circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Viruses Regulate Microbial Community Assembly Together with Environmental Factors in Acid Mine Drainage.

Viruses are widespread in various ecosystems, and they play important roles in regulating the microbial community via host-virus interactions. Recently, metagenomic studies showed that there are extremely diverse viruses in different environments from the ocean to the human gut, but the influences of viral communities on microbial communities are poorly understood, especially in extreme environments. Here, we used metagenomics to characterize microbial communities and viral communities in acid mine drainage (AMD) and evaluated how viruses shape microbial community constrained by the harsh environments. Our results showed that AMD viral communities are significantly associated with the microbial communities, and viral diversity has positive correlations with microbial diversity. Viral community explained more variations of microbial community composition than environmental factors in AMD of a polymetallic mine. Moreover, we found that viruses harboring adaptive genes regulate a relative abundance of hosts under the modulation of environmental factors, such as pH. We also observed that viral diversity has significant correlations with the global properties of microbial cooccurrence networks, such as modularity. In addition, the results of null modeling analyses revealed that viruses significantly affect microbial community phylogeny and play important roles in regulating ecological processes of community assembly, such as dispersal limitation and homogenous dispersal. Together, these results revealed that AMD viruses are critical forces driving microbial network and community assembly via host-virus interactions. IMPORTANCE Viruses as mobile genetic elements play critical roles in the adaptive evolution of their hosts in extreme environments. However, how viruses further influence microbial community structure and assembly is still unclear. A recent metagenomic study observed diverse viruses unexplored in acid mine drainage, revealing the associations between the viral community and environmental factors. Here, we showed that viruses together with environmental factors can constrain the relative abundance of host and microbial community assembly in AMD of copper mines and polymetallic mines. Our results highlight the importance of viruses in shaping the microbial community from the individual host level to the community level.

Correlation of R2* with fat fraction and bone mineral density and its role in quantitative assessment of osteoporosis.

OBJECTIVES: To investigate the correlation of R2* with vertebral fat fraction (FF) and bone mineral density (BMD), and to explore its role in the quantitative assessment of osteoporosis (OP). METHODS: A total of 83 patients with low back pain (59.77 ± 7.46 years, 30 males) were enrolled, which underwent lumbar MRI in IDEAL-IQ sequences and quantitative computed tomography (QCT) scanning within 48h. The FF, R2*, and BMD of all 415 lumbar vertebrae were respectively measured. According to BMD, all vertebrae were divided into BMD normal, osteopenia, and OP groups, and the difference of FF and R2* among groups was analyzed by one-way ANOVA. The correlation between R2*, FF, and BMD was analyzed by Pearson's test. Taking BMD as the gold standard, the efficacies for FF and R2* in diagnosis of OP and osteopenia were assessed by receiver operating characteristic curve, and their area under the curve (AUC) was compared with DeLong's test. RESULTS: The FF and R2* were statistically different among groups (F values of 102.521 and 11.323, both p < 0.05), and R2* were significantly correlated with FF and BMD, respectively (r values of -0.219 and 0.290, both p < 0.05). In diagnosis of OP and osteopenia, the AUCs were 0.776 and 0.778 for FF and 0.638 and 0.560 for R2*, and the AUCs of R2* were lower than those of FF, with Z values of 4.030 and 4.087, both p < 0.001. CONCLUSION: R2* is significantly correlated with FF and BMD and can be used as a complement to FF and BMD for quantitative assessment of OP. KEY POINTS: • R2* based on IDEAL-IQ sequences has a definite but weak linear relationship with FF and BMD. • FF is significantly correlated with BMD and can effectively evaluate BMAT. • R2* can be used as a complement to FF and BMD for fine quantification of bone mineral loss and bone marrow fat conversion.

Quantitative Study of Vertebral Body and Paravertebral Muscle Degeneration Based on Dual-Energy Computed Tomography: Correlation With Bone Mineral Density.

OBJECTIVES: This study aimed to quantify the degeneration of the vertebral body and paravertebral muscles using dual-energy computed tomography (DECT) and study its relationship with osteoporosis. METHODS: A total of 130 patients with chronic low back pain were included in this study, and DECT scanning of the lumbar region was undertaken prospectively. By placing a standard quantitative computed tomography corrected phantom under the waist during the DECT procedure, bone mineral density (BMD) and the following quantitative parameters were obtained: calcium density (CaD), vertebral fat fraction (VFF), psoas major area, psoas major fat fraction, erector spinalis area, and erector spinalis fat fraction (ESFF). Independent sample t test and 1-way analysis of variance were used between different age-BMD groups. Pearson test was applied to determine correlations for all measurements, and a mathematical model of BMD was established through regression analysis. RESULTS: Calcium density, VFF, psoas major area, psoas major fat fraction, erector spinalis area, and ESFF were significantly different among the age-BMD groups (P < 0.05), and BMD was significantly correlated with these parameters (P < 0.05). Calcium density, VFF, and ESFF were included in the BMD regression equation: BMD = 69.062 + 11.637 × CaD - 1.018 × VFF - 0.726 × ESFF (R2 = 0.860, F = 125.979, P < 0.001). CONCLUSIONS: Degeneration of the vertebral body and paravertebral muscles can be quantitatively analyzed using DECT, and CaD, VFF, and ESFF were independent influencing factors of BMD.

Optimizing SCND with carbon-rich hydrolysates from typical organic wastes: Material composition, augmentation performance, microbiome response, and life cycle impact.

The rapid growth of production and consumption has led to severe environmental pollution, creating a major challenge to achieving the United Nations' sustainable development goals (SDGs). To address it, recycling of organic wastes into value-added products is a possible solution. In this work, four typical organic wastes including sewage sludge (SS), chicken manure (CM), food waste (FW), and corn straw (CS) were employed to produce hydrolysates augmenting shortcut nitrification-denitrification (SCND) for nitrogen depletion in wastewater. The hydrolysates were carbon-rich, with total COD (TCOD), soluble COD (SCOD), and volatile fatty acids (VFA) concentrations ranging from 32.5 to 102.7, 5.7 to 48.4, and 2.0-16.5 mg/L, respectively. The most effective nitrogen depletion was obtained in units supplemented with CM and FW hydrolysates, which had reduced average NH3-N concentrations and near-zero TN removal failure rates under legal requirements. The microbial community analysis demonstrated that various functional bacteria from phylum to genus level were detected in all scenarios, which was corroborated by abundant genetic functions involved in nitrogen metabolism. Further, life cycle assessment revealed negative environmental impact on all categories, with an exception of eutrophication potential (EP) with negative values (∼-0.04 kg Phosphate eq.), allowing positive net environmental benefit (NEB). Operational cost analysis revealed that CM and FW are more effective but costlier than SS and CS. Together, these results indicate that, after hydrolysis, organic wastes can be efficient stimulant augmenting SCND performance for nitrogen depletion in wastewater, benefiting the overall environmental impact.

Sensitivity of Sniffer Dogs for a Diagnosis of Parkinson's Disease: A Diagnostic Accuracy Study.

BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.

Alicyclobacillus curvatus sp. nov. and Alicyclobacillus mengziensis sp. nov., two acidophilic bacteria isolated from acid mine drainage.

Two acidophilic strains, designated as ALEF1T and S30H14T, were isolated from acid mine drainage sediment. Cells of both strains were Gram-stain-positive, aerobic, endospore-forming rods. Strains ALEF1T and S30H14T were acidophilic and mesophilic, the former grew at 20-40 °C (optimum, 30 °C) and pH 2.5-4.5 (optimum, pH 3.5), while the latter grew at 20-45 °C (optimum, 30 °C) and pH 2.0-5.5 (optimum, pH 4.5). The 16S rRNA gene-based sequence analysis revealed that strains ALEF1T and S30H14T belonged to the genus Alicyclobacillus, and were phylogenetically close to Alicyclobacillus ferrooxydans TC-34T with 97.1 and 97.4% similarity, respectively. The similarity between the two novel strains was 98.6 %. The average nucleotide identity value between the genome sequences of ALEF1T and S30H14T was 79.5 %, and that between each of the two isolates and A. ferrooxydans TC-34T were 72.0 and 74.3 %. In addition, the digital DNA-DNA hybridization value between ALEF1T and S30H14T was 24.9 %, between strain ALEF1T and A. ferrooxydans TC-34T was 21.7 %, and between S30H14T and A. ferrooxydans TC-34T was 26.3 %, far below the interspecies threshold. Both strains could utilize diverse carbon sources for heterotrophic growth; strain ALEF1T could utilize ferrous iron as the energy source for autotrophic growth. Menaquinone 7 was the only quinone detected in either strain. Both strains contained anteiso-C15 : 0 and anteiso-C17 : 0, while ω-alicyclic fatty acids were not detected. Based on their phylogenetic positions, as well as phenotypic and genomic data, it is considered that strains ALEF1T and S30H14T represent two novel species within the genus Alicyclobacillus, for which the names Alicyclobacillus curvatus sp. nov. (type strain ALEF1T=CGMCC 1.17055T=KCTC 43124T) and Alicyclobacillus mengziensis sp. nov. (S30H14T=CGMCC 1.17050T=KCTC 43125T) are proposed.

The Transformation of 40-Year Coastal Wetland Policies in China: Network Analysis and Text Analysis.

The notable improvement of China's wetland management policies over the last four decades prompted this study's goal to quantitatively analyze the transformation of China's coastal wetland policies from 1979 to 2022 by applying an institutional network analysis and policy text analysis. The results of the institutional network analysis revealed an administrative management transformation from a multidepartmental mode to an integrated management framework. Furthermore, the policy text analysis results revealed a change in policy priorities (from exploitation to protection) and management targets (from a single environmental element to a comprehensive ecosystem and further to collaborative governance). In addition, the overall outcome of this study instigated proposals for the improvement of future wetland policies on climate change, integrated planning, natural capital, and public participation. Hence, this study presents an example of wetland policy analysis based on a quantitative review, which we hope will also be valuable for other countries.

Life cycle assessment and cost analysis for copper hydrometallurgy industry in China.

Understanding the environmental and economic impacts of copper hydrometallurgy throughout the whole life cycle is necessary for sustainable development of the copper industry. In this study, the environmental impacts and economic costs throughout the two major copper hydrometallurgical routes in China, including heap leaching and heap-agitation leaching, are analyzed and compared using the life cycle assessment (LCA) and life cycle cost (LCC) technique. The life cycle inventory compiled from the annual statistics of the Muliashi Copper Mine, and the data regarding energy and materials process are based on the GaBi databases. The environmental impacts are quantified into 12 indicators. The results show that compared with heap leaching route, heap-agitation leaching route reduces 36.8% of abiotic depletion potential (ADP elements), but increases over half of cumulative energy demand (CED), marine aquatic ecotoxicity potential (MAETP) and human toxicity potential (HTP). Furthermore, the stage of electrowinning and agitation leaching contributes the largest environmental impact to heap leaching and heap-agitation leaching route, respectively. This is mainly due to huge consumption of electricity and sulfuric acid. The analysis of economic cost reveals that heap leaching route needs internal cost of $3225/t Cu and external cost of $426/t Cu. Compared with heap leaching route, heap-agitation leaching route increased the internal and external cost by 18.9% and 54.2%, respectively. But the economic return from heap-agitation leaching is double that from heap leaching. Together, these results indicate heap-agitation leaching has a larger environmental impact and higher economic benefit than heap leaching, which is helpful for the government to design ecological compensation policies in the balance between ecological environment and economic development.

Mobile genetic elements mediate the mixotrophic evolution of novel Alicyclobacillus species for acid mine drainage adaptation.

Alicyclobacillus species inhabit diverse environments and have adapted to broad ranges of pH and temperature. However, their adaptive evolutions remain elusive, especially regarding the role of mobile genetic elements (MGEs). Here, we characterized the distributions and functions of MGEs in Alicyclobacillus species across five environments, including acid mine drainage (AMD), beverages, hot springs, sediments, and soils. Nine Alicyclobacillus strains were isolated from AMD and possessed larger genome sizes and more genes than those from other environments. Four AMD strains evolved to be mixotrophic and fell into distinctive clusters in phylogenetic tree. Four types of MGEs including genomic island (GI), insertion sequence (IS), prophage, and integrative and conjugative element (ICE) were widely distributed in Alicyclobacillus species. Further, AMD strains did not possess CRISPR-Cas systems, but had more GI, IS, and ICE, as well as more MGE-associated genes involved in the oxidation of iron and sulfide and the resistance of heavy metal and low temperature. These findings highlight the differences in phenotypes and genotypes between strains isolated from AMD and other environments and the important role of MGEs in rapid environment niche expansions.

Ecological strategies of biological and chemical control agents on wildfire disease of tobacco (Nicotiana tabacum L.).

BACKGROUND: To investigate the ecological effects of chemical and biological control methods on tobacco wildfire disease, a plot field experiment was conducted to compare the control efficiency and mechanisms of a chemical pesticide (kasugamycin wettable powder, KWP) and a biological control agent (BCA) through high-throughput sequencing of bacterial 16S rRNA genes. RESULTS: The results showed that the BCA displayed better performance in decreasing the disease index and morbidity of tobacco than the chemical pesticide. By monitoring the endophytic community within tobacco leaves, it was found that the control effects of these two methods might be mediated by different changes in the endophytic bacterial communities and community assembly patterns. The application of either method decreased the taxonomic diversity of the leaf endophytic community. Compared to the BCA, KWP showed a more significant effect on the endophytic community structure, while the endophytic community treated with the BCA was able to return to the original state, which presented much lower disease infection. The disease control efficiency of KWP and BCA treatments might be achieved by increasing the abundance of Sphingomonas and Streptophyta, respectively. Furthermore, an analysis of the ecological processes in community assembly indicated that the BCA strengthened the homogeneous and variable selection, while KWP enhanced ecological drift. CONCLUSIONS: The results suggested different control mechanisms between KWP and BCA treatments, which will help in developing diverse ecological strategies for plant disease control.

LncRNA LINC00467 acted as an oncogene in esophageal squamous cell carcinoma by accelerating cell proliferation and preventing cell apoptosis via the miR-485-5p/DPAGT1 axis.

BACKGROUND AND AIM: Esophageal carcinoma has been regarded as one of the top 10 common malignancies globally. Esophageal squamous cell carcinoma (ESCC) is an important subtype of esophageal carcinoma with approximately 20% survival rate. Long noncoding RNAs were documented to regulate the occurrence or progression of several tumors. However, neither the biological role nor the molecular mechanism of LINC00467 has been explored. This research is aimed to investigating the regulatory mechanism of LINC00467 in ESCC. METHODS: In this study, a series of experiments including reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8, luciferase reporter, western blot, and RNA immunoprecipitation were designed and conducted to explore the potential function and mechanism of LINC00467 in ESCC. RESULTS: According to experimental results, we found out upregulated LINC00467 improved cell proliferation, but hindered cell apoptosis. In mechanism, miR-485-5p was predicted, screened out, and validated to combine with LINC00467, which displayed lower expression in ESCC. Additionally, miR-485-5p negatively regulated and directly targeted DPAGT1. Rescue assays suggested that DPAGT1 amplification was able to recover the influence of LINC00467 deficiency on cell proliferation and apoptosis. Furthermore, knockdown of LINC00467 suppressed tumor growth in vivo. CONCLUSION: We proved that LINC00467 acted as an oncogene in ESCC by accelerating cell proliferation and preventing cell apoptosis via miR-485-5p/DPAGT1 axis. This may provide a potential diagnostic marker for ESCC treatment.

Dual-Energy Computed Tomography Virtual Noncalcium Technique in Diagnosing Osteoporosis: Correlation With Quantitative Computed Tomography.

OBJECTIVE: The aim of this study was to evaluate dual-energy computed tomography (CT) virtual noncalcium (VNCa) technique as a means of quantifying osteoporosis. METHODS: Dual-energy CT scans were obtained prospectively, targeting lumbar regions of 55 patients with chronic low back pain. A standard quantitative CT (QCT) phantom was positioned at the waist during each procedure, using proprietary software (QCT Pro; Mindways, Tex) to measure bone mineral density (BMD) in each vertebral body. Vendor dual-energy analytic software was altered with a specially modified configuration file to produce a "Virtual Non Calcium" or "VNCa" output, as such output variables were remapped to produce the following calcium values rather than iodine, yielding the following QCT parameters: CT value of calcium (originally "contrast media" [CM]), CT value of mixed energy imaging (regular CT value [rCT]), calcium density (originally "contrast agent density" [CaD]), and fat fraction (FF). Pearson test served to assess correlations between BMD and these parameters. Multiple linear regression analysis was applied to construct an equation for generating regressive BMD (rBMD) values. In gauging diagnostic accuracies, the criterion-standard BMD cutoff point (<80 mg/cm3) was adopted for QCT, whereas the rBMD threshold was defined by receiver operating characteristic curve. RESULTS: Contrast media, rCT, CaD, and FF values (reflecting CT value of calcium, regular CT value, calcium density, and fat fraction, respectively) significantly correlated with BMD (r values: 0.885, 0.947, 0.877, and 0.492, respectively; all P < 0.01). Contrast media, CaD, and FF showed independent associations with BMD; the regressive equation was formulated as follows: rBMD = 54.82 - 0.19 × CM + 20.03 × CaD - 1.24 × FF. The area under the curve of rBMD in diagnosing osteoporosis was 0.966 ± 0.009 (P < 0.01). At an rBMD threshold of less than 81.94 mg/cm3, sensitivity and specificity were 90.0% and 92.0%, respectively. CONCLUSIONS: Dual-energy CT VNCa technique may constitute a valid alternative method for quantifying the mineral content and marrow fat composition of bone in diagnostic assessments of osteoporosis.

The value of bronchial and cavity contraction rates in differentiating benign and malignant pulmonary cavities.

BACKGROUND: The present study aimed to assess the value of bronchial and cavity contraction percentages in differentiating benign and malignant pulmonary cavities. METHODS: Forty-two patients with pulmonary cavities were scanned by dual-phase computed tomography (CT). Then, the cavity and bronchial contraction percentages were respectively measured, the differences between the benign and malignant cavities were compared, and the best diagnostic critical point for differentiating benign and malignant cavities was obtained through the receiver operator characteristic (ROC) curve of the diagnostic test. RESULTS: The contraction percentage of the bronchial end with benign cavities was significantly higher than that of the bronchial end with malignant cavities (P < 0.001). The contraction percentage was significantly higher in the benign group than in the malignant group (P < 0.001). The ROC analysis revealed that the sensitivity and specificity of the bronchial contraction percentage was 90.50 and 86.40%, respectively, while the sensitivity and specificity of the cavity contraction percentage was 90.50 and 90.90%, respectively. CONCLUSION: The dual-phase CT scanning of the bronchial and cavity contraction percentage can distinguish between benign and malignant cavities.

Comparative Genomic Analysis Reveals the Distribution, Organization, and Evolution of Metal Resistance Genes in the Genus Acidithiobacillus.

Members of the genus Acidithiobacillus, which can adapt to extremely high concentrations of heavy metals, are universally found at acid mine drainage (AMD) sites. Here, we performed a comparative genomic analysis of 37 strains within the genus Acidithiobacillus to answer the untouched questions as to the mechanisms and the evolutionary history of metal resistance genes in Acidithiobacillus spp. The results showed that the evolutionary history of metal resistance genes in Acidithiobacillus spp. involved a combination of gene gains and losses, horizontal gene transfer (HGT), and gene duplication. Phylogenetic analyses revealed that metal resistance genes in Acidithiobacillus spp. were acquired by early HGT events from species that shared habitats with Acidithiobacillus spp., such as Acidihalobacter, Thiobacillus, Acidiferrobacter, and Thiomonas species. Multicopper oxidase genes involved in copper detoxification were lost in iron-oxidizing Acidithiobacillus ferridurans, Acidithiobacillus ferrivorans, and Acidithiobacillus ferrooxidans and were replaced by rusticyanin genes during evolution. In addition, widespread purifying selection and the predicted high expression levels emphasized the indispensable roles of metal resistance genes in the ability of Acidithiobacillus spp. to adapt to harsh environments. Altogether, the results suggested that Acidithiobacillus spp. recruited and consolidated additional novel functionalities during the adaption to challenging environments via HGT, gene duplication, and purifying selection. This study sheds light on the distribution, organization, functionality, and complex evolutionary history of metal resistance genes in Acidithiobacillus spp.IMPORTANCE Horizontal gene transfer (HGT), natural selection, and gene duplication are three main engines that drive the adaptive evolution of microbial genomes. Previous studies indicated that HGT was a main adaptive mechanism in acidophiles to cope with heavy-metal-rich environments. However, evidences of HGT in Acidithiobacillus species in response to challenging metal-rich environments and the mechanisms addressing how metal resistance genes originated and evolved in Acidithiobacillus are still lacking. The findings of this study revealed a fascinating phenomenon of putative cross-phylum HGT, suggesting that Acidithiobacillus spp. recruited and consolidated additional novel functionalities during the adaption to challenging environments via HGT, gene duplication, and purifying selection. Altogether, the insights gained in this study have improved our understanding of the metal resistance strategies of Acidithiobacillus spp.

Seco-Dendrobine-Type Alkaloids and Bioactive Phenolics from Dendrobium findlayanum.

Investigation of the 95% EtOH extract of stems of Dendrobium findlayanum afforded four new seco-dendrobines, findlayines A-D (1-4); two known dendrobines, dendrobine (5) and 2-hydroxydendrobine (6); and four new phenolic compounds, dendrofindlaphenols A-C (7, 9, and 10) and 6″-de-O-methyldendrofindlaphenol A (8). Compounds 1 and 2 are the first seco-dendrobines possessing a seven-membered lactam moiety, with 3 and 4 derived from the oxidative cleavage of the C-2-C-3 bond of dendrobine. The structures were established using spectroscopic methods and by comparison with literature data. The absolute configurations of 1-4 were confirmed via single-crystal X-ray diffraction data. Cytotoxic activity assays against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines revealed IC50 values ranging from 2.3 to 5.3 µM for compound 7, from 19.4 to 34.4 µM for 8, and from 49.4 to 96.8 µg/mL for the EtOAc extract. An assay of the inhibition of NO production with RAW 264.7 cells indicated that 8 had an IC50 value of 21.4 µM, and the EtOAc extract, 10.5 µg/mL. The EtOAc extract possessed DPPH radical scavenging activity of 69.93% at 100 µg/mL.

Integrated network analysis reveals the importance of microbial interactions for maize growth.

Microbes play a critical role in soil global biogeochemical circulation and microbe-microbe interactions have also evoked enormous interests in recent years. Utilization of green manures can stimulate microbial activity and affect microbial composition and diversity. However, few studies focus on the microbial interactions or detect the key functional members in communities. With the advances of metagenomic technologies, network analysis has been used as a powerful tool to detect robust interactions between microbial members. Here, random matrix theory-based network analysis was used to investigate the microbial networks in response to four different green manure fertilization regimes (Vicia villosa, common vetch, milk vetch, and radish) over two growth cycles from October 2012 to September 2014. The results showed that the topological properties of microbial networks were dramatically altered by green manure fertilization. Microbial network under milk vetch amendment showed substantially more intense complexity and interactions than other fertilization systems, indicating that milk vetch provided a favorable condition for microbial interactions and niche sharing. The shift of microbial interactions could be attributed to the changes in some major soil traits and the interactions might be correlated to plant growth and production. With the stimuli of green manures, positive interactions predominated the network eventually and the network complexity was in consistency with maize productivity, which suggested that the complex soil microbial networks might benefit to plants rather than simple ones, because complex networks would hold strong the ability to cope with environment changes or suppress soil-borne pathogen infection on plants. In addition, network analyses discerned some putative keystone taxa and seven of them had directly positive interactions with maize yield, which suggested their important roles in maintaining environmental functions and in improving plant growth.

Inhibition of dynamin-related protein 1 protects against myocardial ischemia-reperfusion injury in diabetic mice.

BACKGROUND: Many cardioprotective pharmacological agents failed to exert their protective effects in diabetic hearts subjected to myocardial ischemia/reperfusion (MI/R). Identify the molecular basis linking diabetes with MI/R injury is scientifically important and may provide effective therapeutic approaches. Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in MI/R injury under non-diabetic conditions. Importantly, recent studies indicated that Drp1-mediated mitochondrial fission is enhanced in the myocardium of diabetic mice. The above evidences suggested that Drp1 may be one critical molecule linking diabetes with MI/R injury. We hypothesized that inhibition of Drp1 may be effective to reduce MI/R injury in diabetic hearts. METHODS: High-fat diet and streptozotocin-induced diabetic mice were subjected to MI/R or sham operation. Mdivi-1 (1.2 mg/kg), a small molecule inhibitor of Drp1 or vehicle was administrated 15 min before the onset of reperfusion. Outcome measures included mitochondrial morphology, mitochondrial function, myocardial injury, cardiac function and oxidative stress. RESULTS: Mitochondrial fission was significantly increased following MI/R as evidenced by enhanced translocation of Drp1 to mitochondria and decreased mitochondrial size. Delivery of Mdivi-1 into diabetic mice markedly inhibited Drp1 translocation to the mitochondria and reduced mitochondrial fission following MI/R. Inhibition of Drp1 in diabetic hearts improved mitochondrial function and cardiac function following MI/R. Moreover, inhibition of Drp1 reduced myocardial infarct size and serum cardiac troponin I and lactate dehydrogenase activities. These cardioprotective effects were associated with decreased cardiomyocyte apoptosis and malondialdehyde production and increased activities of antioxidant enzyme manganese superoxide dismutase. CONCLUSIONS: Pharmacological inhibition of Drp1 prevents mitochondrial fission and reduces MI/R injury in diabetic mice. The findings suggest Drp1 may be a potential novel therapeutic target for diabetic cardiac complications.

Different erosion characteristics of sediment deposits in combined and storm sewers.

To investigate the different erosion patterns of sediments in combined and storm sewers, sediments from three separate sewer systems and two combined sewer systems in urban Shanghai were collected for the flushing experiments. These experiments were conducted with different consolidation periods and shear velocities. As the consolidation period increases, dissolved oxygen exhibits a positive effect on the microbial transformations of organic substrates. Potential structural changes and separations of the surface and bottom layers of sediments are observed. The results also reveal that the organic matter, particle size and moisture have different effects on the erosion resistance of sediments. Furthermore, illicit connections behaved as an important factor affecting the viscosity and static friction force of particles, which directly alter the erosion resistance of sewer sediments.

The Formation of Aberrant Collateral Vessels during Coronary Arteriogenesis in Dog Heart.

We previously reported excessive growth of collateral vessels in the dog heart during arteriogenesis induced by implantation of an ameroid constrictor around the circumflex branch of the left coronary artery. In the present study, using histology and immunocofocal microscopy, we further investigated how these aberrant collateral vessels form. By comparison with mature collateral vessels the following findings were made: perivascular space was very narrow where damage of the perivascular myocardium occurred; the neointima was very thick, resulting in a very small lumen; elastica van Gieson staining revealed the absence of the internal elastic lamina and of elastic fibers in the adventitia, but abundant collagen in the adventitia as well as in the neointima; smooth muscle cells of the neointima expressed less α-SM actin and little desmin; expression of the fibroblast growth factors aFGF, bFGF and platelet-derived growth factor (PDGF)-AB was observed mainly in the endothelial cells and abluminal region, but transforming growth factor-ß1 was only present in the adventitia and damaged myocardium; angiogenesis in the neointima was observed in some collateral vessels expressing high levels of eNOS, and cell proliferation was mainly present in the abluminal region, but apoptosis was in the deep neointima. In conclusion, these data for the first time reveal that the formation of the aberrant collateral vessels in the dog heart involves active extracellular proteolysis and a special expression profile of growth factors, eNOS, cell proliferation and apoptosis. The finding of a narrow perivascular space and perivascular myocardial damage suggests that anatomical constraint is most likely the cause for exacerbated inward remodeling in aberrant collateral vessels in dog heart.