect gene cassette sat2 integration and excision efficiency catalyzed by different natural full-length IntI2s. The results showed that all five IntI2s could catalyze attI2 × attCsat2 integration and attCdfrA1/sat2 × attCsat2/aadA1 excision in Escherichia coli. Integration and excision frequency catalyzed by IntI2A176 was highest and was about twofold as high as those catalyzed by IntI2S175_A176. The secondary structure of the IntI2 was predicted by online software. Polymorphisms of these five IntI2s were limited within residues 172, 174, 175, 176 and 256, and these residues were all far away from the predicted DNA binding regions or catalyzed sites. Influence of amino acid sequence polymorphisms of these natural full-length IntI2s on their catalyzed activities is limited.

The application of fluoropyrimidine-based neoadjuvant chemoradiotherapy (Fu-nCRT) of locally advanced rectal cancer (LARC) has become a common therapeutic regimen. In order to improve the efficacy and enable more patients to benefit from this treatment, an accumulation of studies have been carried out on the auxiliary use of other drugs with Fu-nCRT. However, due to specific challenges and the potential opportunities that coexist in this field, a more reasonable approach to the mode of treatment remains to be explored. In this review, we have summarized the results of the studies on the combination of Fu-nCRT with cytotoxic drugs, anti-tumor angiogenesis, and anti-EGFR agents, as well as the status of the application of immune checkpoint inhibitors in the neoadjuvant therapy of LARC patients.

Background: Biochar is an important material for remediation of Cd in contaminated paddy soils. However, different biochars have variable effects on bioavailability of Cd while single biochar can not properly amend immobilized Cd. Co-pyrolysis biochar was produced from peanut shell and maize straw in variable mass mixture ratios. The characteristics, properties and effects of co-pyrolysis biochars on amendments of Cd polluted paddy soil was evaluated.Results: Our research revealed that yield, ash, elemental contents and specific surface area of co-pyrolysis biochars have variable amendment effects compared with single biochar. The co-pyrolysis biochar have produced rich oxygen-containing functional groups and crystal structure, especially 1P3M (co-pyrolysis produced from peanut shell and maize straw in mass ratios of 1:3). The addition of biochar has significantly enhanced pH and EC value, however, content of available Cd during incubation was significantly reduced compared with control treatment. The efficiency of biochars have reduced available Cd in order of 1P3M > M > 1P1M > 1P2M > 2P1M > 3P1M > P after incubation. The 1P3M was most effective in reducing CaCl2-extractable Cd concentration up to 43.97%. The BCR sequential extraction method has produced lowest exchangeable fraction Cd content and highest residual fraction Cd content in 1P3M among all biochar amended treatments. Conclusions: It is concluded that 1P3M has a much greater potential to decreased the bioavailability of Cd in contaminated paddy soil. And 1P3M was highly effective for transporting Cd from soluble form to less toxic stable forms in polluted paddy soils.

Integrons can capture and express foreign gene cassettes through site-specific recombination and are important genetic elements in spreading antibiotic resistance genes among bacteria. We have developed a two-dimensional PCR technology (2D-PCR) based on the base quenching probe technology in detecting three major integrons at the same time. The minimum detection limits were evaluated by detecting three plasmids each harboring different types of integron with different concentrations. The specificity of this method was evaluated by screening and typing three major types of integrons in 105 clinical

BackgroundBrain metastases are the most common cause of intracranial malignancy, often resulting in significant morbidity and mortality. Brain metastases from esophageal squamous cell carcinoma (ESCC) are relatively rare, with a rate of generally less than 2%.Case ReportIn this article, we report a rare case of ESCC with asymptomatic brain metastasis. The combined positive score (CPS) of programmed cell death-ligand 1 (PD-L1) from the primary tumor was 2 by DAKO 22C3 and 3 by VENTANA SP263. The proportion of tumor infiltrating lymphocytes (TILs) was 1%. After receiving 15 cycles of immune checkpoint inhibitors (ICIs), the patient’s brain metastatic lesion had disappeared and was replaced by a local necrotic area. He retains good cognitive function with a stable disease at the primary site.ConclusionsThis is the first to be reported in an ESCC patient whose brain metastatic lesion had a complete response to ICIs, which may provide supporting data for using ICIs as an option of treatment for ESCC patients with brain metastases.

A previous study demonstrated that intracranial tumor volume had some correlation with gastrointestinal cancer patients' outcome. The aim of this study was to analyze patients with esophageal carcinoma (EC) and brain metastases to investigate if intracranial tumor volume would be a predictor of these patients' survival.A total of 52 patients with brain metastases from esophageal squamous cell carcinoma or esophageal adenocarcinoma were retrospectively reviewed. Patients without images of brain metastases in the hospital information system were eliminated.The median follow-up time duration was 8.4 months (interquartile range 4.0-15.2). The median overall survival (OS) from time of brain metastases diagnosis was 8.0 months for all cases. Median OS of patients with small and large cumulative intracranial tumor volume (CITV) (6.65 cmEC patients with small intracranial tumor volume may have longer OS than those with large intracranial tumor volume, but this difference did not reach statistical difference. Future studies with a larger sample size may validate the correlation of intracranial tumor volume and patient survival.

Salmonella enterica serovar 1,4,[5],12:i:- (S. 1,4,[5],12:i:-) has been recognized as an emerging foodborne pathogen in recent years. It can cause human salmonellosis predominated by the contamination of animal-derived foods such as raw poultry and pork. This study aimed to characterize the genetic diversity, plasmid replicon types, and antibiotic resistance of 15 S. 1,4,[5],12:i:- environmental isolates collected from two poultry farms using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), polymerase chain reaction-based replicon typing, and minimum inhibitory concentration approach. Ten different PFGE genotypes were detected, indicating a high diversity among these S. 1,4,[5],12:i:- isolates. Three sequence types (ST19, ST1544, ST34) were identified by MLST. Among them, ST1544 was first detected in S. 1,4,[5],12:i:- environmental isolates from poultry farms. All isolates were resistant to cefazolin, cefotetan, tobramycin, amikacin, and gentamicin, but susceptible to piperacillin-tazobactam, aztreonam, ceftazidime, cefepime, and ertapenem. Five incompatibility groups (Inc) of plasmids were identified, including IncFIIs (66.7%), IncHI2 (20%), IncI1 (6.7%), IncN (6.7%), and IncQ (6.7%). Among these isolates, 80% carried at least one plasmid replicon type, and 20% carried multiple plasmid replicon types. Interestingly, the multidrug-resistant isolate 263 carried numerous resistance genes (i.e. qnrS, aac(6ʹ)-Ib-cr, blaTEM, blaCTX-M-9, blaOXA-1, sul1, sul2, sul3, floR, and mcr-1) and class I integronase gene intI1, which possessed both IncHI2 and IncQ plasmids, suggesting that resistance genes may be horizontally transferred by the combination of IncHI2 and IncQ plasmids. Collectively, antibiotic-resistant S.1,4,[5],12:i:- isolates were first found in poultry farm environments in China, and surveillance should be strengthened to prevent their further spread from poultry farms to foods.

The identification of the source of heavy metal pollution and its quantification are the prerequisite of soil pollution control. The apcs-mlr, UNMIX and PMF models were employed to apportion pollution sources of Cu, Zn, Pb, Cd, Cr and Ni of the farmland soil in vicinity of an abandoned iron and steel plant. The sources, contribution rates and applicability of the models were evaluated. The potential ecological risk index revealed greatest ecological risk from Cd. The results of source apportionment illustrated that apcs-mlr and UNMIX models can verify each other for accurate allocation of pollution sources. The industrial sources were the main sources of pollution (32.41% ~ 38.42%), followed by agricultural sources (29.35% ~ 31.65%), traffic emission sources (21.03% ~ 21.51%), and natural sources of pollution were accounted for smallest proportion (11.2% ~ 14.42%). The PMF model was easily affected by outliers, its fitting degree was not ideal, and it was unable to get more accurate results of source analysis. The combination of multiple models can effectively improve accuracy of pollution source analysis of soil heavy metals. These results can provide a scientific basis for further remediation of heavy metal pollution in farmland soil.

Background: Ferroptosis is an iron-dependent programmed cell death (PCD) form that plays a crucial role in tumorigenesis and might affect the antitumor effect of radiotherapy and immunotherapy. This study aimed to investigate distinct ferroptosis-related genes, their prognostic value and their relationship with immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC).Methods: The differentially expressed ferroptosis-related genes in HNSCC were filtered based on multiple public databases. To avoid overfitting and improve clinical practicability, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were performed to construct a prognostic risk model. Moreover, a nomogram was constructed to forecast individual prognosis. The differences in tumor mutational burden (TMB), immune infiltration and immune checkpoint genes in HNSCC patients with different prognoses were investigated. The correlation between drug sensitivity and the model was firstly analyzed by the Pearson method.Results: Ten genes related to ferroptosis were screened to construct the prognostic risk model. Kaplan-Meier (K-M) analysis showed that the prognosis of HNSCC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001), and the area under the curve (AUC) of the 1-, 3- and 5-year receiver operating characteristic (ROC) curve increased year by year (0.665, 0.743, and 0.755). The internal and external validation further verified the accuracy of the model. Then, a nomogram was build based on the reliable model. The C-index of the nomogram was superior to a previous study (0.752 vs. 0.640), and the AUC (0.729 vs. 0.597 at 1 year, 0.828 vs. 0.706 at 3 years and 0.853 vs. 0.645 at 5 years), calibration plot and decision curve analysis (DCA) also shown the satisfactory predictive capacity. Furthermore, the TMB was revealed to be positively correlated with the risk score in HNSCC patients (R = 0.14; P < 0.01). The differences in immune infiltration and immune checkpoint genes were significant (P < 0.05). Pearson analysis showed that the relationship between the model and the sensitivity to antitumor drugs was significant (P < 0.05).Conclusion: Our findings identified potential novel therapeutic targets, providing further potential improvement in the individualized treatment of patients with HNSCC.

In order to reduce the time and cost of verification, validation and accreditation (VV&A), increase the probability that design will succeed at one time, the traditional product development framework and methodology, which is usually described as the V framework, is extended through the double V framework to the model and data based triple V framework. The new framework provides an opportunity to converge data lifecycle, model lifecycle and product (development) lifecycle together. The paper analyses the interoperability of proposed triple V framework and implements it in a ship damage control system development project.

PurposeDue to the low incidence of intracranial disease among patients with esophageal cancer (EC), optimal management for these patients has not been established. The aim of this real-world study is to describe the clinical characteristics, treatment approaches, and outcomes for esophageal squamous cell carcinoma (ESCC) patients with brain metastases in order to provide a reference for treatment and associated outcomes of these patients.MethodsPatients with ESCC treated at the Fourth Hospital of Hebei Medical University between January 1, 2009 and May 31,2020 were identified in an institutional tumor registry. Patients with brain metastases were included for further analysis and categorized by treatment received. Survival was evaluated by the Kaplan-Meier method and Cox proportional hazards models.ResultsAmong 19,225 patients with ESCC, 66 (0.34%) were diagnosed with brain metastases. Five patients were treated with surgery, 40 patients were treated with radiotherapy, 10 with systemic therapy alone, and 15 with supportive care alone. The median follow-up time was 7.3 months (95% CI 7.4-11.4). At last follow-up, 59 patients are deceased and 7 patients are alive. Median overall survival (OS) from time of brain metastases diagnosis was 7.6 months (95% CI 5.3-9.9) for all cases. For patients who received locoregional treatment, median OS was 10.9 months (95% CI 7.4-14.3), and survival rates at 6 and 12 months were 75.6% and 37.2%, respectively. For patients without locoregional treatment, median OS was 3.0 months (95% CI 2.5-3.5), and survival rates at 6 and 12 months were 32% and 24%, respectively. OS was significantly improved for patients who received locoregional treatment compared to those treated with systematic treatment alone or supportive care (HR: 2.761, 95% CI 1.509-5.053, P=0.001). The median OS of patients with graded prognostic assessment (GPA) score 0-2 was 6.4 months, compared to median OS of 12.3 months for patients with GPA >2 (HR: 0.507, 95% CI 0.283-0.911).ConclusionBrain metastases are rare in patients with ESCC. GPA score maybe a useful prognostic tool for ESCC patients with brain metastases. Receipt of locoregional treatment including brain surgery and radiotherapy was associated with improved survival.

We used the Geriatric Depression Scale to investigate the depression status of empty nesters living in eastern rural China (N = 967). The results showed that more than half of the participants suffered relatively severe depression and that their mental health was not favorable. Gender, age, level of education, and marital status had a significant influence on depression status. The degree of depression of men was lower than that of women. As participants’ age increased, the degree of depression first rose until the age of 84 and then fell thereafter. The depression of unmarried empty nesters was relatively severe compared to that of married ones. Finally, a higher level of education corresponded with a lower degree of depression. There are varied factors affecting the psychological status of empty nesters in China. To improve their mental state, the government, society, and family need to collaborate and take comprehensive measures.

Vulvar lichen sclerosus (VLS) is a common inflammatory condition associated with an increased risk of developing vulvar carcinoma. Recently, high-intensity focused ultrasound (HIFU) has been identified as a promising treatment modality for VLS in several clinical trials. However, in HIFU therapy, therapeutic outcome is routinely assessed visually by an expert using standardized grading criteria. Furthermore, such a therapeutic assessment cannot be made until at least 3 months after treatment. Therefore, an objective and timely method capable of quantitatively evaluating HIFU treatment effectiveness is desired, which may help identify patients whose treatment is insufficient promptly and prevent delay in re-treatment. The purpose of this study is to investigate the feasibility of using active dynamic thermal imaging (ADT) and hyperspectral imaging (HSI) as two individual objective and non-invasive optical methods for prompt quantitative assessment of the therapeutic response to HIFU treatment in VLS. From December 2018 to March 2019, 20 female VLS patients who underwent HIFU treatment were evaluated using both the ADT and HSI methods. The effective damage rate from the ADT method and the entropy of feature index from the HSI method were used to develop a multivariate linear discriminant classification model for grading the effectiveness of HIFU treatment in comparison with clinical evaluation gold standard. It was found that ADT was able to correctly differentiate ineffective treatments from effective ones with a sensitivity of 100% and specificity of 100%, while the sensitivity and specificity of HSI were 75 and 87.5%, respectively. The classification results demonstrate the clinical potential of the ADT and HSI methods for timely non-invasive and quantitative assessment of HIFU treatment for VLS.

Nanozymes merge nanotechnology with biology and provide a lower cost and higher stability options, compared to that of natural enzymes. However, nanozyme catalyzed polymerization under physiological conditions is still a big challenge due to heavy oxygen inhibition. In this study, the simple glucose oxidase system can effectively adjust oxygen concentration and generate hydrogen peroxide, which assists in the realization of nanozyme-catalyzed polymerization. The nanozyme based hydrogel is printable due to its mild preparation with gradually increased viscosity. The antibacterial performance is ascribed to the in situ generated hydroxyl radical via the reaction of the bound nanozyme and glucose.

Understanding human and climate-induced vegetation changes could benefit regional ecological management. In this paper, a framework was established to quantify the relative contribution rates of human and climate factors to vegetation changes in Chongqing, China, from 2000 to 2015. MODIS NDVI time series data were collected, and land use data were produced using Landsat TM/OLI images. A combined analysis of land use and vegetation changes was conducted, and the residual trends method (RESTREND) was explored in the framework. The results showed that Chongqing experienced a significant vegetation increase from 2000 to 2015. The relative contribution rates of human activities and climate to the vegetation changes were 90.96% and 9.04%, respectively. These results indicate that human activities had a dominant role in vegetation restoration in Chongqing in 2000–2015. Throughout the study period, extensive land use changes occurred in Chongqing. During the study period, persistent forested land, farmland-forested land (a land use conversion type), persistent farmland, and grassland-forested land were the four most important land use (changed and unchanged) types attributed to the growing season NDVI (GSN) increases in Chongqing from 2000 to 2015. The contributions of these four land use types were 45.03%, 21.19%, 16.79% and 12.60%, respectively. The farmland-forested land was characterized as the most effective land use conversion type for vegetation restoration. The proposed framework allows for human and climate-induced vegetation changes to be quantitatively distinguished at the regional scale and provides the contribution rates of each changed and unchanged land use type. The framework is expected to be useful for regional ecological management and research.

Purpose/Objective(s) To screen microRNAs that are positively correlated with radiation resistance in rectal cancer, and to investigate their regulatory mechanism. Materials/Methods Fresh rectal cancer tissues were obtained intraoperatively and divided into two equal parts, one of which was pre-stored in a refrigerator at -150℃, and the other was constructed with Patients Derived Xenograft (PDX) models for rectal cancer and irradiated to transplantation tumor screen out radiation-sensitive tumor tissues and radiation-resistant tumor tissues. According to the screening results, the pre-stored samples were screened for differential microRNAs in radiation reactivity, and the microRNAs that were positively correlated with irradiation resistance were obtained. On the base of screening results, the pre-stored samples were screened for differential microRNAs in irradiation reactivity by miRNAs microarrays, and the microRNAs that were positively correlated with irradiation resistance were obtained. Biological prediction software was used to predict the target genes regulated by microRNA, and the prediction results were verified in radiation-resistant rectal cancer cell lines. Lentivirus plasmid transfection technique was used to construct rectal cancer cell lines with down-regulated target microRNA expression, in order to further verify the effects of the changes in the expression of the microRNA on the radiation reactivity, proliferation, invasion and migration of rectal cancer cells. The target genes regulated by microRNAs were screened and verified, and the expression of the key genes in the signal transduction pathways involved in the regulation were detected. Results The results of microRNA screening and validation showed that there were 14 microRNAs with fold change > 1.5. Among them, miRNA-552-3p, miRNA-96-5p, miRNA-182-5p, and miRNA-183-5p were up-regulated in irradiation-resistant tumor tissues. The enrichment signaling pathway analysis showed that the Wnt signal transduction pathway was highly active in irradiation-resistant tumor tissues. The clone formation experiment under radiation interference showed that HR-8348 was the most radiation-resistant cell line among the five cell lines, and the expression level of miRNA-96-5p was positively correlated with the radiation-resistant ability of rectal cancer cell lines. The results of prediction and validation showed that the expression of GPC3 gene was directly regulated by miRNA-96-5p, and the down-regulated expression of miRNA-96-5p inhibited the activity of Wnt signal transduction pathway. Conclusion The high expression of miRNA-96-5p enhanced the radiation resistance of rectal cancer cells, and its effect may be related to the down-regulation of GPC3 expression and the abnormal activation of Wnt signal transduction pathway.

Surface topography plays a key role in the colonization of substrata by the colonizing stages of marine fouling organisms. For the innovation of marine antifouling coatings, it is essential to understand how topographic cues affect the settlement of these organisms. In this study, tapered, spiked microstructures and discrete honeycombs of varying feature dimensions were designed and fabricated in order to examine the influence of topography on the attachment of zoospores of the green macroalga Ulva linza and cells of the diatom (microalga) Navicula incerta. Contrasting results were obtained with these two species of algae. Indeed, the preferred location of cells of N. incerta was dominated by attachment point theory, which suggested a positive correlation between the density of cells adhering and the amount of available attachment points, while the settlement of spores of U. linza was mainly regulated by both Wenzel roughness and local binding geometry.

Folate receptor (FR) is overexpressed in many epithelial cancers and tumor-associated macrophages (TAMs), which enable it to function as an appropriate target for cancer treatment. We have successfully synthesized multifunctional folate-targeted and oxygen/paclitaxel loaded microbubbles (TOPLMBs) for ultrasound (US) mediated delivery for combination therapy in an intraperitoneal ovarian cancer xenograft model. The TOPLMBs target both ovarian cancer cells and TAMs and provide a promising drug delivery strategy for the combination treatment of ovarian cancer and tumor microenvironment. Microscopic imaging and flow cytometric analysis showed that TOPLMBs significantly penetrated into ovarian cancer cells and tumor-associated macrophages (TAMs) within tumor ascites fluid and the tumor nodules. Immunohistochemical analyses of dissected tumor tissue confirmed the increased tumor apoptosis, the reduced expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD), and the reduced expression of CD68 after treatment (P

Integrons play important roles in the dissemination of antimicrobial resistant genes among bacteria. Class 2 integrons usually has an internal stop codon, TAA, in integrase genes (intI2), leading to a truncated integrase, IntI2*. However, a few class 2 integrons with a natural full-length integrase have been reported. In this study, the sequences of natural full-length intI2 were extracted from INTEGRALL database and analyzed. A total of 236 sequences of intI2 were retrieved from INTEGRALL database, only seven of which were natural full-length intI2 genes and could be divided into five types according to their coding amino acid sequence. Quantitative real-time PCR was used to detect gene cassette sat2 integration and excision efficiency catalyzed by different natural full-length IntI2s. The results showed that all five IntI2s could catalyze attI2 × attC

We have successfully fabricated versatile folate-targeted and oxygen/indocyanine green-loaded lipid nanoparticles (FA-OINPs) for dual-mode imaging-guided therapy in ovarian cancer cells and subcutaneous xenograft models. FA-OINPs were demonstrated to have great potential as superb contrast agents to enhance ultrasound and photoacoustic (US/PA) imaging We have successfully fabricated versatile folate-targeted and oxygen/indocyanine green-loaded lipid nanoparticles (FA-OINPs) for dual-mode imaging-guided therapy in ovarian cancer cells and subcutaneous xenograft models. FA-OINPs were demonstrated to have great potential as superb contrast agents to enhance ultrasound and photoacoustic (US/PA) imaging in vitro and in vivo. Confocal laser scanning microscopy and flow cytometry analysis verified that FA-OINPs could specifically target SKOV3 ovarian cancer cells and be endocytosed with a remarkable efficiency. Compared with other therapeutic options, FA-OINPs exhibited an excellent therapeutic outcome after exposure to laser and ultrasound. The MTT assay and flow cytometry analysis confirmed that cytotoxicity effects and apoptosis/necrosis rates were significantly increased. The fluorescence microscopy and fluorescence microplate reader detection validated that the generation of intracellular reactive oxygen species (ROS) was dramatically improved. Immunohistochemical analyses of tumor tissues demonstrated the enhanced tumor apoptosis, the decreased vascular endothelial growth factor (VEGF) and microvascular density (MVD) expression, and the decreased expression of CD68 after treatment. The presented results suggest that photo-sonodynamic/photothermal mediated FA-OINPs could provide a promising strategy for synergistic therapy in ovarian cancer with the guidance of US/PA dual-mode imaging.

Despite the improvement in acute myeloid leukemia (AML) treatments, most patients had a poor prognosis and suffered from chemoresistance and disease relapse. Therefore, there is an urgent need for elucidation of mechanism(s) underlying drug resistance in AML. In the present study, we found that AML cells showed less susceptibility to adriamycin (ADR) in the presence of hypoxia, while inhibition of hypoxia-inducible factor 1α (HIF-1α) by CdCl2 can make AML cells re-susceptibile to ADR even under hypoxia. Moreover, HIF-1α is overexpressed and plays an important role in ADR-resistance maintenance in resistant AML cells. We further found hypoxia or induction of HIF-1α can significantly upregulate yes-associated protein (YAP) expression in AML cells, and resistant cells express a high level of YAP. Finally, we found that YAP may not only enhance HIF-1α stability but also promote HIF-1α's activity on the target gene pyruvate kinase M2. In conclusion, our data indicate that HIF-1α or YAP may represent a therapeutic target for overcoming resistance toward adriamycin-based chemotherapy in AML.

Objectives To describe the molecular characteristics of beta-lactamases in bloodstream-infection Escherichia coli isolated from elderly patients, and to determine the genotypic patterns of blaCMY–2 and blaADC–162. Methods A total of 50 bloodstream-infection E. coli isolates were obtained from patients aged > 50 years at Shanghai Sixth People’s Hospital South Campus during 2015–2018. The isolates were subjected to beta-lactamase detection using phenotypic and molecular methods. Beta-lactamase genes were verified by sequencing and the phylogenetic relationships of the isolates were analyzed by multilocus sequence typing (MLST). The transferability of plasmids carrying blaCMY–2 and blaADC–162 genes was verified by conjugation experiments and plasmid replicon typing. Results Eight beta-lactamase subtypes were detected in 50 isolates of bloodstream-infection E. coli. blaTEM–1 (21/50) was the most common beta-lactamase gene, followed by blaCTX–M–14 (8/50), blaOXA–27 (5/50), blaCTX–M–27 (3/50), blaCTX–M–65 (1/50), blaADC–162 (1/50), and blaCMY–2 (1/50). Of these, blaADC–162 (ST95-A), and blaCMY–2 (ST95-B2) have not previously been reported in bloodstream-infection E. coli. In 21 isolates, beta-lactamase genes were located on conjugative plasmids belonging to incompatibility groups FrepB (n = 7), FIA (n = 1), FIC (n = 2), K (n = 8), N (n = 1), and I (n = 1), and blaCTX–M was associated with the common elements ISEcp1, IS903, and IS26, but with special sequences (region V, region Y, and region W) for ISEcp1 in 14 isolates. Conclusion To the best of our knowledge, this study provides the first molecular characterization of beta-lactamase genes in E. coli isolated from the bloodstream in elderly patients. Beta-lactamase genes were detected at a relatively high frequency in elderly patients with bloodstream E. coli infections. Plasmid replicon analysis showed that horizontal dissemination of beta-lactamase genes was mainly mediated by IncK and IncF plasmids, which could encode multidrug resistance genes. The study also provides the first report of ISAba1-blaADC–162-tnpA and ISEcp1-blaCTX–M–14-IS903-blaCMY–2-blc-sugE in E. coli, and demonstrates IncF plasmid-mediated blaADC–162 and blaCMY–2 gene dissemination among bacteria.

e15084 Background: The transformation to small cell lung cancer (SCLC) is one of the mechanisms of drug resistance in non-small cell lung cancer (NSCLC). However, there are few reports on it. The study aims to analyze the clinicopathological characteristics of the patients, to explore the transformation factors and reasonable treatment strategy for them. Methods: A total of 9 patients with pathologically diagnosed NSCLC transformed into SCLC after first-line or multi-line treatment were involved in the study. Results: Among the 9 patients, there were 8 adenocarcinomas (ADC) and 1 squamous cell carcinoma (SCC), 7 of them were non-smokers. Epidermal growth factor receptor (EGFR) mutations were present in all ADC patients, including 7 with exon19 deletion (87.5%) and 1 with exon21 mutation (12.5%). All of them received EGFR tyrosine kinase inhibitors (TKIs) before the transformation, and the median transformation time was 19.5 months (95% CI, 14.1-32.7months). After first-line chemotherapy with paclitaxel and cisplatin, one SCC patient transformed to SCLC within 5 months. EGFR mutation was still maintained in 6 ADC patients when transformation occurred, of which 2 patients had a new TP53 mutation and 1 had RB1 gene mutation. Serum tumor markers were monitored in 6 patients, of them, progastrin releasing peptide (Pro-GRP) increased apparently at the time of disease progression in 5 patients, and neuron-specific enolase (NSE) also increased in 3 patients. This phenomenon occurred three to six months earlier than the transformation. The median survival time (MST) was 37 months from the initial diagnosis of NSCLC and 13 months after transformation. The median progression-free survival (mPFS) was only 2 months for those treated with chemotherapy (CT) after transformation, whereas 6 months treated with CT combined with TKIs as the first-line treatment. Three patients who received chemotherapy combined with programmed death receptor-1 (PD-1) inhibitor after multi-line therapy underwent progress within 2 months, nevertheless, 1 patient treated with the EP regimen combined with pembrolizumab as the first line treatment after transformation had a PFS of 12 months. After re-progression, the patients got another PFS of 5 months with a pemetrexed-platinum combined with atezolizumab. Conclusions: Phenotypic transformation is one of the mechanisms of drug resistance for NSCLC patients, especially for those with EFGR exon19 deletion received EGFR-TKIs. Tumor heterogeneity, TP53 gene and Rb gene mutation may be responsible for the transformation. The serum Pro-GRP over expression could as an early predictor of transformation. Classical chemotherapy is ineffective after SCLC transformation patients who still have sensitive mutation, it might be suitable to combine with EGFR-TKIs. The early application of immunotherapy could be attempted, but still needs to be explored further.

Natural (−)-Celosine was isolated as a novel endocyclicditerpene with an unprecedented skeleton from Celosia cristata L. Its structure was established by comprehensive 1D and 2D NMR spectroscopic analysis in combination with single-crystal X-ray crystallographic diffraction of synthesized (+)-Celosine. (−)-Celosine was expected to have an anti-atherosclerotic activity in vivo, and myeloperoxidase (MPO) expression may be the mechanism underlying this anti-atherosclerotic activity.

In previous studies, the present authors demonstrated that effective sensitization of ionizing radiation-induced death of tumor cells, including non-small cell lung cancer (NSCLC) cells, could be produced by oleanolic acid (OA), a pentacyclic triterpenoid present in plants. In the present study, it was investigated whether ursolic acid (UA), an isomer of OA, had also the capacity of sensitizing radioresistant NSCLC cells. The radioresistant cell line H1299/M-hypoxia inducible factor-1α (HIF-1α) was established by transfection with a recombinant plasmid expressing mutant HIF-1α (M-HIF-1α). Compared with parental H1299 cells and H1299 cells transfected with empty plasmid, H1299/M-HIF-1α cells had lower radiosensitivity. Following the use of UA to treat NSCLC cells, elevation of the radiosensitivity of cells was observed by MTT assay. The irradiated H1299/M-HIF-1α cells were more sensitive to UA pretreatment than the irradiated cells with empty plasmid and control. The alteration of DNA damage in the irradiated cells was further measured using micronucleus (MN) assay. The combination of UA treatment with radiation could induce the increase of cellular MN frequencies, in agreement with the change in the tendency observed in the cell viability assay. It was further shown that the endogenous glutathione (GSH) contents were markedly attenuated in the differently irradiated NSCLC cells with UA (80 µmol/l) pretreatment through glutathione reductase/5,5'-dithiobis-(2-nitrob-enzoic acid) (DTNB) recycling assay. The results revealed that UA treatment alone could effectively decrease the GSH content in H1299/M-HIF-1α cells. In addition, the inhibition of HIF-1α expression in radioresistant cells was confirmed by western blotting. It was then concluded that UA could upregulate the radiosensitivity of NSCLC cells, and in particular reduce the refractory response of cells expressing HIF-1α to ionizing radiation. The primary mechanism is associated with reduction of endogenous GSH and inhibition of high expression of intracellular HIF-1α. UA should therefore be deeply studied as a potential radiosensitizing reagent for NSCLC radiotherapy.

e16525 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China, but brain metastasis is rare and less reported. The aim of this study is to investigate the clinical characteristics and outcomes of ESCC patients with brain metastasis, so as to provide some references for them. Methods: Between January 1, 2009 and December 31, 2018, 16480 patients with ESCC were registered at the Fourth Hospital of Hebei Medical University. A total of 52 patients (0.32%) were diagnosed of brain metastasis. Thirty-two patients received craniocerebral radiotherapy, of them, 17 cases were treated with radiotherapy alone, the rest were treated with chemotherapy (n = 12) or targeted therapy(n = 13) concurrently. There were 6 patients received chemotherapy (platinum + docetaxel / paclitaxel) alone, and 14 cases received support therapy only. Results: The median interval time from the date of diagnosis of the primary tumor until diagnosis of brain metastasis was 9.2 months (range, 0-249.2 months). The initial stages of the patients in II, III and IV were 6, 25 and 21, respectively. The median length of esophageal tumor was 5.0 cm (range, 2-12cm). Single lesion and multiple foci of brain metastasis were found in 40 and 12 patients, respectively. Twenty-eight patients had extracranial metastasis simultaneously, including lung metastasis in 14 patients, liver metastasis in 13 patients, bone metastasis in 11 patients, and multiple metastases in 16 patients. The median survival was 6.7 months (range, 0.4-43.4 months), the survival rate of 6 months, 12 months and 24 months was 53.8%, 26.9%, and 4.9%, respectively. The median surviva lof craniocerebral radiotherapy group was longer than that of chemotherapy/supportive care group (8.4 months vs 2.9 months, c2= 6.706, P = 0.01). Multivariate analysis demonstrated that craniocerebral radiotherapy (P = 0.008) and Karnofsky (KPS) score (P = 0.027) were significant prognostic factors for survival. Conclusions: Approximately 0.32% of ESCC patients diagnosed or developed brain metastasis since initial registration. A higher KPS score and craniocerebral irradiation were associated with a better survival trend. Craniocerebral radiotherapy should be an importantoption for ESCC patients with brain metastasis owing to poor efficacy of systemic regimens.

To investigate the predictive value of the perfusion (Q) single-photon emission computed tomography (SPECT)-weighted dose-function histogram (DFH) obtained mid-treatment (mid-Tx) with radiotherapy (RT) for radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC).The study population consisted of NSCLC patients who were undergoing RT treatment and enrolled in prospective imaging studies. Q-SPECT was performed prior to and during RT (at ∼40-45 Gy). A baseline dose-volume histogram (DVH) and mid-Tx DVH based on simulation CT as well as a baseline DFH and mid-Tx DFH based on Q-SPECT were calculated. Only patients with stage III NSCLC and visible functional lung (FL) changes on the mid-Tx scan were eligible for this enriched analysis. RILT was graded according to a reported scale.Forty-two stage III NSCLC patients met the criteria for inclusion. The accumulative incidence of grade ≥2 RILT was 31% in this high-risk population. Significant differences in functional metrics such as functional lung volume FV5-FV20 at increments of 5 Gy and functional MLD (FMLD) were observed between patients with and without grade ≥2 RILT (p 0.05). Similar results were also obtained for anatomical metrics from V5-V20 and MLD (p 0.05). The areas under the receiver operating characteristic curves (AUCs) ranged from 0.724to 0.812 for baseline DVH parameters, from 0.745 to 0.830 for mid-Tx DVH parameters, from 0.764 to 0.878 for baseline DFH parameters, and from 0.767 to 0.891 for mid-Tx DFH parameters. Further principal components analysis showed that the AUCs were 0.814/0.817 and 0.790/0.857 for baseline/mid-Tx DVH and baseline/mid-Tx DFH, respectively.Mid-Tx DFH parameters based on Q-SPECT were significantly elevated in patients with grade ≥2 RILT in this study population. Among the metrics compared, mid-Tx DFH seemed to have better predictive accuracy, but this difference did not reach statistical difference.

Chemotherapy and photo-sonodynamic therapy (PSDT) can be combined through drug delivery nano-platforms to enhance the anti-tumor efficacy, however, which is limited by hypoxia in tumor, thereby causing chemotherapy resistance. Perfluoropentane (PFP) has the ability to carry oxygen and to enhance ultrasound or photoacoustic imaging after vaporization. Herein, we constructed a kind of nanoparticles (PTX/ICG and oxygen loaded PLGA nanoparticles (PIO_NPs)), which had PFP core carrying oxygen and PLGA shell loaded indocyanine green (ICG) and paclitaxel (PTX). PIO_NPs harbored good optical stability and the ability to transit phase. Moreover, it could rapidly release PTX and generate ROS under the mediation by near-infrared laser and low-intensity ultrasound. The PIO_NPs enhanced contrast of the ultrasound and PA imaging. In particular, PIO_NPs may be used to monitor and guide treatment for the accumulation of PIO_NPs at tumor site can be observed by PA imaging. Compared with PTX or other nanoparticles, PIO_NPs combined with laser and ultrasound (L.U) significantly induced apoptosis of SKOV3 cells and inhibited SKOV3 tumor growth. Therefore, PIO_NPs are of great potential in cancer imaging and therapy.

Rainfall and land use conversion are important factors influencing soil erosion. Differing from the stationary land use type, land use conversion is a process of dynamic change usually spanning several decades. Soil erosion modeling using historic land use data offers an opportunity to study the impacts of actual land use conversion on soil erosion. However, rainfall has been taken into account only in a few studies because its spatio-temporal distribution often varies greatly over a long period of time. In this article, the erosivity index was used to quantify the erosive force of rainfall. Based on entropy theory, erosivity distribution of study area during the 1988 to 2013 period was analyzed. Two extreme zones, Zone I and Zone II, with highest and lowest annual erosivity, respectively, were identified. The intensity of soil erosion among land use types are: farmland > orchard > grass/open forest > shrub > forest. Zone I has severer soil erosion than Zone II. The effectiveness of land use conversion for reducing soil erosion varies between different erosivity zones. Farmland–forest conversion is considered as the first choice to reduce soil erosion when land use conversion is implemented. The conversions of farmland–grassland and farmland–open forest can be used as important supplements to conversion of farmland–forest in low erosivity zone of the study area, although they do not perform well under higher erosivity situation.

Matrix metalloproteinases (MMPs), mostly abundant in the tumor extracellular matrix (ECM), tumor cells, and tumor vasculatures, are closely correlated with tumor progression and metastasis. In this case, making use of MMPs was supposed to achieve site-specific drug delivery and a satisfactory tumor treatment effect. Herein, we rationally developed a novel tumor microenvironment and tumor cell dual-targeting nanoparticle by integrating a chemotherapeutic-loaded drug-loaded carrier and a versatile polypeptide-LinTT1-PVGLIG-TAT (LPT) which is composed of a multitargeting peptide-LinTT1 and a cell-penetrating peptide-TAT. The functionalized nanoparticles exhibited a superior affinity to A549 lung-cancer cells and microenvironment including angiogenesis and tumor-associated macrophages (TAMs) in our study. In addition, cellular experiments demonstrated that the cell-penetrating ability of TAT was significantly shielded by the addition of LinTT1 to the fourth lysine of the TAT via an MMP cleavable linker PVGLIG and could be recovered under the catalysis of MMPs. This design was supposed to efficiently decrease the toxicological risk to normal tissues induced by the unselectivity of TAT. The finally treatment effect investigation showed that tumor-bearing mice treated with LPT-modified nanoparticles achieved an enhanced efficacy for inhibiting tumor growth and the longest survival time as compared to other groups. Collectively, this study provides a novel robust nanoplatform which could simultaneously target the tumor microenvironment and tumor cell drug delivery for increasing the efficacy of cancer therapy.

Feature extraction is very important in the fault detection of rolling bearing for wind turbine. More features don't mean good performance. Data analysis and experiment based on real wind turbine samples are carried out to achieve efficient fault detection. Firstly, the original signal is decomposed with improved Empirical Mode Decomposition(EMD) to get a finite number of stationary intrinsic mode functions (IMFs). Then, characteristics of amplitude domain parameters, such as mean and variance are extracted, which can be turned into a high dimensional feature matrix. Principal component analysis(PCA) is adopted to reduce the feature matrix of vibration signals from high dimension to low dimension to remove redundant information. Classification experiments show that, this method can accurately extract the effective features of the original signal, and this can reduce the overfitting phenomenon of the machine-learning model, and can also improve the accuracy of fault detection.

To develop and evaluate the clinical application of a multimodal colposcopy combining multispectral reflectance, autofluorescence, and red, green, blue (RGB) imaging for noninvasive characterization of cervical intraepithelial neoplasia (CIN). We developed a multimodal colposcopy system that combined multispectral reflectance, autofluorescence, and RGB imaging for noninvasive characterization of CIN. We studied the optical properties of cervical tissue first; then the imaging system was designed and tested in a clinical trial where comprehensive datasets were acquired and analyzed to differentiate between squamous normal and high grade types of cervical tissue. The custom-designed multimodal colposcopy is capable of acquiring multispectral reflectance images, autofluorescence images, and RGB images of cervical tissue consecutively. The classification algorithm was employed on both normal and abnormal cases for image segmentation. The performance characteristics of this system were comparable to the gold standard histopathologic measurements with statistical significance. Our pilot study demonstrated the clinical potential of this multimodal colposcopic system for noninvasive characterization of CIN. The proposed system was simple, noninvasive, cost-effective, and portable, making it a suitable device for deployment in developing countries or rural regions of limited resources.