Toward the development of chemoprevention agents. Part 1: Design, synthesis, and anti-inflammatory activities of a new class of 2,5-disubstituted-dioxacycloalkanes

A new class of 2,5-disubstituted-dioxacycloalkanes were designed and synthesized via stereoselective synthetic method as cancer chemoprevention agents. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Some of these compounds exhibited comparable or better anti-inflammatory activities than that of aspirin suggesting that they can be further developed as potential anti-inflammatory drug lead compounds. In addition, treatment of these anti-inflammatory agents did not prolong tail bleeding time in mice. The structure/activity relationships were also analyzed among these compounds.     

中国人身体质量指数的地理性分布

2009-2013年测量了中国11个汉语方言族群26954例汉族人的身高、体重值,计算了身体质量指数(I_(bm)),将汉族人的I_(bm)与经度、纬度进行相关分析。研究结果表明:总的说来,随年龄增长,11个方言族群I_(bm)值均呈线性增大,并且年龄组间差异均具有统计学意义。11个族群中,北方话族群I_(bm)值明显大于南方各族群。乡村男性(r=0.671; p0.05)、城市女性(r=0.043; p=0.820>0.05)I_(bm)与经度无相关。按照I_(bm)均数大于24.0、I_(bm)均数在23.1～24.0之间、I_(bm)均数小于23.0,可以将中国方言族群分成3个层次,中国北方话族群均分布在第1、2层次,南方族群主要分布在第2、3层次,也就是说11个族群大致按照纬度高低顺序依次分布在第1、2、3层次。遗传、环境、饮食、劳作强度等因素都不同程度影响身高、体重,也影响中国人的I_(bm)值。     

闽南人的体质特征

在福建漳州地区调查了322例男性(城市男性为149例,乡村汉族男性为173例)和357例女性(城市女性为164例,乡村女性为193例)成人的86项体质指标,计算了24项体质指数,统计了指数分型情况,与我国族群资料进行了比较,对闽南人体质特征进行了初步分析。结果 1)闽南人有皱褶率高,有蒙古褶率低,眼裂高度眼裂多为狭窄型,眼外角多高于眼内角,鼻根高度多为中等型,直鼻背,颧部突出度多为微弱型;鼻基部男性多呈水平,女性多呈上翘;鼻翼高度多为中等,鼻孔最大径多为斜位,鼻翼较宽;男性耳垂多为圆形,女性多为三角形;上唇皮肤部高度多为中等,红唇男性薄型率、中等型均较高,女性薄型率最高,发黑,肤黄、眼褐。2)总体说来,闽南人头面部测量指标值介于北亚、南亚类型族群之间。3)从指数均数来看,闽南人男女性均为圆头型、高头型、狭面型,狭鼻型。城市女性为狭头型,城市男性、乡村男性、乡村女性为中头型。闽南人头面部指数值更接近于南亚类型族群。4)从体部指标值和体部指数来看。闽南人更接近于北亚类型族群。闽南人体质介于南亚与北亚类型族群之间,男性相对接近于北亚类型族群,女性相对接近于南亚类型族群。     

从体型特征来探讨中国夏尔巴人的族源

中国夏尔巴人是未识别民族。本文研究中国夏尔巴人体型特点,并通过夏尔巴人与中国其他族群体型比较,从体质人类学角度为夏尔巴人的族源研究提出新的证据。测量夏尔巴人的体质数据,采用Heath-Carter法计算夏尔巴人的体型值,通过主成分分析法分析夏尔巴人与其他族群体型的特点和相似程度,从体质人类学方面对夏尔巴人的族源提出看法。西藏夏尔巴人男性平均体型为均衡的中胚层体型,体脂发育水平中等,骨骼、肌肉比较发达,身体线性度中等。女性平均体型为偏内胚层的中胚层体型,夏尔巴人女性的体型特点是体脂欠发达,骨骼和肌肉含量中等,身体线性度中等。夏尔巴人男性、女性与怒族、木雅人、尔苏人体型接近。体部特征分析不支持夏尔巴人是藏族分支的观点。体型特征支持夏尔巴人源于党项羌的观点。     

Theoretical study of cyclohexane hydroxylation by three possible isomers of [FeIV(O)(R-TPEN)]2+: does the pentadentate ligand wrapping around the metal center differently lead to the different stability and reactivity?

Density functional theory calculations have been carried out to elucidate the mechanism of cyclohexane hydroxylation by three possible isomers of [Fe^IV(O)(N-R-N,N′,N′-tris(2-pyridylmethyl)ethane-1,2-diamine)]²⁺ (R is methyl or benzyl) (Klinker et al. in Angew Chem Int Ed 44:3690–3694, 2005). The calculations offer a mechanistic view and reveal the following features: (a) all the three isomers possess triplet ground states and low-lying quintet excited states, (b) the relative stability follows the order isomer A > isomer B > isomer C, in agreement with the conclusions of Klinker et al., (c) the theoretical investigations provide a rationale to explain the interconversion of the three isomers, (d) the reaction pathways of the C–H hydroxylation are initiated by a hydrogen-abstraction step, and (e) the three isomers react with cyclohexane via two-state-reactivity patterns on competing triplet and quintet spin-state surfaces. As such, in the gas phase, the relative reactivity exhibits the trend isomer B > isomer A, while at the highest level, B2//B1 with zero point energy and solvation corrections, the relative reactivity follows the order isomer B > isomer A > isomer C. Thus, the calculated reaction pathway shows that pyridine rings perpendicular to the Fe–O axis result in more reactive species, and a pyridine ring coordinated trans to the oxygen atom leads to the least reactive isomer. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.

Health Risks Assessment of Heavy Metal Pollution in the Soil-Crop System from an E-Waste Dismantling Area

Soil is an essential resource for agricultural production. In order to investigate the pollution situation of heavy metals in the soil-crop system in the e-waste dismantling area, the crop and soil samples (226 pairs, including leaf vegetables, solanaceous vegetables, root vegetables, and fruits) around the e-waste dismantling area in southeastern Zhejiang Province were collected. The concentrations of Cd, Cu, Pb, and Cr were determined. The average concentrations of Cd, Cu, Pb, and Cr in soils were 0.94, 107.79, 80.28, and 78.14 mg kg^-1, respectively, and their corresponding concentrations in crops were 0.024, 0.7, 0.041, and 0.06 mg kg^-1, respectively. The transfer capacity of leaf vegetables was significantly higher than that of non-leaf vegetables, and the accumulation of four heavy metals in crops tended to be Cd > Cu > Cr/Pb. The pollution index’s results revealed that the soil pollution degree under different land uses ranked as root vegetables soil > leaf vegetables soil > solanaceous vegetables soil > fruit soil. The carcinogenic and non-carcinogenic risks of heavy metal exposure were ranked as food intake > accidental ingestion > dermal contact > inhalation. The comprehensive non-carcinogenic risk was ranked as Cr > Cd > Pb/Cu. Our results could be used to provide useful information for further crop cultivation layout in the study area, which can guarantee the local residents’ health and food safety.

     

Molecular mechanism underlying adenosine receptor-mediated mitochondrial targeting of protein kinase C

Activation of protein kinase C (PKC) via adenosine receptors is known to be involved in the cardioprotection of ischemic preconditioning (IPC). Specifically, activation of PKCε is critical for cardioprotection. There is ample evidence that PKCε resides in cardiac mitochondria. However, the signals that promote translocation of PKCε are largely unknown. The present study was designed to determine whether and how adenosine receptor activation induces translocation of PKCε to mitochondria. Freshly isolated adult rat cardiac myocytes and rat heart-derived H9c2 were used in the study. Immunofluorescence imaging of isolated mitochondria showed that PKCε but not PKCδ was localized in mitochondria and this mitochondrial localization of PKCε was significantly increased by adenosine treatment. The adenosine-induced increase in PKCε-positive mitochondria was largely prevented not only by PKC inhibitor chelerythrine, but also by the HSP90 inhibitor geldanamycin and by siRNA targeting HSP90. Immunoblot analysis from percoll-purified mitochondria further demonstrated that adenosine mediated a significant increase in mitochondrial PKCε? but not PKCδ. This effect was blocked by inhibiting PKC activity with chelerythrine and bisindolylmaleimide. Furthermore, co-immunoprecipitation data showed that PKCε but not PKCδ was associated with TOM70 and HSP90, and this association was enhanced by adenosine treatment. Moreover, adenosine-induced association of PKCε with TOM70 was reduced by suppressing HSP90 expression with siRNA. In conclusion, we demonstrate that adenosine induces HSP90-dependent translocation of PKCε to mitochondria, possibly through mitochondrial import machinery TOM70. These results point out a novel mechanism in regulating PKC in mitochondria and suggest an important implication in ischemic preconditioning or postconditioning.     

Digit Ratio (2D:4D) and Handgrip Strength in Hani Ethnicity

Introduction

The ratio of the length of the second finger to the fourth finger (2D:4D) in humans is considered as a putative marker of prenatal exposure to testosterone, and has been progressively adopted as one useful tool to evaluate the effect of prenatal hormones in some traits such as physical ability. Handgrip strength is one authentic measure of physical ability and is generally used on the anthropological research within an evolutionary viewpoint.

Methods

Here we present the first evidence on 2D:4D and handgrip strength on adult participants of Hani ethnicity and explore the relationship between digit ratio (2D:4D) and handgrip strength. We examined 2D:4D and handgrip strength of 80 males and 60 females at Bubeng village, in the Yunnan province of China.

Results

The mean 2D:4D in females was higher than that in males for each hand. Females showed significantly higher 2D:4D than males in the right hand rather than in the left hand. Males displayed significantly higher handgrip strength than females for both hands. Handgrip strength decreased with age for both sexes. A significant negative correlation between 2D:4D and handgrip strength was found in the right hand of males.

Conclusion

The relationship between 2D:4D and handgrip strength may be attributed to evolutionary drive of sexual selection operating on fetal programming.     

Assessing the effectiveness of protected areas for conserving range-restricted rain forest butterflies in Sabah,Borneo

Rain forests on Borneo support exceptional concentrations of endemic insect biodiversity, but many of these forest-dependent species are threatened by land-use change. Totally protected areas (TPAs) of forest are key for conserving biodiversity, and we examined the effectiveness of the current TPA network for conserving range-restricted butterflies in Sabah (Malaysian Borneo). We found that mean diurnal temperature range and precipitation of the wettest quarter of the year were the most important predictors of butterfly distributions (N = 77 range-restricted species), and that species richness increased with elevation and aboveground forest carbon. On average across all species, TPAs were effective at conserving ~43% of species’ ranges, but encompassed only ~40% of areas with high species richness (i.e., containing at least 50% of our study species). The TPA network also included only 33%–40% of areas identified as high priority for conserving range-restricted species, as determined by a systematic conservation prioritization analysis. Hence, the current TPA network is reasonably effective at conserving range-restricted butterflies, although considerable areas of high species richness (6,565 km²) and high conservation priority (11,152–12,531 km²) are not currently protected. Sabah's remaining forests, and the range-restricted species they support, are under continued threat from agricultural expansion and urban development, and our study highlights important areas of rain forest that require enhanced protection.     

Paving the way for human vaccination against Rift Valley fever virus: A systematic literature review of RVFV epidemiology from 1999 to 2021

BackgroundRift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, the Arabian Peninsula, and the Indian Ocean. This systematic review’s objective was to consolidate understanding of RVFV epidemiology during 1999–2021 and highlight knowledge gaps relevant to plans for human vaccine trials.Methodology/Principal findingsThe review is registered with PROSPERO (CRD42020221622). Reports of RVFV infection or exposure among humans, animals, and/or vectors in Africa, the Arabian Peninsula, and the Indian Ocean during the period January 1999 to June 2021 were eligible for inclusion. Online databases were searched for publications, and supplemental materials were recovered from official reports and research colleagues. Exposures were classified into five groups: 1) acute human RVF cases, 2) acute animal cases, 3) human RVFV sero-surveys, 4) animal sero-surveys, and 5) arthropod infections. Human risk factors, circulating RVFV lineages, and surveillance methods were also tabulated. In meta-analysis of risks, summary odds ratios were computed using random-effects modeling. 1104 unique human or animal RVFV transmission events were reported in 39 countries during 1999–2021. Outbreaks among humans or animals occurred at rates of 5.8/year and 12.4/year, respectively, with Mauritania, Madagascar, Kenya, South Africa, and Sudan having the most human outbreak years. Men had greater odds of RVFV infection than women, and animal contact, butchering, milking, and handling aborted material were significantly associated with greater odds of exposure. Animal infection risk was linked to location, proximity to water, and exposure to other herds or wildlife. RVFV was detected in a variety of mosquito vectors during interepidemic periods, confirming ongoing transmission.Conclusions/SignificanceWith broad variability in surveillance, case finding, survey design, and RVFV case confirmation, combined with uncertainty about populations-at-risk, there were inconsistent results from location to location. However, it was evident that RVFV transmission is expanding its range and frequency. Gaps assessment indicated the need to harmonize human and animal surveillance and improve diagnostics and genotyping. Given the frequency of RVFV outbreaks, human vaccination has strong potential to mitigate the impact of this now widely endemic disease.