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Meniscus-derived stem cells (MeSCs), a unique type of MSC, have outstanding advantages in meniscal cytotherapy and tissue engineering, but the effects and molecular mechanisms of PBM on MeSCs are still unclear. We used 660-nm LED light with different energy densities to irradiate six human MeSC samples and tested their proliferation rate via cell counting, chondrogenic differentiation capacity via the DMMB assay, mitochondrial activity via the MTT assay, and gene expression via qPCR. The proliferation ability, chondrogenic capacity and mitochondrial activity of the 18 J/cm2 group were greater than those of the 4 J/cm2 and control groups. The mRNA expression levels of Akt, PI3K, TGF-β3, Ki67 and Notch-1 in the 18 J/cm2 group were greater than those in the other groups in most samples. After chondrogenic induction, the expression of Col2A1, Sox9 and Aggrecan in the 18 J/cm2 group was significantly greater than that in the 4 J/cm2 and control groups in most of the samples. The variation in the MTT values and Src, PI3K, Akt, mTOR and GSK3β levels decreased with time. The results showed that 660-nm LED red light promoted proliferation and chondrogenic differentiation and affected the gene expression of MeSCs, and the effects on gene expression and mitochondrial activity decreased with time. [ABSTRACT FROM AUTHOR]

Observational investigations recommend that mineral supplements were associated with a higher risk of polycystic ovary syndrome (PCOS) and its risk factors (insulin resistance, hyperandrogenism, and obesity), but the relationship with risk of PCOS, hyperandrogenism, obesity, and insulin resistance was unclear. This study was to investigate the potential causal impact of genetically predicted levels of magnesium (Mg), calcium (Ca), selenium (Se), zinc (Zn), iron (Fe), and omega-3 (ω-3) on polycystic ovary syndrome (PCOS) and its associated risk factors. A two-sample Mendelian randomization (MR) analysis was conducted. The genetic variations obtained from GWAS of individuals with European ancestry were found to be associated with the genetically predicted levels of Ca, Mg, Zn, Se, Fe, or ω-3. The data obtained from the FinnGen Consortium and MAGIC were utilized for the outcome of GWAS. The study found that there was a correlation between genetically predicted higher levels of Se and a reduced risk of insulin resistance, with a decrease of 2.2% according to random-effect IVW (OR 0.978, 95% CI 0.960–0.996, p = 0.015). The association between genetically determined mineral levels and PCOS was found to be limited, with an odds ratio (OR) ranging from 0.875 (95% CI: 0.637–1.202, p value = 0.411) for Ca. Limited scientific proof was found for the efficacy of other genetically determined mineral levels on hyperandrogenism, obesity, and insulin resistance. These findings suggested a causal relationship between genetically predicted higher levels of Se and a reduced risk of insulin resistance. Nonetheless, there is limited evidence supporting a causal association between various genetically determined mineral levels and the risk factors associated with PCOS. [ABSTRACT FROM AUTHOR]

Triplophysa (Hedinichthys) yarkandensis macroptera is an endemic species in China, that is mainly distributed in Gansu Province. To date, research on this species has been very limited, focusing mainly on its taxonomy, without any available molecular markers. In the present study, we identified 55 SNP markers in T. (Hedinichthys) yarkandensis macroptera. The minor allele frequency ranged from 0.050 to 0.500, and the observed and expected heterozygosity ranged from 0.167 to 1.000 and 0.155 to 0.508, respectively. The polymorphic information content ranged from 0.141 to 0.375. Among these SNP markers, seventeen loci showed significant departures from Hardy-Weinberg equilibrium after Bonferroni correction. These novel SNP markers will be helpful for future studies on genetic management and population conservation in this species. [ABSTRACT FROM AUTHOR]

This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. Conclusion: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. What is Known: • Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. What is New: • To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis. [ABSTRACT FROM AUTHOR]

Schizopygopsis chengi baoxingensis, a species belongs to Schizopygopsis group, is an endemic and rare fish in China. Due to the destruction of the habitat, the natural population of S. c. baoxingensis has decreased dramatically in recent years. Insufficient molecular markers have limited the effective conservation and management of this species. In the present study, we reported the isolation and characterization of 73 SNP markers in S. c. baoxingensis. The minor allele frequency ranged from 0.0139 to 0.500. The observed heterozygosity varied from 0.028 to 0.917, while the expected heterozygosity ranged from 0.028 to 0.507. Polymorphic information content ranged from 0.027 to 0.375. Among these SNPs, only eleven loci showed significant departures from the Hardy–Weinberg equilibrium. The novel polymorphic SNPs will be helpful for the future study on genetic management and population conservation for this species. [ABSTRACT FROM AUTHOR]

During the dam discharging period, the strong aeration of high-speed water leads to the supersaturation of total dissolved gas (TDG) in the downstream water, which causes gas bubble disease (GBD) in fish and threatens their survival. TDG supersaturation has now become an ecological and environmental issue of global concern; however, the molecular mechanism underlying the physiological effect of TDG supersaturation on fish is poorly known. Here, we comprehensively investigated the effect of TDG supersaturation on Pelteobagrus fulvidraco at the histopathological, biochemical, transcriptomic, and metabolomic levels. After exposure to 116% TDG, P. fulvidraco exhibited classic GBD symptoms and pathological changes in gills. The level of superoxide dismutase was highly significantly decreased. Transcriptomic results revealed that heat shock proteins (HSPs) and a large number of genes involved in immunity were increased by TDG stress. A key environmental sensor PI3K/Akt/mTOR pathway was significantly stimulated for defence against stress. Integrated transcriptomic and metabolomic analyses revealed that key metabolites and genes were upregulated in the triacylglycerol synthesis pathway and that amino acid levels decreased, which might be associated with TDG supersaturation stress. The present study demonstrated that TDG supersaturation could cause severe physiological damage in fish. HSP genes, immune functions, and energy metabolic pathways were enhanced to counteract the adverse effects. [ABSTRACT FROM AUTHOR]

Yak has been subject to natural selection, human domestication and interspecific introgression during its evolution. However, genetic variants favored by each of these processes have not been distinguished previously. We constructed a graph-genome for 47 genomes of 7 cross-fertile bovine species. This allowed detection of 57,432 high-resolution structural variants (SVs) within and across the species, which were genotyped in 386 individuals. We distinguished the evolutionary origins of diverse SVs in domestic yaks by phylogenetic analyses. We further identified 334 genes overlapping with SVs in domestic yaks that bore potential signals of selection from wild yaks, plus an additional 686 genes introgressed from cattle. Nearly 90% of the domestic yaks were introgressed by cattle. Introgression of an SV spanning the KIT gene triggered the breeding of white domestic yaks. We validated a significant association of the selected stratified SVs with gene expression, which contributes to phenotypic variations. Our results highlight that SVs of different origins contribute to the phenotypic diversity of domestic yaks. Yaks have been subject to natural selection, human domestication and interspecific introgression during their evolution. Here, the authors have identified genomic structural variations and the linked genes involved in these processes in domestic yaks, to reveal new insight into genetic basis of phenotypic diversity. [ABSTRACT FROM AUTHOR]

NONEXPRESSER OF PATHOGENESIS-RELATED GENES 1 (NPR1) is the master regulator of salicylic acid-mediated basal and systemic acquired resistance in plants. Here, we report that NPR1 plays a pivotal role in restricting compatible infection by turnip mosaic virus, a member of the largest plant RNA virus genus Potyvirus, and that such resistance is counteracted by NUCLEAR INCLUSION B (NIb), the viral RNA-dependent RNA polymerase. We demonstrate that NIb binds to the SUMO-interacting motif 3 (SIM3) of NPR1 to prevent SUMO3 interaction and sumoylation, while sumoylation of NIb by SUMO3 is not essential but can intensify the NIb–NPR1 interaction. We discover that the interaction also impedes the phosphorylation of NPR1 at Ser11/Ser15. Moreover, we show that targeting NPR1 SIM3 is a conserved ability of NIb from diverse potyviruses. These data reveal a molecular "arms race" by which potyviruses deploy NIb to suppress NPR1-mediated resistance through disrupting NPR1 sumoylation. Salicylic acid (SA) signaling pathway restricts the compatible infection of potyviruses. Here, Liu et al. show that potyviral NIb interacts with NPR1, the SA receptor in plants, preventing its sumoylation by SUMO3 and subsequent phosphorylation at Ser11/Ser15. This way, NPR1-mediated immunity is suppressed to promote virus infection. [ABSTRACT FROM AUTHOR]

In the present study, we identified 46 SNP markers for Gymnocypris chilianensis, an endemic economic fish in Heihe River and Shule River in China. The minor allele frequency ranged from 0.028 to 0.500. Observed heterozygosity ranged from 0.028 to 1.000, and expected heterozygosity from 0.055 to 0.507. The polymorphic information content ranged between 0.053 and 0.375. Among these SNP markers, sixteen loci showed significant departures from Hardy-Weinberg equilibrium after Bonferroni correction. These novel SNP markers will be helpful for future studies on genetic management and population conservation in this species. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether the use and display of license plate readers (LPRs) enhance the crime prevention effects of police patrol, particularly by increasing initial and residual deterrence from patrol presence. Methods: Crime hot spots in a large suburban jurisdiction were randomly assigned to receive intermittent patrols (15–30 min each) by officers with or without LPRs on their vehicles for 4.5 months. Data on 785 patrols at 33 hot spots were used to compare initial and residual outcomes of LPR and non-LPR patrols. Outcomes analyzed for each patrol visit via chi-square tests, survival analyses, and/or logistic regression included the following: the likelihood of a vehicle recovery or arrest; the likelihood of a new crime or disorder call in the location while the officer was present (measuring initial deterrence); time until a new crime or disorder call following the officer's departure (measuring residual deterrence); and first type of call (crime or disorder) following the officer's departure (measuring residual deterrence). Results: LPR use increased stolen vehicle recoveries but not arrests. LPR use did not reduce the likelihood of a new call in the hot spot while an officer was present, nor did it affect the timing or seriousness of the next call following a patrol. Conclusions: This study provides little clear evidence for the crime prevention efficacy of using LPRs in general patrol, which is a common practice in the USA. Police and researchers should give more attention to testing the relative benefits of different LPR uses and modes of deployment. [ABSTRACT FROM AUTHOR]

This study was intended to evaluate the anticancer activity of three newly synthesized iridium(III) complexes [Ir(ppy)2(PEIP)](PF6) (1) (ppy = 2-phenylpyridine, PEIP = 2-phenethyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(SIP)](PF6) (2) (SIP = (E)-2-styryl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(PEYIP)](PF6) (3) (PEYIP = 2-phenethynyl-1H-imidazo[4,5-f][1,10]phenanthroline). The cytotoxic activity in vitro against A549, SGC-7901, HepG2, HeLa and normal NIH3T3 cells was investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. We found that the complexes 1, 2 and 3 significantly inhibited cell proliferation, in particular, complexes 2 and 3 show high cytotoxic effect on SGC-7901 cells with an IC50 value of 5.8 ± 0.7 and 4.4 ± 0.1 μM. Moreover, cell cycle assay revealed that the complexes could block G2/M phase of the cell cycle. Apoptotic evaluation by Annexin V/PI staining indicated that complexes 1–3 can induce apoptosis in SGC-7901 cells. In addition, microscopy detection suggested that disruption of mitochondrial functions, characterized by increased generation of intracellular ROS and Ca2+ as well as decrease of mitochondrial membrane potential. Western blot analysis shows that the complexes upregulate the expression of pro-apoptotic Bax and downregulate the expression of anti-apoptotic Bcl-2, which further activates caspase-3 and prompts the cleavage of PARP. Taken together, these results demonstrated that complexes 1–3 exert a potent anticancer effect on SGC-7901 cells via ROS-mediated endoplasmic reticulum stress-mitochondrial apoptotic pathway and have a potential to be developed as novel chemotherapeutic agents for human gastric cancer. Three new iridium(III) complexes [Ir(ppy)2(PEIP)](PF6) (1) (ppy = 2-phenylpyridine, PEIP = 2-phenethyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(SIP)](PF6) (2) (SIP = 2-styryl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(PEYIP)](PF6) (3) (PEYIP = 2-phenethynyl-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The anticancer activity in vitro was investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results show that the complexes induce apoptosis via ROS-mediated endoplasmic reticulum stress-mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

The benefits and risks of inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) remain a subject of debate. In this study, we investigated the effect of ferulic acid (FA) on the proliferation and migration of VSMCs induced by platelet-derived growth factor (PDGF) and the associated mechanism and used ApoE-/- mice to study whether the effect of FA on VSMC proliferation and migration is beneficial in alleviating AS plaques. It was found that FA not only reduced blood lipid levels but also promoted the production of nitric oxide (NO) by MOVAS cells through the endothelial nitric oxide synthase (eNOS) pathway, inhibited the migration and proliferation of VSMCs induced by PDGF, promoted the expression of p21 in VSMCs, and exerted a therapeutic effect against AS. [ABSTRACT FROM AUTHOR]

Objectives: To examine how the practice of daily proactivity affects and responds to changes in crime at micro geographic and temporal scales. Methods: Police calls for service and automated vehicle location data from a large suburban jurisdiction were used to create comprehensive measures of police proactivity. Panel data and the generalized method of moments framework were applied to tease out the endogenous relationships between crime and police proactivity and understand the unique impact of proactive patrol and crime upon one another. Results: Daily police proactivity in this locality was highly stable at micro places, although police did intensify their activities very briefly in response to recent changes in crime. In turn, increases in proactive patrol generated immediate increases in crime reporting, followed by fleeting residual deterrent effects that were weaker and less robust. The patterns remained relatively consistent when varying the units of analysis or focusing on hot spots with different profiles of proactivity, but the deterrent effects appeared more sensitive to model specification. Of all measures of proactivity, patrols of medium length and non-traffic enforcement activities were associated with stronger evidence of crime reduction effects. Conclusions: Short-term adjustments in hot spot patrols appear to produce both reporting effects and temporary residual deterrent effects as measured through calls for service and police vehicle location data. Police could potentially enhance and prolong their deterrence by adopting more deliberate strategies with their daily proactive behaviors, including making their proactive activities more targeted and sustained. [ABSTRACT FROM AUTHOR]

Triplophysa tenuis is an endemic species of ray finned fish native to China, which is mainly distributed in Xinjiang and Gansu Province. Effective conservation and management of this species is limited by insufficient availability of molecular markers. In the present study, we report the isolation and characterization of 45 SNP markers in T. tenuis. The minor allele frequency ranged from 0.046 to 0.500, and the observed and expected heterozygosity ranged from 0.061 to 0.667 and 0.088 to 0.508, respectively. Polymorphic information content ranged from 0.083 to 0.375. Among these SNPs, three loci showed significant departures from the Hardy–Weinberg equilibrium. The novel polymorphic SNPs will be helpful for the future study on genetic management and population conservation for this species. [ABSTRACT FROM AUTHOR]

Triplophysa hsutschouensis is an endemic species in China, that is mainly distributed in the Hexi Corridor of Gansu Province. Studies on molecular markers in this species are limited. 45 single nucleotide polymorphism markers were developed and characterized in T. hsutschouensis for the first time using restriction site-associated DNA tag sequencing. The minor allele frequency ranged from 0.033 to 0.500, and the observed and expected heterozygosities ranged from 0.067 to 0.600 and 0.066 to 0.508, respectively. The polymorphism information content ranged from 0.062 to 0.375. Among these SNPs, two loci showed significant departures from Hardy–Weinberg equilibrium after Bonferroni correction. The novel polymorphic SNPs will be helpful for further population genetic analysis and natural resource conservation. [ABSTRACT FROM AUTHOR]

The development of new antibiotics to treat infections caused by drug-resistant Gram-negative pathogens is of paramount importance as antibiotic resistance continues to increase worldwide1. Here we describe a strategy for the rational design of diazabicyclooctane inhibitors of penicillin-binding proteins from Gram-negative bacteria to overcome multiple mechanisms of resistance, including β-lactamase enzymes, stringent response and outer membrane permeation. Diazabicyclooctane inhibitors retain activity in the presence of β-lactamases, the primary resistance mechanism associated with β-lactam therapy in Gram-negative bacteria2,3. Although the target spectrum of an initial lead was successfully re-engineered to gain in vivo efficacy, its ability to permeate across bacterial outer membranes was insufficient for further development. Notably, the features that enhanced target potency were found to preclude compound uptake. An improved optimization strategy leveraged porin permeation properties concomitant with biochemical potency in the lead-optimization stage. This resulted in ETX0462, which has potent in vitro and in vivo activity against Pseudomonas aeruginosa plus all other Gram-negative ESKAPE pathogens, Stenotrophomonas maltophilia and biothreat pathogens. These attributes, along with a favourable preclinical safety profile, hold promise for the successful clinical development of the first novel Gram-negative chemotype to treat life-threatening antibiotic-resistant infections in more than 25 years.A lead-optimization strategy combining porin permeation properties and biochemical potency leads to development of a new class of antibiotic based on broad inhibition of penicillin-binding proteins from Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies. The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SLFN12 is an RNase. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing. [ABSTRACT FROM AUTHOR]

The present study was performed to screen the potential biomarkers of cimaterol in rat, using an untargeted metabonomics approach. The liver and serum samples were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC–QTOF-MS) after treatment of rats with cimaterol. The principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were applied to distinguish control group (CG) and experimental group (EG). Eleven potential biomarkers existing in both liver and serum samples were obtained, including 2-Indolecarboxylic acid, 1,2-Dioleoyl PC, xanthine, PC(14:0/20:1(11z)), hexadecanedioic acid,PE(22:4(7Z,10Z,13Z,16Z)/14:0),lysoPE(0:0/18:2(9Z,12Z)), fluorometholone acetate, PE(MonoMe(9,5)/MonoMe(13,5)), chenodeoxyglycocholic acid and ethyl abietate. These potential biomarkers were involved in pantothenate and CoA biosynthesis, synthesis and degradation of ketone bodies, sphingolipid metabolism, vitamin B6 metabolism, linoleic acid metabolism and arachidonic acid metabolism. After withdrawal of cimaterol, the duration time of fluorometholone acetate in serum and liver of rats was both more than 15 days, which were much longer than that of parent drugs cimaterol. Therefore, the fluorometholone acetate was more suitable for supervising to the illegal use of cimaterol from the views of accessibility and accuracy. This study can provide the theoretical basis for the accurate monitoring method of cimaterol based on potential biomarker fluorometholone acetate. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the damage of long-term high concentrate diet feeding pattern on Yak jejunal structure, physiological function and protein composition during cold season. Twelve Datong male Yak (Bos grunniens) with the same age from cold season were randomly selected and slaughtered to determine Yak jejunal digestive enzyme activity, morphology and protein composition on different feeding patterns in Tibetan Plateau. The results showed that Yak jejunum digestive enzyme activity and morphology of grazing reared group were better than those in the intensively reared group. A total of 96 differentially expressed proteins were identified by label-free Mass Spectrometry (MS), which could be concluded to two predominant themes: protein structure and inflammatory response. Nine differentially expressed proteins were correlated in Yak jejunum damage in different feeding patterns. According to this research, we found that feeding pattern resulted the differences in Yak jejunum physiological function, morphology and protein composition. This fact was confirmed long-term high dietary concentrate feeding could damage the jejunum epithelial morphology and function. [ABSTRACT FROM AUTHOR]

Monitoring of bisphenols (BPs) in feed is a necessary process for the security of food of animal origin. In this study, a method was established to simultaneously detect bisphenol A (BPA), bisphenol B (BPB), bisphenol C (BPC), bisphenol E (BPE), bisphenol F (BPF), bisphenol AP (BPAP), bisphenol Z (BPZ), bisphenol P (BPP) and bisphenol PH (BPPH) in feed. A simple and rapid pretreatment procedure was developed using ultrasound-assisted extraction (UAE) and dispersive solid-phase extraction (DSPE), and then the prepared sample was analysed by high-performance liquid chromatographic (HPLC) with fluorescence detector (FLD). Finally, the operating conditions of UAE, DSPE, and HPLC were all optimised to increase the sample throughput and sensitivity. Under the optimized conditions, good linearities were obtained for nine BPs with the correlation coefficients (R2) above 0.995; the recoveries of nine BPs in spiked feed samples were in the range of 82.56–103.87% and relative standard deviations (RSDs) were in the range of 2.4–13.40%; the limits of detections (LODs) and quantitations (LOQs) were in the range of 1.0–5.0 and 3.3–16.6 μg kg − 1, respectively. The results clearly demonstrated the developed method provided the reliable screening and quantification of nine BPs in feed and possessed the advantages including low cost, quick, and simple. [ABSTRACT FROM AUTHOR]

Background: The higher level of neutrophil on admission has been reported to predict worse 3-month outcomes in ischemic stroke patients. Our study was to explore the dynamic changes of neutrophil and lymphocyte after r-tPA thrombolysis of ischemic stroke and the relationship with parenchymal hemorrhage (PH) and 3-month function outcome. Methods: A total of 208 acute ischemic stroke (AIS) patients with intravenous thrombolysis were included and then received 3-month follow-up in the present study. Blood samples for neutrophil and lymphocyte counts were obtained on admission, at 24 h and at 7 days after r-tPA infusion. The associations of increase in neutrophil, lymphocyte, and neutrophil to lymphocyte ratio (NLR) with PH or 3-month poor outcome were examined by logistic regression. Results: Increasing trends in the neutrophil and NLR were observed in AIS patients after r-tPA treatment. Increased level of neutrophil at 24 h after r-tPA infusion but not that on admission was associated with PH (OR = 2.86, P = 0.029) and 3-month poorer functional outcomes (OR = 2.67, P = 0.009). Moreover, patients were divided into four groups according to the percent change in neutrophil within 24 h following r-tPA treatment, and we found that there was a trend of incremental OR when compared higher increase group with lower ones. Conclusions: Dynamic increase in neutrophil and NLR after stroke may predict PH and 3-month poor outcome in AIS patients receiving r-tPA treatment. Therefore, neutrophil and NLR may serve as activity markers for PH and 3-month poor prognosis in AIS patients with intravenous thrombolysis. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to assess the evidential value of the knowledgebase in criminology after accounting for the presence of potential Type I errors. Methods: The present study examines the distribution of 1248 p-values (that inform 84 statistically significant outcomes across 26 systematic reviews) in meta-analyses on the topic of crime and justice published by the Campbell Collaboration (CC) using p-curve analysis. Results: The distribution of all CC p-values have a significant cluster of p-values immediately below 0.05, which is indicative of p-hacking. Evidential value (right skewed p-curves) is detected in most meta-analytic topic areas but not motivational interviewing (substance use outcome), sex offender treatment (sexual/general recidivism), police legitimacy (procedural justice), street-level drug law enforcement (total crime), and treatment effectiveness in secure corrections (juvenile recidivism). Conclusions: More studies, especially carefully designed and implemented randomized experiments with sufficiently large sample sizes, are needed before we are able to affirm the presence of evidential value and replicability of studies in all CC topic areas with confidence. [ABSTRACT FROM AUTHOR]

Objectives: This cohort study explores the prevalence and effect of suspected outcome reporting bias in clinical trials on substance use disorders. Methods: Protocols on the ClinicalTrials.gov registry are compared with the corresponding trial reports for 95 clinical trials across 3,162 outcomes. Variation in average effect size is examined by completeness and accuracy of reporting using ordinary least squares regression with robust standard errors (Eicker-Huber-White sandwich estimator). Results: Trials reports are frequently incomplete and inconsistent with their protocol. The most commonly practiced biased reporting practices are added outcomes not prespecified on the protocol, insufficiently pre-specifying outcomes, and omitting outcomes that were pre-specified on the protocol. There is a linear trend between the number of different biased reporting practices the trialist(s) engaged in and mean study-level Cohen's d (+ 0.214 with each additional type of biased reporting practice). Trials with omitted pre-specified outcomes have a significantly higher Cohen's d on average when compared to trials that did not omit such outcomes (+ 0.315). Added outcomes have a Cohen's d that is 0.385 higher in comparison to reported outcomes that were pre-specified on the protocol. Conclusions: The magnitude of outcome reporting bias raises considerable concern regarding inflated type I error rates. Implications for clinical trials on substance abuse, and randomized experiments in criminology, more generally, are discussed. [ABSTRACT FROM AUTHOR]

Introduction: CRISPR/CAS9 systems, which can be utilized in vitro biological experiments, have recently captured much attention for their important roles and benefits. However, full realization of the potential of CRISPR/CAS9 approaches requires addressing many challenges and side effects. The expression of genes and potential side effects of CRISPR/CAS9 in human cells remains to be elucidated. The aim of our study was to explore the effect of CRISPR/CAS9 on gene expression in 293T cells. Methods: A Cas9-expressing PX458 plasmid and Cas9-deactivated PX458-T2A plasmid were used to study the role of CRISPR/CAS9 on regulating gene expression in 293T cells. Gene expression in 293T cells after transfection of the PX458 plasmid or PX458-T2A plasmid was detected by RNA sequencing and correlative statistical analysis. Differential gene expression in both PX458 transfected 293T cells and PX458-T2A transfected 293T cells compared with normal 293T cells was detected using quantitative reverse transcription polymerase chain reaction (RT qPCR). The mRNA and protein levels were measured using reverse transcription PCR and Western blot. Co-IP assay combined with shotgun LC-MS/MS were used to investigate the differences of NGFR-interaction proteins between PX458 transfected 293T cells and PX458-T2A transfected 293T cells. Results: In this study, we observed that PX458 plasmid transfection and Cas9 expression can affect the expression of different genes, including FOSB (FBJ murine osteosarcoma viral oncogene homolog B), IL-11 (Interleukin-11), MMP1 (matrix metalloproteinase), CYP2D6 (CytochromeP4502D6), and NGFR (matrix metalloproteinase 1). Downregulation of NGFR after PX458 transfection was confirmed by RT qPCR and western blot analysis. NGFR expression was significantly lower in PX458 transfected 293T cells than in normal 293T cells and PX458-T2A transfected 293T cells. The co-IP dilutions analyzed by shotgun LC-MS/MS showed a total of 183 proteins interact with NGFR in PX458 transfected 293T cells while 221 proteins interact with NGFR were identified in PX458-T2A transfected 293T cells using the MASCOT engine. Conclusions: Cas9 expression by transfection of the PX458 plasmid was negatively correlated with the NGFR mRNA level and NGFR protein expression in 293T cells, while PX458-T2A, in which Cas9 is deactivated, did not affect NGFR expression. The decrease in NGFR expression also affects the amount of proteins that interact with NGFR. These results suggest that the effect of Cas9 on NGFR expression and the expression of other genes should be noticed when developing cell-based studies and therapies utilizing CRISPR/CAS9 systems. [ABSTRACT FROM AUTHOR]

A new geminivirus was identified in common bean (Phaseolus vulgaris) showing severe stunt and leaf curling symptoms in Heilongjiang province of China, via sequencing and assembly of small RNAs. The genome of this geminivirus comprises 2,959 nucleotides (nt) and shares 21.77-54.97% nt sequence identity with other geminiviruses. The coat protein (CP) shares the highest amino acid (aa) sequence identity (23.5%) with that of sesame curly top virus (SeYMV; genus Turncurtovirus), whereas the C1 (Rep) shares the highest aa sequence identity (66.5%) with that of beet severe curly top virus (BSCTV; genus Curtovirus). This geminivirus neighbors the turncurtoviruses in phylogenetic trees based on the full genome sequence or the amino acid sequence of the Rep protein, but it forms a distinct clade in the phylogenetic tree based on the coat protein. Recombination analysis showed that parts of the C1 coding region of this geminivirus were recombined from a curtovirus or turncurtovirus. Based on these results, the name "common bean curly stunt virus" (CBCSV) is proposed for this virus. [ABSTRACT FROM AUTHOR]

Objective: BAT1706 is a proposed biosimilar of bevacizumab (BEV). The objective of this phase I clinical trial was to establish pairwise similarity between BAT1706, US-sourced BEV (US-BEV), and EU-sourced BEV (EU-BEV) after a single intravenous (IV) infusion in healthy male subjects. Methods: This phase I clinical trial was a randomized, double-blinded, three-arm study in 128 healthy adult male subjects. Every subject received a single IV infusion of 1 mg/kg of study drug and was subsequently monitored for 14 weeks. Pharmacokinetic, safety, and immunogenicity data were collected from each patient. The primary pharmacokinetic endpoint of this clinical study was area under the concentration curve from time zero to infinity (AUC0–inf). Biosimilarity of the study drugs was confirmed if the two-sided 90% confidence interval (CI) ratios of the geometric means for the three pairwise comparisons were contained within the range 80–125%. Other pharmacokinetic parameters including area under the concentration curve to time t (AUC0–t), maximum concentration of drug in plasma (Cmax), half-life (t½), and time to Cmax (tmax) were also measured. Results: The pharmacokinetic parameters were comparable for the three drug products evaluated. The 90% CI for the AUC0–inf was 99–112% for BAT1706 versus EU-BEV, 97–110% for BAT1706 vs US-BEV and 92–104% for EU-BEV versus US-BEV comparisons, respectively, demonstrating biosimilarity. There were no significant adverse events attributable to BAT1706, as compared to EU-BEV and US-BEV. BAT1706 demonstrated a similar safety profile to EU-BEV and US-BEV. In addition, no anti-drug antibody positive result was reported for any subject included in the study. Conclusion: In this study, BAT1706, a proposed biosimilar of BEV, was shown to be highly similar to EU-BEV and US-BEV in terms of pharmacokinetic equivalence, safety, and immunogenicity in healthy subjects after a single IV infusion. Trial Registration: NCT03030430. [ABSTRACT FROM AUTHOR]

Through sequencing and assembly of small RNAs, an orthotospovirus was identified from a celtuce plant (Lactuca sativa var. augustana) showing vein clearing and chlorotic spots in the Zhejiang province of China. The S, M, and L RNAs of this orthotospovirus were determined to be 3146, 4734, and 8934 nt, respectively, and shared 30.4-72.5%, 43.4-80.8%, and 29.84-82.9% nucleotide sequence identities with that of known orthotospoviruses. The full length nucleoprotein (N) of this orthotospovirus shared highest amino acid sequence identity (90.25%) with that of calla lily chlorotic spot virus isolated from calla lily (CCSV-calla) [China: Taiwan: 2001] and tobacco (CCSV-LJ1) [China: Lijiang: 2014]. Phylogenetic analyses showed that this orthotospovirus is phylogenetically associated with CCSV isolates and clustered with CCSV, tomato zonate spot virus (TZSV), and tomato necrotic spot-associated virus (TNSaV) in a separate sub-branch. These results suggest that this orthotospovirus is a divergent isolate of CCSV and was thus named CCSV-Cel [China: Zhejiang: 2017]. [ABSTRACT FROM AUTHOR]

Objectives: To measure where officers engage in proactive, self-initiated activities, how much time they spend being proactive, and whether their proactive activities coincide with crime patterns. Methods: This study uses Andresen's Spatial Point Pattern Test to compare the spatial similarity between police proactivity and crime, as well as regression modeling to explore the relationship between proactivity and crime and the time spent on proactivity and crime. Results: In the jurisdiction examined, high levels of proactivity are noted. This proactive activity is more likely to occur in places where crime is most concentrated. Additionally, the number of proactive calls and the proactive time spent per crime-and-disorder call remain high and stable across spatial scales. For each crime call received at a street block, police initiated 0.7 proactive activities and spent approximately 28 min carrying out proactive works. Conclusions: This study develops a way of measuring proactive activity by patrol officers using calls for service data. We find that not only do officers in this jurisdiction exhibit higher levels of proactivity to prevent crime (compared to reacting to crime), but they also do so in targeted, micro-place ways. Agencies may consider using similar techniques to gauge the levels of proactivity in their agencies if proactive activity is a goal. [ABSTRACT FROM AUTHOR]

Background: Tea polyphenols are the prominent component in tea. After the fermentation process, tea polyphenols are oxidized by polyphenol oxidase to form oxidized tea polyphenols (OTPs). OTPs contain a significant amount of hydrophobic phenyl groups that can bind with non-aqueous materials. Here, we determined whether OTPs can bind with lipids and reduce fat uptake and assessed the effect of OTPs on decreasing obesity and alleviating hyperlipidaemia and other metabolic syndromes. Methods: Rats were divided into three groups: control, high-fat diet (HFD) and OTP groups. The control and HFD groups were fed a chow diet and a high-fat diet, respectively, for 12 weeks; the OTP group was fed a high-fat diet for 6 weeks and then a high-fat diet containing 2 % OTP for 6 weeks. The serum and excrement triglyceride (TAG) and total cholesterol (CHOL) concentrations were determined, and liver tissue and white adipose tissue were collected to detect the expression levels of genes involved in lipid metabolism. Results: Our results revealed that OTPs failed to decrease the serum concentrations of TAG and CHOL. OTPs alleviated the accumulation of lipids in the liver tissue and changed the expression levels of the regulators of lipid metabolism, i.e., peroxisome proliferation-activated receptors ( ppars), compared with the rats fed a high-fat diet alone. We also observed a significantly decreased reduction of weight in the visceral white adipose, enhanced regulation of fatty acid β-oxidation by PPARα and enhanced biosynthesis of mitochondria in the visceral white adipose of the OTP rats compared with the HFD rats. Additionally, OTPs promoted the excretion of lipids. Conclusion: Our results suggest that OTPs alleviate the accumulation of lipids in liver and visceral white adipose tissue and promote lipid excretion in rats in vivo. [ABSTRACT FROM AUTHOR]

Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumours and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood. Here we molecularly characterize this therapy-resistant high-mesenchymal cell state in human cancer cell lines and organoids and show that it depends on a druggable lipid-peroxidase pathway that protects against ferroptosis, a non-apoptotic form of cell death induced by the build-up of toxic lipid peroxides. We show that this cell state is characterized by activity of enzymes that promote the synthesis of polyunsaturated lipids. These lipids are the substrates for lipid peroxidation by lipoxygenase enzymes. This lipid metabolism creates a dependency on pathways converging on the phospholipid glutathione peroxidase (GPX4), a selenocysteine-containing enzyme that dissipates lipid peroxides and thereby prevents the iron-mediated reactions of peroxides that induce ferroptotic cell death. Dependency on GPX4 was found to exist across diverse therapy-resistant states characterized by high expression of ZEB1, including epithelial-mesenchymal transition in epithelial-derived carcinomas, TGFβ-mediated therapy-resistance in melanoma, treatment-induced neuroendocrine transdifferentiation in prostate cancer, and sarcomas, which are fixed in a mesenchymal state owing to their cells of origin. We identify vulnerability to ferroptic cell death induced by inhibition of a lipid peroxidase pathway as a feature of therapy-resistant cancer cells across diverse mesenchymal cell-state contexts. [ABSTRACT FROM AUTHOR]

BRAF small-molecule inhibitors have recently received increasing attention as very effective agents for the therapy of cancer, especially melanoma. In this current work, a computational investigation was performed to investigate the interaction details of BRAF kinase with inhibitors Vemurafenib (PLX4032) and its analog PLX4720. Binding free energy calculations based on molecular dynamics simulations reveal that ligands PLX4032 and PLX4720 bind to and stabilize the DFG-in conformation of BRAF. Component analysis of binding free energy revealed that vdWaals interactions play a dominating effect on BRAF inhibition. Furthermore, the per-residue binding free energy decomposition revealed that the most favorable contribution came from Ile463, Val471, Ala481, Lys483, Leu514, Ile527, Thr529, Gln530, Trp531, Cys532, Phe583, Gly593, and Asp594. These results agree well with experimental data, which provide valuable resources for understanding the inhibition mechanism of BRAF by PLX4032 and PLX4720 and clues for the design of novel potent BRAF inhibitors. [ABSTRACT FROM AUTHOR]

Shigaste humped cattle (Bos taurus), generated through long-term breeding, is a distinctive but threatened species native to China. This species plays an essential role in local stockbreeding and breeding newer species. Its population has been declining rapidly over the past few years owing to poor understanding of the significance of conservation of germplasm resources and the introduction of abundant species. To effectively protect and wisely utilise cattle breed resources, researchers have performed extensive studies on genetic diversity of domestic animals. In this study, the complete mitochondrial genome sequence of Shigaste humped cattle was successfully obtained by Illumina Hiseq Xten platform. The circular genome is 16,340 bp, which is composed of 13 protein-coding genes, two rRNA genes, 22 tRNA genes and a control region. Base composition of the genome is A (33.4%), C (26.0%), G (13.4%), T (27.2%), with an A + T content of 60.6%. Phylogenetic relationship based on 10 mitochondrial genome sequences indicated that Shigaste humped cattle was clustered with domestic cattle from China, and was closely related to Bos indicus. This study provided detailed molecular genetic information for the conservation and utilization of cattle germplasm resources. [ABSTRACT FROM AUTHOR]

The Zhangmu cattle (Bos taurus) is a rare breed native to the central Himalayas, which has recently suffered drastic reduction in its population. In the present study, the complete mitochondrial genome of Zhangmu cattle was determined. The 16,340 bp circular mitochondrial genome contained a common set of 37 mitochondrial genes, including 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a control region. The gene order was identical to that of other B. taurus breeds. The overall base composition of this genome was as follows: 33.4% A, 26.0% C, 27.2% T and 13.4% G, with a total A+T content of 60.6%. Both phylogenetic trees based on the maximum likelihood and neighbor joining methods showed that Zhangmu cattle was grouped with other Asian breeds such as Korean cattle. [ABSTRACT FROM AUTHOR]

Anxi cattle (Bos taurus) is an endangered species native to China. It has strong adaptive abilities to harsh desert conditions such as heat, cold, and drought tolerance; disease resistance; and stable inheritance. However, it is on the brink of extinction because of its shrinking population in the past few years due to the introduction and invasion of exotic species and the lack of awareness of germplasm resource protection. Mitochondrial DNA, a well-known genetic marker, has been successfully applied to molecular phylogenetics and population genetics. This study reported a whole mitogenome for Anxi cattle (B. taurus), which was sequenced using Illumina Hiseq 2500 platform. The length of complete mitogenome of Anxi cattle (B. taurus) breed was 16,341 bp (bp), containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a non-coding control region. It also contained the origin of L-strand replication (32 bp long), which was between tRNA-Asn and tRNA-Cys. The base composition of the genome was A (33.4%), C (26.0%), G (13.4%), and T (27.2%) with an A + T content of 60.6%. The molecular phylogenetic analysis revealed four major lineages, and the Anxi cattle breed had a close genetic connection with B. taurus and B. indicus clusters but was still distinctly outside them. This study identified the phylogenetic status of Anxi cattle (B. taurus) breed and offered essential molecular genetic information for the conservation of germplasm resources. [ABSTRACT FROM AUTHOR]

The Kunlun Mountain type wild yak (Bos mutus) is one of the most charismatic members of the Tibet/Qinghai Plateau, but its population is reduced. In this study, the complete mitochondrial genome of Kunlun Mountain type wild yak has been determined by polymerase chain reaction method for the first time. The circular genome was 16,325 base pairs (bp), containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding control region. The base composition of the genome was A (33.70%), C (25.81%), G (13.22%) and T (27.28%) with an A+T content of 60.98%. A phylogenetic analysis based on complete mitochondrial genome sequences showed that Kunlun Mountain type wild yak (Bos mutus) was closer to domesticated yaks (Bos gruuniens) and bison (Bison bison). [ABSTRACT FROM AUTHOR]

We report a facile approach to synthesize superhydrophobic and superoleophilic 'sponge-like' aerogels through sol-gel reaction followed by supercritical drying, in which MTES and DMDES are used as co-precursors, EtOH as a solvent, CTAB as a surfactant, and HCl and NH·HO as catalysts. The MTES-DMDES-based aerogels formed at the optimal molar ratio of MTES: DMDES: EtOH: HO: HCl: NH·HO: CTAB at 1.1: 0.9: 6: 12: 2 × 10: 2 × 10: 0.14 with a low density of 0.0897 g/cm show a compression ratio of 80 % under 36.85 kPa stress. They are superhydrophobic and superoleophilic with a water contact angle of 153.6° and an oil contact angle of 0°. We find that the MTES-DMDES-based aerogels show the high adsorption capacity for various kinds of organic liquids and the excellent recyclability in removing oil from water. [ABSTRACT FROM AUTHOR]

We report the synthesis of flexible, hydrophobic, and oleophilic silica aerogels through a two-step acid-base sol-gel reaction followed by supercritical drying, in which methyltriethoxysilane (MTES) is used as a precursor, ethanol (EtOH) as a solvent, and hydrochloric acid (HCl) and ammonia (NH·HO) as catalysts. At the optimal molar ratio of MTES:EtOH:HO:HCl:NH·HO is 1:18:3.5:1.44 × 10:1.2, MTES-based silica aerogels show the minimum density of 0.046 g/cm and the maximum compression ratio of 80 % with 15.09 kPa stress. They are superhydrophobic with a water contact angle of 157° and thermally stable up to 350 °C. We also find that they show the excellent adsorption for ethanol with a ratio of 1400 %. [ABSTRACT FROM AUTHOR]

Geminiviridae consists of a large group of single-stranded DNA viruses that cause tremendous losses worldwide. Frequent mixed infection and high rates of recombination and mutation allow them to adapt rapidly to new hosts and overcome hosts' resistances. Therefore, an effective strategy able to confer plants with resistance against multiple begomoviruses is needed. In the present study, artificial zinc finger proteins were designed based on a conserved sequence motif of begomoviruses. DNA-binding affinities and specificities of these artificial zinc fingers were evaluated using electrophoretic mobility shift assay. Artificial zinc finger nuclease (AZFNs) were then constructed based on the ones with the highest DNA-binding affinities. In vitro digest and transient expression assay showed that these AZFNs can efficiently cleave the target sequence and inhibit the replication of different begomoviruses. These results suggest that artificial zinc finger protein technology may be used to achieve resistance against multiple begomoviruses. [ABSTRACT FROM AUTHOR]

BRAF have been identified as new promising targets for the design of novel anticancer agents. It is reported that the inhibitors based on 2,3-dihydroimidazo[4,5]pyridin-2-one scaffold and a meta-substituted middle ring exhibit potent inhibitory activities toward BRAF. To investigate how their chemical structures relate to the inhibitory activities and to identify the key structural elements that are required in the rational design of potential drug candidates of this class, molecular docking simulations and three-dimensional quantitative structure-activity relationship (3D-QSAR) methods were performed. The bioactive conformation was explored by docking one potent compound 1 into the active site of BRAF in its DFG-out inactive conformation. The constructed CoMFA and CoMSIA models produced statistically significant results with the cross-validated correlation coefficients q of 0.563 and 0.624, non-cross-validated correlation coefficients r of 0.982 and 0.962, and predicted correction coefficients r of 0.822 and 0.875, respectively. In addition, the CoMFA and CoMSIA models were used to guide the design of a series of new inhibitors of this class with predicted excellent activities. Thus, these models may be used as an efficient tool to predict the inhibitory activities and to guide the future rational design of 2,3-dihydroimidazo[4,5]pyridin-2-one derivatives with a meta substitution pattern as BRAF inhibitors with potent activities. [ABSTRACT FROM AUTHOR]

The phylogenetic relationships of European and African Barbus and their West Asian relatives in Cyprininae remain largely unresolved. Consequently, little is known about the drivers of their evolution, including the possible association of uplifting of the Qinghai-Tibetan Plateau (QTP) with the early divergence of the subfamily. We use complete sequence data of the mitochondrial DNA gene encoding the protein cytochrome b ( Cytb) to hypothesize the phylogeny of 85 species belonging to 47 genera in the Cyprininae plus 6 species from the Leuciscinae. We employ 6 other species from Cypriniformes as outgroup taxa and estimate divergence times. Our results indicate that European Barbus sensu stricto lineage including Aulopyge shares a common ancestor with specialized and highly specialized schizothoracins and the genera Cyprinion and Scaphiodonichtys. The common ancestor appears to have originated in the Qinghai-Tibetan Plateau (QTP) region about 19.4-17.8 Ma. Barbus sensu stricto lineage appears to have originated about 16.6-15.5 Ma. Small to medium sized African Barbus sensu lato appear to have had an Oriental origin about 19.1-15.3 Ma and are closely related to Asian Puntius. West Asian Carasobarbus lineage including large African Barbus sensu lato might have originated about 9.94 Ma, also in Oriental Realm and has a close relationship to Asian Neolissochilus and Tor. The large-sized Barbus sensu lato appear to have diverged from Carasobarbus about 7.7 Ma. Finally, the Cyprininae appear to have radiated rapidly into nine lineages and many sublineages from about 27.8 to 17.8 Ma, close to the time of the second-stage tectonic movements of the QTP. Our analyses provide evidence that the uplifting of the QTP drove early diversification of the Cyprininae. Our extensive sampling of species involving all of the important areas results in clear evolutionary scenario for the Cyprininae. [ABSTRACT FROM AUTHOR]

The phylogenetic relationships of European and African Barbus and their West Asian relatives in Cyprininae remain largely unresolved. Consequently, little is known about the drivers of their evolution, including the possible association of uplifting of the Qinghai-Tibetan Plateau (QTP) with the early divergence of the subfamily. We use complete sequence data of the mitochondrial DNA gene encoding the protein cytochrome b ( Cytb) to hypothesize the phylogeny of 85 species belonging to 47 genera in the Cyprininae plus 6 species from the Leuciscinae. We employ 6 other species from Cypriniformes as outgroup taxa and estimate divergence times. Our results indicate that European Barbus sensu stricto lineage including Aulopyge shares a common ancestor with specialized and highly specialized schizothoracins and the genera Cyprinion and Scaphiodonichtys. The common ancestor appears to have originated in the Qinghai-Tibetan Plateau (QTP) region about 19.4–17.8 Ma. Barbus sensu stricto lineage appears to have originated about 16.6–15.5 Ma. Small to medium sized African Barbus sensu lato appear to have had an Oriental origin about 19.1–15.3 Ma and are closely related to Asian Puntius. West Asian Carasobarbus lineage including large African Barbus sensu lato might have originated about 9.94 Ma, also in Oriental Realm and has a close relationship to Asian Neolissochilus and Tor. The large-sized Barbus sensu lato appear to have diverged from Carasobarbus about 7.7 Ma. Finally, the Cyprininae appear to have radiated rapidly into nine lineages and many sublineages from about 27.8 to 17.8 Ma, close to the time of the second-stage tectonic movements of the QTP. Our analyses provide evidence that the uplifting of the QTP drove early diversification of the Cyprininae. Our extensive sampling of species involving all of the important areas results in clear evolutionary scenario for the Cyprininae. [ABSTRACT FROM AUTHOR]

A new fluorescence labeling reagent 2-(12-benzo[ b]acridin-5(12 H)-yl)-acetohydrazide (BAAH) has been designed for fatty acids labeling. Eleven fatty acids containing seven saturated and four unsaturated fatty acids were used to evaluate the analytical potential of this reagent. The labeling reaction of BAAH with fatty acids was completed at 85 °C for 60 min using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC·HCl) as the condensing agent. Separation of the derivatized fatty acids was carried out on a reversed-phase Thermo Hypersil Gold C18 column (4.6 mm × 250 mm, 5 μm) in combination with a gradient elution with a good baseline resolution. The fluorescence excitation and emission wavelengths were set at λ 280 and λ 510 nm, respectively. The identification was carried out by the online APCI-MS in positive-ion detection mode. Linear correlation coefficients for all fatty acid derivatives were of >0.9994. Detection limits, at a signal-to-noise ratio of 3:1, were 3.89-12.5 nmol L for the labeled fatty acids. The developed method was successfully applied to the accurate determination of fatty acids in five traditional Chinese herbs with satisfactory results. [ABSTRACT FROM AUTHOR]

Vascular endothselial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2 or kinase insert domain receptor (KDR) have been identified as new promising targets for the design of novel anticancer agents. It is reported that 4-(1 H-indazol-4-yl)phenylamino and aminopyrazolopyridine urea derivatives exhibit potent inhibitory activities toward KDR. To investigate how their chemical structures relate to the inhibitory activities and to identify the key structural elements that are required in the rational design of potential drug candidates of this class, molecular docking simulations and three-dimensional quantitative structure-activity relationship (3D-QSAR) methods were performed on 78 4-(1 H-indazol-4-yl)phenylamino and aminopyrazolopyridine urea derivatives as KDR inhibitors. Surflex-dock was used to determine the probable binding conformations of all the compounds at the active site of KDR. As a result, multiple hydrophobic and hydrogen-bonding interactions were found to be two predominant factors that may be used to modulate the inhibitory activities. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) 3D-QSAR models were developed based on the docking conformations. The CoMFA model produced statistically significant results with the cross-validated correlation coefficient q of 0.504 and the non-cross-validated correlation coefficient r of 0.913. The best CoMSIA model was obtained from the combination of steric, electrostatic and hydrophobic fields. Its q and r being 0.595 and 0.947, respectively, indicated that it had higher predictive ability than the CoMFA model. The predictive abilities of the two models were further validated by 14 test compounds, giving the predicted correction coefficients r of 0.727 for CoMFA and 0.624 for CoMSIA, respectively. In addition, the CoMFA and CoMSIA models were used to guide the design of a series of new inhibitors of this class with predicted excellent activities. Thus, these models may be used as an efficient tool to predict the inhibitory activities and to guide the future rational design of 4-(1 H-indazol-4-yl)phenylamino and aminopyrazolopyridine urea derivatives-based novel KDR inhibitors with potent activities. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]