Knowledge mapping and research trends of exosomes in pancreatic cancer: a bibliometric analysis and review (2013-2023).

Objective: This review aims to provide a quantitative and qualitative bibliometric analysis of literature from 2013 to 2023 on the role of exosomes in PC, with the goal of identifying current trends and predicting future hotspots. Methods: We retrieved relevant publications concerning exosomes in PC, published between 2013 and 2023, from the Web of Science Core Collection. Bibliometric analyses were conducted using VOSviewer(1.6.19), CiteSpace(6.2.R4), and Microsoft Excel (2019). Results: A total of 624 papers were analyzed, authored by 4017 researchers from 55 countries/regions and 855 institutions, published in 258 academic journals. China (n=285, 34.42%) and the United States (n=183, 24.87%) were the most frequent contributors and collaborated closely. However, publications from China had a relatively low average number of citations (41.45 times per paper). The output of Shanghai Jiao Tong University ranked first, with 28 papers (accounting for 4.5% of the total publications). Cancers (n=31, 4.9%); published the most papers in this field. Researcher Margot Zoeller published the most papers (n=12) on this topic. Research hotspots mainly focused on the mechanisms of exosomes in PC onset and progression, the role of exosomes in PC early diagnosis and prognosis, exosomes promote the development of PC chemoresistance, and potential applications of exosomes as drug carriers for PC therapies. We observed a shift in research trends, from mechanistic studies toward clinical trials, suggesting that clinical applications will be the focus of future attention. Emerging topics were pancreatic stellate cells, diagnostic biomarkers, mesenchymal stem cells, extracellular vesicles. Conclusion: Our scientometric and visual analysis provides a comprehensive overview of the literature on the role of exosomes in PC published during 2013-2023. This review identifies the frontiers and future directions in this area over the past decade, and is expected to provide a useful reference for researchers in this field.

Investigating potential biomarkers of acute pancreatitis in patients with a BMI>30 using Mendelian randomization and transcriptomic analysis.

BACKGROUND: Acute pancreatitis (AP) has become a significant global health concern, and a high body mass index (BMI) has been identified as a key risk factor exacerbating this condition. Within this context, lipid metabolism assumes a critical role. The complex relationship between elevated BMI and AP, mediated by lipid metabolism, markedly increases the risk of complications and mortality. This study aimed to accurately define the correlation between BMI and AP, incorporating a comprehensive analysis of the interactions between individuals with high BMI and AP. METHODS: Mendelian randomization (MR) analysis was first applied to determine the causal relationship between BMI and the risk of AP. Subsequently, three microarray datasets were obtained from the GEO database. This was followed by an analysis of differentially expressed genes and the application of weighted gene coexpression network analysis (WGCNA) to identify key modular genes associated with AP and elevated BMI. Functional enrichment analysis was then performed to shed light on disease pathogenesis. To identify the most informative genes, machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were employed. Subsequent analysis focused on the colocalization of the Quantitative Trait Loci (eQTL) data associated with the selected genes and Genome-Wide Association Studies (GWAS) data related to the disease. Preliminary verification of gene expression trends was conducted using external GEO datasets. Ultimately, the diagnostic potential of these genes was further confirmed through the development of an AP model in mice with a high BMI. RESULTS: A total of 21 intersecting genes related to BMI>30, AP, and lipid metabolism were identified from the datasets. These genes were primarily enriched in pathways related to cytosolic DNA sensing, cytokine‒cytokine receptor interactions, and various immune and inflammatory responses. Next, three machine learning techniques were utilized to identify HADH as the most prevalent diagnostic gene. Colocalization analysis revealed that HADH significantly influenced the risk factors associated with BMI and AP. Furthermore, the trend in HADH expression within the external validation dataset aligned with the trend in the experimental data, thus providing a preliminary validation of the experimental findings.The changes in its expression were further validated using external datasets and quantitative real-time polymerase chain reaction (qPCR). CONCLUSION: This study systematically identified HADH as a potential lipid metabolism-grounded biomarker for AP in patients with a BMI>30.

Discovery of a Macrocyclic Influenza Cap-Dependent Endonuclease Inhibitor.

Influenza viruses (IFVs) have caused several pandemics and have claimed numerous lives since their first record in the early 20th century. While the outbreak of COVID-19 seemed to expel influenza from the sight of people for a short period of time, it is not surprising that it will recirculate around the globe after the coronavirus has mutated into a less fatal variant. Baloxavir marboxil (1), the prodrug of baloxavir (2) and a cap-dependent endonuclease (CEN) inhibitor, were approved by the FDA for the first treatment in almost 20 years. Despite their high antiviral potency, drug-resistant variants have been observed in clinical trials. Herein, we report a novel CEN inhibitor 8 with a delicately designed macrocyclic scaffold that exhibits a significantly smaller shift of inhibitory activity toward baloxavir-resistant variants.

Experimental warming accelerates positive soil priming in a temperate grassland ecosystem.

Unravelling biosphere feedback mechanisms is crucial for predicting the impacts of global warming. Soil priming, an effect of fresh plant-derived carbon (C) on native soil organic carbon (SOC) decomposition, is a key feedback mechanism that could release large amounts of soil C into the atmosphere. However, the impacts of climate warming on soil priming remain elusive. Here, we show that experimental warming accelerates soil priming by 12.7% in a temperate grassland. Warming alters bacterial communities, with 38% of unique active phylotypes detected under warming. The functional genes essential for soil C decomposition are also stimulated, which could be linked to priming effects. We incorporate lab-derived information into an ecosystem model showing that model parameter uncertainty can be reduced by 32-37%. Model simulations from 2010 to 2016 indicate an increase in soil C decomposition under warming, with a 9.1% rise in priming-induced CO2 emissions. If our findings can be generalized to other ecosystems over an extended period of time, soil priming could play an important role in terrestrial C cycle feedbacks and climate change.

Iodine-promoted transfer of dihydrogen from ketones to alkenes, triphenylmethyl, and diphenylmethyl derivatives.

Herein, a novel class of transfer hydrogenation agent, cycloheptanone, was successfully employed in metal-free hydrogenation facilitated by iodine. A series of alkenes, triphenylmethyl derivatives, and diphenylmethyl derivatives were reduced to the desired compounds in moderate to excellent yields. The transfer hydrodeuteration of alkenes using α-deuterated cyclododecanone exhibited high regioselectivity. Preliminary mechanism studies confirmed the origins of the two hydrogen atoms involved in the reduction of alkenes. The current study paves the way for the use of ketones as unique transfer hydrogenation agents in chemical synthesis.

[A preliminary study on the effects of fecal microbiota transplantation on the intestinal microecology of patients with severe pneumonia during the convalescence period].

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and ß diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS: FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.

The future of robotic pancreaticoduodenal surgery: a bibliometric analysis.

OBJECTIVES: Robotic pancreaticoduodenectomy (RPD) has garnered significant research attention in the last decade. However, no bibliometric studies have been conducted on this field yet. Therefore, the aim of this study is to provide an up-to-date analysis of the current state of research, as well as future trends and hotspots in RPD, through a bibliometric analysis. MATERIALS AND METHODS: We conducted a thorough search of all literature related to RPD in the Web of Science Core Collection (WoSCC). We then analyzed this literature for a variety of factors, including authorship, country of origin, institutional affiliations, and keywords. To visualize our findings, we utilized Citespace 6.1.R3, which enabled us to create network visualization maps, perform cluster analysis, and extract burst words. RESULTS: A total of 264 articles were retrieved. Zureikat is the author with the largest contribution in this field, and Surgical Endoscopy and Other International Techniques is the journal with the largest number of papers in this field. The United States is the core research country in this field. The University of Pittsburgh is the most productive institution. According to the data, outcome, pancreas fistula, definition, risk factor, stay, survival, learning curve and experience are recognized as research hotspots in this field. CONCLUSIONS: This study is the first bibliometric study in the field of RPD. Our data will help us better understand the development trend of the field, and determine research hotspots and research directions. The research results provide practical information for other scholars to understand key directions and cutting-edge information.

The entry of unclosed autophagosomes into vacuoles and its physiological relevance.

It is widely stated in the literature that closed mature autophagosomes (APs) fuse with lysosomes/vacuoles during macroautophagy/autophagy. Previously, we showed that unclosed APs accumulated as clusters outside vacuoles in Vps21/Rab5 and ESCRT mutants after a short period of nitrogen starvation. However, the fate of such unclosed APs remains unclear. In this study, we used a combination of cellular and biochemical approaches to show that unclosed double-membrane APs entered vacuoles and formed unclosed single-membrane autophagic bodies after prolonged nitrogen starvation or rapamycin treatment. Vacuolar hydrolases, vacuolar transport chaperon (VTC) proteins, Ypt7, and Vam3 were all involved in the entry of unclosed double-membrane APs into vacuoles in Vps21-mutant cells. Overexpression of the vacuolar hydrolases, Pep4 or Prb1, or depletion of most VTC proteins promoted the entry of unclosed APs into vacuoles in Vps21-mutant cells, whereas depletion of Pep4 and/or Prb1 delayed the entry into vacuoles. In contrast to the complete infertility of diploid cells of typical autophagy mutants, diploid cells of Vps21 mutant progressed through meiosis to sporulation, benefiting from the entry of unclosed APs into vacuoles after prolonged nitrogen starvation. Overall, these data represent a new observation that unclosed double-membrane APs can enter vacuoles after prolonged autophagy induction, most likely as a survival strategy.

Reduction of microbial diversity in grassland soil is driven by long-term climate warming.

Anthropogenic climate change threatens ecosystem functioning. Soil biodiversity is essential for maintaining the health of terrestrial systems, but how climate change affects the richness and abundance of soil microbial communities remains unresolved. We examined the effects of warming, altered precipitation and annual biomass removal on grassland soil bacterial, fungal and protistan communities over 7 years to determine how these representative climate changes impact microbial biodiversity and ecosystem functioning. We show that experimental warming and the concomitant reductions in soil moisture play a predominant role in shaping microbial biodiversity by decreasing the richness of bacteria (9.6%), fungi (14.5%) and protists (7.5%). Our results also show positive associations between microbial biodiversity and ecosystem functional processes, such as gross primary productivity and microbial biomass. We conclude that the detrimental effects of biodiversity loss might be more severe in a warmer world.

Permafrost thaw with warming reduces microbial metabolic capacities in subsurface soils.

Microorganisms are major constituents of the total biomass in permafrost regions, whose underlain soils are frozen for at least two consecutive years. To understand potential microbial responses to climate change, here we examined microbial community compositions and functional capacities across four soil depths in an Alaska tundra site. We showed that a 5-year warming treatment increased soil thaw depth by 25.7% (p = .011) within the deep organic layer (15-25 cm). Concurrently, warming reduced 37% of bacterial abundance and 64% of fungal abundances in the deep organic layer, while it did not affect microbial abundance in other soil layers (i.e., 0-5, 5-15, and 45-55 cm). Warming treatment altered fungal community composition and microbial functional structure (p < .050), but not bacterial community composition. Using a functional gene array, we found that the relative abundances of a variety of carbon (C)-decomposing, iron-reducing, and sulphate-reducing genes in the deep organic layer were decreased, which was not observed by the shotgun sequencing-based metagenomics analysis of those samples. To explain the reduced metabolic capacities, we found that warming treatment elicited higher deterministic environmental filtering, which could be linked to water-saturated time, soil moisture, and soil thaw duration. In contrast, plant factors showed little influence on microbial communities in subsurface soils below 15 cm, despite a 25.2% higher (p < .05) aboveground plant biomass by warming treatment. Collectively, we demonstrate that microbial metabolic capacities in subsurface soils are reduced, probably arising from enhanced thaw by warming.

Copper(i)-catalyzed asymmetric intramolecular C-arylation with ureas as the additives: highly enantioselective formation of spirooxindoles.

A cooperative catalytic strategy is developed for a copper-catalyzed asymmetric intramolecular C-arylation reaction with ureas as the co-catalysts. By forming hydrogen bonds with 1,3-dicarbonyl structures, ureas can activate the substrates, stabilize the carbanion intermediates and the products, and fix the syn-configurations of 1,3-dicarbonyl structures. They help enhance the reactivity, prevent side reactions and improve the enantioselectivities.

Review of research into bioregenerative life support system(s) which can support humans living in space.

To travel beyond the Earth and realize long-term survival in deep space, humans need to construct Bioregenerative Life Support System (BLSS), which reduces the requirement for supplies from the Earth by in situ regenerating oxygen, water and food needed by astronauts, and prevents pollution to extraterrestrial bodies by recycling waste. Since the 1960s, the USSR/Russia, the United States, Europe, Japan, and China carried out a number of studies with abundant achievements in BLSS systematic theories, plants/animals/microorganisms unit technologies, design/construction, and long-term operation/regulation. China's "Lunar Palace 365″ experiment realized Earth-based closed human survival for a year, with a material closure of >98%. However, a lot of research work is still needed to ultimately realize BLSS application in space, especially given the space experiment of BLSS never carried out, and the overall impact of space environment on BLSS unknown. Lunar exploration projects such as lunar village and lunar research station are successively proceeding. Therefore, future BLSS research will focus on lunar probe payload carrying experiments to study mechanisms of small uncrewed closed ecosystem in space and clarify the impact of space environmental conditions on the ecosystem, so as to correct the design and operation parameters of Earth-based BLSS. Such research will provide theoretical and technological support for BLSS application in crewed deep space exploration.

LRG1 promotes hypoxia-induced cardiomyocyte apoptosis and autophagy by regulating hypoxia-inducible factor-1α.

Cardiomyocyte apoptosis and autophagy play important roles in acute myocardial infarction (AMI), but the effect of leucine-rich alpha-2-glycoprotein 1 (LRG1) on the apoptosis and autophagy of H9c2 has not yet been reported. It was found through differential gene analysis and LASSO analysis that LRG1 was the key gene in AMI. In this study, western blot was applied to detect the protein expression of Bax, Bcl2, LC3, p62, LRG1 and hypoxia-inducible factor-1α (HIF-1α); CCK-8 assay was employed to detect cell viability; Annexin V-FITC/PI staining was adopted to evaluate apoptosis, and immunofluorescence assay was applied to detect autophagy. Under hypoxia conditions in H9c2 cells, LRG1 protein levels were increased, the cell activity was decreased, and apoptosis and autophagy were promoted; the downregulated LRG1 significantly enhanced cell viability but inhibited apoptosis and autophagy. When knocking down HIF-1α in the overexpressed LRG1 cells, the effects of LRG1 were reversed under hypoxia condition. In conclusion, LRG1/HIF-1α promoted H9c2 cell apoptosis and autophagy in hypoxia, potentially providing new ideas for the determination and treatment of AMI.Abbreviation: LRG1: Leucine-rich alpha-2-glycoprotein 1; LRR: leucine-rich repeat; HIF-1α: Hypoxia-inducible factor-1α; AMI: acute myocardial infarction.

Accurate Structure Prediction for Protein Loops Based on Molecular Dynamics Simulations with RSFF2C.

Protein loops, connecting the α-helices and ß-strands, are involved in many important biological processes. However, due to their conformational flexibility, it is still challenging to accurately determine three-dimensional (3D) structures of long loops experimentally and computationally. Herein, we present a systematic study of the protein loop structure prediction via a total of ∼850 µs molecular dynamics (MD) simulations. For a set of 15 long (10-16 residues) and solvent-exposed loops, we first evaluated the performance of four state-of-the-art loop modeling algorithms, DaReUS-Loop, Sphinx, Rosetta-NGK, and MODELLER, on each loop, and none of them could accurately predict the structures for most loops. Then, temperature replica exchange molecular dynamics (REMD) simulations were conducted with three recent force fields, RSFF2C with TIP3P water model, CHARMM36m with CHARMM-modified TIP3P, and AMBER ff19SB with OPC. We found that our recently developed residue-specific force field RSFF2C performed the best and successfully predicted 12 out of 15 loops with a root-mean-square deviation (RMSD) < 1.5 Å. As an alternative with lower computational cost, normal MD simulations at high temperatures (380, 500, and 620 K) were investigated. Temperature-dependent performance was observed for each force field, and, for RSFF2C+TIP3P, we found that three independent 100-ns MD simulations at 500 K gave comparable results with REMD simulations. These results suggest that MD simulations, especially with enhanced sampling techniques such as replica exchange, with the RSFF2C force field could be useful for accurate loop structure prediction.

Microbial Functional Responses Explain Alpine Soil Carbon Fluxes under Future Climate Scenarios.

Soil microorganisms are sensitive to temperature in cold ecosystems, but it remains unclear how microbial responses are modulated by other important climate drivers, such as precipitation changes. Here, we examine the effects of six in situ warming and/or precipitation treatments in alpine grasslands on microbial communities, plants, and soil carbon fluxes. These treatments differentially affected soil carbon fluxes, gross primary production, and microbial communities. Variations of soil CO2 and CH4 fluxes across all sites significantly (r > 0.70, P < 0.050) correlated with relevant microbial functional abundances but not bacterial or fungal abundances. Given tight linkages between microbial functional traits and ecosystem functionality, we conclude that future soil carbon fluxes in alpine grasslands can be predicted by microbial carbon-degrading capacities.IMPORTANCE The warming pace in the Tibetan Plateau, which is predominantly occupied by grassland ecosystems, has been 0.2°C per decade in recent years, dwarfing the rate of global warming by a factor of 2. Many Earth system models project substantial carbon sequestration in Tibet, which has been observed. Here, we analyzed microbial communities under projected climate changes by 2100. As the soil "carbon pump," the growth and activity of microorganisms can largely influence soil carbon dynamics. However, microbial gene response to future climate scenarios is still obscure. We showed that the abundances of microbial functional genes, but not microbial taxonomy, were correlated with carbon fluxes and ecosystem multifunctionality. By identifying microbial traits linking to ecosystem functioning, our results can guide the assessment of future soil carbon fluxes in alpine grasslands, a critical step toward mitigating climate changes.

Gene-informed decomposition model predicts lower soil carbon loss due to persistent microbial adaptation to warming.

Soil microbial respiration is an important source of uncertainty in projecting future climate and carbon (C) cycle feedbacks. However, its feedbacks to climate warming and underlying microbial mechanisms are still poorly understood. Here we show that the temperature sensitivity of soil microbial respiration (Q10) in a temperate grassland ecosystem persistently decreases by 12.0 ± 3.7% across 7 years of warming. Also, the shifts of microbial communities play critical roles in regulating thermal adaptation of soil respiration. Incorporating microbial functional gene abundance data into a microbially-enabled ecosystem model significantly improves the modeling performance of soil microbial respiration by 5-19%, and reduces model parametric uncertainty by 55-71%. In addition, modeling analyses show that the microbial thermal adaptation can lead to considerably less heterotrophic respiration (11.6 ± 7.5%), and hence less soil C loss. If such microbially mediated dampening effects occur generally across different spatial and temporal scales, the potential positive feedback of soil microbial respiration in response to climate warming may be less than previously predicted.

Winter warming in Alaska accelerates lignin decomposition contributed by Proteobacteria.

BACKGROUND: In a warmer world, microbial decomposition of previously frozen organic carbon (C) is one of the most likely positive climate feedbacks of permafrost regions to the atmosphere. However, mechanistic understanding of microbial mediation on chemically recalcitrant C instability is limited; thus, it is crucial to identify and evaluate active decomposers of chemically recalcitrant C, which is essential for predicting C-cycle feedbacks and their relative strength of influence on climate change. Using stable isotope probing of the active layer of Arctic tundra soils after depleting soil labile C through a 975-day laboratory incubation, the identity of microbial decomposers of lignin and, their responses to warming were revealed. RESULTS: The ß-Proteobacteria genus Burkholderia accounted for 95.1% of total abundance of potential lignin decomposers. Consistently, Burkholderia isolated from our tundra soils could grow with lignin as the sole C source. A 2.2 °C increase of warming considerably increased total abundance and functional capacities of all potential lignin decomposers. In addition to Burkholderia, α-Proteobacteria capable of lignin decomposition (e.g. Bradyrhizobium and Methylobacterium genera) were stimulated by warming by 82-fold. Those community changes collectively doubled the priming effect, i.e., decomposition of existing C after fresh C input to soil. Consequently, warming aggravates soil C instability, as verified by microbially enabled climate-C modeling. CONCLUSIONS: Our findings are alarming, which demonstrate that accelerated C decomposition under warming conditions will make tundra soils a larger biospheric C source than anticipated. Video Abstract.

Warming-induced permafrost thaw exacerbates tundra soil carbon decomposition mediated by microbial community.

BACKGROUND: It is well-known that global warming has effects on high-latitude tundra underlain with permafrost. This leads to a severe concern that decomposition of soil organic carbon (SOC) previously stored in this region, which accounts for about 50% of the world's SOC storage, will cause positive feedback that accelerates climate warming. We have previously shown that short-term warming (1.5 years) stimulates rapid, microbe-mediated decomposition of tundra soil carbon without affecting the composition of the soil microbial community (based on the depth of 42684 sequence reads of 16S rRNA gene amplicons per 3 g of soil sample). RESULTS: We show that longer-term (5 years) experimental winter warming at the same site altered microbial communities (p < 0.040). Thaw depth correlated the strongest with community assembly and interaction networks, implying that warming-accelerated tundra thaw fundamentally restructured the microbial communities. Both carbon decomposition and methanogenesis genes increased in relative abundance under warming, and their functional structures strongly correlated (R2 > 0.725, p < 0.001) with ecosystem respiration or CH4 flux. CONCLUSIONS: Our results demonstrate that microbial responses associated with carbon cycling could lead to positive feedbacks that accelerate SOC decomposition in tundra regions, which is alarming because SOC loss is unlikely to subside owing to changes in microbial community composition. Video Abstract.

Copper(I)-Catalyzed Intramolecular Asymmetric Double C-Arylation for the Formation of Chiral Spirocyclic Bis-oxindoles.

A copper-catalyzed intramolecular asymmetric double C-arylation reaction was developed. The method provides a facile approach to chiral spiro bis-oxindoles in high yields and with good to excellent enantioselectivities. It also shows a broad substrate scope and good functional group tolerance. Density functional theory (DFT) calculations were conducted and revealed that the enantioselectivity is determined at the oxidative addition of Cu(I) into the second C-I bond.