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Primula meishanensis K.Huang & Z.X.Fu, sp. nov., a new species of Primulaceae from Meishan City, Sichuan Province, China, is described and illustrated. The morphological data and phylogenetic analysis, based on the complete chloroplast genome, suggest that Primula meishanensis is a separate species closely related to Primula dejuniana. The complete chloroplast genome of Primula meishanensis was 152,175 bp and the complete chloroplast genome of Primula dejuniana was 151,988 bp. The new species differs from the latter by the solitary scape, the length of petiole, acute leaf blade apex and pin flower. The distribution map, morphological comparison of related species and conservation status of the new species are also provided.

Abstract To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery (P = 0.031) and age (P

Abstract Structural variants (SVs) significantly contribute to human genome diversity and play a crucial role in precision medicine. Although advancements in single-molecule long-read sequencing offer a groundbreaking resource for SV detection, identifying SV breakpoints and sequences accurately and robustly remains challenging. We introduce VolcanoSV, an innovative hybrid SV detection pipeline that utilizes both a reference genome and local de novo assembly to generate a phased diploid assembly. VolcanoSV uses phased SNPs and unique k-mer similarity analysis, enabling precise haplotype-resolved SV discovery. VolcanoSV is adept at constructing comprehensive genetic maps encompassing SNPs, small indels, and all types of SVs, making it well-suited for human genomics studies. Our extensive experiments demonstrate that VolcanoSV surpasses state-of-the-art assembly-based tools in the detection of insertion and deletion SVs, exhibiting superior recall, precision, F1 scores, and genotype accuracy across a diverse range of datasets, including low-coverage (10x) datasets. VolcanoSV outperforms assembly-based tools in the identification of complex SVs, including translocations, duplications, and inversions, in both simulated and real cancer data. Moreover, VolcanoSV is robust to various evaluation parameters and accurately identifies breakpoints and SV sequences.

Abstract Background Spatial transcriptomics (ST) is advancing our understanding of complex tissues and organisms. However, building a robust clustering algorithm to define spatially coherent regions in a single tissue slice and aligning or integrating multiple tissue slices originating from diverse sources for essential downstream analyses remains challenging. Numerous clustering, alignment, and integration methods have been specifically designed for ST data by leveraging its spatial information. The absence of comprehensive benchmark studies complicates the selection of methods and future method development. Results In this study, we systematically benchmark a variety of state-of-the-art algorithms with a wide range of real and simulated datasets of varying sizes, technologies, species, and complexity. We analyze the strengths and weaknesses of each method using diverse quantitative and qualitative metrics and analyses, including eight metrics for spatial clustering accuracy and contiguity, uniform manifold approximation and projection visualization, layer-wise and spot-to-spot alignment accuracy, and 3D reconstruction, which are designed to assess method performance as well as data quality. The code used for evaluation is available on our GitHub. Additionally, we provide online notebook tutorials and documentation to facilitate the reproduction of all benchmarking results and to support the study of new methods and new datasets. Conclusions Our analyses lead to comprehensive recommendations that cover multiple aspects, helping users to select optimal tools for their specific needs and guide future method development.

Abstract Background We investigated the presence of Chlamydia psittaci in poultry and the environment in live poultry wholesale markets in Changsha during 2021–2022 and conducted a phylogenetic analysis to understand its distribution in this market. Methods In total, 483 samples were analyzed using real-time polymerase chain reaction and 17 C. psittaci-positive samples using high-throughput sequencing, BLAST similarity, and phylogenetic analysis. Results Twenty-two out of 483 poultry and environmental samples were positive for C. psittaci (overall positivity rate: 4.55%) with no difference in positivity rates over 12 months. Chlamydia psittaci was detected at 11 sampling points (overall positivity rate: 27.5%), including chicken, duck, and pigeon/chicken/duck/goose shops, with pigeon shops having the highest positivity rate (46.67%). The highest positivity rates were found in sewage (12.5%), poultry fecal (7.43%), cage swab (6.59%), avian pharyngeal/cloacal swab (3.33%), and air (2.29%) samples. The ompA sequences were identified in two strains of C. psittaci, which were determined to bear genotype B using phylogenetic analysis. Thus, during monitoring, C. psittaci genotype B was detected in the poultry and environmental samples from the poultry wholesale market in Changsha. Conclusions To address the potential zoonotic threat, C. psittaci monitoring programs in live poultry markets should be enhanced.

Abstract To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: “urinal collecting apparatus dominated pattern” (40.3%), “bladder compression dominated pattern” (30.7%), “intermittent catheterization dominated pattern” (19.3%) and “urethral indwelling catheterization dominated pattern” (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.

BackgroundGiven the complexity and diversity of lichenoid vulvar disease (LVD) risk factors, it is crucial to actively explore these factors and construct personalized warning models using relevant clinical variables to assess disease risk in patients. Yet, to date, there has been insufficient research, both nationwide and internationally, on risk factors and warning models for LVD. In light of these gaps, this study represents the first systematic exploration of the risk factors associated with LVD. ObjectiveThe risk factors of LVD in women were explored and a medically evidence-based warning model was constructed to provide an early alert tool for the high-risk target population. The model can be applied in the clinic to identify high-risk patients and evaluate its accuracy and practicality in predicting LVD in women. Simultaneously, it can also enhance the diagnostic and treatment proficiency of medical personnel in primary community health service centers, which is of great significance in reducing overall health care spending and disease burden. MethodsA total of 2990 patients who attended West China Second Hospital of Sichuan University from January 2013 to December 2017 were selected as the study candidates and were divided into 1218 cases in the normal vulvovagina group (group 0) and 1772 cases in the lichenoid vulvar disease group (group 1) according to the results of the case examination. We investigated and collected routine examination data from patients for intergroup comparisons, included factors with significant differences in multifactorial analysis, and constructed logistic regression, random forests, gradient boosting machine (GBM), adaboost, eXtreme Gradient Boosting, and Categorical Boosting analysis models. The predictive efficacy of these six models was evaluated using receiver operating characteristic curve and area under the curve. ResultsUnivariate analysis revealed that vaginitis, urinary incontinence, humidity of the long-term residential environment, spicy dietary habits, regular intake of coffee or caffeinated beverages, daily sleep duration, diabetes mellitus, smoking history, presence of autoimmune diseases, menopausal status, and hypertension were all significant risk factors affecting female LVD. Furthermore, the area under the receiver operating characteristic curve, accuracy, sensitivity, and F1-score of the GBM warning model were notably higher than the other 5 predictive analysis models. The GBM analysis model indicated that menopausal status had the strongest impact on female LVD, showing a positive correlation, followed by the presence of autoimmune diseases, which also displayed a positive dependency. ConclusionsIn accordance with evidence-based medicine, the construction of a predictive warning model for female LVD can be used to identify high-risk populations at an early stage, aiding in the formulation of effective preventive measures, which is of paramount importance for reducing the incidence of LVD in women.

Abstract Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C 2 - or C 1 -symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies.

Abstract Background Currently, different guidelines recommend using different methods to determine whether deduplication is necessary when determining the detection rates of multidrug-resistant organisms (MDROs). However, few studies have investigated the effect of deduplication on MDRO monitoring data. In this study, we aimed to investigate the influence of deduplication on the detection rates of MDROs in different specimens to assess its impact on infection surveillance outcomes. Methods Samples were collected from hospitalized patients admitted between January 2022 and December 2022; four types of specimens were collected from key monitored MDROs, including sputum samples, urine samples, blood samples, and bronchoalveolar lavage fluid (BALF) samples. In this study, we compared and analysed the detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Escherichia coli (CRECO), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA) under two conditions: with and without deduplication. Results When all specimens were included, the detection rates of CRKP, CRAB, CRPA, and MRSA without deduplication (33.52%, 77.24%, 44.56%, and 56.58%, respectively) were significantly greater than those with deduplication (24.78%, 66.25%, 36.24%, and 50.83%, respectively) (all P

Abstract Long-read sequencing offers long contiguous DNA fragments, facilitating diploid genome assembly and structural variant (SV) detection. Efficient and robust algorithms for SV identification are crucial with increasing data availability. Alignment-based methods, favored for their computational efficiency and lower coverage requirements, are prominent. Alternative approaches, relying solely on available reads for de novo genome assembly and employing assembly-based tools for SV detection via comparison to a reference genome, demand significantly more computational resources. However, the lack of comprehensive benchmarking constrains our comprehension and hampers further algorithm development. Here we systematically compare 14 read alignment-based SV calling methods (including 4 deep learning-based methods and 1 hybrid method), and 4 assembly-based SV calling methods, alongside 4 upstream aligners and 7 assemblers. Assembly-based tools excel in detecting large SVs, especially insertions, and exhibit robustness to evaluation parameter changes and coverage fluctuations. Conversely, alignment-based tools demonstrate superior genotyping accuracy at low sequencing coverage (5-10×) and excel in detecting complex SVs, like translocations, inversions, and duplications. Our evaluation provides performance insights, highlighting the absence of a universally superior tool. We furnish guidelines across 31 criteria combinations, aiding users in selecting the most suitable tools for diverse scenarios and offering directions for further method development.

Background Currently, the global ageing population is becoming increasingly severe, and the incidence of pelvic organ prolapse (POP) is rising year by year, which seriously impacts the psychosomatic health and the quality of life in female patients. Surgical treatments for POP still face enormous challenges.Methods The aim of this review is to discuss the laparoscopic lateral suspension (LLS) approach to the management of POP. We use MeSH terms for each topic to retrieve relevant literature from the PubMed and Embase databases. Our group reviewed, synthesised and summarised included studies.Results LLS has been widely applied in the treatment of middle pelvic compartment defects. In comparison to sacrocolpopexy (SC), the most significant advantage of LLS is that it avoids dissecting the complex sacral region and possesses simple surgical procedures. But its cure, recurrence, reoperation and complication rates have been widely discussed. Issues regarding its value and its potential equivalence in surgical therapeutic effects compared with SC have gained continuous attention.Conclusions Based on the existing research, LLS demonstrates advantages in the treatment of POP, particularly in cases of middle pelvic compartment defects. However, solely based on current clinical studies, it is premature to establish superiority or inferiority compared with SC. LLS is not yet a substitute for SC.

Abstract We conducted a cross-sectional study using an online questionnaire to investigate the current status of urinary tract infections (UTIs) and the use of clean intermittent catheterization (CIC) in Chinese community-based SCI patients and to explore the risk factors for UTIs in patients using CIC. Our findings suggest that the prevalence of UTIS is higher in Chinese community-based SCI patients compared with patients in medically developed countries. In addition, we found that CIC had the lower incidence of UTIs than urinary indwelling catheter (UIC) and suprapubic catheter (SPC), and that SCI patients with CIC had low rates of use and poor compliance. Further analysis indicated that most of the risk factors for UTIs in CIC patients were associated with irregular use of CIC. Therefore, we call for not only the need to provide stronger caregiver support and financial assistance to improve CIC adherence in Chinese community SCI patients, but also the establishment of a database of Chinese SCI patients in order to enhance the management of bladder emptying methods and further standardize the CIC operation in such patients, thus reducing the risk of UTIs in Chinese community SCI patients.

Discarded eggshells and wet soybean dregs are rich sources of calcium and nitrogen. This study aimed to establish a novel optimized method for the utilization of agricultural wastes. Eggshells and soybean dregs were the primary raw materials used in this study. Bacillus subtilis, Lactobacillus plantarum, and Enterococcus faecalis were the probiotic strains selected for mixed fermentation. Harman’s single-factor test based on the assessment of calcium lactate content in the fermented forage was used to screen the following process parameters: Ratio of soybean dregs to eggshells, solid to water ratio, addition of glucose, inoculation amount, ratio of probiotic strains, fermentation temperature and duration. Optimum fermentation conditions were determined using response surface methodology. The results revealed that the conditions required for optimum fermentation were as follows: Soybean dregs to eggshells ratio of 90:10, solid to water ratio of 1:2.5, addition of 15.6% glucose, inoculation amount of 14.7%, Bacillus subtilis, Lactobacillus plantarum and Enterococcus faecalis in the ratio of 1:1:1 (v/v), and fermentation duration of 6 days at 37 °C. The amount of calcium lactate in the fermented forage was 13.58%. Free amino acid and calcium lactate concentrations in the fermented forage were significantly higher (P

The shaft-type tubular pumping station has the remarkable characteristics of a large flow rate and high efficiency. It can realize the functions of irrigation, pumping, and drainage through pumping and generating conditions considering tides. Moreover, it is widely used in the plain area of eastern China and the tidal area along the marine region. Due to the different topological features of the airfoil of the impeller, the energy evolution characteristics of the shaft-type tubular pumping station during pumping and generating conditions remain unclear. The entropy generation theory was introduced to numerically simulate the flow pattern and energy characteristics in the shaft-type channel, impeller, and straight channel in operation conditions. The results show that the flow pattern is stable when the shaft-type channel and the straight-type channel are used as the inlet channel under pumping and generating conditions, and a low-pressure region occurs in the contraction section of the shaft-type channel. The velocity of sections of the inlet and outlet and the middle section of the impeller in the generating condition is larger than that in the pumping condition. In addition, the difference in the static pressure on the blade surface nearby the hub is large. With a change in the position of the wingspan, the difference gradually decreases from the small flow condition to the large flow condition. There is a high-entropy production rate zone in the channel contraction section and the shaft-type wall surface of the shaft-type flow channel. When the straight-type channel is used as the outlet flow channel, a high-entropy production region appears near the inlet water surface. In the pumping condition, a high-entropy production area is found at the inlet of the impeller, the blade groove channel, and the inlet of the guide vane. In the generating condition, a high-entropy production area is found at the out-of-impeller outlet, the blade groove channel, and the outlet of the guide vane. These research achievements have some reference value for the design of the shaft-type tubular pumping station considering tides and the study of hydraulic performance, along with the energy characteristics of the channels.

Background: Fractional CO2 laser (FCL) has been gradually used in the management of genitourinary syndrome of menopause (GSM) in recent years, but the results remain uncertain. We aimed to estimate the efficacy and safety of FCL as a novel treatment for controlling the GSM, especially sexual dysfunction, compared with intravaginal estrogen. Methods: The following digital databases were searched, including PubMed, Web of Science, Cochrane Library, and Embase. All the studies were limited to randomized controlled trials (RCTs). Included literatures must be in English, without limitation about region and race. The pooled dates were analyzed by Review Manger version 5.4 (Cochrane Collaboration’s Information Management System, London, UK). Results: 3 RCTs were included, which involved 160 patients, 79 of whom received FCL treatment, 81 received intravaginal estrogen treatments. This meta-analysis results showed no statistical significance existed in improving the patient’s vaginal health index (VHI) (mean difference (MD) = 0.59; 95% confidence interval (95% CI): –1.07~2.25; p = 0.49) after FCL treatment. In terms of the female sexual function index (FSFI) total scores, we observed no improvement without statistical significance (MD = –0.13; 95% CI: –3.32~3.06; p = 0.94). Furthermore, all the FSFI domains showed no statistical significance. No serious complications were reported in all included trials. Conclusions: FCL therapy was an interesting and novel treatment for menopausal female sexual dysfunction. However, no statistical evidence existed, which recommended that FCL was superior to intravaginal estrogen. Our results will be confirmed by high-quality and multicentric RCTs in the future.

To study the internal flow characteristics and energy characteristics of a large bulb perfusion pump. Based on the CFX software of the ANSYS platform, the steady calculation of the three-dimensional model of the pump device is carried out. The numerical simulation results obtained by SST k-ω and RNG k-ε turbulence models are compared with the experimental results. Finally, SST k-ω is selected for subsequent calculation. With the help of the flow line diagram and turbulent kinetic energy table of the whole flow channel of the pump device, the flow components of the pump device under different working conditions are analyzed, and the pressure and velocity distribution at the impeller and guide vane are analyzed by pressure cloud diagram and velocity cloud diagram. It is found that there are three high-pressure areas in the impeller and guide vane section, and the high-pressure regions are mainly distributed in the middle of the impeller channel. As the head decreases, the pressure at the impeller and guide vane positions decreases gradually, and the flow rate increases. Based on the entropy production principle, the wall entropy production and the distribution of mainstream entropy production at the impeller and guide vane parts are analyzed.

To investigate the optimal process conditions for the production of water-soluble polysaccharides from Polygonatum odoratum by aprobiotics and compare the change of antioxidant activities of polysaccharides fermented and unfermented. In this study, Bacillus subtilis LY-05 was used as fermentation strain, and increasing rate of water-soluble polysaccharides was index. Seven factors including Polygonatum odoratum addition, nitrogen source, inorganic salt, inoculation amount, temperature, stirring speed and fermentation time were studied with the increasing rate of water-soluble polysaccharides. On the basis of single-factor experiment, the fermentation conditions were optimized with response surface method; and evaluating the changes of the DPPH·scavenging rate, ABTS+·scavenging rate, OH· scavenging rate and total reducing power in the antioxidant activity of Polygonatum odoratum polysaccharides fermented and unfermented. The results showed that optimal fermentation condition was as follows: Polygonatum odoratum addition 4%, yeast extract powder 3%, NaCl 1%, inoculation amount 3%, fermention temperature 35 ℃, stirrig speed 160 r/min, fermentation time 48 h. Under these conditions, the polysaccharide content reached 7.83 mg/mL, which was 71.78% higher than that before fermentation(4.56 mg/mL). The antioxidant experiment showed that the DPPH·, ABTS+·, OH· scavenging rate and total reducing power of the fermented polysaccharide increased at certain concentrations and showed polysaccharide concentration dependence. The semi-inhibitory concentration (IC50) of the fermented polysaccharide POP2 on ABTS+·radical scavenging was 2.21 mg/mL, and the semi-inhibitory concentration on OH·radical scavenging was 0.49 mg/mL. These results implied that fermentation with Bacillus subtilis could significantly improve the extraction efficiency of Polygonatum odoratum polysaccharides, and polysaccharides in fermentated Polygonatum odoratum had better antioxidant capacity.

The shaft tubular pump device is widely used in low head pumping stations in plain areas. The N-S equation and the SST k-ω turbulence model are adopted. Then, the investigation on the influence of the shaft transition form on the inflow pattern and hydrodynamic characteristics of the pre-shaft tubular pump device is carried out. By designing three transition forms of shafts, different inflow patterns are provided for the tubular pump device. The characteristic parameters of the shafts and external and internal flow characteristics of the pumping device under different inflow patterns are compared and analyzed. Finally, the optimal transition form is selected for model tests, and unsteady pressure pulsation characteristics are studied. The results show that the flow pattern in the inlet passage of each case is relatively uniform and smooth, and the range of the high-efficiency zone of the pump device is roughly within 0.9Qd–1.2Qd. The energy loss and the weighted average angle on the outlet of each case are similar. The axial velocity distribution uniformity on the impeller inlet of case 1 is better than that of the other cases. The numerical simulation results are consistent with the experimental results, and the numerical simulation method is reliable. Under the design condition, the pressure pulsation amplitude at the impeller inlet is the largest. It gradually increases from the hub to the shroud. The main frequency of pressure pulsation is the blade frequency. The pressure pulsation amplitude at the impeller outlet decreases from the hub to the shroud. The main frequency is not constant due to the rotor–stator interaction between the impeller and the guide vane. The outcome will be beneficial to the design and optimization of the shaft tubular pump device, which is helpful for broadening the corresponding theory and applying it to the actual project.

PurposeTo investigate the safety and efficacy of a reverse puncture device (RPD) and specimen eversion of the rectum for resection in total laparoscopic proctectomy.MethodsIn a prospective study from August 2019 to March 2021, 40 patients underwent a procedure with an RPD and specimen eversion of the rectum for total laparoscopic low rectal cancer resection, that is natural orifice specimen extraction surgery (NOSES), were included in the NOSES group. Forty patients in the control group underwent conventional laparoscopic radical resection for low rectal cancer and were included in the LAP group. Intraoperative- and postoperative-related indicators, recovery and inflammatory factors, quality of life (QOL) and mental health were compared.ResultsAll operations were successfully completed. Compared with the LAP group, the NOSES group showed better short-term outcomes, such as time to eating, postoperative pain, and especially postoperative incision-related complications. At the same time, postoperative inflammatory factor levels, psychological trauma, life-related anxiety and depression scores, and QOL were better in the NOSES group than in the LAP group.ConclusionsThe application of an RPD and specimen eversion of the rectum for total laparoscopic low rectal cancer resection is a technically feasible and safe approach with a short-term curative effect.

Abstract Background Klebsiella pneumoniae is a leading cause of hospital-associated (HA) infections. It has been reported that gastrointestinal colonization (GI) is likely to be a common and significant reservoir for the transmission and infections of K. pneumoniae in both adults and neonates. However, the homologous relationship between clinically isolated extraintestinal and enteral K. pneumoniae in neonates hasn’t been characterized yet. Results Forty-three isolates from 21 neonatal patients were collected in this study. The proportion of carbapenem resistance was 62.8%. There were 12 patients (12/21, 57.4%) whose antibiotic resistance phenotypes, genotypes, and ST types (STs) were concordant. Six sequence types were detected using MLST, with ST37 and ST54 being the dominant types. The results of MLST were consist with the results of PFGE. Conclusions These data showed that there might be a close homologous relationship between extraintestinal K. pneumoniae (EXKP) and enteral K. pneumoniae (EKP) in neonates, indicating that the K. pneumoniae from the GI tract is possibly to be a significant reservoir for causing extraintestinal infections.

Abstract Background Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a role in the development of cervical cancer (CC) and the exact mechanism of its role has not been elucidated. Methods Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of messenger RNA of ACTA2-AS1, miR-143-3p and SMAD3 in tumor tissues and cells. Additionally, SMAD3 protein expression by western blots in cells. Small interference RNA against ACTA2‐AS1 or SMAD3 and miR‐143‐3p mimic/inhibitor was designed and transfected into CC cell lines to investigate their correlations and potential impacts on cell function. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell cycle assay, transwell assay and flow cytometry analysis were performed to detect the specific effects on cell line proliferation, metastasis and apoptosis. Results ACTA2-AS1 was significantly increased in CC tissues and cells and miR‐143‐3p was down-regulated. Clinically, the higher expression of ACTA2-AS1 was significantly correlated with higher FIGO stage. Loss-of-function assay revealed that silencing of ACTA2-AS1 inhibited cell proliferation, colony formation, migration and promoted apoptosis in CC. Additionally, Pearson correlation analysis showed that the expression of ACTA2-AS1 and miR-143-3p were negatively correlated. Dual-luciferase reporter assay and further mechanistic experiments confirmed that ACTA2-AS1 could sponge and regulate the expression of miR-143-3p. Furthermore, SMAD3 was the target gene of miR-143-3p and ACTA2-AS1 could upregulate SMAD3 through acting as a competitive endogenous RNA (ceRNA) of miR-143-3p. Finally, rescue assay demonstrated that the ACTA2-AS1/miR-143-3p/SMAD3 axis played an important role in the proliferation, migration and apoptosis of CC cells. Conclusions In summary, our study revealed that ACTA2-AS1 upregulates SMAD3 by competitively binding miR-143-3p, thereby accelerating CC progression. The ACTA2-AS1/miR-143-3p/SMAD3 axis can play a crucial role in cervical carcinogenesis, providing new clues for the early diagnosis and treatment of CC.

Polymyxin B (PB) is introduced into the clinic as the last-line therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP). Unfortunately, increased resistance to PB in Klebsiella pneumoniae (K. pneumoniae) has threatened global health. Resistance of K. pneumoniae to PB was induced by passaging in serial concentrations of PB and determined by microbroth dilution method. Growth characteristics of induced strains including growth curve, reversibility of resistance, and biofilm formation (crystal violet staining method) were measured. This study employed TMT-labeled quantitative proteomics and LC-MS/MS metabolomics analysis to investigate the key biological processes associated with PB resistance in K. pneumoniae. A total of 315 differentially expressed proteins (DEPs) were identified, of which 133 were upregulated and 182 were downregulated in the PB-resistant K. pneumoniae. KEGG enrichment analysis revealed that the DEPs were mainly involved in ATP-binding cassette (ABC) transporters and cationic antimicrobial peptide (CAMP) resistance. Proteins related to central carbon metabolism were inhibited in the PB-resistant K. pneumoniae, but proteins mediating LPS modification were activated. Transcriptional levels of CAMP resistance-related proteins were significantly different between PB-susceptible and -resistant K. pneumoniae. PB treatment led to an increase in reactive oxygen species (ROS) levels of K. pneumoniae. Metabolomics data demonstrated that 23 metabolites were significantly upregulated in PB-resistant K. pneumoniae and 5 were downregulated. The differential metabolites were mainly lipids, including glycerophospholipids, sphingolipids, and fatty acids. Exposure to PB resulted in increased level of phospholipid transport gene mlaF in K. pneumoniae. Our study suggested that membrane remodeling and inhibited central carbon metabolism are conducive to the development of PB resistance in K. pneumoniae.

Objective. To investigate the expression of Yin-Yang-1 (YY1) in esophageal carcinoma (ESCA) and its effect on glutamine metabolism in ESCA. Methods. The expression and roles of YY1 in ESCA were investigated using a series of bioinformatics databases and tools. The expression of YY1 between ESCA tissues with the corresponding adjacent tissues was validated using real-time PCR, western blot, and immunohistochemical staining method. Furthermore, the effects of YY1 on ESCC cell proliferation and migration were examined. The correlation between the YY1 and glutamine metabolism was evaluated by western blot. Results. YY1 gene was highly conserved in evolution and upregulated in ESCA tissues and ESCC cell lines (ECA109 and TE-1). In addition, YY1 may affect the level of immune cell infiltration and promote tumor cell immune escape. Functional enrichment analysis found that YY1 involved in many biological processes, such as cell division and glutathione and glutamine metabolism. After siRNA knockdown of YY1 in ECA109 and TE-1, the proliferation and the migration of ECA109 and TE-1 were suppressed. The glutamine consumption and glutamate production were significantly decreased. The protein expression of alanine-, serine-, cysteine-preferring transporter 2 (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLUD1) was significantly downregulated. Conclusion. YY1 is highly expressed in ESCA and may promote glutamine metabolism of ESCC cells, indicating it may be as a diagnostic biomarker for ESCA.

Abstract Background Blocking programmed death-1 (PD-1) is considered to be a promising strategy to improve T cell function, and this is being explored in many ongoing clinical trials. In fact, our knowledge about PD-1 is primarily based on the results of short-term experiments or observations, but how long-lasting PD-1 blockade can affect T cell function remains unclear. Methods We planned to use shRNA-based gene knockdown technology to mimic long-lasting PD-1 blockade. We constructed PD-1 steadily blocked chimeric antigen receptor modified T (CAR-T) cells, and with these cells we can clearly study the effects of PD-1 knockdown on T cell function. The anti-tumor function, proliferation ability and differentiation status of PD-1 silenced CAR-T cells were studied by in vitro and animal experiments. Results According to short-term in vitro results, it was reconfirmed that the resistance to programmed death-ligand 1 (PD-L1)-mediated immunosuppression could be enhanced by PD-1 blockade. However, better anti-tumor function was not presented by PD-1 blocked CAR-T cells in vitro or in vivo experiments. It was found that PD-1 knockdownmight impair the anti-tumor potential of CAR-T cells because it inhibited T cells’ proliferation activity. In addition, we observed that PD-1 blockade would accelerate T cells’ early differentiation and prevent effector T cells from differentiating into effect memory T cells, and this might be the reason for the limited proliferation of PD-1 silenced CAR-T cells. Conclusion These results suggest that PD-1 might play an important role in maintaining the proper proliferation and differentiation of T cells, and PD-1 silencing would impair T cells’ anti-tumor function by inhibiting their proliferation activity.

Text classification is an essential task in many natural language processing (NLP) applications; we know each sentence may have only a few words that play an important role in text classification, while other words have no significant effect on the classification results. Finding these keywords has an important impact on the classification accuracy. In this paper, we propose a network model, named RCNNA, recurrent convolution neural networks with attention (RCNNA), which models on the human conditional reflexes for text classification. The model combines bidirectional LSTM (BLSTM), attention mechanism, and convolutional neural networks (CNNs) as the receptors, nerve centers, and effectors in the reflex arc, respecctively. The receptors get the context information through BLSTM, the nerve centers get the important information of the sentence through the attention mechanism, and the effectors capture more key information by CNN. Finally, the model outputs the classification result by the softmax function. We test our NLP algorithm on four datasets containing Chinese and English for text classification, including a comparison of random initialization word vectors and pre-training word vectors. The experiments show that the RCNNA achieves the best performance by comparing with the state-of-the-art baseline methods.

Named entity recognition (NER) is an essential part of natural language processing tasks. Chinese NER task is different from the many European languages due to the lack of natural delimiters. Therefore, Chinese Word Segmentation (CWS) is usually regarded as the first step of processing Chinese NER. However, the word-based NER models relying on CWS are more vulnerable to incorrectly segmented entity boundaries and the presence of out-of-vocabulary (OOV) words. In this paper, we propose a novel character-based Gated Convolutional Recurrent neural network with Attention called GCRA for Chinese NER task. In particular, we introduce a hybrid convolutional neural network with gating filter mechanism to capture local context information and a highway neural network after LSTM to select characters of interest. The additional gated self-attention mechanism is used to capture the global dependencies from different multiple subspaces and arbitrary adjacent characters. We evaluate the performance of our proposed model on three datasets, including SIGHAN bakeoff 2006 MSRA, Chinese Resume, and Literature NER dataset. The experiment results show that our model outperforms other state-of-the-art models without relying on any external resources like lexicons and multi-task joint training.

Water jet propulsion technology has broad application prospects in the field of ships, and water jet technology is a kind of high and new technology that is booming and has a wide range of applications. However, there are a few studies on the effect of the external jet on the performance of the water jet propulsion pump, and it is urgent to carry out this research. In this paper, the standard k-ε turbulence model is used to carry out the numerical simulation study of the influence of the external jet on the hydraulic performance and flow field characteristics of the water jet propulsion pump device. This paper discusses the selection of calculation models, the division of grids and the setting of turbulence models, and an in-depth analysis of the calculation results. The research results show that when a high-speed water jet enters a moving water body, it will cause turbulence in the moving water body. With the increase of jet flow, the turbulence phenomenon will be improved. The average velocity of the outlet section of the nozzle is consistent with the change of the total pressure. The average vortex gradually decreases, the turbulent kinetic energy changes little, the turbulence dissipation first decreases and then increases, and the nozzle axial force changes more and more. The axial force and thrust of the device will obviously increase when the two water streams merge and spray, and they will increase with the increase of the jet flow rate. By revealing the influence mechanism of the external jet on the water jet propulsion pump device, it can provide a theoretical basis and guiding direction for further optimizing the hydraulic performance of the entire device.

This study uses a combination of computational fluid dynamics (CFD) and experimental research to explore the influence of the length of the inlet duct on the hydraulic performance of the water jet propulsion pump device. By extending the oblique, straight, and long pipe section of the inlet duct, six sets of schemes were designed. The research results show that as the length of the inlet duct increases, the head, thrust, and inlet duct efficiency of the water jet propulsion pump first increase and then decrease, reaching the maximum value in scheme 4, but it has little effect on the efficiency of the entire water jet propulsion system. In addition, after extending the obliquely straight long pipe section of the inlet flow channel, the velocity distribution of the outlet section of the flow channel is gradually uniform, and the absolute value of the vorticity first increases and decreases, but the uniformity of the velocity distribution and the weighted average angle change little. This research enriches the research theory of the inlet duct and also provides a reference for the selection of inlet duct length and its performance optimization.

The intake grid is always installed technically to protect the impeller at the entrance of the waterjet propulsion device’s inlet duct affecting its performance. Therefore, this study discussed the complex features of the circular, rectangular, and streamlined intake grid. Consistent geometry size of the intake grid mentioned above is to be maintained to guarantee the identical flow capacity at the entrance of inlet duct. Using experimental and simulated method, the outcomes are drawn as below. Rather than the circular and rectangular intake grid, the streamlined intake grid can improve the hydraulic performance of the waterjet propulsion device. The numerical method is proved to be correct as the consistence of the hydraulic characteristic between the test and simulated results. The causes of hydraulic loss in the contraction segment and straight pipe segment are the intake grid and the inflow velocity, respectively; meanwhile, the loss in the belt pipe segment owes to the vortex, flow separation, and impact on the back. The intake grid has a positive effect on the depth of the inlet velocity profile, but a negative effect on the width of it. The intake grid installation results in thrust reduction, the progress of velocity-weighted average angle, and the regress of axial velocity uniformity. The performance of waterjet propulsion device is complex and evaluated by the hydraulic performance index (HPI), thrust performance index (TPI), and characteristic of flow pattern index (CFPI). Based on the three evaluation indexes, the streamlined scheme is raised to be the recommended scheme.

Breast cancer has become one of the most serious disease threatening mankind health in the world. Accumulating studies indicated that circRNAs played an important role in the occurrence and progression of breast cancer, however, the roles of circRNA_103809 in breast cancer progression remain unclear. Therefore, in this study, we aimed to clarify the potential role and regulatory mechanism of circRNA_103809 in the development of breast cancer. Firstly, the expression level of circRNA_103809 and microRNA-532-3p (miR-532-3p) in breast cancer tissues and normal tissues were detected with the quantitative real-time polymerase chain reaction (RT-qPCR). In addition, the cell proliferation ability, metastasis ability and related pathways were identified by Cell Counting Kit-8 (CCK-8), flow cytometry, and western blot, respectively. Furthermore, the connection between circRNA_103809 and miR-532-3p was detected by dual-luciferase reporter assay. Then, our data showed that circRNA_103809 was down-regulated in breast cancer tissues in contrast to adjacent non-tumor tissues, and the relative expression level of circRNA_103809 was closely associated with distant metastasis size, TNM stage, HER-2 status and overall survival time. In addition, our in vitro assays showed that the overexpression of circRNA_103809 could significantly inhibit epithelial-mesenchymal transition (EMT) pathway, then suppress breast cancer cell proliferation and metastasis ability. Moreover, we also found that the antitumor effect induced by circRNA_103809 could be reversed with the addition of miR-532-3p mimics. Taken together, this study showed that circRNA_103809 could inhibit cell proliferation and metastasis in breast cancer by sponging miR-532-3p, and circRNA_103809 might be a prospective target of breast cancer therapy.

The rotating stall is a kind of flow phenomenon in the impeller harming the navigation speed of vessels propelled by a waterjet propulsion device when the waterjet propulsion device operates at the small flow rate conditions. The numerical simulated hydraulic performance was compared with experimental results so that the reliability of the CFD method was verified. The grooves are proposed before the inlet of an impeller to suppress the rotating stall. The orthogonal experiment is designed to seek the appropriate values of the parameters such as the length, width, depth, and number of the groove. The results show that the width of groove has the greatest influence on the performance of the device, followed by the number, the depth, and the length. The width, number, depth, and length of the selected groove scheme are 3.10 × 10−2D, 72, 3.10 × 10−2D, and 7.75 × 10−2D, respectively. At the rotating stall conditions, the selected groove scheme is numerically calculated. In contradistinction to the original scheme, it is found that the groove can improve the flow in the impeller and enhance the head of valley point condition, but the efficiency drops due to the increasing local hydraulic loss near the groove. When the groove is installed, the positive slop region on the flow rate-head curve disappears related to the static pressure difference on the blade, especially depending on the static pressure on the suction side. The flow pattern on the span surface of the vortex core is smooth, and then, the head increases. On the contrary, the head decreases. The outcome is beneficial to improve the performance of the waterjet propulsion device and enrich the rotating stall theory.

Abstract Background Limited studies have evaluated the effectiveness of pharmacist interventions on outpatient prescription. The goal of this study was to evaluate the clinical and economic impacts of pharmacist interventions on randomly sampled outpatient prescriptions. Method Outpatient prescriptions of our hospital were sampled automatically and reviewed by pharmacists since 2011. Pharmacists intervened in inappropriate prescriptions (IPs) real-timely, and summarized and analyzed the information monthly. Cost-benefit analysis was performed to estimate the economic benefit of the pharmacist intervention. Results From 2011 to 2016, pharmacists reviewed 101,271 prescriptions and intervened in 5155 prescriptions. With the interventions of pharmacists, the number of IPs decreased from 1845 to 238, while the inappropriate percentage decreased from 12.60 to 1.22%. The inappropriate rates of different departments and the types decreased annually. IPs were mainly from the Department of Medicine and Department of Surgery and category 1 (Non-indicated medications) in all years. The benefit-to-cost ratios of pharmacist interventions were always more than 1. In the same years, the benefit-to-cost ratios in public payments were higher than those with insurance and self-payment. Conclusion This form of pharmacist intervention constitutes a method that showed positive clinical and economic benefits and is worth expanding in large hospitals. Pharmacists should pay more attention on prescriptions in department of surgery or prescriptions with public payments.

Abstract Background Schistosomiasis is a water-borne disease caused by trematode worms belonging to genus Schistosoma, which is prevalent most of the developing world. Transmission of the disease is usually associated with multiple biological characteristics and social factors but also factors can play a role. Few studies have assessed the exact and interactive influence of each factor promoting schistosomiasis transmission. Methods We used a series of different detectors (i.e., specific detector, risk detector, ecological detector and interaction detector) to evaluate separate and interactive effects of the environmental factors on schistosomiasis prevalence. Specifically, (i) specific detector quantifies the impact of a risk factor on an observed spatial disease pattern, which were ranked statistically by a value of Power of Determinate (PD) calculation; (ii) risk detector detects high risk areas of a disease on the condition that the study area is stratified by a potential risk factor; (iii) ecological detector explores whether a risk factor is more significant than another in controlling the spatial pattern of a disease; (iv) interaction detector probes whether two risk factors when taken together weaken or enhance one another, or whether they are independent in developing a disease. Infection data of schistosomiasis based on conventional surveys were obtained at the county level from the health authorities in Anhui Province, China and used in combination with information from Chinese weather stations and internationally available environmental data. Results The specific detector identified various factors of potential importance as follows: Proximity to Yangtze River (0.322) > Land cover (0.285) > sunshine hours (0.256) > population density (0.109) > altitude (0.090) > the normalized different vegetation index (NDVI) (0.077) > land surface temperature at daytime (LSTday) (0.007). The risk detector indicated that areas of schistosomiasis high risk were located within a buffer distance of 50 km from Yangtze River. The ecological detector disclosed that the factors investigated have significantly different effects. The interaction detector revealed that interaction between the factors enhanced their main effects in most cases. Conclusion Proximity to Yangtze River had the strongest effect on schistosomiasis prevalence followed by land cover and sunshine hours, while the remaining factors had only weak influence. Interaction between factors played an even more important role in influencing schistosomiasis prevalence than each factor on its own. High risk regions influenced by strong interactions need to be targeted for disease control intervention.

Biomimetic giant membrane vesicles, with size and lipid compositions comparable to cells, have been recognized as an attractive experimental alternative to living systems. Due to the similarity of their membrane structure to that of body cells, cell-derived giant plasma membrane vesicles have been used as a membrane model for studying lipid/protein behavior of plasma membranes. However, further application of biomimetic giant membrane vesicles has been hampered by the side-effects of chemical vesiculants and the utilization of osmotic buffer. We herein develop a facile strategy to derive giant membrane vesicles (GMVs) from mammalian cells in biofriendly medium with high yields. These GMVs preserve membrane properties and adaptability for surface modification and encapsulation of exogenous molecules, which would facilitate their potential biological applications. Moreover, by loading GMVs with therapeutic drugs, GMVs could be employed for drug transport to tumor cells, which represents another step forward in the biomedical application of giant membrane vesicles. This study highlights biocompatible GMVs with biomimicking membrane surface properties and adaptability as an ideal platform for drug delivery strategies with potential clinical applications.

An amendment to this paper has been published and can be accessed via the original article.

Table of contents A1 Proceedings of 2016 China Cancer Immunotherapy Workshop, Beijing, China Bin Xue, Jiaqi Xu, Wenru Song, Zhimin Yang, Ke Liu, Zihai Li A2 Set the stage: fundamental immunology in forty minutes Zihai Li A3 What have we learnt from the anti-PD-1/PD-L1 therapy of advanced human cancer? Lieping Chen A4 Immune checkpoint inhibitors in lung cancer Edward B. Garon A5 Mechanisms of response and resistance to checkpoint inhibitors in melanoma Siwen Hu-Lieskovan A6 Checkpoint inhibitor immunotherapy in lymphoid malignancies Wei Ding A7 Translational research to improve the efficacy of immunotherapy in genitourinary malignancies Chong-Xian Pan A8 Immune checkpoint inhibitors in gastrointestinal malignancies Weijing Sun A9 What’s next beyond PD-1/PDL1? Yong-Jun Liu A10 Cancer vaccines: new insights into the oldest immunotherapy strategy Lei Zheng A11 Bispecific antibodies for cancer immunotherapy Delong Liu A12 Updates on CAR-T immunotherapy Michel Sadelain A13 Adoptive T cell therapy: personalizing cancer treatment Cassian Yee A14 Immune targets and neoantigens for cancer immunotherapy Rongfu Wang A15 Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with advanced and metastatic solid tumors Meixia Chen, Yao Wang, Zhiqiang Wu, Hanren Dai, Can Luo, Yang Liu, Chuan Tong, Yelei Guo, Qingming Yang, Weidong Han A16 Cancer immunotherapy biomarkers: progress and issues Lisa H. Butterfield A17 Shaping of immunotherapy response by cancer genomes Timothy A. Chan A18 Unique development consideration for cancer immunotherapy Wenru Song A19 Immunotherapy combination Ruirong Yuan A20 Immunotherapy combination with radiotherapy Bo Lu A21 Cancer immunotherapy: past, present and future Ke Liu A22 Breakthrough therapy designation drug development and approval Max Ning A23 Current European regulation of innovative oncology medicines: opportunities for immunotherapy Harald Enzmann, Heinz Zwierzina

Expressed by cancer stem cells of various epithelial cell origins, CD133 is an attractive therapeutic target for cancers. Autologous chimeric antigen receptor-modified T-cell directed CD133 (CART-133) was first tested in this trial. The anti-tumor specificity and the postulated toxicities of CART-133 were first assessed. Then, we conducted a phase I clinical study in which patients with advanced and CD133-positive tumors received CART-133 cell-infusion. We enrolled 23 patients (14 with hepatocellular carcinoma [HCC], 7 with pancreatic carcinomas, and 2 with colorectal carcinomas). The 8 initially enrolled patients with HCC were treated by a CART-133 cell dose escalation scheme (0.05–2 × 106/kg). The higher CAR-copy numbers and its reverse relationship with the count of CD133+ cells in peripheral blood led to the determination of an acceptable cell dose is 0.5–2 × 106/kg and reinfusion cycle in 23 patients. The primary toxicity is a decrease in hemoglobin/platelet (≤ grade 3) that is self-recovered within 1 week. Of 23 patients, three achieved partial remission, and 14 achieved stable disease. The 3-month disease control rate was 65.2%, and the median progression-free survival was 5 months. Repeated cell infusions seemed to provide a longer period of disease stability, especially in patients who achieved tumor reduction after the first cell-infusion. 21 out of 23 patients had not developed detectable de novo lesions during this term. Analysis of biopsied tissues by immunohistochemistry showed CD133+ cells were eliminated after CART-133 infusions. This trial showed the feasibility, controllable toxicities, and effective activity of CART-133 transfer for treating patients with CD133-postive and late-stage metastasis malignancies.

Melatonin (MLT) plays an important role in regulating the physiological cycle of seasonal breeding animals. Melatonin receptor I (MT1) is effectively expressed in the cambium layer of deer antler. However, the function and metabolic mechanism of MLT/MT1 signaling in the mesenchymal cells of sika deer remain to be further elucidated. In this work, we detected the effects of MLT/MT1 signaling on mesenchymal cells proliferation and the interaction between MLT/MT1 and IGF1/IGF1-R signaling. The results show that (1) deer antler mesenchymal cells actually express MT1; (2) exogenous melatonin significantly promotes mesenchymal cells proliferation, while MT1 knock-down significantly impairs the positive effects of melatonin; and (3) melatonin significantly enhanced IGF1/IGF1-R signaling, as both the expression of IGF1 and IGF-1R increased, while MT1 knock-down significantly decreased IGF1-R expression and IGF1 synthesis. In summary, these data verified that MLT/MT1 signaling plays a crucial role in antler mesenchymal proliferation, which may be mediated by IGF1/IGF1-R.

In this study, our objective is to evaluate the potential of a novel Sorafenib derivative, named HLC-080, as a new anticancer agent for colon cancer. We firstly carried out MTT assay, colony formation assay, flow cytometry analysis and transwell invasion assay to determine effect of our compound HLC-080 on cell viability, anti-proliferation activity, cell cycle arrest and the intervention on cell invasion, respectively. On the other hand, in vivo antitumor activity of HLC-080 was also tested using H22 xenograft model and the angiogenesis effect of HLC-080 was measured by EA.hy926 tube formation assay. The expression levels of various proteins in HLC-080 treated with HT-29 cell lines were examined using Western blot and ELISA experiments. The results showed that HLC-080 could dramatically inhibit the growth and colony formation of various tumor cells, therefore exhibited remarkable antitumor activity. HLC-080 can induce cell cycle arrest at G1 phase in HT-29 cells and subsequently inhibit the invasive potential of colon cancer cells. HLC-080 also exhibits anti-angiogenesis effect in EA.hy926 model. Additionally, the in vivo study showed that HLC-080 was able to reduced the tumor weight with the rate of 35.81%. And at the concentration of 0.352±0.034 µM, HLC-080 is able to reduce half of the regular protein level of p-c-Raf (Ser259), consequently block Raf/MEK/ERK signaling in HT-29 cell lines. In conclusion, our study suggests that Sorafenib derivative HLC-080 has the potential to inhibit cell proliferation and angiogenesis, Since, HLC-080 is particularly active against human colon cancer cells, our study highlights that HLC-080 and its related analogues may serve as a new anti-cancer drug, particularly against colon cancer.