A facile and intelligent detection method for diclazuril based on a stable dual emissive Eu3+-dopped metal-organic framework.

Diclazuril (DIC) is a broad-spectrum anti-coccidiosis drug of the triazine class, widely used in poultry farming. The overuse of DIC may lead to its accumulation in animal bodies, which may enter the food chain and threaten human health. In this work, we fabricated a stable Eu3+-doped UiO-66 fluorescence sensor (EuUHIPA-30) for the sensitive detection of DIC. Among 20 veterinary drugs, the fluorescence of EuUHIPA-30 selectively responds to DIC, with a low detection limit (0.19 µM) and fast response (10 s). EuUHIPA-30 is recyclable and can detect DIC in chicken and eggs with good recoveries. Moreover, a smartphone-integrated paper-based sensor enables the instrument-free, rapid, visual, and intelligent detection of DIC in chickens and eggs. This work provides a promising candidate for practical fluorescent DIC sensing in animal-derived food to promote food safety.

Progress of Clinical Studies Targeting Claudin18.2 for the Treatment of Gastric Cancer.

Claudin18.2 is a tight junction protein, highly selective, generally expressed only in normal gastric mucosal epithelial cells, which can effectively maintain the polarity of epithelial and endothelial cells, thus effectively regulating the permeability and conductance of the paracellular pathway. Abnormal expression of Claudin18.2 can occur in various primary malignant tumors, especially gastrointestinal tumors, and even in metastatic foci. It regulates its expression by activating the aPKC/MAPK/AP-1 pathway, and therefore, the Claudin18.2 protein is a pan-cancer target expressed in primary and metastatic lesions in human cancer types. Zolbetuximab (IMAB362), an antibody specific for Claudin18.2, has been successfully tested in a phase III clinical trial, and the results of the study showed that combining Zolbetuximab with chemotherapy notably extends patients' survival and is expected to be a potential first-line treatment for patients with Claudin18.2(+)/HER-2(-) gastric cancer. Here, we systematically describe the biological properties and oncogenic effects of Claudin18.2, centering on its clinical-pathological aspects and the progress of drug studies in gastric cancer, which can help to further explore its clinical value.

An Amphiphilic Star-Shaped Polymer (Star-PEG-PCL2) used as a Stationary Phase for GC.

A star-shaped polymer (Star-PEG-PCL2) was synthesized with PCL and PEG and used as a stationary phase for gas chromatography. The statically coated Star-PEG-PCL2 column exhibited an efficiency of 2260 plates/m determined by naphthalene at 120 °C and moderate polarity. The Star-PEG-PCL2 column showed high resolution performance for isomers of a wide ranging polarity, including methylnaphthalenes, halogenated benzenes, nitrobenzene, phenols, and anilines, and displayed dual-nature selectivity for a mixture of 17 analytes. Also, the Star-PEG-PCL2 column exhibited good separation performance and column inertness for Grob test mixture and a series of cis-/trans-isomers. In addition, it exhibited advantageous separation performance over the commercial HP-35 and PEG-20M columns for chloroaniline and bromoaniline isomers through its unique three-dimensional framework. In conclusion, it has good potential as a new stationary phase for separating a variety of analytes because of its special structure and excellent separation performance.

ROS1-positive non-small cell lung cancer (NSCLC): biology, diagnostics, therapeutics and resistance.

ROS1 is a proto-oncogene encoding a receptor tyrosine protein kinase (RTK), homologous to the v - Ros sequence of University of Manchester tumours virus 2 (UR2) sarcoma virus, whose ligands are still being investigated. ROS1 fusion genes have been identified in various types of tumours. As an oncoprotein, it promotes cell proliferation, activation and cell cycle progression by activating downstream signalling pathways, accelerating the development and progression of non-small cell lung cancer (NSCLC). Studies have demonstrated that ROS1 inhibitors are effective in patients with ROS1-positive NSCLC and are used for first-line clinical treatment. These small molecule inhibitors provide a rational therapeutic option for the treatment of ROS1-positive patients. Inevitably, ROS1 inhibitor resistance mutations occur, leading to tumours recurrence or progression. Here, we comprehensively review the identified biological properties and Differential subcellular localisation of ROS1 fusion oncoprotein promotes tumours progression. We summarise recently completed and ongoing clinical trials of the classic and new ROS1 inhibitors. More importantly, we classify the complex evolving tumours cell resistance mechanisms. This review contributes to our understanding of the biological properties of ROS1 and current therapeutic advances and resistant tumours cells, and the future directions to develop ROS1 inhibitors with durable effects.

Synthesis, Crystal Structure and Separation Performance of p-tert-butyl(tetradecyloxy)calix[6]arene.

This work describes the investigation of separation performance of the p-tert-butyl(tetradecyloxy)calix[6]arene (C6A-C10-OH) as stationary phase for gas chromatography (GC) separations. Its structure was characterized by IR, 1H NMR, 13C NMR, MS and single-crystal X-ray diffraction analysis. The C6A-C10-OH column shows good separation capacity for aliphatic, aromatic and cis-/trans- isomers. Especially, it exhibits multiple molecular recognition interactions for the analytes with a wide range of polarity, including dispersion, π-π, H-bonding and dipole-dipole interactions. The present work provides experimental and theoretical basis for the designing of the new calixarene stationary phases in GC analyses.

Exploring Sex Differences and Force Level Effects on Grip Force Perception in Healthy Adults.

This study aimed to explore the effect of sex and force level on grip force reproduction in healthy adults by conducting a force reproduction task. Participants (n = 28) were instructed to replicate a range of reference grip force levels (10-130 N in 10 N increments). We found that women (absolute error: 16.2 ± 8.7 N) replicated these force levels more accurately than men (absolute error: 23.1 ± 9.5 N) at higher force levels (90-130 N). Furthermore, the force reproductions were most accurate at the 30-50 N range for men and the 50-60 N range for women. These results may offer significant insights into the higher rates of musculoskeletal disorders among women, enabling researchers and clinicians to design novel interventions and tools that can improve grip force perception and reduce hand injury rates in both men and women.

Optimal number of harvested lymph nodes for curatively resected gallbladder adenocarcinoma based on a Bayesian network model.

BACKGROUND AND OBJECTIVES: To identify the optimal range and the minimum number of lymph nodes (LNs) to be examined to maximize survival time of patients with curatively resected gallbladder adenocarcinoma (GBAC). METHODS: Data were collected from the surveillance, epidemiology, and end results database on patients with GBAC who underwent curative resection between 2004 and 2015. A Bayesian network (BN) model was constructed to identify the optimal range of harvested LNs. Model accuracy was evaluated using the confusion matrix and receiver operating characteristic (ROC) curve. RESULTS: A total of 1268 patients were enrolled in this study. Accuracy of the BN model was 72.82%, and the area under the curve of the ROC for the testing dataset was 78.49%. We found that at least seven LNs should be harvested to maximize survival time, and that the optimal count of harvested LNs was in the range of 7 to 10 overall, with an optimal range of 10 to 11 for N+ patients, 7 to 10 for stage T1-T2 patients, and 7 to 11 for stage T3-T4 patients. CONCLUSIONS: According to a BN model, at least seven LNs should be retrieved for GBAC with curative resection, with an overall optimal range of 7 to 10 harvested LNs.

Estimating survival benefit of adjuvant therapy based on a Bayesian network prediction model in curatively resected advanced gallbladder adenocarcinoma.

BACKGROUND: The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma (GBC) after curative resection remain unclear. AIM: To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy. METHODS: Patients with curatively resected advanced gallbladder adenocarcinoma (T3 and T4) were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. A survival prediction model based on Bayesian network (BN) was constructed using the tree-augmented naïve Bayes algorithm, and composite importance measures were applied to rank the influence of factors on survival. The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3. The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy. RESULTS: A total of 818 patients met the inclusion criteria. The median survival time was 9.0 mo. The accuracy of BN model was 69.67%, and the area under the curve value for the testing dataset was 77.72%. Adjuvant radiation, adjuvant chemotherapy (CTx), T stage, scope of regional lymph node surgery, and radiation sequence were ranked as the top five prognostic factors. A survival prediction table was established based on T stage, N stage, adjuvant radiotherapy (XRT), and CTx. The distribution of the survival time (>9.0 mo) was affected by different treatments with the order of adjuvant chemoradiotherapy (cXRT) > adjuvant radiation > adjuvant chemotherapy > surgery alone. For patients with node-positive disease, the larger benefit predicted by the model is adjuvant chemoradiotherapy. The survival analysis showed that there was a significant difference among the different adjuvant therapy groups (log rank, surgery alone vs CTx, P < 0.001; surgery alone vs XRT, P = 0.014; surgery alone vs cXRT, P < 0.001). CONCLUSION: The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients. Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease.

Decision of surgical approach for advanced gallbladder adenocarcinoma based on a Bayesian network.

BACKGROUND AND OBJECTIVES: To determine whether radical resection can benefit patients with advanced gallbladder adenocarcinoma using a Bayesian network (BN) with clinical data. METHODS: In total, 362 patients who had undergone surgical treatment of gallbladder adenocarcinoma at a tertiary institute were evaluated to establish two BN models using a tree-augmented naïve Bayes algorithm. We then chose 250 patients with T3-4N0-2M0 stage gallbladder adenocarcinoma to test the posterior probability after the surgical type was taken into account. RESULTS: In total, 170 patients (≤7 months) and 137 patients (>7 months) were correctly classified in the median survival time model (accuracy, 84.81%), and 204 patients (≤12 months), 15 patients (12-36 months), 17 patients (36-60 months), and 34 patients (>60 months) were correctly classified in the 1-, 3-, and 5-year survival model (accuracy, 74.59%), respectively. Every posterior probability in the two models upregulated the ratio of the longer survival time and suggested a better prognosis for gallbladder adenocarcinoma that can be improved by R0 resection. CONCLUSIONS: These BN models indicate that stages T4 and N2 gallbladder adenocarcinoma are not contraindications for surgery and that R0 resection can improve survival in patients with advanced gallbladder adenocarcinoma.

Analysis of prognostic factors for survival after surgery for gallbladder cancer based on a Bayesian network.

The factors underlying prognosis for gallbladder cancer (GBC) remain unclear. This study combines the Bayesian network (BN) with importance measures to identify the key factors that influence GBC patient survival time. A dataset of 366 patients who underwent surgical treatment for GBC was employed to establish and test a BN model using BayesiaLab software. A tree-augmented naïve Bayes method was also used to mine relationships between factors. Composite importance measures were applied to rank the influence of factors on survival time. The accuracy of BN model was 81.15%. For patients with long survival time (>6 months), the true-positive rate of the model was 77.78% and the false-positive rate was 15.25%. According to the built BN model, the sex, age, and pathological type were independent factors for survival of GBC patients. The N stage, liver infiltration, T stage, M stage, and surgical type were dependent variables for survival time prediction. Surgical type and TNM stages were identified as the most significant factors for the prognosis of GBC based on the analysis results of importance measures.

[CT and MRI manifestation of primary spinal large B cell lymphoma].

OBJECTIVE: To investigate CT and MRI characteristics of primary spinal large B cell lymphoma. METHODS: CT and MRI data of 23 patients with primary spinal large B cell lymphoma confirmed by histopathology were retrospectively analyzed from March 2011 to August 2015. Among them, including 14 males and 9 females aged from 28 to 70 years old with an average of 53.4 years old. The clinical manifestation mainly focus on pain around spinal and minority peripheral nerve symptom. The courses of disease ranged from 2 weeks to 3 months with an average of 9 weeks. Nine patients underwent CT plain scan, 8 patients underwent plain and enhanced CT; 21 patients underwent MRI plain scan and enhanced; 15 patients underwent CT and MRI examination. The location, bone changes, shape, density, signal intensity and enhancement characteristics of lesions were observed and compared with pathology. RESULTS: Location and size of lesion showed cervical vertebrae in 1 case, thoracic vertebrae in 16 cases, lumbar vertebrae in 2 cases, and sacral vertebrae in 4 cases. Mass was larger, the largest cross-sectional size of group was up to 73 mm× 125 mm. CT examination showed that 11 cases with "cloud and mist" shape change, 6 cases with compression fractures, and with "floating ice" shape change, 9 cases with "oversleeve" shape change, 11 cases with spinal stenosis; enhancement scan showed obvious reinforcement. MRI showed slightly low signal on T1WI and T2WI were slightly high signal, and signal was uneven, and enhancement scan showed obvious reinforcement, 13 of 16 cases with spinal canal stenosis changed like "oversleeve", intervertebral space showed no significant stenosis. Comparison of CT and MRI showed the manifestation of bone destruction by CT was superior than that of MRI, but the range of lesion, and related surrounding structures were not better than MRI. MRI displayed the range of lesion usually bigger than CT. Pathology results showed that 23 patients were all primary spinal large B cell lymphoma. CONCLUSIONS: Primary spinal large B cell lymphoma has certain features in age, location and imaging findings. The "cloud and mist", "floating ice" and "oversleeve" shape bony destruction by CT and MRI has certain significance to diagnosis of primary spinal large B cell lymphoma.

Analysis of prognostic factors for survival after hepatectomy for hepatocellular carcinoma based on a bayesian network.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) after hepatectomy involves many factors. Previous studies have evaluated the separate influences of single factors; few have considered the combined influence of various factors. This paper combines the Bayesian network (BN) with importance measures to identify key factors that have significant effects on survival time. METHODS: A dataset of 299 patients with HCC after hepatectomy was studied to establish a BN using a tree-augmented naïve Bayes algorithm that could mine relationships between factors. The composite importance measure was applied to rank the impact of factors on survival time. RESULTS: 124 patients (>10 months) and 77 patients (≤10 months) were correctly classified. The accuracy of BN model was 67.2%. For patients with long survival time (>10 months), the true-positive rate of the model was 83.22% and the false-positive rate was 48.67%. According to the model, the preoperative alpha fetoprotein (AFP) level and postoperative performance of transcatheter arterial chemoembolization (TACE) were independent factors for survival of HCC patients. The grade of preoperative liver function reflected the tendency for postoperative complications. Intraoperative blood loss, tumor size, portal vein tumor thrombosis (PVTT), time of clamping the porta hepatis, tumor number, operative method, and metastasis were dependent variables in survival time prediction. PVTT was considered the most significant for the prognosis of survival time. CONCLUSIONS: Using the BN and importance measures, PVTT was identified as the most significant predictor of survival time for patients with HCC after hepatectomy.

Prevalence of and risk factors for symptomatic dry eye disease in Singapore.

BACKGROUND: The aim of this study was to describe the prevalence and risk factors of symptomatic dry eye disease (SDED) in Singapore. METHODS: A cross-sectional dry eye survey was carried out using the McMonnies dry eye questionnaire. Members of the public were interviewed at the 46 (out of 62) randomly-selected mass rapid transit (MRT) stations and their vicinity. A total of 1,004 questionnaires were collected from participants aged between 15 and 83 years. Symptomatic dry eye disease (SDED) was defined as at least one of five self-reported symptoms that were reported as often or constantly. Non-dry eye (NDE) subjects were those with no related symptoms reported. Prevalence of symptomatic dry eye disease in the studied population and confidence interval (CI) were calculated. Risk factors were also evaluated using logistic regression analysis at 95% CI. RESULTS: The prevalence for symptomatic dry eye disease was found to be 12.3 per cent with prevalence greater in females than males. Symptomatic dry eye disease was significantly associated with contact lens wear (odds ratio [OR] 2.96, 95% CI: 1.81 to 4.83), those having had previous treatment for dry eye (OR 2.09, 95% CI: 1.33 to 3.29), those taking medication (OR 1.84, 95% CI: 0.99 to 3.44), those with unusual sensitivity of eyes (OR 3.04, 95% CI: 1.92 to 4.83), constant mucous membrane dryness (OR 4.11, 95% CI: 1.62 to 10.45) and irritation on waking (OR 2.38, 95% CI: 1.34 to 4.22). Smoking was not found to be associated with symptomatic dry eye disease. CONCLUSION: Singapore has a symptomatic dry eye disease prevalence of 12.3 per cent and was associated with contact lens wear, those who had previous treatment for dry eye, medication, those having unusual sensitivity of eyes, mucous membrane dryness and waking irritation. These new data will be of value to the eye-care community in Singapore and elsewhere.

Concurrent weekly cisplatin versus triweekly cisplatin with radiotherapy in the treatment of cervical cancer: a meta-analysis result.

AIMS: To evaluate the adverse effect and survival outcome of weekly and triweekly cisplatin with radiotherapy in treatment of cervical cancer. METHODS: After an extensive literature search between 1995-2011,we analyzed 7 studies to compare weekly cisplatin and triweekly cisplatin combined radiotherapy. RESULTS: Our analysis established that weekly cisplatin has a lower risk of hematologic toxicity than triweekly cisplatin with concurrent radiotherapy in the treatment of cervical cancer. However, there were no differences in progression free survival and overall survival between weekly cisplatin and triweekly cisplatin (p>0.05). CONCLUSIONS: Weekly cisplatin combined with concurrent radiation has lower risk in hematologic toxicity than triweekly cisplatin, but does not improve survival. Triweekly cisplatin treatment has longer intervals and is therefore more convenient. Clinicians and patients can choose either weekly cisplatin or triweekly cisplatin combined radiotherapy for cervical cancer.

3-(2,4-Dichloro-phen-yl)-5-(4-fluoro-phen-yl)-2-phenyl-7-(trifluoro-meth-yl)pyrazolo-[1,5-a]pyrimidine.

In the title compound, C(25)H(13)Cl(2)F(4)N(3), there are four planar systems, viz. three benzene rings and a pyrazolo-[1,5-a]pyrim-idine system [r.m.s. deviation = 0.002 Å]. The dihedral angle between the dichloro-phenyl ring and the unsubstituted phenyl ring is 69.95 (5)°, while that between the fluoro-phenyl ring and the unsubstituted phenyl ring is 7.97 (10)°. The crystal packing is dominated by van der Waals inter-actions. A Cl⋯Cl inter-action of 3.475 (3) Šalso occurs.

3-(2,4-Dichloro-phen-yl)-5-(4-fluoro-phen-yl)-2-methyl-7-(trifluoro-meth-yl)pyrazolo-[1,5-a]pyrimidine.

In the title compound, C(20)H(11)Cl(2)F(4)N(3), the central pyrazolo-[1,5-a]pyrimidine unit is almost planar [the mean deviation from the best least-square plane through the nine atoms is 0.006 (2) Å]. The fluoro-benzene ring is rotated out of this plane by 10.3 (3)°, whereas the dichloro-benzene ring is rotated by 46.2 (3)°. The crystal packing is dominated by Cl⋯Cl inter-actions of 3.475 (3) Šand van der Waals inter-actions.

1-(2,4-Dichloro-phen-yl)-5-(2-nitro-anilino)-1H-pyrazole-4-carbonitrile.

In the title compound, C(16)H(9)Cl(2)N(5)O(2), the folded mol-ecular conformation is characterized by a dihedral angle between the two benzene rings of 74.03 (5)°. An intra-molecular N-H⋯O hydrogen bond is observed between the H atom of the amide group and a nitro-group O atom. Inter-molecular C-H⋯O and N-H⋯N hydrogen bonds feature in the crystal packing.

Dabigatran etexilate tetra-hydrate.

In the title compound, C34H41N7O5·4H2O (systematic name: ethyl 3-{[2-({4-[(Z)-amino-(hexyl-oxycarbonyl-imino)-meth-yl]anilino}meth-yl)-1-meth-yl-benzimidazole-5-carbon-yl]pyridin-2-yl-amino}-propano-ate tetra-hydrate), the benzene and pyridine rings form dihedral angles of 5.4 (1) and 43.8 (1)°, respectively, with the benzimidazole mean plane. The terminal butyl group is disordered over two conformations in a 0.756 (10):0.244 (10) ratio. There is an intramolecular N-H⋯O hydrogen bond present. In the crystal, the water mol-ecules are involved in the formation of O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds, which link the components into layers parallel to the ab plane.

Biosynthesis of benzoylformic acid from benzoyl cyanide by a newly isolated Rhodococcus sp. CCZU10-1 in toluene-water biphasic system.

Benzoylformic acid was synthesized from the hydrolysis of benzoyl cyanide by a newly isolated Rhodococcus sp. CCZU10-1. In this study, an aqueous-toluene biphasic system was developed for highly efficient production of benzoylformic acid from the hydrolysis of benzoyl cyanide. In the aqueous-toluene biphasic system, the phase volume ratio, buffer pH and reaction temperature were optimized. Using fed-batch method, a total of 932 mM benzoylformic acid accumulated in the reaction mixture after the 10th feed. Moreover, enzymatic hydrolysis of benzoyl cyanide using calcium alginate entrapped resting cells was carried out in the aqueous-toluene biphasic system, and efficient biocatalyst recycling was achieved as a result of cell immobilization in calcium alginate, with a product-to-biocatalyst ratio of 14.26g benzoylformic acid g(-1) dry cell weight (DCW) cell after 20 cycles of repeated use.

4-(3-Fluoro-4-nitro-phen-yl)morpholin-3-one.

In the title compound, C(10)H(9)FN(2)O(4), the dihedral angle between the benzene ring and the nitro group plane is 11.29 (3)°. The morpholinone ring adopts a twist-chair conformation. In the crystal, mol-ecules are linked by inter-molecular C-H⋯O hydrogen bonds into a chain along the a-axis direction.