Two 2D Metal-Organic Frameworks Based on Purine Carboxylic Acid Ligands for Photocatalytic Oxidation of Sulfides and CO2 Chemical Fixation.

Two two-dimensional (2D) layered metal-organic frameworks (MOFs), namely, {[Yb(L)(H2O)2NO3]·2H2O}n (Yb-MOF) and [Er(L)(H2O)3Cl]n (Er-MOF) (H2L = 5-((6H-purin-6-yl)amino)isophthalic acid), were constructed by a solvothermal method and characterized. The catalytic performance study showed that the Yb-MOF could efficiently catalyze the oxidation of sulfides to sulfoxides under 15 W light-emitting diode (LED) blue light irradiation. Electron paramagnetic resonance spectroscopy and free-radical trapping experiments demonstrated that the photocatalytic reaction process involved •O2-, and the corresponding mechanism was proposed. Moreover, Er-MOF exhibited good catalytic efficiency and excellent substrate tolerance in the cycloaddition reaction of CO2, and the reaction conditions were mild. After 5 cycles, the catalytic activities of two MOFs did not significantly decrease, and the framework structures remained unchanged. Therefore, the Yb-MOF and Er-MOF were considered efficient and stable heterogeneous catalysts.

Assembly of Functional Co(II) Metal-Organic Frameworks through a Mixed Ligand Strategy: Structure and Photocatalytic Degradation Properties.

Four Co(II)-based metal-organic frameworks (MOFs) were constructed by a mixed ligand strategy under solvothermal conditions. The controllable modification of the bridging groups in the secondary building units was realized by changing the anions in MOFs 1-3. The MOF 4 with 3D framework structure was obtained by regulating the solvent ratio following the synthesis process of MOF 3. Furthermore, the MOFs 1-4 exhibited efficient photocatalytic activity for the degradation of malachite green (MG) dye without any photosensitizer or cocatalyst under a low-energy light source, the decolorization ratio of MG all reached more than 96.0% within 60 min, and maximal degradation was obtained to be 99.4% (MOF 4). The recycling experiments showed that the degradation rate of MG was still higher than 91% after 10 cycles. In the MOF 4 as representation, the photocatalytic process was explored systematically. The possible mechanism of catalytic degradation was discussed, which proved the existence of efficient oxidation active factors (•O2-, •OH, and h+). The possible intermediates and degradation pathways were investigated based on high-performance liquid chromatography tandem mass spectrometry. Additionally, MOFs 1-4 also exhibited excellent photocatalytic activity for the degradation of methylene blue, methyl violet, rhodamine B, and basic red 9.

[Contamination and Probabilistic Health Risk Assessment of Heavy Metals in Agricultural Soils Around a Lead-Zinc Smelter].

In order to identify the contamination and health risks of heavy metals in agricultural soils, a total of 56 surface soil samples (0-20 cm) were collected around a Pb-Zn smelter in Yunnan Province, and six heavy metals (Pb, Cd, Zn, As, Cu, and Hg) and pH were analyzed to assess heavy metal status, ecological risk, and probabilistic health risk. The results revealed that the average contents of six heavy metals (Pb:4413.93 mg·kg-1, Cd:6.89 mg·kg-1, Zn:1672.76 mg·kg-1, As:44.45 mg·kg-1, Cu:47.61 mg·kg-1, and Hg:0.21 mg·kg-1) were higher than their background values in Yunnan Province. Cd had the highest mean geo-accumulation index (Igeo) of 0.24, the highest mean pollution index (Pi) of 30.42, and the greatest average ecological risk index (Er) of 1312.60, indicating that Cd was the primary enriched and highest-ecological risk pollutant. The mean hazard index (HI) through exposure to six HMs was 2.42E-01 and 9.36E-01 for adults and children, respectively, with 36.63% of HI values for children exceeding the risk threshold of 1. Moreover, the mean total cancer risks (TCR) were 6.98E-05 and 5.93E-04 for adults and children, respectively, with 86.85% of TCR values for children exceeding the guideline value of 1E-04. The probabilistic health risk assessment suggested that Cd and As were the main contributors for the non-carcinogenic risks and carcinogenic risks. This work will provide scientific reference for the precise risk management and effective remediation strategy of soil heavy metal pollution in this study area.

[Fucoidan-Modified Phase-Transitional Contrast Agent for Ultrasound Imaging and Targeting of Hepatoma Cells].

Objective: To prepare a fucoidan-modified phase-transitional contrast agent (FPCA) and to evaluate its in vitro capabilities for ultrasound imaging and targeting of hepatoma cells. Methods: Nano-liposomes encapsulated with perfluoropentane were prepared using thin-film hydration and ultrasonic emulsification methods. Then, FPCA nanoparticles were prepared through chemical grafting of fucoidan and the characterization of their physical and chemical properties was performed. After applying external stimuli of heating with hot water bath and microwave irradiation, the phase-transition status of FPCA was observed with microscope. The imaging abilities of phase-transited FPCA on two-dimensional ultrasound and contrast-enhanced ultrasound were observed with ultrasonic diagnostic instrument. The ability of FPCA to target at hepatoma cells was evaluated and verified with fluorescence confocal observation and flow cytometry analysis. Results: The FPCA prepared in the study had an average diameter of (222.1±32.5) nm, displaying spherical appearance, good dispersion, good stability, and good biocompatibility. The phase-transition of FPCA was induced by both heating with hot water bath and microwave irradiation. For phase transition, the optimal temperature was found to be 50 ℃ and the preferred microwave power was 1.5 W/cm 2. Moreover, after phase transition, FPCA showed significant imaging enhancement on both two-dimensional ultrasonography and contrast-enhanced ultrasonography. Through fluorescein isothiocyanate (FITC) labeling, FPCA could specifically bind with hepatoma cells at a high binding rate of (96.19±1.62)%, while it rarely bound with normal liver cells, showing a binding rate of less than 10%. Conclusion: A new type of phase-transitional ultrasound contrast agent with good stability and biocompatibility was successfully prepared. It not only could enhance ultrasound imaging through phase transition, but also had specific active hepatoma cell-targeting properties.

Arsenic Trioxide Cooperate Cryptotanshinone Exerts Antitumor Effect by Medicating Macrophage Polarization through Glycolysis.

Hepatocellular carcinoma (HCC) is an often-fatal malignant tumor with high lethality. Despite advances and significant efficacy in monotherapy, cancer therapy continues to pose several challenges. Novel combination regimens are an emerging strategy for anti-HCC and have demonstrated to be effective. Here, we propose a potential combination for HCC treatment named arsenic trioxide cooperate cryptotanshinone (ACCS). A remarkable synergistic therapeutic effect has been achieved compared with drugs alone in both in vivo and in vitro experiments. Mechanism study indicated that ACCS exerts its therapeutic actions by regulating macrophage-related immunity and glycolysis. ACCS potentiates the polarization of M1 macrophages and elevates the proportion of M1/M2 to remodel tumor immunity. Further molecular mechanism study revealed that ACCS intensifies the glucose utilization and glycolysis in the macrophage by increasing the phosphorylation of AMPK to activating the AMPK singling pathway. In conclusion, ACCS is a highly potential combination regimen for HCC treatment. The therapeutic potential of ACCS as a candidate option for anticancer drugs in restoring the balance of immunity and metabolism deserves further investigation.

Driver mutations of intrahepatic cholangiocarcinoma shape clinically relevant genomic clusters with distinct molecular features and therapeutic vulnerabilities.

Purpose: To establish a clinically applicable genomic clustering system, we investigated the interactive landscape of driver mutations in intrahepatic cholangiocarcinoma (ICC). Methods: The genomic data of 1481 ICCs from diverse populations was analyzed to investigate the pair-wise co-occurrences or mutual exclusivities among recurrent driver mutations. Clinicopathological features and outcomes were compared among different clusters. Gene expression and DNA methylation profiling datasets were analyzed to investigate the molecular distinctions among mutational clusters. ICC cell lines with different gene mutation backgrounds were used to evaluate the cluster specific biological behaviors and drug sensitivities. Results: Statistically significant mutation-pairs were identified across 21 combinations of genes. Seven most recurrent driver mutations (TP53, KRAS, SMAD4, IDH1/2, FGFR2-fus and BAP1) showed pair-wise co-occurrences or mutual exclusivities and could aggregate into three genetic clusters: Cluster1: represented by tripartite interaction of KRAS, TP53 and SMAD4 mutations, exhibited large bile duct histological phenotype with high CA19-9 level and dismal prognosis; Cluster2: co-association of IDH/BAP1 or FGFR2-fus/BAP1 mutation, was characterized by small bile duct phenotype, low CA19-9 level and optimal prognosis; Cluster3: mutation-free ICC cases with intermediate clinicopathological features. These clusters showed distinct molecular traits, biological behaviors and responses to therapeutic drugs. Finally, we identified S100P and KRT17 as "cluster-specific", "lineage-dictating" and "prognosis-related" biomarkers, which in combination with CA19-9 could well stratify Cluster3 ICCs into two biologically and clinically distinct subtypes. Conclusions: This clinically applicable clustering system can be instructive to ICC prognostic stratification, molecular classification, and therapeutic optimization.

[Study on anti-hyperlipidemia effect of Linderae Radix via regulating reverse cholesterol transport].

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.

[Heavy Metal Contamination and Health Risk Assessment of Corn Grains from a Pb-Zn Mining Area].

A total of 92 corn grain samples, around the Pb-Zn mining area in Southwest China, were collected to evaluate the contamination and health risk of heavy metals. Heavy metals including Pb, Zn, Cd, Cr, and Ni in samples were analyzed. A single factor pollution index and comprehensive pollution index were calculated to assess the quality of corn grains. The potential health risks to adults and children due to the intake of these heavy metals through consumption of crops were evaluated using the health risk index. The results showed that the average contents of Pb, Zn, Cd, Cr, and Ni in corn grains were 0.30, 23.75, 0.21, 1.33, and 1.15 mg ·kg-1, respectively, Among the metals, the content of Zn, Pb, Cd, Cr, and Ni exceeded the national food hygiene standards. The Nemero index of Pb, Cd, Cr, and Ni ranged from 4.32 to 9.07, indicating an extremely high level, whereas the contamination of Zn reached an alarming level. The assessment results of the comprehensive health risk index for the corn grains indicated that the contamination of heavy metals poses health risks to adults and children by food ingestion; moreover, the children were more sensitive to various heavy metals than the adults. Principle component analysis revealed that the first main component dominated the sources of Pb, Cd, Cr, and Ni, while the second main component, Zn, might have originated from sources different from the other heavy metals. Positive correlations were not observed between the heavy metals in corns and soils.

[Preparation of VEGFR2 Targeted Ultrasound Microbubbles by Freeze-drying and Targeting Study in vitro].

OBJECTIVE: To prepare vascular endothelial growth factor receptor2 (VEGFR2) targeted ultrasound contrast agent (microbubbles, MBs) by freeze-dried method and to evaluate its contrast enhanced effect and targeting capability through in vitro experiments. METHODS: Targeted MBs were prepared using the biotin-avidin linkage to conjugate rat anti-mouse VEGFR2 monoclonal antibody to the surface of biotinylated MBs. Morphology, size and distribution of MBs were assessed. The binding of streptavidin (FITC marker) and VEGFR2 monoclonal antibody (PE labeled rabbit IgG) to MBs was verified by immunofluorescence staining. In vitro targeting experiments were performed with human umbilical vein endothelial cells (HUVECs). The binding capacity of MBs to HUVECs were detected by three groups including untargeted MBs group (adding 1×107 untargeted MBs), antibody presaturation added VEGFR2 targeted MBs group (after being incubated with excess VEGFR2 antibody, 1×107 VEGFR2 targeted ultrasound MBs were added) and VEGFR2 targeted MBs group (adding 1×107 VEGFR2 targeted ultrasound MBs). Contrast enhanced effects of VEGFR2 targeted MBs were preliminarily examined using an ultrasound imaging system and a home-made extracorporeal circulating device. RESULTS: The monoclonal antibody of streptomycin and rat anti-mouse VEGFR2 can be combined with the biotinized MBs to construct the targeted ultrasound MBs of VEGFR2 by immunofluorescence staining. Under the microscope, VEGFR2 targeted MBs were round, uniform in size and uniform in distribution, with a mean diameter of (1.31±0.93) µm. Microscopy showed a small number of MBs around HUVECs in non-targeted MBs group, almost no MBs around HUVECs of antibody presaturation+VEGFR2 targeted ultrasound MBs group, and many MBs around HUVECs of VEGFR2 targeted ultrasound MBs group. The binding capacity was significantly higher than that of untargeted MBs. The self-made MBs developed well and no significant attenuation was observed as time extension in the mode of enhanced ultrasonography. CONCLUSIONS: The freeze-drying method can be used to prepare VEGFR2 targeted ultrasound contrast agent, which has good in vitro targeting ability and contrast enhanced effects for ultrasound molecular imaging.

Tissue-specific significance of BAP1 gene mutation in prognostic prediction and molecular taxonomy among different types of cancer.

BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis. Although the pooled results demonstrated that BAP1 mutation was a negative indicator of overall survival (hazard ratio = 1.73; 95% confidence interval = 1.23-2.42) and disease-free survival (hazard ratio = 2.25; 95% confidence interval = 1.47-3.45), this prognostic value was only applicable to uveal melanoma and clear cell renal cell carcinoma, but not to malignant pleural mesothelioma or cholangiocarcinoma. Consistently, BAP1 mutation was correlated with critical clinicopathological features only in uveal melanoma and clear cell renal cell carcinoma. In uveal melanoma, BAP1 mutation and SF3B1/EIF1AX mutations were negatively correlated, and BAP1-mutant tumors indicated significant worse prognosis than SF3B1/EIF1AX-mutant tumors ( p = 0.028). While in clear cell renal cell carcinoma, BAP1 mutation was mutually exclusive with PBRM1 mutations, and BAP1-mutant clear cell renal cell carcinomas also showed significantly worse prognosis than PBRM1-mutant clear cell renal cell carcinomas ( p = 0.001). Our study revealed a unique tissue-specific significance of BAP1 mutation in prognostic prediction among different types of cancer. Clinically, combining detection of BAP1 mutation and other driver mutations may further allow for a more precise molecular taxonomy to stratify patients into distinct subgroups in uveal melanoma and clear cell renal cell carcinoma.

Tidal chemotherapy in premenopausal patients with hormone receptor positive breast cancer.

Neoadjuvant chemotherapy remains an inseparable part of systemic therapy for hormone receptor positive (HR+) advanced breast cancer. However, efficacy of neoadjuvant chemotherapy in this subtype of patients is inferior to its hormone receptor negative counterpart. Several preclinical and clinical studies have suggested that it was growth rate rather than hormone receptor status that determined sensitivity to chemotherapy. In addition, estrogen was proved to recruit more HR+ breast cancer cells into actively dividing phase according to various studies. For premenopausal females, sexual hormone like estradiol fluctuates with menstrual cycle. When menstruation occurs, women have the lowest level of estradiol, which is resemble to pharmaceutical effect of endocrine therapy. If chemotherapy is given to females during menstruation, it's almost equal to concurrent use of chemotherapy and endocrine therapy, which is not recommended by guideline. Accordingly, chemotherapy would attain best efficacy applied at the peak of estradiol, because more tumor cells being in actively dividing phase recruited by comparatively high level of estradiol would help cytotoxic agents function better given that majority of chemotherapeutic drugs are cellular phase dependent. We name this rhythmic mode of chemotherapy for premenopausal HR+breast cancer females, giving chemotherapy to patients when estradiol rises and avoiding prescription at menstruation, tidal chemotherapy. It's postulated that tidal chemotherapy would improve efficacy of neoadjuvant chemotherapy for premenopausal HR+breast cancer females, achieve more pathologic complete response and in the long run improve prognosis.

Comparison of the preliminary characterizations and antioxidant properties of polysaccharides obtained from Phellinus baumii growth on different culture substrates.

Three polysaccharides (PPB-MB, PPB-MW and PPB-MM) were obtained from the fruiting body of Phellinus baumii growth on different culture substrates (mulberry branches, mixed wood sawdust and an equal combination of the two materials) and their chemical composition was investigated. PPB-MM contained the highest contents of neutral sugar (66.59%) and uronic acid (23.38%), followed by PPB-MW and PPB-MB, with PPB-MW having the highest protein content. The three polysaccharides were all composed of six kinds of monosaccharides, namely fucose, mannose, glactose, xylose, arabinose and glucose. The antioxidant activities of the three polysaccharides were determined using lipid peroxidant inhibition, ABTS radical scavenging, and Fe(2+)-chelating assay. Results showed that PPB-MM exhibited the highest antioxidant properties in all the assays. As a result, an equal combination of mulberry branches and mixed wood sawdust serves as a good culture substrate for producing such antioxidant polysaccharides.

Incidences of diabetes and prediabetes among female adult breast cancer patients after systemic treatment.

Patients with cancer frequently show glucose intolerance. This study is to estimate the status of total diabetes and prediabetes in breast cancer patients after systemic treatment through an oral glucose tolerance test (OGTT) in China. All the 119 breast cancer patients more than 3 months after systemic treatment with surgery and chemotherapy participated in the study. All the patients without the diagnosis of diabetes underwent OGTT, and fasting and 2-h glucose levels were measured to identify undiagnosed diabetes and prediabetes. Previously diagnosed diabetes were determined on the self-report and the medical record. Of the 119 breast cancer patients, with the median age of 50.1 years and the mean age of about 48 years when they were initially diagnosed with breast cancer, which showed the similar characters of China and Asia breast cancer patients, the overall incidences of total diabetes and prediabetes were 21.8 and 43.7 %, respectively. About 80 % of the diabetes were previously undiagnosed. About 80.0 % of the cases of undiagnosed diabetes and prediabetes met the criteria for elevated 2-h plasma glucose levels through OGTT but not the criteria for elevated fasting glucose levels. Our study firstly documents high incidences of previously undiagnosed diabetes and prediabetes in breast cancer patients during follow-up after systemic treatment through OGTT, indicating that greater diabetes screening, especially through OGTT, prevention, and treatment strategies among breast cancer patients, after systemic treatment for these patients is needed.

[Biosorption of crystal violet and malachite green by Rhodotorula graminis Y-5].

With a shaker, this paper studied the characteristics of the biosorption of crystal violet and malachite green by Rhodotorula graminis Y-5 under different adsorption time, initial pH, and temperature, as well as the desorption and recycling use of the dyes. The biosorption of crystal violet and malachite green by R. graminis Y-5 had the peaks (93.8% and 87.7%, respectively) at pH 7.0, dye concentration 50 mg x L(-1), 150 r x min(-1), 30 degrees C, and lasting 10 hours. After desorption, the biosorption rate of crystal violet and malachite green by R. graminis was 85.5% and 78.5%, respectively, indicating that the biosorption of crystal violet and malachite green was reversible, and the recycling use of the dyes by R. graminis was quite good, i. e., the dyes were renewable and could be recycled. Biosorption could be the mechanism of the decolorization of the dyes. The dyes were mostly adsorbed on the R. graminis surface -OH. The adsorption process was fast, efficient, and reversible, suggesting that R. graminis had a high potential for waste water treatment.

[Induce of laccase from Trametes gallica and its degradation on neutral dyes and organophosphorus pesticides].

The characteristics of the induction of laccase in Trametes gallica under different initial cultural pH, incubation time by different inducers were discussed, as well as the effects of temperature, pH and time on laccase degradation of six dyes and four organophosphors. The results showed that RB-bright blue, ABTS and o-toluidine affected the production of laccase at different levels, and ABTS was the best inductive agent in our test conditions, whose optimal initial pH and incubation time were 4.0 and 13 days, respectively. The appropriate reaction temperature of the laccase produced was 38 degrees C, and it got a good stability, for it could retain 78.6% of the enzyme activity after 20 min holding at 40 degrees C. Mediated by ABTS, the optimal temperature for laccase to degrade the six types of neutral dyes could be divided into two cases, that was 30 degrees C (neutral black, neutral bordeaux, neutral pink, methyl orange) and 60 degrees C (neutral dark yellow, cresol red), the optimal pH were 6.0 (neutral black), 2.0 (neutral bordeaux, neutral pink) and 4.0 (methyl orange, neutral dark yellow, cresol red), respectively, while the optimal times separately were 6 h (methyl orange, neutral dark yellow, cresol red), 12 h (neutral pink) and 24 h (neutral bordeaux). And using the same inductive agent, the best temperature for laccase to degrade dimethoate, chlorpyrifos, trichlorfon and parathion-pyridazine was 25 degrees C, the suitable time was 9 h, and the optimal pH was 10.0 for dimethoate, chlorpyrifos and parathion-pyridazine, and 8.0 for trichlorfon.