Visualization of Deep Tissue G-quadruplexes with a Novel Large Stokes-Shifted Red Fluorescent Benzothiazole Derivative.

G-quadruplex (G4) is a noncanonical nucleic acid secondary structure that has implications for various physiological and pathological processes and is thus essential to exploring new approaches to G4 detection in live cells. However, the deficiency of molecular imaging tools makes it challenging to visualize the G4 in ex vivo tissue samples. In this study, we established a G4 probe design strategy and presented a red fluorescent benzothiazole derivative, ThT-NA, to detect and image G4 structures in living cells and tissue samples. By enhancing the electron-donating group of thioflavin T (ThT) and optimizing molecular structure, ThT-NA shows excellent photophysical properties, including red emission (610 nm), a large Stokes shift (>100 nm), high sensitivity selectivity toward G4s (1600-fold fluorescence turn-on ratio) and robust two-photon fluorescence emission. Therefore, these features enable ThT-NA to reveal the endogenous RNA G4 distribution in living cells and differentiate the cell cycle by monitoring the changes of RNA G4 folding. Significantly, to the best of our knowledge, ThT-NA is the first benzothiazole-derived G4 probe that has been developed for imaging G4s in ex vivo cancer tissue samples by two-photon microscopy techniques.

Assessing the Impacts of COVID-19 on the Industrial Sectors and Economy of China.

Since December 2019, the COVID-19 epidemic has been spreading continuously in China and many countries in the world, causing widespread concern among the whole society. To cope with the epidemic disaster, most provinces and cities in China have adopted prevention and control measures such as home isolation, blocking transportation, and extending the Spring Festival holiday, which has caused a serious impact on China's output of various sectors, international trade, and labor employment, ultimately generating great losses to the Chinese economic system in 2020. But how big is the loss? How can we assess this for a country? At present, there are few analyses based on quantitative models to answer these important questions. In the following, we describe a quantitative-based approach of assessing the potential impact of the COVID-19 epidemic on the economic system and the sectors taking China as the base case. The proposed approach can provide timely data and quantitative tools to support the complex decision-making process that government agencies (and the private sector) need to manage to respond to this tragic epidemic and maintain stable economic development. Based on the available data, this article proposes a hypothetical scenario and then adopts the Computable General Equilibrium (CGE) model to calculate the comprehensive economic losses of the epidemic from the aspects of the direct shock on the output of seriously affected sectors, international trade, and labor force. The empirical results show that assuming a GDP growth rate of 4-8% in the absence of COVID-19, GDP growth in 2020 would be -8.77 to -12.77% after the COVID-19. Companies and activities associated with transportation and service sectors are among the most impacted, and companies and supply chains related to the manufacturing subsector lead the economic losses. Finally, according to the calculation results, the corresponding countermeasures and suggestions are put forward: disaster recovery for key sectors such as the labor force, transportation sector, and service sectors should be enhanced; disaster emergency rescue work in highly sensitive sectors should be carried out; in the long run, precise measures to strengthen the refined management of disaster risk with big data resources and means should be taken.

Dual-Product Synergistically Enhanced Colorimetric Assay for Sensitive Detection of Lipid Transferase Activity.

Lipid transferase-catalyzed protein lipidation plays critical roles in many physiological processes and it has been an increasingly attractive therapeutic target from cancer to neurodegeneration, while sensitive detection of lipid transferase activity in biological samples remains challenging. Here, we presented an AuNP-based colorimetric method with dual-product synergistically enhanced sensitivity for convenient detection of lipid transferase activity. Homo sapiens N-myristoyltransferase 1 (HsNMT1), a key lipid transferase, was selected as the model. Accordingly, positively charged substrate peptides (Pep) of HsNMT1 can induce the aggregation of AuNPs through disrupting their electrostatic repulsion, while the HsNMT1-catalyzed lipid modification generates aggregated lipidated peptides (C14-Pep) and negatively charged HS-CoA, which will eliminate the disruption and stabilize the AuNPs by the formation of Au-S bonds, respectively. Consequently, charge reversal of the biomolecules and the formation of Au-S bonds synergistically contribute to the stability of AuNPs in the presence of HsNMT1. Therefore, the HsNMT1 activity can be visually detected by the naked eye through the color change of the AuNPs originated from the change in their distance-dependent surface plasmon resonance absorptions. Here, the A520/A610 ratio can sensitively reflect the activity of HsNMT1 in the linear range of 2-75 nM with a low detection limit of 0.56 nM. Moreover, the method was successfully applied for probing the HsNMT1 activities in different cell lysates and inhibitor screening. Furthermore, given the replaceability of the substrate peptide, the proposed assay is promising for universal application to other lipid transferases and exhibits great potential in lipid transferase-targeted drug development.

Enzyme-activated anchoring of peptide probes onto plasma membranes for selectively lighting up target cells.

In a cellular microenvironment, numerous biomolecules are involved in various physiological and pathological processes. However, for the in-depth and comprehensive understanding of their roles at the molecular level, there is still a lack of detection techniques for the in situ tracking of these biomolecules in a local environment. Herein, we engineered a membrane insertion peptide (MIP) as an enzyme-activated membrane insertion peptide probe (eaMIP) that allowed the in situ tracking of the activity of target enzymes in living cells. In this strategy, the membrane insertion capacity of the MIP motif in each eaMIP was caged by appending a chemical moiety. In the presence of target enzymes, the caging moiety in each eaMIP was removed by enzymatic decaging, leading to the generation of active MIPs. The versatility of this design was demonstrated by lighting up different tumor cells with distinct fluorescence signal patterns, affording an alternative tool for clinical diagnostics, biochemical research and membrane engineering.

Expression of miR-93-5p in patients with esophageal carcinoma and its relationship with the curative effect and prognosis of radiotherapy.

This study aimed to investigate the expression of miR-93-5p in esophageal carcinoma-patients and its relationship with the curative effect and prognosis of radiotherapy. 102 patients with esophageal carcinoma treated in Yiwu Central Hospital from May 2013 to July 2015 were considered as the experimental group, and 89 healthy people for physical examination during the same period were selected as the control group. The expression of miR-93-5p in the serum of the two groups was compared. Based on the mean expression of miR-93-5p in serum, esophageal carcinoma patients were divided into high expression and low expression groups. Then the relationship between clinical-pathological characteristics and the expression of miR-93-5p was analyzed. The curative effect of radiotherapy in patients with esophageal carcinoma was evaluated, and the relationship between the expression of miR-93-5p, the curative effect of radiotherapy and the 3-year survival rate in patients with esophageal carcinoma was analyzed. The expression of miR-93-5p in the serum of the experimental group was significantly higher than that of the control group (P< 0.05); there was a significant correlation between the expression of miR-93-5p and pathological stage (P< 0.05). The expression of miR-93-5p in the effective radiotherapy group was significantly lower than that in the ineffective radiotherapy group (P< 0.05). ROC curve showed that the sensitivity and specificity of miR-93-5p in predicting radiotherapy response of esophageal carcinoma were 88.57 and 64.69% respectively, AUC was 0.864 (95%CI:0.791~0.936), P< 0.001; the 3-year survival rate of low expression group was significantly higher than that of high expression group (P< 0.05). In Conclusion, the expression of miR-93-5p was high in esophageal carcinoma patients, and the higher the expression, the worse the curative effect of radiotherapy and the worse the prognosis, which may be a new predictor of radiotherapy effect and prognosis in patients with esophageal carcinoma.

A new economic loss assessment system for urban severe rainfall and flooding disasters based on big data fusion.

BACKGROUND: and Purpose: Increasingly frequent meteorological disasters have brought severe challenges that should be urgently handled in the sustainable development. However, meteorological data, loss data, social economic data and so forth relating to meteorological disasters rarely be effectively fused, failing to generate, rapidly and efficiently, economic losses and thus hindering the emergency management of disasters. METHODS: A new economic losses evaluation information system has been developed for monitoring severe rainfall and flooding disasters in cities. The data mining method, econometric regression model and input-output model are implemented in the system, on the basis of multi-source data including hourly rainfall, geographical conditions, historical and real-time disaster information, socioeconomic data, and defense countermeasure. RESULTS: Combined with the weather forecast information, this system can has the capability for reporting the real-time direct and indirect economic losses incurred by urban heavy rainfall and flooding disasters, automatically generating defense countermeasure reports for typical rainstorm and flooding points, and providing the spatial distribution of disasters. CONCLUSIONS: Finally, the system is conducive to improving the ability to manage disaster emergencies and eventually reducing the economic losses from the disaster.

Retrovirus-Mediated Transfection of the Tissue-type Plasminogen Activator Gene Results in Increased Thrombolysis of Blood Clots.

Tissue-type plasminogen activator (tPA) is involved in the lysis of blood clots. In this study, we attempted to target thrombolysis and enhance blood clot lysis by generating a construct (pLEGFP-N1-tPA) to integrate tPA gene into the genome of different cell lines. pLEGFP-N1-tPA construct was generated and used to target the tPA gene in different cell lines. The thrombolytic effects mediated by the supernatant from transfected HeLa cells and Linx cells were assessed using plasma thrombus plates. Furthermore, enhanced green fluorescent protein (EGFP), which was fused to the tPA gene in the pLEGFP-N1-tPA construct, was analyzed under the fluorescent microscope to assess tPA localization. We also monitored tPA activity and expression in the transfected cell lines. As part of the study, we successfully generated the pLEGFP-N1-tPA construct. The sequence of this construct was verified and the construct was subsequently used to generate the PT67/pLEGFP-N1-tPA cell line. The pLEGFP-N1-tPA construct was also used to transfect HeLa cells and Linx cells. We observed that supernatants from transfected cells were capable of lysing thrombi. In addition, tPA activity and tPA concentration were elevated in the latter supernatants and tPA was rapidly and stably expressed in the transfected cell lines. These results reveal a potentially important thrombolytic role for tPA-targeted gene therapy following cardiac valve replacement.

The Evaluation of Colorectal Cancer Risk in Serum by anti-DESMIN-conjugated CdTe/CdS Quantum Dots.

BACKGROUND: DESMIN is a novel prognostic predictor and therapeutic target for colorectal cancer (CRC). Enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence (ELC) assays are large-scale and highcost projects; therefore, it is necessary to develop a new, fast, and simple yet highly sensitive and specific method to detect DESMIN in serum. Semiconducting quantum dots (QDs) possess high fluorescence quantum yield, stability against photobleaching, and size-controlled luminescence properties, thus being utilized in photoelectrochemical tumor marker detection, especially in ameliorating the diagnostic value in complex biological ambient ionization. However, CdTe/CdS quantum dots (QDs) have not been applied in detecting DESMIN in serum. METHODS: DESMIN in serum has been established using anti-DESMIN-conjugated CdTe/CdS quantum dots (QDs) and measurements. The assay sensitivity was determined by measurement of quenched fluorescence intensity of DESMIN at 0.1, 0.5, 1.0, 2.0, or 5.0 ng/mL in PBS or 0.25%, 0.5%, 1.0%, 2.0%, or 5% human serum diluted in PBS. The assay was optimized under different pH (7.00 - 7.40) for different reaction durations (10 - 60 minutes). The specificity of anti-DESMIN-QDs was determined by testing the interference of DESMIN activity with CEA, IgG, or AFP, each at 1 ng/mL. RESULTS: Under the optimized incubation time (30 minutes) at room temperature and optimal pH 7.1 - 7.2, a correlation between the decreased fluorescence intensity of anti-DESMIN-conjugated CdTe/CdS QDs and the concentration of DESMIN in the range from 0.05 to 100 ng/mL, was established. The sensitivity for the detection of DESMIN in the range from 0.05 to 100 ng/mL, with a detection limit of 0.02 ng/mL. The assay presented a high specificity because the anti-DESMIN-conjugated CdTe/CdS QDs only reacted with ABR1B10 in the sera in the presence of CEA, IgG or AFP. CONCLUSIONS: The immunofluorescence assay to detect DESMIN in serum using anti-DEMSIN-conjugated CdTe/ CdS QDs was fast and simple yet presented high sensitivity and specificity. Our method provides a promising tool for early prediction of CRC risk.

Factors associated with hand joint destruction in Chinese patients with rheumatoid arthritis.

BACKGROUND: There have been no previous report of hand joint destruction prevalence in Chinese rheumatoid arthritis (RA) patients. Therefore, the aim of this study was to investigate the prevalence and potential factors of hand joint destruction among RA patients from Nantong China. In addition, we wanted to examine the differences between functional capacity, psychological status, and quality of life in patients with hand joint destruction compared to those without hand joint destruction. METHODS: A cross-sectional study was conducted from the Affiliated Hospital of Nantong University between July 2015 and June 2016. RA patients completed questionnaires for demographic or clinical variables, the 10-cm Visual Analog Scale for pain, the 28-joint Disease Activity Score-erythrocyte sedimentation rate for disease activity, the Health Assessment Questionnaire-disability index for physical function, the Hospital Anxiety and Depression Scale for anxiety and depression, and the Short Form 36 health survey for quality of life. Laboratory examinations were taken to obtain some biochemical indicators (e.g., rheumatoid factor, anti-cyclic citrullinated peptide antibody). X-ray assessment of hand was performed and hand joint destruction was defined as Sharp score > 0. Independent sample t-test, Mann-Whitney U-test, Chi-square test, and multivariate analysis using backward stepwise logistic regression model were used to analyze these data. RESULTS: One hundred and sixty-one RA patients were included in this study. Radiographic findings revealed that almost 47.2% (n = 76) of patients had hand joint destruction. Multivariate analysis found that education ≤ 9 years (p = 0.041), anti-cyclic citrullinated peptide antibody positive (p = 0.021), high disease activity (p = 0.020), and long disease duration (p < 0.001) were important potential risk factors of hand joint destruction. Participants with hand joint destruction tended to have lower physical function and quality of life, and more severe depressive symptoms compared to individuals without hand joint destruction. CONCLUSIONS: 47.2% of people with RA from Nantong China experienced hand joint destruction. Education, anti-cyclic citrullinated peptide antibody, disease activity, and disease duration had great impacts on hand joint destruction. The results suggested that rheumatologists should pay attention to RA patients' hand joint destruction, especially those with low education levels, anti-cyclic citrullinated peptide antibody positive, high disease activity, and long disease duration by patient education or other ways to improve patients' prognosis.

Significance of the ADC ratio in the differential diagnosis of breast lesions.

BACKGROUND: Magnetic resonance imaging (MRI) has high sensitivity but low specificity for breast cancer, and consequently, new techniques to improve the specificity of breast MRI in diagnosing breast cancer are under development. PURPOSE: To assess the ability of the apparent diffusion coefficient (ADC) compared with the ADC ratio (ADCr) to differentially diagnose benign compared with malignant breast lesions. MATERIAL AND METHODS: Forty-eight women with breast lesions (average age, 45 years) underwent MRI scanning including T1-weighted dynamic contrast-enhanced (DCE) scanning and diffusion-weighted imaging (DWI). The average ADC and ADCr values for both lesions and pectoralis major muscles (ADCrmuscle and ADCrmuscle) were measured in patients with malignant (n = 25) and benign (n = 23) breast lesions. The ADCr of the contralateral breast (ADCr contralateral) was also evaluated. All histology was confirmed by pathological analysis of biopsied tissue. ADC and ADCr values were analyzed using receiver-operating characteristic (ROC) curves. RESULTS: For benign lesions compared with malignant lesions, lesion-side ADC was 1.45 vs. 1.05, respectively (P < 0.001), normal-side ADC was 1.82 vs.1.64 (P = 0.002), ADCrmuscle was 1.35 vs. 0.9 (P < 0.001), and ADCrcontralateral was 0.79 vs. 0.64 (P = 0.001). ADCrmuscle showed higher sensitivity (82.61%) and specificity (96.00%) than ADCrcontralateral (60.87% and 92.00%, respectively) and ADC (69.57% and 96.00%) for discriminating malignant from benign lesions. The AUC using ADCrmuscle had higher discriminatory power (0.92, P < 0.001) for malignant versus benign breast lesions compared with either ADC (0.82, P < 0.001) or ADCrcontralateral (0.78, P = 0.001). CONCLUSION: The ADCrmuscle value showed higher sensitivity and specificity and improved diagnostic accuracy compared with either ADC or ADCrcontralateral in differentiating benign from malignant breast lesions.

A comprehensive estimation of the economic effects of meteorological services based on the input-output method.

Concentrating on consuming coefficient, partition coefficient, and Leontief inverse matrix, relevant concepts and algorithms are developed for estimating the impact of meteorological services including the associated (indirect, complete) economic effect. Subsequently, quantitative estimations are particularly obtained for the meteorological services in Jiangxi province by utilizing the input-output method. It is found that the economic effects are noticeably rescued by the preventive strategies developed from both the meteorological information and internal relevance (interdependency) in the industrial economic system. Another finding is that the ratio range of input in the complete economic effect on meteorological services is about 1 : 108.27-1 : 183.06, remarkably different from a previous estimation based on the Delphi method (1 : 30-1 : 51). Particularly, economic effects of meteorological services are higher for nontraditional users of manufacturing, wholesale and retail trades, services sector, tourism and culture, and art and lower for traditional users of agriculture, forestry, livestock, fishery, and construction industries.

The value of the combined MR imaging features and clinical factors Nomogram model in predicting intractable postpartum hemorrhage due to placenta accreta.

To explore the value of the combined MR imaging features and clinical factors Nomogram model in predicting intractable postpartum hemorrhage (IPH) due to placenta accreta (PA). We conducted a retrospective study with 270 cases of PA patients admitted to our hospital from January 2015 to December 2022. The clinical data of these patients were analyzed, and they were divided into 2 groups: the IPH group and the non-IPH group based on the presence of IPH. The differences in data between the 2 groups were compared, and the risk factors for IPH were analyzed. A Nomogram model was constructed using independent high-risk factors, and the predictive value of this model for IPH was analyzed. The results of multivariable binary Logistic regression analysis showed higher number of cesareans, placenta previa, placenta accreta type (implantation, penetration), low signal strip on T2 weighted image (T2WI) were independent high-risk factor for IPH (P < .05). ROC analysis and Hosmer-Lemeshow goodness-of-fit test showed the Nomogram predictive model constructed with the high-risk factor has good discrimination and calibration. Decision curve analysis (DCA) showed that when the probability threshold for the Nomogram model's prediction was in the range from 0.125 to 0.99, IPH patients could obtain more net benefits, making it suitable for clinical application. The higher number of cesareans, placenta previa, placental accreta type (implantation, penetration), and low signal strip on T2WI are independent high-risk factor for IPH. The Nomogram predictive model constructed with the high-risk factor demonstrates good clinical efficacy in predicting the occurrence of IPH due to PA.

The impact of Japanese nuclear wastewater discharge into the sea on the global economy: Input-output model approach.

As the division of work within the world economic system becomes increasingly complex, the impact of disturbing events on the economic system is expanding. Recently, Japan proposed to discharge nuclear wastewater into the Pacific Ocean, which will cause damage to marine fisheries, thereby seriously affecting fisheries and other industries in Japan and other countries and regions around the world. Considering different scenarios of final and intermediate demand shifting, this paper uses the Inoperability Input-Output Model (IIM) and Multi-Region Input-Output Model (MRIO) to simulate the economic consequences of nuclear wastewater discharge in Japan and calculate the economic changes of each industry and country (region). The results show that: In the short term, when only the final demand for Japanese fishery products decreases. (1) The ten countries (regions) with significant economic losses are Japan, the United States, Chinese Taipei, Canada, Chile, South Africa, Mexico, Peru, the United Kingdom, and Ireland. (2) The ten countries (regions) with a significant increase in total output due to demand shift are China (People's Republic of), the Rest of the World, India, Indonesia, Viet Nam, the Philippines, Brazil, Myanmar, the Russian Federation, and Malaysia. (3) A ranking of changes in the total output of different industries. In the long term, when both intermediate and final demand for Japanese fishery products decrease. (4) The change in value added in Japan. (5) The change in value added of 67 countries (regions) worldwide. The ten countries (regions) with the most significant increase in value-added are the Russian Federation, China (People's Republic of), the Rest of the World, the United States, Indonesia, Australia, Norway, Korea, Viet Nam, and Myanmar. The ten countries (regions) with the most significant decrease in value-added are Japan, Chinese Taipei, Chile, South Africa, Peru, Thailand, Mexico, Cambodia, Costa Rica, and Morocco. Changes in value added of 45 industrial sectors worldwide.

A spatiotemporal XGBoost model for PM2.5 concentration prediction and its application in Shanghai.

This paper innovatively constructed an analytical and forecasting framework to predict PM2.5 concentration levels for 16 municipal districts in Shanghai. By means of XGBoost parameters adjustment, empirical mode decomposition, and model fusion, improvements are made on XGBoost prediction accuracy and stability so that prediction deviation at extreme points can be avoided. The main findings of this paper can be summarized as follows: 1) Compared with the original model, the goodness of fit of the modified XGBoost model on the test set increased by 17 %, and the root mean square error decreased by 28 %; 2) The variation of PM2.5 concentration in Shanghai has a significant seasonal (cyclical) effect, and its fluctuation period is 3 months (a quarter). In winter, the frequency of extreme value points is significantly higher than that in other seasons; 3) In terms of spatial distribution, the PM2.5 concentration in the central city of Shanghai is higher than that in the rural areas, and the PM2.5 concentration gradually decreases from center city to the surrounding areas. The innovation and contribution of this paper can be summarized as follows: 1) EEMD algorithm verified by SSA was used to decompose the original model without reconstructing all subsequences and get the best weighing among each part of the hybrid model by using variable weight assignment; 2) The city was cut into pieces according to administrative districts in avoid of the duplicate analysis when utilizing advised Kriging interpolation; 3) IDW method was applied to verified Kriging interpolation to increase the accuracy; 4) The latitude and longitude were innovatively converted into the arc length of the corresponding spherical surface; 5) Hierarchical analysis method was used to obtain the order of importance among the PM2.5 monitoring stations, which could improve the accuracy and achieve dimension reduction.

Visual analysis of global air pollution impact research: a bibliometric review (1996-2022).

The impact of air pollution is one of the hotspots attracting continuous scholarly attention, but the comprehensive statistical and visual analysis reviews are few. Employing the method of bibliometric analysis, this paper took the relevant literature from 1996 to April 2022 on the Web of Science as the research object. Through the methods of keyword co-occurrence analysis and burst analysis, the spatiotemporal evolution trend, cooperation network, outstanding scholars, knowledge base, and research focus of air pollution impact research are visually presented. Via constructing a common word matrix of high-frequency words, clustering analysis is used to aggregate high-frequency keywords into 24 clusters. By the strategic coordinate analysis method, the relationships within and between clusters were revealed. The main findings include (1) research on the impact of air pollution mainly focusing on human health; (2) the six keywords with the highest centrality are California, hydrocarbons, dioxide, generation, Asia, and diesel; (3) these 11 clusters may be developed into future research hotspots: particulate matter, nitrogen oxides, mortality, ozone, pollution, air quality, asthma, children, epidemiology, aerosols, and polycyclic aromatic hydrocarbons; and (4) seven topics are research hot: daily mortality, long-term exposure, coronary heart disease, concentration, North China plain, traffic-related air pollution, and air pollution.

The green halo effect of China's OFDI: evidence from countries along the Belt and Road.

The growth of China's OFDI (outward foreign direct investment) is a unique feature of the "Belt and Road" project. Does China's OFDI have a green halo effect on countries along the Belt and Road (B&R)? Is this green halo effect somehow asymmetrical? What is the underlying mechanism? This paper systematically examines how China's OFDI exerts its influence on green technology spillovers, based on 56 B&R countries' 2003-2019 panel data. This study makes three significant findings: Firstly, China's OFDI has positive asymmetric characteristics in promoting green technology spillovers to host countries mentioned, which have lower income levels and openness. Secondly, strict relative environmental regulation can act as a "pressure pool," significantly enhancing the "green halo effect"; Thirdly, China's OFDI can help host countries obtain more green technology spillovers through three channels: expanding host countries' economic scale, upgrading host countries' industrial structure, and suppressing host countries' use of non-renewable energy. These findings point the way for 56 host countries to better accessing green technology spillovers.

Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models.

BACKGROUND: Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models. METHODS: PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC) tissues into immunodeficient (SCID/nude) mice. HER-2 gene copy number (GCN) and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group). Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient's ESCC tissues. Similarity between the PDECX models and their corresponding patient's ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation. RESULTS: None of the PDECX models (or their corresponding patient's ESCC tissues) harbored HER-2 gene amplification. IHC staining showed HER-2 positivity (IHC 2+) in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+). A second HER-2 positive (IHC 2+) model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model. CONCLUSIONS: This study demonstrates Trastuzumab-induced tumor regressions in HER-2 positive tumors, and highlights PIK3CA mutation as a potential resistance mechanism to Trastuzumab treatment in pre-clinical patient-derived EC xenograft models.

Effect of music-based movement therapy on the freezing of gait in patients with Parkinson's disease: A randomized controlled trial.

Background: Progression of freezing of gait (FOG), a common pathological gait in Parkinson's disease (PD), has been shown to be an important risk factor for falls, loss of independent living ability, and reduced quality of life. However, previous evidence indicated poor efficacy of medicine and surgery in treating FOG in patients with PD. Music-based movement therapy (MMT), which entails listening to music while exercising, has been proposed as a treatment to improve patients' motor function, emotions, and physiological activity. In recent years, MMT has been widely used to treat movement disorders in neurological diseases with promising results. Results from our earlier pilot study revealed that MMT could relieve FOG and improve the quality of life for patients with PD. Objective: To explore the effect of MMT on FOG in patients with PD. Materials and methods: This was a prospective, evaluator-blinded, randomized controlled study. A total of 81 participants were randomly divided into music-based movement therapy group (MMT, n = 27), exercise therapy group (ET, n = 27), and control group (n = 27). Participants in the MMT group were treated with MMT five times (1 h at a time) every week for 4 weeks. Subjects in the ET group were intervened in the same way as the MMT group, but without music. Routine rehabilitation treatment was performed on participants in all groups. The primary outcome was the change of FOG in patients with PD. Secondary evaluation indicators included FOG-Questionnaire (FOG-Q) and the comprehensive motor function. Results: After 4 weeks of intervention, the double support time, the cadence, the max flexion of knee in stance, the max hip extension, the flexion moment of knee in stance, the comprehensive motor function (UPDRS Part III gait-related items total score, arising from chair, freezing of gait, postural stability, posture, MDS-UPDRS Part II gait-related items total score, getting out of bed/a car/deep chair, walking and balance, freezing), and the FOG-Q in the MMT group were lower than that in the control group and ET group (p < 0.05). The gait velocity, the max ankle dorsiflexion in stance, ankle range of motion (ROM) during push-off, ankle ROM over gait cycle, the knee ROM over gait cycle, and the max extensor moment in stance (ankle, knee) in the MMT group were higher than that in the control group and ET group (p < 0.05). However, no significant difference was reported between the control group and ET group (p > 0.05). The stride length and hip ROM over gait cycle in the MMT group were higher than that in the control group (p < 0.05), and the max knee extension in stance in the MMT group was lower than that in the control group (p < 0.05). Nevertheless, there was no significant difference between the ET group and MMT group (p > 0.05) or control group (p > 0.05). Conclusion: MMT improved gait disorders in PD patients with FOG, thereby improving their comprehensive motor function.

Spatiotemporal impact of major events on air quality based on spatial differences-in-differences model: big data analysis from China.

In an attempt to investigate the impact of major events on urban air quality in terms of the extent, duration and spatial scope, data on the daily air quality index and the concentrations of individual pollutants are collected in 140 cities of China from January 2, 2015, to November 28, 2017. Based on a spatial differences-in-differences, the impact of major events, such as political conferences, sporting events at the national level, on urban air quality in the dimensions of time and space are explored. It is concluded that major events not only affected the air quality of the host city, but also exercised influence on the air quality of the surrounding areas. Recommendations for mitigating the impact of major events on urban air quality have been proposed, such as establish regional atmospheric environment management system and formulate regional unified standards for pollutant discharge, industrial access and law enforcement.