Real-world outcomes associated with bevacizumab combined with chemotherapy in platinum-resistant ovarian Cancer.

OBJECTIVES: The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical trials. We explored real-world outcomes in Ontario, Canada, and compared survival in the pre- and post-bevacizumab era. METHODS: Administrative databases were utilized to identify all patients treated with bevacizumab for PL-R OC. Time on treatment (ToT) was used as surrogate for PFS. Median OS was determined using the Kaplan-Meier method. Factors associated with ToT/OS were identified using a Cox proportional hazard model. A before and after comparative effectiveness analysis was performed to determine mOS for patients treated pre- and post-bevacizumab approval. RESULTS: From 2017 to 2019, 176 patients received bevacizumab. Median ToT was 3 months and OS was 11 months. Sixty-four percent received liposomal doxorubicin and 34% received paclitaxel. ToT (6 vs 3 months; HR 0.44; p < 0.0001) and OS (14 vs 9 months; HR 0.45; p = 0.0089) were longer with bevacizumab/paclitaxel. OS was not significantly different pre- and post-bevacizumab funding (8 vs 9 months; HR 1.01; 0.937). Median OS increased for those receiving paclitaxel (6 vs 11 months), but those in the post group were younger, more likely to have undergone primary surgery and had less co-morbidities. CONCLUSION: Real-world outcomes with bevacizumab in PL-R OC are inferior to those in the pivotal clinical trial. Survival has not significantly improved since funding became publicly available, indicating a substantial efficacy-effectiveness gap between trial and real-world outcomes. Median OS and ToT were significantly better when bevacizumab was given with paclitaxel.

Precipitation Drives Soil Protist Diversity and Community Structure in Dry Grasslands.

Protists are essential components of soil microbial communities, mediating nutrient cycling and ecosystem functions in terrestrial ecosystems. However, their distribution patterns and driving factors, particularly, the relative importance of climate, plant and soil factors, remain largely unknown. This limits our understanding of soil protist roles in ecosystem functions and their responses to climate change. This is particularly a concern in dryland ecosystems where soil microbiomes are more important for ecosystem functions because plant diversity and growth are heavily constrained by environmental stresses. Here, we explored protist diversity and their driving factors in grassland soils on the Tibetan Plateau, which is a typical dryland region with yearly low temperatures. Soil protist diversity significantly decreased along the gradient of meadow, steppe, and desert. Soil protist diversity positively correlated with precipitation, plant biomass and soil nutrients, but these correlations were changed by grazing. Structural equation and random forest models demonstrated that precipitation dominated soil protist diversity directly and indirectly by influencing plant and soil factors. Soil protist community structure gradually shifted along meadow, steppe and desert, and was driven more by precipitation than by plant and soil factors. Soil protist community compositions were dominated by Cercozoa, Ciliophora and Chlorophyta. In particular, Ciliophora increased but Chlorophyta decreased in relative abundance along the gradient of meadow, steppe and desert. These results demonstrate that precipitation plays more important roles in driving soil protist diversity and community structure than plant and soil factors, suggesting that future precipitation change profoundly alters soil protist community and functions in dry grasslands.

Identification of a novel PTH1R variant in a family with primary failure of eruption.

BACKGROUND: Primary failure of tooth eruption (PFE) is a rare autosome genetic disorder that causes open bite. This work aimed to report a small family of PFE(OMIM: # 125,350) with a novel PTH1R variant. One of the patients has a rare clinical phenotype of the anterior tooth involved only. CASE PRESENTATION: The proband was a 13-year-old young man with an incomplete eruption of the right upper anterior teeth, resulting in a significant open-bite. His left first molar partially erupted. Family history revealed that the proband's 12-year-old brother and father also had teeth eruption disorders. Genetic testing found a novel PTH1R variant (NM_000316.3 c.1325-1336del), which has never been reported before. The diagnosis of PFE was based on clinical and radiographic characteristics and the result of genetic testing. Bioinformatic analysis predicted this variant would result in the truncation of the G protein-coupled receptor encoded by the PTH1R, affecting its structure and function. CONCLUSION: A novel PTH1R variant identified through whole-exome sequencing further expands the mutation spectrum of PFE. Patients in this family have different phenotypes, which reflects the characteristics of variable phenotypic expression of PFE.

Similar heterotrophic communities but distinct interactions supported by red and green-snow algae in the Antarctic Peninsula.

Snow algae are predicted to expand in polar regions due to climate warming, which can accelerate snowmelt by reducing albedo. Green snow frequently occurs near penguin colonies, and red snow distributes widely along ocean shores. However, the mechanisms underpinning the assemblage of algae and heterotrophs in colored snow remain poorly characterized. We investigated algal, bacterial, and fungal communities and their interactions in red and green snows in the Antarctic Peninsula using a high-throughput sequencing method. We found distinct algal community structure in red and green snows, and the relative abundance of dominant taxa varied, potentially due to nutrient status differences. Contrastingly, red and green snows exhibited similar heterotrophic communities (bacteria and fungi), whereas the relative abundance of fungal pathogens was substantially higher in red snow by 3.8-fold. Red snow exhibited a higher network complexity, indicated by a higher number of nodes and edges. Red snow exhibited a higher proportion of negative correlations among heterotrophs (62.2% vs 3.4%) and stronger network stability, suggesting the red-snow network is more resistant to external disturbance. Our study revealed that the red snow microbiome exhibits a more stable microbial network than the green snow microbiome.

Incidence, Timing, and Outcomes of Venous Thromboembolism in Patients Undergoing Surgery for Esophagogastric Cancer: A Population-Based Cohort Study.

BACKGROUND: Abdominal surgery and chemotherapy are well-established risk factors for venous thromboembolism (VTE) in patients with cancer, but their specific contribution in patients with esophageal and gastric cancer is unclear. We aim to quantify the risk of VTE, identify risk factors associated with VTE, and determine the association between VTE and survival in patients undergoing surgery for esophageal or gastric cancer. METHODS: A retrospective, population-based cohort study was conducted using linked administrative healthcare databases. We used the Ontario Cancer Registry to identify patients with esophageal or gastric cancer between January 1, 2007 and December 31, 2016 who underwent surgical resection. Incidence of first VTE event was identified using International Classification of Diseases 9 and 10 codes. VTE incidence was calculated at clinically relevant time points 180 days before and after surgery. Logistic regression was used to identify factors associated with VTE with odds ratios (OR) and 95% confidence intervals (CI) reported. Cox proportional hazards regression models were used to estimate associations between covariates and survival. Kaplan-Meier method was used to compare overall (OS) and cancer-specific survival (CSS) by VTE status. RESULTS: A total of 4894 patients had esophagectomy or gastrectomy, of which 8% (n = 383/4894) had VTE. VTE risk was 2.5% (n = 123/4894) 180 days before surgery, 2.8% (n = 138/4894) within 30 days of surgery, and 2.5% (n = 122/4894) from 31 to ≤ 180 days after surgery. Of the patients with VTE within 30 days of surgery, 34% (n = 47/138) were diagnosed after discharge from hospital. Receipt of preoperative chemotherapy was associated with VTE 180 days before surgery (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.41, 6.11). Increased hospital length of stay (LOS) was associated with VTE 30 days after surgery (OR 1.08, 95% CI 1.02, 1.14, per week). Patients with VTE had inferior median OS and CSS (2.2 vs. 3.7 years; 2.3 vs. 4.4 years, respectively). In adjusted models VTE was associated with inferior OS (HR 1.36, 95% CI 1.13, 1.63) and CSS (HR 1.42, 95% CI 1.16, 1.75). CONCLUSIONS: The highest risk of VTE is within 30 days of surgery with one third of patients diagnosed after discharge from hospital. Longer hospital LOS and receipt of preoperative chemotherapy are associated with increased risk of VTE. VTE is an independent risk factor for inferior survival in patients with esophageal or gastric cancer.

Transcriptome analysis of gene expression in the tomato leaf premature senescence mutant.

Premature senescence of leaves can critically influence tomato yield and quality. In this study, the leaf premature senescence mutant MT318 was a spontaneous mutant and was controlled by a single recessive nuclear gene. The maximum photochemical efficiency (Fv/Fm), superoxide dismutase (SOD), and chlorophyll content in the leaves of mutant MT318 gradually decreased, while malondialdehyde (MDA) content significantly increased. Under the level 2 category, Gene Ontology (GO) enrichment analysis indicated that 45 terms were enriched, comprising 22 in biological process, 12 in cellular component, and 11 in molecular function. Genes are mainly involved in the metabolic processes (696 differentially expressed genes, DEGs), cellular processes (573 DEGs), single-organism processes (503 DEGs), and catalytic activity (675 DEGs). Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the 4 pathways with the largest number of genes were biosynthesis of secondary metabolites, plant-pathogen interaction, plant hormone signal transduction, and MAPK signaling pathway-plant. The 'plant hormone signal transduction' pathway was the most significantly enriched at the T2 stage. Pearson correlation analysis showed that the auxin regulatory pathway and SA signal transduction pathway may play important roles. These results not only lay the foundation for the further cloning and functional analysis of the MT318 premature senescence gene but also provide a reference for the study of tomato leaf senescence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01223-2.

Grazing greatly reduces the temporal stability of soil cellulolytic fungal community in a steppe on the Tibetan Plateau.

Excessive livestock grazing degrades grasslands ecosystem stability and sustainability by reducing soil organic matter and plant productivity. However, the effects of grazing on soil cellulolytic fungi, an important indicator of the degradation process for soil organic matter, remain less well understood. Using T-RFLP and sequencing methods, we investigated the effects of grazing on the temporal changes of cellulolytic fungal abundance and community structure in dry steppe soils during the growing months from May to September, on the Tibetan Plateau using T-RFLP and sequencing methods. The results demonstrated that the abundance of soil cellulolytic fungi under grazing treatment changed significantly from month to month, and was positively correlated with dissolved organic carbon (DOC) and soil temperature, but negatively correlated with soil pH. Contrastingly, cellulolytic fungal abundance did not change within the fencing treatment (ungrazed conditions). Cellulolytic fungal community structure changed significantly in the growing months in grazed soils, but did not change in fenced soils. Grazing played a key role in determining the community structure of soil cellulolytic fungi by explaining 8.1% of the variation, while pH and DOC explained 4.1% and 4.0%, respectively. Phylogenetically, the cellulolytic fungi were primarily affiliated with Ascomycota (69.65% in relative abundance) and Basidiomycota (30.35%). Therefore, grazing substantially reduced the stability of soil cellulolytic fungal abundance and community structure, as compared with the fencing treatment. Our finding provides a new insight into the responses of organic matter-decomposing microbes for grassland managements.

Microbial anhydrobiosis.

The loss of cellular water (desiccation) and the resulting low cytosolic water activity are major stress factors for life. Numerous prokaryotic and eukaryotic taxa have evolved molecular and physiological adaptions to periods of low water availability or water-limited environments that occur across the terrestrial Earth. The changes within cells during the processes of desiccation and rehydration, from the activation (and inactivation) of biosynthetic pathways to the accumulation of compatible solutes, have been studied in considerable detail. However, relatively little is known on the metabolic status of organisms in the desiccated state; that is, in the sometimes extended periods between the drying and rewetting phases. During these periods, which can extend beyond decades and which we term 'anhydrobiosis', organismal survival could be dependent on a continued supply of energy to maintain the basal metabolic processes necessary for critical functions such as macromolecular repair. Here, we review the state of knowledge relating to the function of microorganisms during the anhydrobiotic state, highlighting substantial gaps in our understanding of qualitative and quantitative aspects of molecular and biochemical processes in desiccated cells.

Symptom Evolution in Patients with Esophageal and Gastric Cancer Receiving Palliative Chemotherapy: A Population-Based Study.

INTRODUCTION: Palliative chemotherapy (PC) is associated with a modest survival benefit in patients with incurable esophageal and gastric cancer; however, changes in symptom profile during treatment are not well described. Understanding the trajectory of symptoms during treatment may lead to improved care and facilitate shared decision making. In this study, we address this knowledge gap among all patients receiving PC in the Canadian province of Ontario. METHODS: Patients diagnosed with incurable esophageal and gastric cancer who received PC from 2012 to 2017 were identified from the Ontario Cancer Registry. Patients with one or more recorded Edmonton Symptom Assessment System (ESAS) scores in the 12 months following cancer diagnosis were included. The ESAS includes scores from 0 to 10 in nine domains (anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and lack of well-being). Symptom severity is categorized as none-mild (≤ 3), moderate (4-6), or severe (7-10). We focused on potentially modifiable symptoms, i.e. nausea, pain, and anxiety/depression. Logistic regression was used to identify factors associated with moderate-severe ESAS scores in these domains. Among those patients with serial ESAS scores (at 8 ± 2 and 12 ± 2 weeks) receiving chemotherapy, we describe changes during treatment (decrease by ≥ 1 = improved; - 1 > 0 > 1 = unchanged; increase by ≥ 1 = deteriorated). RESULTS: The cohort included 1900 patients who received PC, of whom 79% (1497/1900) had one or more recorded ESAS scores. In multivariate analysis, younger patients were more likely to have moderate-severe scores in nausea (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.23-2.90 [p < 0.01] in patients aged 41-50 years compared with patients aged ≥ 71 years) and pain (OR 1.88, 95% CI 1.36-2.60 [p < 0.01] in patients aged 51-60 years compared with patients aged ≥ 71 years). Compared with males, females were more likely to report moderate-severe scores in anxiety/depression (OR 1.58, 95% CI 1.21-2.08 [p < 0.01]). At 8 ± 2 weeks from PC initiation, symptom scores were unchanged in 19-42% of patients, improved in 30-51% of patients, and deteriorated in 17-35% of patients. The greatest change in symptom burden was observed for appetite (51% improvement) and anxiety/depression (35% deterioration). Similar trends were observed at 12 ± 2 weeks. CONCLUSIONS: In this large, population-based study, we observed that younger patients were more likely to report moderate-severe symptoms in pain and nausea, and females were more likely to report moderate-severe symptoms in anxiety/depression. Anxiety/depression symptoms become increasingly problematic for a substantial proportion of patients receiving PC. Supportive care efforts to mitigate these symptoms in routine practice are needed.

Apoptosis-promoting properties of miR-3074-5p in MC3T3-E1 cells under iron overload conditions.

BACKGROUND: Iron overload can promote the development of osteoporosis by inducing apoptosis in osteoblasts. However, the mechanism by which miRNAs regulate apoptosis in osteoblasts under iron overload has not been elucidated. METHOD: The miRNA expression profile in MC3T3-E1 cells under iron overload was detected by next generation sequencing. qRT-PCR was used to determine the expression of miR-3074-5p in MC3T3-E1 cells under iron overload. The proliferation of MC3T3-E1 cells was tested using CCK-8 assays, and apoptosis was measured using flow cytometry. The miRanda and TargetScan databases were used to predict the target genes of miR-3074-5p. Interaction between miR-3074-5p and the potential target gene was validated by qRT-PCR, luciferase reporter assay and western blotting. RESULTS: We found that iron overload decreased the cell viability and induced apoptosis of MC3T3-E1 cells. The results of next generation sequencing analysis showed that miR-3074-5p expression was significantly increased in MC3T3-E1 cells under iron overload conditions, which was confirmed by further experiments. The inhibition of miR-3074-5p attenuated the apoptosis of iron-overloaded MC3T3-E1 cells. Furthermore, the expression of Smad4 was decreased and was inversely correlated with miR-3074-5p expression, and overexpression of Smad4 partially reversed the viability inhibition of iron-overloaded MC3T3-E1 cells by relieving the suppression of ERK, AKT, and Stat3 phosphorylation, suggesting its regulatory role in the viability inhibition of iron-overloaded MC3T3-E1 cells. The luciferase reporter assay results showed that Smad4 was the target gene of miR-3074-5p. CONCLUSION: miR-3074-5p functions as an apoptosis promoter in iron-overloaded MC3T3-E1 cells by directly targeting Smad4.

Distinct assembly mechanisms underlie similar biogeographical patterns of rare and abundant bacteria in Tibetan Plateau grassland soils.

Rare biosphere represents the majority of Earth's biodiversity and performs vital ecological functions, yet little is known about its biogeographical patterns and community assembly processes in terrestrial ecosystems. Herein, we investigated the community composition and phylogeny of rare (relative abundance <0.1%) and abundant (>1%) bacteria in dryland grassland soils on the Tibetan Plateau. Results revealed similar biogeographical patterns of rare and abundant bacteria at both compositional and phylogenetic levels, but rare subcommunity was more heavily influenced by stochasticity (72%) than the abundant (57%). The compositional variation of rare bacteria was less explained by environmental factors (41%) than that of the abundant (80%), while the phylogeny of rare bacteria (36%) was more explained than that of the abundant (29%). The phylogeny of rare bacteria was equally explained by local factors (soil and vegetation) and geospatial distance (11.5% and 11.9% respectively), while that of the abundant was more explained by geospatial distance (22.1%) than local factors (11.3%). Furthermore, a substantially tighter connection between the community phylogeny and composition was observed in rare (R2 = 0.65) than in abundant bacteria (R2 = 0.08). Our study provides novel insights into the assembly processes and biographical patterns of rare and abundant bacteria in dryland soils.

Finite element analysis of the effect of power arm locations on tooth movement in extraction space closure with miniscrew anchorage in customized lingual orthodontic treatment.

INTRODUCTION: More patients are choosing customized orthodontic appliances because of their excellent esthetics. It is essential that clinicians understand the biomechanics of the tooth movement tendency in customized lingual orthodontics. This study aimed to evaluate the tooth movement tendency during space closure in maxillary anterior teeth with the use of miniscrew anchorage in customized lingual orthodontics with various power arm locations. METHODS: Three-dimensional finite element models of the maxilla were created with miniscrews and power arms; the positions were varied to change the force directions. A retraction force (1.5 N) was applied from the top of the miniscrews to the selected points on the power arm, and the initial displacements of the reference nodes of the maxillary teeth were analyzed. RESULTS: After applying force in different directions, power arms located at the distal side of the canines led to larger initial lingual crown tipping and occlusal crown extrusion of the maxillary incisors compared with power arms located at the midpoint between the lateral incisors and canines, and caused a decreasing trend of the intercanine width. CONCLUSIONS: In customized lingual orthodontic treatment, power arms located at the distal side of the canines are unfavorable for anterior teeth torque control and intercanine width control. Power arms located at the midpoint between the lateral incisors and canines can get better torque control, but still cannot achieve excepted torque without extra torque control methods, no matter whether its force application point is higher than, lower than, or equal to the level of the top of the miniscrews.

Iron overload induces G1 phase arrest and autophagy in murine preosteoblast cells.

This study aimed to investigate the cell cycle arrest and autophagy induced by iron overload in MC3T3-E1 cells. MC3T3-E1 cells were cultured in different concentrations of ferric ammonium citrate (FAC), and Perls' Prussian blue reaction was used to detect the iron levels of the cells. CCK-8 assays were used to detect the growth of MC3T3-E1. The level of reactive oxygen species (ROS) within cells was investigated with DCFH-DA. PI staining was used to analyze the cell cycle distribution of MC3T3-E1 cells. Finally, the expression levels of cell cycle related proteins, autophagy related proteins, AKT, p38 MAPK, Stat3, and their downstream proteins were detected with Western blot assays. The results showed that the iron levels of MC3T3-E1 cells increased with increasing concentrations of FAC. High levels of ferric ion inhibited proliferation of MC3T3-E1 cells and increased their ROS levels. Additionally, iron overload induced G1arrest in MC3T3-E1 cells and down-regulated the expression of Cyclin D1 , Cyclin D3 , CDK2, CDK4 and CDK6, but up-regulated p27 Kip1. In addition, the expression levels of Beclin-1 and LC3 II increased, but that of p62 decreased. Further experiments showed that the phosphorylation of AKT and its downstream proteins p-GSK-3ß(Ser9) and p-mTOR (Ser2448) were decreased. The levels of p-p38 and p53 were up-regulated while those of cdc25A and p-ERK 1/2 were down-regulated. Phosphorylation of Stat3 and its downstream proteins was all decreased. These results show that iron overload generates ROS, blocks the PI3K/AKT and Jak/Stat3 signal pathways, and activates p38 MAPK, subsequently inducing G1 arrest and autophagy in MC3T3-E1 cells.

Elevational diversity and distribution of ammonia-oxidizing archaea community in meadow soils on the Tibetan Plateau.

Unraveling elevational diversity patterns of plants and animals has long been attracting scientific interests. However, whether soil microorganisms exhibit similar elevational patterns remains largely less explored, especially for functional microbial communities, such as ammonia oxidizers. Here, we investigated the diversity and distribution pattern of ammonia-oxidizing archaea (AOA) in meadow soils along an elevation gradient from 4400 m to the grassline at 5100 m on the Tibetan Plateau using terminal restriction fragment length polymorphism (T-RFLP) and sequencing methods by targeting amoA gene. Increasing elevations led to lower soil temperature and pH, but higher nutrients and water content. The results showed that AOA diversity and evenness monotonically increased with elevation, while richness was relatively stable. The increase of diversity and evenness was attributed to the growth inhibition of warm-adapted AOA phylotypes by lower temperature and the growth facilitation of cold-adapted AOA phylotypes by richer nutrients at higher elevations. Low temperature thus played an important role in the AOA growth and niche separation. The AOA community variation was explained by the combined effect of all soil properties (32.6%), and 8.1% of the total variation was individually explained by soil pH. The total AOA abundance decreased, whereas soil potential nitrification rate (PNR) increased with increasing elevations. Soil PNR positively correlated with the abundance of cold-adapted AOA phylotypes. Our findings suggest that low temperature plays an important role in AOA elevational diversity pattern and niche separation, rising the negative effects of warming on AOA diversity and soil nitrification process in the Tibetan region.

Customized Lingual Orthodontic Treatment of Skeletal Class II Malocclusion with Bilateral Maxillary First Premolar Extraction: Case Report.

This report describes the orthodontic camouflage treatment for a 52-year-old Chinese man using eBrace customized lingual appliance with bilateral maxillary first premolar extraction. The treatment results showed that using the eBrace customized lingual appliance can achieve expected effects and has a high level of safety for periodontal health.

The relationship between time to initiation of adjuvant chemotherapy and survival in breast cancer: a systematic review and meta-analysis.

BACKGROUND: It is known that adjuvant chemotherapy improves survival in women with breast cancer. It is not known whether the interval between surgery and the initiation of chemotherapy influences its effectiveness. PURPOSE: To determine the relationship between time to initiation of adjuvant chemotherapy and survival in women with breast cancer, through a systematic review of the literature and meta-analysis. METHODS: Systematic review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Controlled Trials, Google Scholar, and abstracts presented at major international oncology conferences. The primary meta-analysis included only high-validity studies which directly measured the time from surgery to initiation of adjuvant chemotherapy and which controlled for major prognostic factors. Outcomes reported in the original studies were converted to a regression coefficient (ß) and standard error corresponding to a 4-week delay in the initiation of chemotherapy. These relative risks were combined in both fixed- and random-effects models. Homogeneity was assessed by the Cochran χ 2 statistic and the I 2 statistic. Potential publication bias was investigated using standard error-based funnel plots. RESULTS: Meta-analysis of 8 high-validity studies demonstrated that a 4-week increase in TTAC was associated with a significant increase in the risk of death in both the fixed-effects model (RR 1.04; 95 % CI, 1.01-1.08) and random-effects model (RR 1.08; 95 % CI, 1.01-1.15). The association remained significant when the most highly weighted studies were sequentially removed from this analysis, and also when additional, lower validity studies were included in this analysis. Funnel plots showed no significant asymmetry to suggest publication bias. CONCLUSIONS: Increased waiting time from surgery to initiation of adjuvant chemotherapy is associated with a significant decrease in survival. Avoidance of unnecessary delays in the initiation of adjuvant chemotherapy has the potential to save the lives of many women with breast cancer.

A monomer purified from Paris polyphylla (PP-22) triggers S and G2/M phase arrest and apoptosis in human tongue squamous cell carcinoma SCC-15 by activating the p38/cdc25/cdc2 and caspase 8/caspase 3 pathways.

Recent studies have shown that the aqueous, ethanolic extracts and a monomer compound of Paris polyphylla exhibit anticancer activity toward several types of cancer cell lines, but the anticancer activity of (3ß,17α,25R)-spirost-5-ene-3,17-diol 3-O-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-glucopyranoside, a monomer isolated from P. polyphylla (PP), named PP-22, has not been reported previously. In this study, we investigated the effect of PP-22 on human tongue squamous cell carcinoma SCC-15 cells in vitro. MTT assays showed that PP-22 inhibited the growth of SCC-15 cells and had no obvious inhibitory effects on human liver L02 cells. Flow cytometry assays showed that the percentages of apoptotic cells were increased. In addition, cleaved caspase-8, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) could be detected by Western blotting. Flow cytometry also showed that PP-22 triggered S and G2/M phases arrest in SCC-15 cells, and on the other hand, the expression of cyclin A, cyclin E2, cyclin B1, phospho-cell division cycle2 (p-cdc2)(Tyr15), p-Wee1, Myt1, and p53 was upregulated. Moreover, p-p38 levels increased, p-extracellular signal-regulated kinase (ERK) levels decreased, and cdc25B expression was inhibited. Furthermore, the p38/mitogen-activated protein kinase (MAPK) inhibitor SB203580 reversed the increase of the expression level of p38, p-cdc2 (Tyr15), cleaved caspase 3, cleaved PARP, p-p53, and p53 and reversed the decrease in cdc25B expression. In conclusion, these results demonstrated that PP-22 activated p38, inhibited cdc25B, increased p-cdc2 (Tyr15), and triggered S and G2/M phase arrest, as well as activated p53 through the p38-p53 pathway, inhibited the MAPK/ERK pathway, activated the caspase 8/caspase 3 pathway, and triggered the extrinsic apoptotic pathway in SCC-15 cells.

Bacterial diversity and community along the succession of biological soil crusts in the Gurbantunggut Desert, Northern China.

Biological soil crusts (BSCs) are common and play critical roles in semi-arid and arid ecosystems. Bacteria, as an important community in BSCs, play critical roles in biochemical processes. However, how bacterial diversity and community change in different successional stages of BSCs is still unknown. We used 454 pyrosequencing of 16S rRNA to investigate the bacterial composition and community, and the relationships between bacterial composition and environmental factors were also explored. In different successional stages of BSCs, the number of bacteria operational taxonomic units (OTUs) detected in each sample ranged from 2572 to 3157. Proteobacteria, Cyanobacteria, Bacteroidetes were dominant in BSCs, followed by Firmicutes, Acidobacteria, and Actinobacteria. At the successional stages of BSCs, bacterial communities, OTU composition and their relative abundance notably differentiated, and Cyanobacteria, especially Microcoleus vaginatus, dominated algal crust and lichen crust, and were the main C-fixing bacteria in BSCs. Proteobacteria and Bacteroidetes increased with the development of BSCs. OTUs related to Planomicrobium Chinese, Desulfobulbus sp., Desulfomicrobium sp., Arthrobacter sp., and Ahhaerbacter sp. showed higher relative abundance in bare sand than other successional stages of BSCs, while relative abundance of Sphingomonas sp. Niastella sp., Pedobacter, Candidatus solobacter, and Streptophyta increased with the development of BSCs. In successional stages of BSCs, bacterial OTUs composition demonstrated strong correlations with soil nutrients, soil salts, and soil enzymes. Additionally, variation of bacterial composition led to different ecological function. In bare sand, some species were related with mineral metabolism or promoting plant growth, and in algal crust and lichen crust, C-fixing bacteria increased and accumulated C to the desert soil. In later developed stage of BSCs, bacteria related with decomposition of organic matter, such as Sphingomonas sp. Niastella sp., Pedobacter, and Candidatus solobacter increased. Therefore, bacterial community composition and their key ecological roles shifted to the development of BSCs.

Applications of cone-beam computed tomography to assess the effects of labial crown morphologies and collum angles on torque for maxillary anterior teeth.

INTRODUCTION: Currently, cone-beam computed tomography (CBCT) has been widely used because of its capacity to evaluate the anatomic structures of the maxilla, mandible, and teeth in 3 dimensions. However, articles about the use of CBCT to evaluate the relationships between the morphology of individual teeth and torque expression remain rare. In this study, we aimed to determine the influence of labial crown morphologies and collum angles on torque for maxillary anterior teeth using CBCT. METHODS: A total of 206 extracted maxillary anterior teeth were selected to establish scanning models using dental wax, and they were scanned by CBCT. Three-dimensionally reconstructed images and median sagittal sections of the teeth were digitized and analyzed with AutoCAD software (Autodesk, San Rafael, Calif). The angle α, formed by the intersection of the tangent at a certain vertical height on the labial surface from the incisal edge with the crown long axis, and the collum angle, were measured. RESULTS: The variations in angle α at different heights from the incisal edge for the same type of tooth were statistically significantly different (P <0.001). Moreover, the variations between collum angles and 0° for any type of maxillary anterior tooth were statistically significant (P <0.01). CONCLUSIONS: This study suggested that there are great differences in labial crown morphologies and collum angles for maxillary anterior teeth between persons, indicating that the morphologies of these teeth do play important roles in torque variations.

Diversity and distribution of autotrophic microbial community along environmental gradients in grassland soils on the Tibetan Plateau.

Soil microbial autotrophs play a significant role in CO2 fixation in terrestrial ecosystem, particularly in vegetation-constrained ecosystems with environmental stresses, such as the Tibetan Plateau characterized by low temperature and high UV. However, soil microbial autotrophic communities and their driving factors remain less appreciated. We investigated the structure and shift of microbial autotrophic communities and their driving factors along an elevation gradient (4400-5100 m above sea level) in alpine grassland soils on the Tibetan Plateau. The autotrophic microbial communities were characterized by quantitative PCR, terminal restriction fragment length polymorphism (T-RFLP), and cloning/sequencing of cbbL genes, encoding the large subunit for the CO2 fixation protein ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO). High cbbL gene abundance and high RubisCO enzyme activity were observed and both significantly increased with increasing elevations. Path analysis identified that soil RubisCO enzyme causally originated from microbial autotrophs, and its activity was indirectly driven by soil water content, temperature, and NH4 (+) content. Soil autotrophic microbial community structure dramatically shifted along the elevation and was jointly driven by soil temperature, water content, nutrients, and plant types. The autotrophic microbial communities were dominated by bacterial autotrophs, which were affiliated with Rhizobiales, Burkholderiales, and Actinomycetales. These autotrophs have been well documented to degrade organic matters; thus, metabolic versatility could be a key strategy for microbial autotrophs to survive in the harsh environments. Our results demonstrated high abundance of microbial autotrophs and high CO2 fixation potential in alpine grassland soils and provided a novel model to identify dominant drivers of soil microbial communities and their ecological functions.