Development and Validation of a Prediction Model for Venous Thrombus Embolism (VTE) in Patients With Colorectal Cancer.

Cancer patients are at high risk of developing venous thromboembolism (VTE). The risk of VTE could be mitigated with the administration of prophylactic anticoagulants. Therefore, risk assessment models would be a useful tool in order to identify those patients who are at higher risk and will be benefited more by prophylactic anticoagulants. This study retrospectively examined 528 newly diagnosed colorectal cancer patients from January 2019 to January 2021. Specified logistic regression models were employed to screen the factors and establish prediction tools based on nomograms according to the final included variables. Discrimination, calibration, and clinical applicability were used to assess the performance of screening tools. In addition, internal verifications were conducted through 10-fold cross-verification, leave-one-out cross-validation, and Bootstrap verification. Four risk factors, closely related to the occurrence of VTE in colorectal cancer patients, were identified after univariate and multivariate logistic regression, including age, body mass index, activated partial thromboplastin time, and D-Dimer value. Besides, the risk assessment model named ABAD was built on the basis, displaying good discriminations and calibrations. The area under the curve was 0.705 (95% confidence interval [CI], 0.644 to 0.766). According to Hosmer-Lemeshow goodness-of-fit test, a good agreement between the predicted and observed VTE events in patients with newly-diagnosed gastrointestinal cancer was observed for χ2 = 6.864, P = .551. Internal validation was applied with a C-index of 0.669 in the 10-fold cross-verification, 0.658 in the leave-one-out cross verification and 0.684 in the bootstrap verification. We developed a prediction model called ABAD for newly diagnosed colorectal cancer patients, which can be used to predict the risk of VTE. After evaluation and internal verification, we believe that ABAD exhibited high predictive performance and availability and could be recommended.

New insights into vascular aging: Emerging role of mitochondria function.

Vascular aging, a major risk factor for cardiovascular disease, contributes to morbidity and mortality in older people. Mitochondria play an important role in vascular aging. In endothelial and smooth muscle cells, multiple changes in the mitochondrial structure and function contribute to aging, including the effects of mitochondrial oxidative stress, mitochondrial DNA mutations, mitochondrial dynamics, and mitophagy. Mitochondrial dysfunction also contributes to other age-related molecular and cellular mechanisms, such as crosstalk with telomeres, senescence-associated secretory phenotypes, and low-grade inflammation. Thus, enhancing mitochondrial biogenesis, reducing oxidative stress, recovering dynamics, and mitophagy have been suggested as effective interventions to delay vascular aging and age-related cardiovascular diseases. Furthermore, accumulating evidence has shown that commonly used herbs and their natural compounds have great potential to improve mitochondrial function during vascular aging. Herein, we review the cellular and molecular mechanisms of mitochondrial effects on vascular aging, emphasizing the efficacy of natural compounds in the treatment of vascular aging by improving mitochondrial structure and function. We aim to provide new insights into delaying vascular aging and preventing cardiovascular diseases.

[Screening and Control Measures for New Priority Pollutants in Surface Water of Tianjin].

Emerging pollutants are frequently detected in surface water, threatening the regional aquatic ecosystem and human health. Due to their complex types and large differences in risk and toxicity, research based on the comprehensive assessment of the pollution characteristics to determine the new priority pollutants remains incomplete. This study established a multi-criterion scoring method targeting 41 emerging pollutants with the goal of protecting aquatic organisms and human health, using five key indicators including environmental exposure level, persistence, bioaccumulation, ecological risk, and health risk of pollutants. The emerging pollutants were screened and identified in the surface water of Tianjin. The priority levels of different congeners were divided, and the ecological and health risks of pollutants in the priority control list were evaluated. The results showed that 41 emerging pollutants were generally detected in the study area. The average concentration of sulfonamide antibiotics (SAs) and other drugs (Others) were the largest, with 200.04 ng·L-1 and 176.30 ng·L-1, respectively, followed by perfluorinated compounds (PFASs, 57.98 ng·L-1). In terms of pollutant categories, high-priority emerging pollutants were dominated by PFASs, accounting for 50%. Medium-priority emerging pollutants were still dominated by PFASs (26.32%), but the proportion was lower. Low-priority emerging pollutants were dominated by SAs, accounting for 31.25%. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), carbamazepine (CBZ), caffeine (CAF), perfluorohexyl sulfonic acid (PFHxA), and clarithromycin (CLA) were defined as a priority control list. Compared with other pollutants, PFOS and PFOA had higher scores in persistence, bioaccumulation, and health risk, whereas CBZ and CAF had higher scores in ecological risk. The average risk quotient (RQ) of CAF was 4.8, which indicated a relatively high ecological risk. Health risk indicated that the potential risk caused by PFOA (average hazard quotient was 0.018) cannot be ignored. For the priority control list, because of the high removal rate of CAF in sewage treatment plants, the construction of a pipe network and riverside belt with high vegetation coverage should be strengthened to reduce the impact of untreated sewage discharge and rainfall runoff. Pollutants with low removal rates in sewage treatment plants should be treated with combined technologies to improve the removal efficiency. In addition, industry substitution work should be accelerated to reduce emissions of PFOS, PFOA, and PFHxA.

Tackling the Taxonomic Challenges in the Family Scoliidae (Insecta, Hymenoptera) Using an Integrative Approach: A Case Study from Southern China.

Species of the family Scoliidae are larval parasitoids of scarabaeoid beetles and pollinators of various plants. Despite their great importance in pest biological control and plant pollination, the taxonomy and systematics of these parasitoids are far from clear. Some species of the family are extremely morphologically similar and difficult to identify, especially in males. In this study, an integrative taxonomic approach, combining morphology and molecular data, was used to discriminate the species of Scoliidae from southern China. In total, 52 COI sequences belonging to 22 morphospecies of 9 genera in two tribes were obtained. The COI sequences worked well for the identification of all the studied species, with intraspecific genetic distances generally less than 2%, while interspecific distances ranged between 5.3% and 20.8%. The delimitations of the problematic species and subspecies of Scolia and Megacampsomeris are well solved by COI sequences, suggesting that DNA barcoding could be a useful identification tool for Scoliidae. Based on both morphological and molecular evidence, we discovered one undescribed cryptic species of the polytypic species Solia (Discolia) superciliaris Saussure, 1864, five newly recorded species, i.e., Scolia (Discolia) sikkimensis Bingham, 1896, Sericocampsomeris flavomaculata Gupta and Jonathan, 1989, Megacampsomeris asiatica (Saussure, 1858), Megacampsomeris pulchrivestita (Cameron, 1902) and Megacampsomeris shillongensis (Betrem, 1928) and one pending subspecies of Scolia (Discolia) watanabei (Matsumura, 1912) from China. Our study indicates that such an integrative approach, combing both molecular and morphological evidence, is a potent tool to tackle the taxonomic challenges in the family Scoliidae, or even, in other diverse groups of Aculeata, of which sexual dimorphism and cryptic species are common.

[Distribution, Sources, and Risk Assessment of Polyfluoroalkyl Substances in Main Rivers and Soils of Tianjin].

Rapid urbanization and industrialization may potentially impact the spatial distribution and transmission of polyfluoroalkyl substances (PFASs). Tianjin, a typical industrialized city with a high urbanization level around Bohai Bay, was selected to evaluate the spatial distribution and ecological risks of PFASs. Water and soil samples were systematically collected and analyzed by using solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS-MS) methods. The results showed that all 12 PFASs were detected in water and soils, and the detection rates of the other congeners were low. The concentrations of ΣPFASs in water ranged from 3.93 to 357.85 ng ·L-1, and the levels of ΣPFASs in soils ranged from 4.60 to 63.85 ng ·g-1. PFBA was the major component in water and soils, and the contribution of PFBA was 37% and 67% in water and soils, respectively. The spatial difference in ΣPFASs in the water bodies was significant. ΣPFAS concentrations in the surface water were higher in the north (mean value of 63.83 ng ·L-1) than in the south (mean value of 51.71 ng ·L-1) and higher in the eastern coastal area (mean value of 71.36 ng ·L-1) than in the western area (mean value of 36.08 ng ·L-1). ΣPFAS concentrations from upstream to downstream of the rivers showed an increasing trend. The highest PFAS concentration was found in the Chaobai River, and the lowest was detected in the South Canal. The spatial distribution of PFASs in soils was higher in the south (mean value of 13.33 ng ·g-1) than in the north (mean value of 6.38 ng ·g-1) and higher in the eastern coastal region (mean value of 11.45 ng ·g-1) than in the western region (mean value of 6.94 ng ·g-1). The soil concentrations of ΣPFASs in the Haihe River Basin were the highest. The source analysis results showed that the emulsification of rubber products, food packaging process, paper surface treatment, fire extinguishing agent use, and electrochemical fluorination process in industrial production were the main sources of PFASs in the soils in the study area. PFOS/PFOA, PFOA/PFNA, and PFHpA/PFOA analyses showed that the main source of PFASs in water bodies was the degradation of precursors. ΣPFASs in a few areas originated from the direct emissions from production, but the atmospheric deposition was small. The results of the ecological risk evaluation indicated that the exposure concentrations of PFASs in water and soils in the study area were at a low ecological risk level. However, the long-term ecological effects of PFASs cannot be ignored because of their long-distance transport capability and high food chain (web) accumulation capability.

A simple and convenient method for the preparation of antioxidant peptides from walnut (Juglans regia L.) protein hydrolysates.

BACKGROUND: Walnut (Juglans regia L.), that belongs to the Juglandaceae family, is one of the nuts commonly found in Chinese diets. Researchers had obtained peptides from walnut protein hydrolysates, and these peptides exhibited the high antioxidant activities. The objective of this study was to develop a simple and convenient method for a facile and reproducible preparation of antioxidant peptides from walnut protein hydrolysates. RESULTS: Walnut proteins were extracted from walnut kernels using continuous countercurrent extraction process, and were separately hydrolyzed with six types of proteases (neutrase, papain, bromelain, alcalase, pepsin, and pancreatin). Then, hydrolysates were purified by ultrafiltration. The yields and purity of the peptides prepared using neutrase and papain were 16 and 81 % at least, respectively, higher than others, and had low molecular weight, 99 % of which were less than 1500 Da. Furthermore, the bioassay indicated that the two peptides exhibited the high antioxidant activities in the DPPH (IC50 values: 59.40 and 31.02 µg/mL, respectively), ABTS (IC50 values: 80.36 and 62.22 µg/mL, respectively), and superoxide radical scavenging assay (IC50 values: 107.47 and 80.00 µg/mL, respectively). CONCLUSIONS: The method combines the advantages of generality, rapidity, simplicity, and is useful for the mass production of walnut peptides.Graphical AbstractPreparation of antioxidant peptides from walnut (Juglans regia L.) protein hydrolysates.

Synthesis and in vitro antitumor evaluation of betulin acid ester derivatives as novel apoptosis inducers.

Nineteen betulin derivatives modified at the C-3 and C-28 positions were synthesized and assessed for antitumor activities against the MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines in vitro by MTT assay. Some derivatives (compounds 3a-3d and 5) displayed strong antitumor properties, with IC50 values between 4 and 18 µM. Compound 3c, containing piperidine group at C-28 position, had IC50 values of 4.3, 4.5, 5.2, 7.5, and 5.2 µM on the five cancer cell lines, respectively. Subsequent fluorescence staining and flow cytometric analysis indicated that compound 3c induced apoptosis in MGC-803 cell line, with an apoptosis ratio of 31.11% after 36 h of treatment at 10 µM 3c.

Synthesis and biological evaluation of betulonic acid derivatives as antitumor agents.

Structural modification was performed at the C-28 position of betulonic acid (BetA). Twenty-five BetA derivatives were synthesized, and evaluated for their antitumor activities against MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines by MTT assay. Among the derivatives, most of the derivatives had significant antiproliferative ability (IC50 < 19 µM). Compound 3k, the most active compound, showed IC50 values of 3.6, 5.6, 4.2, 7.8, and 5.2 µM on the five cancer cell lines respectively, and was selected to investigate cell apoptosis by subsequent florescence staining and flow cytometry analysis. The results revealed that compound 3k could induce apoptosis in MGC-803 cell lines, and the apoptosis ratios reached 28.33% after 36 h of treatment at 10 µM. In addition, the study of cancer cell apoptotic signaling pathway indicated that the apoptosis of MGC-803 cells induced by compound 3k could be through the mitochondrial intrinsic pathway.

Chemical constituents of Cyrtomium fortumei (J.) Smith.

Five known compounds, 6'-methylglucuronide-5-hydroxy-chromone (1), ethyl α-d-glactopyranoside (2), neoechinulin A (3), 9,12,13-trihydroxyoctadeca-10(E),15(Z)-dienoic acid (4) and phellopterin (5), were isolated from water extract of Cyrtomium fortumei (J.) Smith. Compounds 1-5 were isolated from this genus for the first time, and all the compounds were evaluated in vitro against a panel of human cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Among them, compounds 3 and 4 exhibited significant cytotoxic activities, with IC50 values of 15.2 and 18.3 µg/mL on MGC-803 cells, respectively.

Chemical constituents of Caesalpinia decapetala (Roth) Alston.

The current study targets the chemical constituents of Caesalpinia decapetala (Roth) Alston and investigates the bioactivities of the isolated compounds. Fourteen known compounds were isolated using column chromatography, and structural identification was performed by physical and spectral analyses. The biological activities of the compounds were also evaluated by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 2,2-diphenlyl-1-picrylhydrazyl (DPPH) assays. Emodin (6), baicalein (9), and apigenin (12) displayed antitumor activities against the MGC-803 cell line, while quercetin (2), rutin (5), baicalein (9), and epicatechin (13) showed stronger DPPH scavenging activities compared with ascorbic acid. Andrographolide (1), quercetin (2), bergenin (4), rutin (5), emodin (6), betulin (7), baicalein (9), polydatin (10), salicin (11), and apigenin (12), were obtained from C. decapetala (Roth) Alston for the first time.

Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety.

This study designed and synthesized a series of novel ursolic acid derivatives in an attempt to develop potent antitumor agents. Their structures were confirmed using MS, IR, (1)H NMR and (13)C NMR. The inhibitory activities of the title compounds against the MGC-803 (gastric cancer cell) and Bcap-37 (breast cancer cell) human cancer cell lines were evaluated using standard MTT assay in vitro. The pharmacological results showed that some of the compounds displayed moderate to high levels of antitumor activities against the tested cancer cell lines and that most exhibited more potent inhibitory activities compared with ursolic acid. The mechanism of compound 4b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, TUNEL assay and flow cytometry, which revealed that the compound can induce cell apoptosis in MGC-803 cells.