Population genetic differentiation and phenotypic plasticity of Ambrosia artemisiifolia under different nitrogen levels.

Rapid adaptive evolution and phenotypic plasticity are two mechanisms that often underlie invasiveness of alien plant species, but whether they can co-occur within invasive plant populations under altered environmental conditions such as nitrogen (N) enrichment has seldom been explored. Latitudinal clines in plant trait responses to variation in environmental factors may provide evidence of local adaptation. Here, we inferred the relative contributions of phenotypic plasticity and local adaptation to the performance of the invasive plant Ambrosia artemisiifolia under different soil N levels, using a common garden approach. We grew A. artemisiifolia individuals raised from seeds that were sampled from six invasive populations along a wide latitudinal cline in China (23°42' N to 45°43' N) under three N (0, 5, and 10 g N m-2 ) levels in a common garden. Results show significant interpopulation genetic differentiation in plant height, number of branches, total biomass, and transpiration rate of the invader A. artemisiifolia across the N treatments. The populations also expressed genetic differentiation in basal diameter, growth rate, leaf area, seed width, root biomass, aboveground biomass, stomatal conductance, and intercellular CO2 concentration regardless of N treatments. Moreover, plants from different populations of the invader displayed plastic responses in time to first flower, hundred-grain weight, net photosynthetic rate, and relative biomass allocation to roots and shoots and seed length under different N treatments. Additionally, individuals of A. artemisiifolia from higher latitudes grew shorter and allocated less biomass to the roots regardless of N treatment, while latitudinal cline (or lack thereof) in other traits depended on the level of N in which the plants were grown. Overall, these results suggest that rapid adaptive evolution and phenotypic plasticity in the various traits that we quantified may jointly contribute to invasiveness of A. artemisiifolia under different levels of N availability. More broadly, the results support the idea that phenotypic plasticity and rapid adaptive evolution can jointly enable invasive plants to colonize a wide range of environmental conditions.

The interval between the onset of increased blood pressure and proteinuria in preeclampsia and the contributing factors.

PURPOSE: New-onset proteinuria, as a pivotal sign of representative renal lesions in preeclampsia, is still the most common diagnostic tool for this condition and has been proven to be related to a significantly abnormal sFlt-1/VEGF ratio in circulation. At the same time, blood pressure control plays a vital role in the occurrence and evolution of proteinuria. Therefore, it is particularly helpful to investigate their interval, not only for performing urinalysis for protein more accurately but also for evaluating blood pressure as well as the aggravation of illness, as the related research is limited. METHODS: This retrospective study included 515 preeclampsia patients and 358 normotensive pregnant women who labored in the Second Hospital of Tianjin Medical University from January 2016 to January 2020. First, we described the onset circumstance of high blood pressure and proteinuria as well as the interval among the case group and the subgroups. Then, we determined whether there were significant differences in the basic information, laboratory test results, and newborns between the case and normal groups. Finally, multifactor ANOVA was used to determine the factors influencing the interval. RESULTS: 1. The two most common complications in preeclampsia were proteinuria (88.35%) and placental dysfunction (5.05%). Moreover, 72.04% of preeclampsia cases were diagnosed by abnormal blood pressure together with new-onset proteinuria. 2. The average interval between high blood pressure and proteinuria was 22 gestational days (from 0 to 106 days), and this interval was not significantly different between mild and severe PE (26 days vs. 21 days, P > 0.05) but significantly differed between early-onset and late-onset PE (9 days vs. 28 days, P < 0.05). 3. The number of prenatal visits, serum creatinine in the early trimester, gestational time and diastolic blood pressure value when increased blood pressure was initially detected may influence the interval between the onset of increased blood pressure and proteinuria. CONCLUSION: New-onset proteinuria was still the main parameter for identifying preeclampsia. The interval between increased blood pressure and proteinuria was probably related to the imbalance in the sFlt-1/VEGF ratio; therefore, we should pay attention to monitor proteinuria during the prenatal visits, especially for patients with a lower frequency of prenatal visits, higher serum creatinine in the early trimester, earlier onset and higher diastolic blood pressure at the initial onset of increased blood pressure.

Combined assessment of health hazard and odour impact of soils at a contaminated site: a case study on a defunct pharmaceuticals factory in China.

Surveys and assessments of contaminated sites primarily focus on hazardous pollutants in the soil with less attention paid to odorants. This makes the management of contaminated sites difficult. In this study, hazardous and odorous pollutants in the soil were assessed for a large site that was previously used for production of pharmaceuticals to determine the degree and characteristics of soil contamination at pharmaceutical production sites, for undertaking rational remediation measures. The main hazardous pollutants at the study site were triethylamine, n-butyric acid, benzo(a)pyrene (BaP), N-nitrosodimethylamine (NDMA), dibenzo(a,h)anthracene (DBA), total petroleum hydrocarbons (C10-C40) (TPH), and 1,2-dichloroethane; TEA, BA, and isovaleric acid (IC) were the main odorants. As the type and distribution of hazardous and odorous pollutants differ, it is necessary to separately assess the impact of these pollutants at a contaminated site. Soils in the surface layer pose significant non-carcinogenic (HI = 68.30) and carcinogenic risks (RT = 3.56E-5), whereas those in the lower layer only pose non-carcinogenic risks (HI > 7.43). Odorants were found at considerable concentrations both in the surface and lower layers, with the maximum concentrations being 29,309.91 and 41.27, respectively. The findings of this study should improve our understanding of soil contamination at former pharmaceutical production sites and should inform the assessment of the risks posed by contaminated sites, with problems associated with odour, and possible remediation strategies.

Association between early childhood caries and diet quality among Chinese children aged 2-5 years.

Background: Early childhood caries (ECC) is a major oral problem affecting the health and wellbeing of children worldwide. Diet quality is a better predictor of ECC risk than single foods or specific nutrients. The purposes of this study were to assess the associations between ECC and diet quality among 2- to 5-year-old Chinese children. Methods: A total of 150 eligible children were included in this study. The decayed, missing, or filled surface (dmfs) score was recorded for each child by dental examination. All participants were divided into three groups based on their age and dmfs score [the caries-free group, the ECC group, and the severe early childhood caries (S-ECC) group]. Parents were invited to complete a questionnaire on the general characteristics and oral health behaviors of the participants. The information of 24-h dietary intake from each child was captured via a mobile APP. The Chinese diet balance index for preschool children (DBI_C) indicators score, high bound score (HBS), low bound score (LBS), and diet quality distance (DQD) score were calculated to assess the diet quality of study subjects. The associations of ECC with HBS, LBS, DQD score, and DBI_C indicators score were analyzed by Mann-Whitney U test and multivariable logistic regression analysis. Results: In this study, 21, 31, and 98 children were diagnosed with caries-free, ECC, and S-ECC, respectively. Statistical analysis revealed that the risk of ECC and S-ECC were significantly increased with the DQD score (OR = 1.283 and 1.287, respectively), but both were not associated with HBS and LBS (P > 0.05). In the meantime, the risk of ECC and S-ECC were significantly increased with the Grains score (OR = 1.623 and 1.777, respectively), and significantly decreased with the Food diversity score (OR = 0.271 and 0.315, respectively). Moreover, the risk of S-ECC also significantly decreased with the Vegetables score (OR = 0.137). Conclusion: Both ECC and S-ECC were associated with a high degree of dietary imbalance and grains intake as well as a low degree of food diversity among Chinese children aged 2-5 years. In addition, S-ECC was also associated with a low degree of vegetable intake.

Phylogenetic Relationships and Disturbance Explain the Resistance of Different Habitats to Plant Invasions.

Invasive alien plants have invaded various habitats, posing a threat to biodiversity. Several hypotheses have been proposed to explain the mechanisms of invasion, but few studies have considered the characteristics of the invaded communities and the effects of human interference in the invasion. In this study, we compared the invasibility of three different habitats: abandoned land, eucalyptus plantations, and natural secondary forests. We explored the effects of species diversity, phylogenetic diversity, and disturbance factors on the invasibility of different habitats. The results showed that the invasibility of abandoned land was the highest and the invasibility of the natural secondary forest was the lowest. Phylogenetic indicators affected the invasibility of abandoned land and eucalyptus plantations, and disturbance factors affected the invasibility of all three habitats, while the characteristics of the invaded communities had a weak impact. Our research provided supporting evidence for Darwin's naturalization hypothesis and his disturbance hypothesis but found no relationship between biotic resistance and invasibility. This study indicated that the differences among habitats should be considered when we prove Darwin's naturalization hypothesis in nature reserves.

Relationship between preterm, low birth weight, and development defects of enamel in the primary dentition: A meta-analysis.

Background: This study aimed to systematically analyze the relationship between preterm (PT), low birth weight (LBW), and developmental defects of enamel (DDE) in the primary dentition. Methods: Following the retrieval of the databases, case-control studies, cross-sectional studies, and cohort studies on the relationship between PT, LBW and DDE, which had been published in English or Chinese up to January 2022 were included. The data about odds ratio (OR) and 95% confidence interval (95% CI) were extracted and calculated using STATA 12.0 Software. Case-control studies were evaluated using the Newcastle-Ottawa Scale (NOS), while cross-sectional studies and cohort studies were evaluated using the JBI scale. The heterogeneity of each study was evaluated using the Q test. Results: A total of 15 studies were included, of which 8 studied the relationship between PT and DDE, and 13 explored the relationship between LBW and DDE including three about the relationship between very low birth weight (VLBW) and DDE. Seven studies explored the relationship between PT, LBW, and DDE. The results of this meta-analysis showed that both PT and LBW especially VLBW (OR = 7.19, 95% CI: 4.98-10.38) were risk factors for DDE in the primary dentition (OR = 2.33, 95% CI: 1.55-3.51) (OR = 1.67, 95% CI: 1.08-2.59). The subgroup results showed that PT and LBW were both associated with the occurrence of enamel hypoplasia (EHP) (OR = 6.89, 95% CI: 3.33-14.34; OR = 2.78, 95% CI: 2.10-3.68) rather than enamel opacity (OR = 0.94, 95% CI: 0.55-1.61; OR = 1.03, 95% CI: 0.66-1.61). There was no publication bias about the included studies (P = 0.75 > 0.05; P = 0.47 > 0.05). Conclusion: This meta-analysis demonstrated that both PT and LBW especially VLBW are associated with a higher risk of DDE in the primary dentition. PT and LBW are both related to the occurrence of EHP. However, the relationship between PT, LBW, and enamel opacity has not been verified. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42021262761.

Elevated CO2 and Increased N Intensify Competition between Two Invasive Annual Plants in China.

As multiple invaders often co-occur, understanding the interactions between different invasive species is important. Previous studies have reported on invasional meltdown and neutral and interference relationships between invasive species. However, interspecific interactions may vary with environmental change owing to the different responses of interacting invaders. To better understand the interaction of notorious invasive alien plants under CO2 enrichment and N deposition, the growth characteristics of common ragweed (Ambrosia artemisiifolia) and redroot pigweed (Amaranthus retroflexus) were studied when they were planted in monoculture (4Rag and 4Pig) or mixture (1Rag:3Pig, 2Rag:2Pig, 3Rag:1Pig) under four environmental treatments: elevated CO2, increased N, elevated CO2 + increased N and a control. Increased N positively affected almost all the traits (basal stem diameter, height, shoot biomass, root biomass and total biomass) of common ragweed, except for branch number and root-shoot ratio. But increased N only promoted redroot pigweed's height and basal stem diameter. interspecific competition promoted basal stem diameter and number of branches but decreased root biomass of common ragweed, and the basal stem diameter was significantly higher in 1Rag:3Pig and 2Rag:2Pig compared to the other two treatments. interspecific competition inhibited almost all the characteristics of redroot pigweed. The interaction between elevated CO2 and increased N also increased the biomass characteristics (shoot biomass, root biomass and total biomass) of common ragweed. However, elevated CO2 inhibited the root biomass of redroot pigweed. The results indicated that common ragweed was a superior competitor under conditions of elevated CO2 and increased N. Moreover, environmental change might strengthen the super-invasive plant common ragweed's competitive ability.

Ameliorative effects of chickpea flavonoids on redox imbalance and mitochondrial complex I dysfunction in type 2 diabetic rats.

Chickpeas are an important source of flavonoids in the human diet, and researchers have demonstrated that flavonoids have antidiabetic compositions in chickpeas. Because the NAD+/NADH redox balance is heavily perturbed in diabetes and complex I is the only site for NADH oxidation and NAD+ regeneration, in the present study, mitochondrial complex I was used as a target for anti-diabetes. The objective of this study was to investigate the effects of a crude chickpea flavonoid extract (CCFE) on NAD+/NADH redox imbalance and mitochondrial complex I dysfunction in the pancreas as well as oxidative stress in type 2 diabetes mellitus (T2DM) rats. Our results demonstrated that the degree of NAD+/NADH redox imbalance in the pancreas of T2DM rats was alleviated by CCFE, which is likely attributed to the inhibition of the polyol pathway and the decrease in poly ADP ribose polymerase (PARP) and sirtuin 3 (Sirt3) activities. Moreover, mitochondrial complex I dysfunction in the pancreas of T2DM rats was ameliorated by CCFE through the suppression of the activity of complex I. Furthermore, CCFE treatment could attenuate oxidative stress in T2DM rats, which was proven by the reduction in hydrogen peroxide (H2O2) and malondialdehyde (MDA) as well as the upregulation of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in serum. CCFE treatment significantly improved dyslipidemia in T2DM rats.

Water Uptake Tradeoffs of Dominant Shrub Species in the Coastal Wetlands of the Yellow River Delta, China.

Tamarix chinensis and Ziziphus jujuba are two dominant shrub species on Chenier Island in the Yellow River Delta, China. Water is a restrictive factor determining the plant growth, vegetation composition, and community succession in this coastal zone. We investigated how water uptake tradeoffs of the two shrub species responded to soil water fluctuations caused by seasonal variations of precipitation. The soil water content, salinity and δ18O values of potential water sources (soil water in 0-20, 20-40, 40-60, and 60-100 cm soil layers, and groundwater) and plant xylem water were measured in wet (July 2013) and dry (July 2014) seasons. The IsoSource model was employed to calculate the contributions of different water sources to plant xylem water. The results showed that δ18O values of soil water decreased significantly with soil depth in the dry season, while increased significantly with soil depth in the wet season. In the wet season, when the soil water was abundant, Z. jujuba mostly used the soil water from the 60-100 cm layer, while T. chinensis took up a mixture of groundwater and soil water from the 60-100 cm layer. In the dry season, when the soil water was depleted because of low precipitation, Z. jujuba mainly took up a mixture of the soil water from 20 to 100 cm soil layers, while T. chinensis mainly used groundwater. T. chinensis and Z. jujuba showed different ecological amplitudes of water sources during dry and wet seasons. The niche differentiation of major water sources for T. chinensis and Z. jujuba demonstrated their adaptabilities to the fluctuations of soil moisture in water-limited ecosystems. Water niche differentiations of coexisting shrub species were expected to minimize their competition for limited water sources, contributing to successful coexistence and increasing the resilience of the coastal wetland ecosystem to drought.

The Role of Genetic Factors in the Differential Invasion Success of Two Spartina Species in China.

Biological invasions have become one of the greatest threats to global biodiversity and ecosystem conservation. Most previous studies have revealed how successful invasive species adapt to new environments and climate change through phenotypic and genetic evolution. Some researchers suggested that understanding unsuccessful or less successful biological invasions might be important for understanding the relationships between invasion adaptability and climate factors. We compared the sexual reproduction ability, genetic diversity, and gene × environment interaction in two intentionally introduced alien species in China (Spartina anglica and Spartina alterniflora) based on restriction site-associated DNA (RAD) sequencing. After more than 50 years, the distribution of S. alterniflora has rapidly expanded, while S. anglica has experienced extreme dieback. A total of 212,939 single nucleotide polymorphisms (SNPs) for the two Spartina species were used for analysis. The multilocus genotype (MLG) analysis revealed that clonal reproduction was the prevalent mode of reproduction in both species, indicating that a change in the mode of reproduction was not the key factor enabling successful invasion by Spartina. All genetic diversity indicators (He, Ho, π) in S. alterniflora populations were at least two times higher than those in S. anglica populations, respectively (p < 0.001). Furthermore, the population genetic structure and stronger patterns of climate-associated loci provided support for rapid adaptive evolution in the populations of S. alterniflora in China. Altogether, our results highlight the importance of genetic diversity and local adaptation, which were driven by multiple source populations, in increasing the invasiveness of S. alterniflora.

Computational methods, databases and tools for synthetic lethality prediction.

Synthetic lethality (SL) occurs between two genes when the inactivation of either gene alone has no effect on cell survival but the inactivation of both genes results in cell death. SL-based therapy has become one of the most promising targeted cancer therapies in the last decade as PARP inhibitors achieve great success in the clinic. The key point to exploiting SL-based cancer therapy is the identification of robust SL pairs. Although many wet-lab-based methods have been developed to screen SL pairs, known SL pairs are less than 0.1% of all potential pairs due to large number of human gene combinations. Computational prediction methods complement wet-lab-based methods to effectively reduce the search space of SL pairs. In this paper, we review the recent applications of computational methods and commonly used databases for SL prediction. First, we introduce the concept of SL and its screening methods. Second, various SL-related data resources are summarized. Then, computational methods including statistical-based methods, network-based methods, classical machine learning methods and deep learning methods for SL prediction are summarized. In particular, we elaborate on the negative sampling methods applied in these models. Next, representative tools for SL prediction are introduced. Finally, the challenges and future work for SL prediction are discussed.

Probing depth reduction of laser application in periodontal therapy: a network meta-analysis.

The aim was to systematically evaluate the probing depth (PD) reduction of lasers in scaling and root planing (SRP) of chronic periodontitis by network meta-analysis (NMA). Randomized controlled clinical trials (RCTs) were searched through electronic-search and hand-search up to January 2020. Standard mean different (SMD) and 95% confidence interval (CI) were counted for PD reduction. The random-effects NMA were performed using mvmeta routine in STATA software (version 13). This NMA analysed seven periodontal treatments through 37 RCTs. No inconsistency was detected. Compared with mechanical SRP, significant differences were in favour of diode laser (DL) as adjunct at 3 months (SMD = 0.61; 95% CI range: 0.27-0.96) and Nd:YAG as adjunct (SMD = 0.29; 95% CI range: 0.03-0.55), Er,Cr:YSGG as monotherapy (SMD = 0.37; 95% CI range: 0.04-0.71) and Er,Cr:YSGG as adjunct (SMD = 0.53; 95% CI range: 0.23-0.84) at 6 months after treatment. Compared with Er:YAG as monotherapy, significant differences were in favour of DL as adjunct at 6 months (SMD = 0.51; 95% CI range: 0.07-0.95) after treatment. In terms of PD reduction at 3-month follow-up, the ranking result from best to worst was Nd:YAG as adjunct, DL as adjunct, Er:YAG as adjunct, Er,Cr:YSGG as monotherapy, Er:YAG as monotherapy and mechanical SRP. In terms of PD reduction at 6-month follow-up, the ranking result was DL as adjunct, Nd:YAG as adjunct, Er:YAG as adjunct, Er,Cr:YSGG as adjunct, Er:YAG as monotherapy, Er,Cr:YSGG as monotherapy and mechanical SRP. Laser-assisted periodontal treatment has better PD reduction.

Fusing multidimensional hierarchical information into finer spatial landscape metrics.

One of the core issues of ecology is to understand the effects of landscape patterns on ecological processes. For this, we need to accurately capture changes in the fine landscape structures to avoid losing information about spatial heterogeneity. The landscape pattern indicators (LPIs) can characterize the spatial structures and give some information about landscape patterns. However, researches on LPIs had mainly focused on the horizontal structure of landscape patterns, while few studies addressed vertical relationships between the levels of hierarchical landscape structures. Thus, the ignorance of the vertical hierarchical relationships may cause serious biases and reduce LPIs' representational ability and accuracy. The hierarchy theory about the landscape pattern structures could notably reduce the loss of hierarchical information, and the information entropy could quantitatively describe the vertical status of landscape units. Therefore, we established a new multidimensional fusion method of LPIs based on hierarchy theory and information entropy. Here, we created a general fusion formula for commonly used simple LPIs based on two-grade land use data (whose land use classification system contains two grades/levels) and derived 3 fusion landscape pattern indicators (FLIs) with a case study. The results show that the information about fine spatial structure is captured by the fusion method. The regions with the most differences between the FLIs and the traditional LPIs are those with the largest vertical structure such as the ecological ecotones, where vertical structure was ignored before. The FLIs have a finer spatial representational ability and accuracy, not only retaining the main trend information of first-grade land use data, but also containing the internal detail information of second-grade land use data. Capturing finer spatial information of landscape patterns should encourage the application of fusion method, which should be suitable for more LPIs or more dimensional data. And the increased accuracy of FLIs will improve ecological models that rely on finer spatial information.

Distribution, sources, and ecological risk assessment of polycyclic aromatic hydrocarbons (PAHs) in the tidal creek water of coastal tidal flats in the Yellow River Delta, China.

The concentrations, distribution, sources and ecological risk levels of polycyclic aromatic hydrocarbons (PAHs) in tidal creek water from coastal tidal flats of the Yellow River Delta were investigated. The concentrations of 16 PAHs ranged from 0.113 to 1.533, with a mean value of 0.496 ± 0.035 µg L-1, which indicated a moderate level of pollution. The main long-term sources of PAHs in the coastal tidal flats of the Yellow River Delta were petroleum combustion and petroleum pollution. The ecological risk assessment showed that the levels of PAHs in tidal creek water of the coastal tidal flats in the Yellow River Delta corresponded to medium to high ecological risk levels, and a high probability of potential ecological risk, posing harm to aquatic organisms. Among the 7 sampling sites, site 5, site 6, and site 7 were at high ecological risk, and the other sites were at moderate ecological risk. PAH pollution in the tidal creek water near the Yellow River Estuary and farther south, in the coastal tidal wetland of Laizhou Bay, deserves special attention, especially with respect to the prevention and control of benzo[a]pyrene (BaP) pollution in the water.

NtAIDP1, a novel NtJAZ interacting protein, binds to an AT-rich region to activate the transcription of jasmonate-inducible genes in tobacco.

In plants, jasmonate ZIM-domain proteins (JAZs) act as critical regulators, interacting physically with transcription factors (TFs) and other transcriptional regulators to modulate jasmonate (JA)-responsive gene expression and participate in crosstalk with other hormone signalling pathways. Identifying novel JAZ-interacting proteins will provide new insights into JA signalling cascades in plants. Here, we performed yeast two-hybrid screening to identify 70 NtJAZ1-interacting proteins, including an A/T-rich interaction domain containing protein 1 (NtAIDP1) from JA-treated tobacco Bright Yellow-2 (BY-2) cells. NtAIDP1 is localised in the nucleus and interacts with NtJAZ1 via its C-terminal heat shock protein 20 (HSP) domain. Aside from NtJAZ1, NtAIDP1 also interacts with other JA-inducible NtJAZs, including NtJAZ2b, NtJAZ2b.2, NtJAZ5, NtJAZ7, NtJAZ11 and NtJAZ12, but not with NtJAZ3, NtJAZ3b or NtJAZ10, and interacts with NtNINJA, NtDELLA1 and NtDELLA2 in the yeast two-hybrid assay. Furthermore, NtAIDP1 binds to the AT-rich region of the GAG fragment of the putrescine N-methyltransferase 1a (NtPMT1a) promoter and activates the transcriptional activity of the GAG fragment, whereas NtMYC2a interacts with and competitively inhibits the transactivational activity of NtAIDP1 in Arabidopsis mesophyll protoplasts. Overexpression of NtAIDP1 promotes the transcription of NtPDF1.2 and NtJAZ1, but has little effect on the expression of NtPMT1a, quinolinate phosphoribosyltransferase 2 (NtQPT2), and NtMYC2a in tobacco. These results indicate that NtAIDP1 is a new component of the JA signalling pathway and is involved in JA-regulated gene expression.

Safety, Pharmacokinetics and Pharmacodynamics of Multiple Escalating Doses of PEGylated Exenatide (PB-119) in Healthy Volunteers.

BACKGROUND AND OBJECTIVE: At present, the deficiency of ß-cell function is progressive in patients with type 2 diabetes mellitus. Exenatide cannot only control blood glucose well, but also promotes the regeneration and proliferation of islet ß-cells and improves the function of ß cells. However, it needs to be given twice a day, and there are many adverse reactions such as nausea. PEGylated exenatide (study code: PB-119) needs to be administered only once a week. The purpose of this experiment was to evaluate the safety, pharmacokinetics and pharmacodynamics of an escalating dose regimen of subcutaneous PEGylated exenatide injections in healthy subjects. METHODS: Twelve healthy young adult subjects in each group received once-weekly subcutaneous injections of 165 µg, 330 µg, and 660 µg PEGylated exenatide for 6 weeks. Plasma drug concentration was determined in venous blood collected across selected time points. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, and electrocardiogram. Blood glucose, insulin,  glucagon and C peptide were monitored at different time points to evaluate the pharmacodynamics of PEGylated exenatide. RESULTS: A total of 11, 10, and 12 subjects completed the study in 165 µg, 330 µg, and 660 µg dose groups, respectively. After 6 consecutive weeks of administration, the t1/2 in the 165 µg, 330 µg, and 660 µg dose groups was 55.67 ± 11.03 h, 56.99 ± 21.37 h, and 54.81 ± 13.87 h, respectively. The Cavg was 4.22 ± 0.78 ng/ml, 6.03 ± 1.43 ng/ml, and 10.50 ± 3.06 ng/ml, respectively. AUCss was 708.59 ± 131.87 h•ng/ml, 1012.63 ± 240.79 h•ng/ml, and 1763.81 ± 514.50 h•ng/ml, respectively. The accumulation index was 1.15 ± 0.07, 1.17 ± 0.11, and 1.14 ± 0.07. The CLss/F was 241.25 ± 51.13 ml/h, 341.53 ± 73.62 ml/h, and 450.06 ± 313.76 ml/h, respectively. A total of 10 of 36 (27.78%) subjects in the three dose groups developed specific antibodies after consecutive subcutaneous injections of PEGylated exenatide. The Cavg and Cmax were higher than those of antibody-negative subjects. Furthermore, in antibody-positive subjects, CLss/F, t1/2, AUCτ, accumulation index, MRT(0-inf) and other parameters were lower than those of antibody-negative subjects. In the 165 µg dose group, two subjects (16.67%) experienced 4 adverse events. In the 330 µg dose group, no subjects reported adverse events. In the 660 µg dose group, 8 subjects (66.67%) reported 16 adverse events, which were mostly gastrointestinal. There were no significant changes in the pharmacodynamic parameters except the glucagon level at day 36 in the 660 µg dose group, the 2h postprandial insulin and C peptide levels at day 36 and day 50 in the 165 µg dose group compared with baseline (- 1 day). CONCLUSION: A once-weekly subcutaneous injection of 165 µg and 330 µg PEGylated exenatide is safe. No significant effects on blood glucose or pancreatic hormone levels were observed in the subjects within these dose groups. The pharmacokinetic parameters of PEGylated exenatide may be affected by immunogenicity. CLINICAL TRIALS REGISTRATION: The study is registered at clinicaltrials.gov (No. NCT03062774).

Phase I safety, tolerability, and pharmacokinetic studies of tetramethylpyrazine nitrone in healthy Chinese volunteers.

BACKGROUND: The purpose of this study was to investigate the safety, tolerability and pharmacokinetics of tetramethylpyrazine nitrone (TBN) in healthy Chinese volunteers. METHODS: A single-ascending-dose (SAD) study where 68 subjects were randomized to a single dose of placebo or TBN (50, 100, 200, 400, 700, 1,000, 1,400, or 1,800 mg) through IV infusion over 30 min. A multiple-ascending-dose (MAD) study where 24 subjects received TBN twice daily (with 12 hr interval) for total 6.5 days at doses of either 700 or 1,400 mg. Adverse events were recorded and pharmacokinetic samples were collected during the whole study period. RESULTS: No serious adverse events were found in the study. All of the observed adverse events, including increased white blood cell (4.4% subjects) and neutrophil counts (4.4% subjects), and decreased hemoglobin levels (4.2% subjects), were laboratory test abnormalities. All the adverse events were mild and tolerable, and returned to normal without any intervention. In the SAD study, linear Cmax values were observed in the dose interval of 50-1,800 mg. In the MAD study, the average steady-state concentrations (Cavg.ss ) of TBN in the 700 and 1,400 mg dose group were 2,407 and 5,837 ng/ml, respectively. No drug accumulation was observed in this study. CONCLUSIONS: TBN is well tolerated in healthy volunteers. Linear Cmax values were observed in the interval of 50-1,800 mg, and target exposures of TBN were achieved without accumulation after twice daily administration to subjects. (This study has been registered at ChiCTR.org.cn. Identifier: ChiCTR1800016225 and ChiCTR1800019627.).

Clinical effectiveness of Er,Cr:YSGG lasers in non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled trials.

The meta-analysis aimed to systematically evaluate all the available pieces of evidence concerning the clinical effectiveness of Er,Cr:YSGG lasers (erbium, chromium, yttrium scandium gallium garnet laser) in the non-surgical treatment of patients with chronic periodontitis, and provide guidance for clinicians about the application of Er,Cr:YSGG lasers during the process of non-surgical periodontal treatments. The meta-analysis was conducted with data extracted from 16 randomized controlled clinical trials (RCTs) that compare Er,Cr:YSGG lasers adjunct/substitute to scaling and root planing (SRP) with SRP alone for the treatment of chronic periodontitis published in English or Chinese from January 2000 to January 2020. The weighted mean differences (WMDs) and 95% confidence intervals (CIs) were counted for probing depth (PD) reduction, clinical attachment level (CAL) gain, and visual analogue scale (VAS) score. Heterogeneity of each study was evaluated with the Q test. The publication bias was measured using Begg's adjusted rank correlation test. Sixteen RCTs with 606 patients were included in the meta-analysis. There were statistically significant differences between Er,Cr:YSGG lasers adjunct/substitute to SRP and SRP alone in the PD reduction at 1-month follow-up (WMD = ­ 0.35, 95% CI [- 0.63, ­ 0.07], P = 0.013), 3-month follow-up (WMD = - 0.342, 95% CI [- 0.552, - 0.132], P = 0.001), CAL gain at 3-month follow-up (WMD = - 0.17, 95% CI [- 0.31, 0.03], P = 0.017), and VAS score (WMD = - 2.395, 95% CI [- 3.327, - 1.464], P = 0.000) immediately after treatment. There were no significant differences of PD reduction and CAL change at 6-month follow-up. The present meta-analysis indicated that Er,Cr:YSGG lasers provided additional effectiveness in PD reduction and CAL gain at short-term follow-ups and there was less pain compared with SRP alone.

Validation of Stenus (Hypostenus) primivenatus and Stenus (Hypostenus) yiae (Coleoptera, Staphylinidae, Steninae).

Holotype depository was not indicated for the new species, Stenus (Hypostenus) primivenatus and Stenus (Hypostenus) yiae, described as new in the publication Zhao Zhou (2008). Missing this important message made these two species-group names unavailable according to the fourth edition of the International Code of Zoological Nomenclature (the Code, ICZN, 1999: Article 16.4). This problem was first denoted by Schülke, M. Smetana, A. (2015).

Relationship between preterm, low birth weight and early childhood caries: a meta-analysis of the case-control and cross-sectional study.

Early childhood caries (ECC) is one of the most prevalent chronic infectious diseases in children. The effective prevention and treatment are heavy burdens and study hotspots for pediatric dentists. Many studies had investigated the relationship between preterm, low birth weight (LBW) and ECC; however, the results were inconsistent. The present study was conducted with an evidence-based study to figure out the relationship between preterm, LBW and ECC for the first time. After searching the database, case-control and cross-sectional studies relevant to the relationship between preterm, LBW and ECC up to December 2019 were included. The data about odds ratio (OR) and 95% confidence interval (95% CI) were extracted and calculated with STATA 14.0 Software. A total of 22 studies were included in this meta-analysis, 9 studies of which did not only explore the relationship between ECC with preterm, but also study the relationship between ECC and LBW, 7 studies of which explored the relationship between preterm and ECC, and 6 studies of which studied the relationship between LBW and ECC. The meta-analysis results showed that the preterm increased the risk of ECC (OR = 1.59, 95% CI: 1.36-1.87) significantly. There was no difference between LBW and normal birth weight in the incidence of ECC (OR = 1.12, 95% CI: 0.94-1.33). The meta-analysis results of adjustment OR about LBW were similar to the crude OR (OR = 1.05, 95% CI: 0.71-1.57). This meta-analysis indicated that preterm increased the risk of ECC significantly; however, LBW was not a risk factor for ECC.