Drug-induced tooth discoloration: An analysis of the US food and drug administration adverse event reporting system

Background: Certain drugs can cause intrinsic or extrinsic tooth discoloration, which is not only a clinical issue but also an esthetic problem. However, limited investigations have focused on drug-induced tooth discoloration. The present work aimed to determine the drugs causing tooth discoloration and to estimate their risks of causing tooth discoloration.Methods: An observational, retrospective, and pharmacovigilance analysis was conducted, in which we extracted adverse event (AE) reports involving tooth discoloration by using the data of the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021. Disproportionality analyses were performed to examine risk signals for tooth discoloration and determine the drugs inducing tooth discoloration.Results: Based on predefined inclusion criteria, 1188 AE reports involving 302 suspected drugs were identified. After data mining, 25 drugs generated positive risk signals for tooth discoloration, of which 10 were anti-infectives for systemic use. The top reported drug was tetracycline (n = 106), followed by salmeterol and fluticasone (n = 68), amoxicillin (n = 60), chlorhexidine (n = 54), and nicotine (n = 52). Cetylpyridinium (PRR = 472.2, ROR = 502.5), tetracycline (PRR = 220.4, ROR = 277), stannous fluoride (PRR = 254.3, ROR = 262.8), hydrogen peroxide (PRR = 240.0, ROR = 247.6), and chlorhexidine (PRR = 107.0, ROR = 108.4) showed stronger associations with tooth discoloration than the remaining drugs. Of 625 AE reports involving 25 drugs with positive risk signals, tooth discoloration was mostly reported in patients aged 45–64 (n = 110) and ≤18 (n = 95), and 29.4% (192/652) of the reports recorded serious outcomes.Conclusion: This study revealed that certain drugs are significantly associated with tooth discoloration. Caution should be exercised when using these drugs, especially during pregnancy and early childhood

Efficacy and safety of immunotherapy combined with single-agent chemotherapy as second- or later-line therapy for metastatic non-small cell lung cancer

ObjectiveThis study sought to assess the efficacy and safety of immunotherapy combined with single-agent chemotherapy as a second- or later-line setting for metastatic non-small cell lung cancer (NSCLC) and to provide clinical evidence for this treatment regimen. The predictive value of extracellular vesicle (EV) membrane proteins was explored in patients who underwent this treatment.MethodsClinical data from patients diagnosed with metastatic NSCLC who received immunotherapy plus single-agent chemotherapy as a second- or later-line setting were retrospectively collected between March 2019 and January 2022. A total of 30 patients met the inclusion criteria, and all were pathologically confirmed to have NSCLC. Short-term efficacy, progression-free survival (PFS), EV markers for response prediction, and adverse events were assessed.ResultsEfficacy data were available for all 30 patients and included a partial response in 5 patients, stable disease in 18 patients, and disease progression in 7 patients. The objective response rate was 16.7%, the disease control rate was 76.7%, and the median PFS was 3.2 months. Univariate analysis showed that PFS was not associated with sex, age, smoking status, treatment lines, prior use of immunotherapy, or prior use of antiangiogenic drugs. The EV membrane proteins MET proto-oncogene, receptor tyrosine kinase (c-MET), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptor 2 (VEGFR2) at baseline were associated with poor prognosis and correlated with the efficacy of immunotherapy plus chemotherapy. According to the receiver operating characteristics and Kaplan–Meier curve analyses, patients with high c-MET, EGFR, and VEGFR2 expression at baseline had significantly shorter PFS than those with low expression. In addition, VEGFR2 expression was increased after combined immunotherapy in responders, which was decreased in non-responders. The most common grade 2 or higher adverse events were neutropenia, gastrointestinal reactions, and thyroid dysfunction, all of which were tolerated.ConclusionsImmunotherapy plus single-agent chemotherapy as a second- or later-line treatment is safe, effective, and tolerable for metastatic NSCLC. EV markers can be used as predictive markers of efficacy in patients with metastatic NSCLC treated with immunotherapy plus chemotherapy to help monitor treatment efficacy and guide treatment decisions

The Sihailongwan Maar Lake, northeastern China as a candidate Global Boundary Stratotype Section and Point for the Anthropocene Series

Sihailongwan Maar Lake, located in Northeast China, is a candidate Global boundary Stratotype Section and Point (GSSP) for demarcation of the Anthropocene. The lake’s varved sediments are formed by alternating allogenic atmospheric inputs and authigenic lake processes and store a record of environmental and human impacts at a continental-global scale. Varve counting and radiometric dating provided a precise annual-resolution sediment chronology for the site. Time series records of radioactive (239,240Pu, 129I and soot 14C), chemical (spheroidal carbonaceous particles, polycyclic aromatic hydrocarbons, soot, heavy metals, δ13C, etc), physical (magnetic susceptibility and grayscale) and biological (environmental DNA) indicators all show rapid changes in the mid-20th century, coincident with clear lithological changes of the sediments. Statistical analyses of these proxies show a tipping point in 1954 CE. 239,240Pu activities follow a typical unimodal globally-distributed profile, and are proposed as the primary marker for the Anthropocene. A rapid increase in 239,240Pu activities at 88 mm depth in core SHLW21-Fr-13 (1953 CE) is synchronous with rapid changes of other anthropogenic proxies and the Great Acceleration, marking the onset of the Anthropocene. The results indicate that Sihailongwan Maar Lake is an ideal site for the Anthropocene GSSP

Genomic Insights into the Formation of Human Populations in East Asia

厦门大学人类学研究所、厦门大学生命科学学院细胞应激生物学国家重点实验室王传超教授课题组与哈佛医学院David Reich教授团队合作，联合全球43个单位的85位共同作者组成的国际合作团队通过古DNA精细解析东亚人群形成历史。研究人员利用古DNA数据检验了东亚地区农业和语言共扩散理论，综合考古学、语言学等证据，该研究系统性地重构了东亚人群的形成、迁徙和混合历史。这是目前国内开展的东亚地区最大规模的考古基因组学研究，此次所报道的东亚地区古人基因组样本量是以往国内研究机构所发表的样本量总和的两倍，改变了东亚地区尤其是中国境内考古基因组学研究长期滞后的局面。 该研究是由王传超教授团队与哈佛医学院（David Reich教授）、德国马普人类历史科学研究所（Johannes Krause教授）、复旦大学现代人类学教育部重点实验室（李辉教授和金力院士）、维也纳大学进化人类学系（Ron Pinhasi副教授）、南洋理工大学人文学院（Hui-Yuan Yeh助理教授）、俄罗斯远东联邦大学科学博物馆（Alexander N Popov研究员）、西安交通大学（张虎勤教授）、蒙古国国家博物馆研究中心、乌兰巴托国立大学考古系、华盛顿大学人类学系、台湾成功大学考古所、加州大学人类学系等全球43个单位的85位共同作者组成的国际合作团队联合完成的。厦门大学人类学研究所、厦门大学生命科学学院细胞应激生物学国家重点实验室为论文第一完成单位。厦门大学人类学研究所韦兰海副教授、胡荣助理教授、郭健新博士后、何光林博士后和杨晓敏硕士参与了研究工作。The deep population history of East Asia remains poorly understood due to a lack of ancient DNA data and sparse sampling of present-day people1,2. We report genome-wide data from 166 East Asians dating to 6000 BCE-1000 CE and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan plateau are linked by a deeply-splitting lineage likely reflecting a Late Pleistocene coastal migration. We follow Holocene expansions from four regions. First, hunter-gatherers of Mongolia and the Amur River Basin have ancestry shared by Mongolic and Tungusic language speakers but do not carry West Liao River farmer ancestry contradicting theories that their expansion spread these proto-languages. Second, Yellow River Basin farmers at ～3000 BCE likely spread Sino-Tibetan languages as their ancestry dispersed both to Tibet where it forms up ～84% to some groups and to the Central Plain where it contributed ～59-84% to Han Chinese. Third, people from Taiwan ～1300 BCE to 800 CE derived ～75% ancestry from a lineage also common in modern Austronesian, Tai-Kadai and Austroasiatic speakers likely deriving from Yangtze River Valley farmers; ancient Taiwan people also derived ～25% ancestry from a northern lineage related to but different from Yellow River farmers implying an additional north-to-south expansion. Fourth, Yamnaya Steppe pastoralist ancestry arrived in western Mongolia after ～3000 BCE but was displaced by previously established lineages even while it persisted in western China as expected if it spread the ancestor of Tocharian Indo-European languages. Two later gene flows affected western Mongolia: after ～2000 BCE migrants with Yamnaya and European farmer ancestry, and episodic impacts of later groups with ancestry from Turan.We thank David Anthony, Ofer Bar-Yosef, Katherine Brunson, Rowan Flad, Pavel Flegontov,Qiaomei Fu, Wolfgang Haak, Iosif Lazaridis, Mark Lipson, Iain Mathieson, Richard Meadow,Inigo Olalde, Nick Patterson, Pontus Skoglund, Dan Xu, and the four reviewers for valuable comments. We thank Naruya Saitou and the Asian DNA Repository Consortium for sharing genotype data from present-day Japanese groups. We thank Toyohiro Nishimoto and Takashi Fujisawa from the Rebun Town Board of Education for sharing the Funadomari Jomon samples, and Hideyo Tanaka and Watru Nagahara from the Archeological Center of Chiba City who are excavators of the Rokutsu Jomon site. The excavations at Boisman-2 site (Boisman culture), the Pospelovo-1 site (Yankovsky culture), and the Roshino-4 site (Heishui Mohe culture) were funded by the Far Eastern Federal University and the Institute of History,Archaeology and Ethnology Far Eastern Branch of the Russian Academy of Sciences; research on Pospelovo-1 is funded by RFBR project number 18-09-40101. C.C.W was funded by the Max Planck Society, the National Natural Science Foundation of China (NSFC 31801040), the Nanqiang Outstanding Young Talents Program of Xiamen University (X2123302), the Major project of National Social Science Foundation of China (20&ZD248), a European Research Council (ERC) grant to Dan Xu (ERC-2019-ADG-883700-TRAM) and Fundamental Research Funds for the Central Universities (ZK1144). O.B. and Y.B. were funded by Russian Scientific Foundation grant 17-14-01345. H.M. was supported by the grant JSPS 16H02527. M.R. and C.C.W received funding from the ERC under the European Union’s Horizon 2020 research and innovation program (grant No 646612) to M.R. The research of C.S. is supported 30 by the Calleva Foundation and the Human Origins Research Fund. H.L was funded NSFC (91731303, 31671297), B&R International Joint Laboratory of Eurasian Anthropology (18490750300). J.K. was funded by DFG grant KR 4015/1-1, the Baden Württemberg Foundation, and the Max Planck Institute. Accelerator Mass Spectrometry radiocarbon dating work was supported by the National Science Foundation (NSF) (BCS-1460369) to D.J.K. and B.J.C. D.R. was funded by NSF grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul M. Allen Frontiers Group, John Templeton Foundation grant 61220, a gift from Jean-Francois Clin, and the Howard Hughes Medical Institute. 该研究得到了国家自然科学基金“中国东南各族群的遗传混合”、国家社科基金重大项目“多学科视角下的南岛语族的起源和形成研究”、厦门大学南强青年拔尖人才支持计划A类、中央高校基本科研业务费等资助

Gut microbiota and urine metabolomics based exploration of Coreopsis tinctoria Nutt. tea on type 2 diabetic mellitus

Scented tea, as an integral part of tea culture for several centuries, is important to prevent chronic metabolic diseases. Coreopsis tinctoria Nutt. (CT) tea is often used to prevent and treat diabetes, but the mechanism of action needs further study. Liquid chromatography-mass spectrometry was used to analyze 23 chemical components of CT extracts, and a “compounds-target-healthy function” network was constructed while the pathway enrichment analysis was carried out. Eleven CT compounds, including flavanomarein, luteolin, isookanin, marein, 7,3′,5′-trihydroxy-flavanone, okanin, caffeic acid, cynaroside, acetylcoreopsin, quercetin-7-O-β-D-glucoside, protocatechuic acid, were obtained through network pharmacology screening. The corresponding targets SRC, TP53, HSP90AA1, STAT3, MAPK1, PIK3R1, AKT1 and PIK3CA were associated with anti-glycemic effects. The rat model of type 2 diabetic mellitus (T2DM) was induced by a high-fat diet combined with low-dose streptozotocin injection and biochemical indexes (blood glucose, serum total cholesterol, and triglyceride) were determined. The low-dose water extract of CT can significantly regulate the total cholesterol level of diabetic rats (p < 0.01). 16S rDNA sequencing showed that CT could reverse the imbalance of intestinal flora, especially Lactobacillus, Prevotella, Succinivibrio, unidentified_Ruminococcaceae, and Treponema. Urine metabolomics observed 31 differential metabolites, mainly related to Glycerophospholipid metabolism. The correlation study showed that CT could treat T2DM by modulating the interaction of gut microbiota composition, changes in key bacterial genera, and the levels of endogenous metabolites to act on carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways. Therefore, CT water extract can effectively alleviate the changes of T2DM may be related to the combined changes of intestinal flora and metabolic characteristics

The Petrography, Mineralogy and Geochemistry of Some Cu- and Pb-Enriched Coals from Jungar Coalfield, Northwestern China

The petrological, geochemical, and mineralogical composition of the Carboniferous-Permian coal deposit in the Jungar coalfield of inner Mongolia, Northwestern China, were investigated using optical microscopy and field emission scanning electron microscopy in conjunction with an energy-dispersive X-ray spectrometer (SEM-EDX), as well as X-ray powder diffraction, X-ray fluorescence, and inductively coupled plasma mass spectrometry. The Jungar coal is of high volatile C/B bituminous quality with 0.58% vitrinite reflectance and has a low sulfur content of 0.70% on average. Inertinite (mineral-free basis) generally dominates in coal from the lower part of the Shanxi formation, and vitrinite is the major maceral assemblage in the coal from the Taiyuan formation, which exhibits forms suggesting variation in the sedimentary environment. The Jungar coal is characterized by higher concentrations of copper (Cu) in No. 6 coal, at 55 μg/g, and lead (Pb) in No. 4 coal at 42 μg/g. Relative to the upper continental crust, the rare earth elements (REE) in the coal are characterized by light and medium–heavy REE enrichment. The minerals in the Jungar coal are mainly kaolinite, dickite, pyrite, calcite, siderite, quartz, and, to a lesser extent, gypsum and K-feldspar. The enrichment and occurrence of the trace elements, and of the minerals in the coal, are attributed to the fragmental parent rock during diagenesis and coalification. The main elements with high enrichment factors, Cu and Pb, overall exhibit a notably inorganic sulfide affinity and a weak organic affinity. Primary and epigenetic sedimentary environment and the lithology of the terrigenous parent rock are the key factors that influence the occurrence and formation of Cu and Pb in coal. The depositional environment is more influential in the formation of Cu than Pb in coal. Lead is more easily affected by the terrigenous factors than Cu when they are under a similar depositional environment

Low expression of PRMT5 in peripheral blood may serve as a potential independent risk factor in assessments of the risk of stable CAD and AMI

Abstract Background Protein arginine methyltransferases (PRMTs) can catalyse the methylation of arginine and participate in many important cellular reaction processes. The purpose of this research is to determine whether the expression levels of the PRMT5 gene in peripheral blood can be used as a biomarker for predicting the risk of Acute Myocardial Infarction (AMI). Methods In this research, peripheral blood was collected from 91 patients with AMI and 87 patients with stable coronary artery disease (CAD). Real-time fluorescent quantitative PCR was performed to measure the expression levels of the PRMT5 gene at the mRNA level, and a western blot analysis was performed to measure the expression levels of the PRMT5 gene at the protein level. Results The results indicate that at both the RNA and protein levels, the expression levels of the PRMT5 gene in peripheral blood from patients with AMI are significantly lower than those in peripheral blood from patients with stable CAD (Z = − 4.813, P = 0.000). The low expression of the PRMT5 gene is relevant to the Gensini score of the coronary artery (rs = − 0.205, P = 0.015) but is irrelevant to the serum level of blood lipids, level of cardiac troponin (rs = − 0.125, P = 0.413) and time intervals of occurrence (rs = − 0.146, P = 0.211). Patients who have a low PRMT5 expression in the peripheral blood are 5.472 times more likely to suffer from AMI than other patients. Conclusion Compared to stable CAD patients, AMI patients have a lower expression of the PRMT5 gene in their peripheral blood. Patients who have low PRMT5 gene expression in the peripheral blood are more likely to suffer from AMI than those with stable CAD. A low expression of the PRMT5 gene serves as an independent risk factor for the occurrence of AMI

Construction and Identification of Cold Tolerance in Different Broccoli Cultivars at the Seedling Stage

This study aimed to develop a systematic method for assessing the cold tolerance of broccoli seedlings, which is helpful to evaluating the cold tolerance of broccoli cultivars. We selected 14 classical broccoli cultivars and evaluated their cold tolerance by examining physiological indicators including the levels of cold resistance, electrical conductivity, malondialdehyde (MDA), soluble sugar, and hydrogen peroxide (H2O2). The results showed that there were significant differences in detected characteristics in all cultivars after cold stress during the seedling stage (p p p < 0.05). This study not only firstly provides a fundamental method for evaluating the cold tolerance in different broccoli genotypes and the other cruciferous vegetables, but also offers a scientific evidence explaining the cold tolerance of the Meiqing, King 11, and Zhongqing 15 cultivars widely cultivated in China

Tectono-Thermal Events of Coal-Bearing Basin in the Northern North China Craton: Evidence from Zircon&ndash;Apatite Fission Tracks and Vitrinite Reflectance

In order to further reveal the tectonic activity of the central and northern North China Craton (NCC) since late Paleozoic, the Datong coal-bearing basin was selected as the research object. The tectono-thermal events and uplifting cooling events of the basin were retrieved through zircon and apatite fission tracks and vitrinite reflectance measurements. The research shows that the Datong coal-bearing basin experienced three tectono-thermal events with ages of 245&ndash;207 Ma (middle&ndash;late Triassic), 179 &plusmn; 9 Ma (early Jurassic), and 140 Ma to 78 &plusmn; 11 Ma (middle&ndash;late Cretaceous), respectively. That just coincides with the lamprophyre activity, Kouquan fault activity, and Zuoyun basaltic andesite magmatic activity which surround the Datong coalfield. The basin also experienced three uplift events with the peak ages of 202 &plusmn; 18 Ma (late Triassic), 157 &plusmn; 7 Ma (late Jurassic), and 45 &plusmn; 3 Ma or 36 &plusmn; 3 Ma (middle Eocene), respectively. The Datong Permo-Carboniferous and Jurassic coal vitrinite reflectance proved that the average metamorphism temperature is 104&ndash;108 &deg;C, even reaching 163&ndash;367 &deg;C. The fission track results showed that the paleotemperature was even higher than 170&ndash;250 &deg;C from 117 to 282 Ma and 80&ndash;120 &deg;C from 20 to 68 Ma, in the Datong coal-bearing basin. The results show that the deep tectonic activities of the NCC were still active in the Mesozoic and even Cenozoic Paleogene