Quorum sensing bacteria improve microbial networks stability and complexity in wastewater treatment plants.

Quorum-sensing bacteria (QSB) are crucial factors for microbial communication, yet their ecological role in wastewater treatment plants (WWTPs) remains unclear. Here, we developed a method to identify QSB by comparing 16S rRNA gene sequences. QSB in 388 activated sludge samples collected from 130 WWTPs across China primarily were identified as rare taxa and conditionally rare taxa. A co-occurrence network shared by all sludge communities revealed that QSB exhibited higher average clustering coefficient (0.46) than non-QSB (0.15). Individual sludge networks demonstrated that quorum sensing microbiomes were positively correlated with network robustness and network complexity, including average clustering coefficient and link density. We confirmed that QSB keystones and QSB nodes have a positive impact on network complexity by influencing network modularity through a structural equation model. Meanwhile, QSB communities directly contributed to maintaining network robustness (r = 0.29, P < 0.05). Hence, QSB play an important role in promoting network complexity and stability. Furthermore, QSB communities were positively associated with the functional composition of activated sludge communities (r = 0.33, P < 0.01), especially the denitrification capacity (r = 0.45, P < 0.001). Overall, we elucidated the ecological significance of QSB and provided support for QS-based regulation of activated sludge microbial communities.

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.

Global diversity and biogeography of DNA viral communities in activated sludge systems.

BACKGROUND: Activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses that regulate microbial metabolism and nutrient cycling, significantly influencing the stability of AS systems. However, our knowledge about the diversity of viral taxonomic groups and functional traits in global AS systems is still limited. To address this gap, we investigated the global diversity and biogeography of DNA viral communities in AS systems using 85,114 viral operational taxonomic units (vOTUs) recovered from 144 AS samples collected across 54 WWTPs from 13 different countries. RESULTS: AS viral communities and their functional traits exhibited distance-decay relationship (DDR) at the global scale and latitudinal diversity gradient (LDG) from equator to mid-latitude. Furthermore, it was observed that AS viral community and functional gene structures were largely driven by the geographic factors and wastewater types, of which the geographic factors were more important. Carrying and disseminating auxiliary metabolic genes (AMGs) associated with the degradation of polysaccharides, sulfate reduction, denitrification, and organic phosphoester hydrolysis, as well as the lysis of crucial functional microbes that govern biogeochemical cycles were two major ways by which viruses could regulate AS functions. It was worth noting that our study revealed a high abundance of antibiotic resistance genes (ARGs) in viral genomes, suggesting that viruses were key reservoirs of ARGs in AS systems. CONCLUSIONS: Our results demonstrated the highly diverse taxonomic groups and functional traits of viruses in AS systems. Viral lysis of host microbes and virus-mediated HGT can regulate the biogeochemical and nutrient cycles, thus affecting the performance of AS systems. These findings provide important insights into the viral diversity, function, and ecology in AS systems on a global scale. Video Abstract.

Photo-crosslinked adhesive hydrogel loaded with extracellular vesicles promoting hemostasis and liver regeneration.

Hepatectomy is an effective surgical method for the treatment of liver diseases, but intraoperative bleeding and postoperative liver function recovery are still key issues. This study aims to develop a composite hydrogel dressing with excellent hemostatic properties, biocompatibility, and ability to promote liver cell regeneration. The modified gelatin matrix (GelMA, 10%) was mixed with equal volumes of sodium alginate-dopamine (Alg-DA) at concentrations of 0.5%, 1%, and 2%. Then a cross-linking agent (0.1%) was added to prepare different composite hydrogels under UV light, named GelMA/Alg-DA-0.5, GelMA/Alg-DA-1 and GelMA/Alg-DA-2, respectively. All the prepared hydrogel has a porous structure with a porosity greater than 65%, and could be stabilized in a gel state after being cross-linked by ultraviolet light. Physicochemical characterization showed that the elastic modulus, water absorption, adhesion, and compressibility of the composite hydrogels were improved with increasing Alg-DA content. Furthermore, the prepared hydrogel exhibits in vitro degradability, excellent biocompatibility, and good hemostatic function. Among all tested groups, the group of GelMA/Alg-DA-1 hydrogel performed the best. To further enhance its application potential in the field of liver regeneration, adipose-derived mesenchymal stem cell exosomes (AD-MSC-Exo) were loaded into GelMA/Alg-DA-1 hydrogel. Under the same conditions, GelMA/Alg-DA-1/Exo promoted cell proliferation and migration more effectively than hydrogels without extracellular vesicles. In conclusion, the prepared GelMA/Alg-DA-1 composite hydrogel loaded with AD-MSC-Exo has great application potential in liver wound hemostasis and liver regeneration.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Spike-based adenovirus vectored COVID-19 vaccine does not aggravate heart damage after ischemic injury in mice.

An unprecedented number of COVID-19 vaccination campaign are under way worldwide. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases.

Deterministic mechanisms drive bacterial communities assembly in industrial wastewater treatment system.

Microbial communities are responsible for biological treatment of many industrial wastewater, but our knowledge of their diversity, assembly patterns, and function is still poor. Here, we analyzed the bacterial communities of wastewater and activated sludge samples taken from 11 full-scale industrial wastewater treatment plants (IWWTPs) characterized by the same process design but different wastewater types and WWTP compartments. We found significantly different diversity and compositions of bacterial assemblages among distinct wastewater types and IWWTPs compartments. IWWTPs bacterial communities exhibited a clear species abundance distribution. The dispersal-driven process was weak in shaping IWWTP communities. Meanwhile, environmental and operating conditions were important factors in regulating the structure of the activated sludge community and pollutants removal, indicating that bacterial community was largely driven by deterministic mechanisms. The core microbial community in IWWTPs was different from that in municipal wastewater treatment plants (MWWTPs), and many taxa (e.g. the genus Citreitalea) rarely were detected before, indicating IWWTPs harbored unique core bacterial communities. Furthermore, we found that bacterial community compositions were strongly linked to activated sludge function. These findings are important to both microbial ecologists and environmental engineers, who may optimize the operation strategies jointly for maintaining biodiversity, which in turn may promote a more stable performance of the IWWTP. Overall, our study enhances the mechanistic understanding of the IWWTP microbial community diversity, assembly patterns, and function, and provides important implications for microbial ecology and wastewater treatment processes.

A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy.

Nanomedicine has been widely studied for the diagnosis and treatment of hepatocellular carcinoma (HCC). How to synthesize a nanoplatform possessing a high synergistic therapeutic efficacy remains a challenge in this emerging research field. In this study, a convenient all-in-one therapeutic nanoplatform (FTY720@AM/T7-TL) is designed for HCC. This advanced nanoplatform consists of multiple functional elements, including gold-manganese dioxide nanoparticles (AM), tetraphenylethylene (T), fingolimod (FTY720), hybrid-liposome (L), and T7 peptides (T7). The nanoplatform is negatively charged at physiological pH and can transit to a positively charged state once moving to acidic pH environments. The specially designed pH-responsive charge-reversal nanocarrier prolongs the half-life of nanodrugs in blood and improves cellular uptake efficiency. The platform achieves a sustained and controllable drug release through dual stimulus-response, with pH as the endogenous stimulus and near-infrared as the exogenous stimulus. Furthermore, the nanoplatform realizes in situ O2 generation by catalyzing tumor over-expressed H2O2, which alleviates tumor microenvironment hypoxia and improves photodynamic therapy. Both in vitro and in vivo studies show the prepared nanoplatform has good photothermal conversion, cellular uptake efficiency, fluorescence/magnetic resonance imaging capabilities, and synergistic anti-tumor effects. These results suggest that the prepared all-in-one nanoplatform has great potential for dual-modal imaging-guided synergistic therapy of HCC.

Immune checkpoint inhibitor therapy for malignant tumors in liver transplantation recipients: A systematic review of the literature.

BACKGROUND: Treatment for de novo or recurrent tumors of liver transplantation (LT) recipients is challenging and immune checkpoint inhibitor (ICI) is recently well developed and could be a potentially effective option for this population. There remains limited evidence on the safety and efficacy of ICI therapy in LT recipients. METHODS: A systematic literature search was conducted on PubMed database through April 1, 2022, to identify publications reporting ICI treatment for malignant tumors in LT recipients. We summarized the allograft rejection, mortality, and tumor response of ICI treatment. RESULTS: 24 articles with 41 LT recipients were identified. The age of LT recipients ranged from 14 to 78, 76.2% were male, 56.1% had recurrent HCC, and 87.8% received anti-PD-1 therapy. Allograft rejection occurred in 31.7% of patients, death was reported in 46.3% and 6 cases died secondary to allograft rejection. Progressive disease rate of this population was 48.8% and 10 patients responded to immunotherapy. Half of recipients with positive PD-L1 staining (4/8) experienced allograft rejection. CONCLUSIONS: ICI therapy has potential therapeutic value on malignant tumors for LT recipients, accompanied by a high rate of allograft rejection and mortality. PD-L1 expression, type of ICI, and immunosuppression agent should be taken into consideration before initiation of immunotherapy. Further studies are needed to optimize this anticancer treatment approach in these patients.

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.

Reprogramming of fibroblasts into expandable cardiovascular progenitor cells via small molecules in xeno-free conditions.

A major hurdle in cardiac cell therapy is the lack of a bona fide autologous stem-cell type that can be expanded long-term and has authentic cardiovascular differentiation potential. Here we report that a proliferative cell population with robust cardiovascular differentiation potential can be generated from mouse or human fibroblasts via a combination of six small molecules. These chemically induced cardiovascular progenitor cells (ciCPCs) self-renew long-term in fully chemically defined and xeno-free conditions, with faithful preservation of the CPC phenotype and of cardiovascular differentiation capacity in vitro and in vivo. Transplantation of ciCPCs into infarcted mouse hearts improved animal survival and cardiac function up to 13 weeks post-infarction. Mechanistically, activated fibroblasts revert to a plastic state permissive to cardiogenic signals, enabling their reprogramming into ciCPCs. Expanded autologous cardiovascular cells may find uses in drug discovery, disease modelling and cardiac cell therapy.

Nutrient supply controls the linkage between species abundance and ecological interactions in marine bacterial communities.

Nutrient scarcity is pervasive for natural microbial communities, affecting species reproduction and co-existence. However, it remains unclear whether there are general rules of how microbial species abundances are shaped by biotic and abiotic factors. Here we show that the ribosomal RNA gene operon (rrn) copy number, a genomic trait related to bacterial growth rate and nutrient demand, decreases from the abundant to the rare biosphere in the nutrient-rich coastal sediment but exhibits the opposite pattern in the nutrient-scarce pelagic zone of the global ocean. Both patterns are underlain by positive correlations between community-level rrn copy number and nutrients. Furthermore, inter-species co-exclusion inferred by negative network associations is observed more in coastal sediment than in ocean water samples. Nutrient manipulation experiments yield effects of nutrient availability on rrn copy numbers and network associations that are consistent with our field observations. Based on these results, we propose a "hunger games" hypothesis to define microbial species abundance rules using the rrn copy number, ecological interaction, and nutrient availability.

Disentangling direct from indirect relationships in association networks.

Networks are vital tools for understanding and modeling interactions in complex systems in science and engineering, and direct and indirect interactions are pervasive in all types of networks. However, quantitatively disentangling direct and indirect relationships in networks remains a formidable task. Here, we present a framework, called iDIRECT (Inference of Direct and Indirect Relationships with Effective Copula-based Transitivity), for quantitatively inferring direct dependencies in association networks. Using copula-based transitivity, iDIRECT eliminates/ameliorates several challenging mathematical problems, including ill-conditioning, self-looping, and interaction strength overflow. With simulation data as benchmark examples, iDIRECT showed high prediction accuracies. Application of iDIRECT to reconstruct gene regulatory networks in Escherichia coli also revealed considerably higher prediction power than the best-performing approaches in the DREAM5 (Dialogue on Reverse Engineering Assessment and Methods project, #5) Network Inference Challenge. In addition, applying iDIRECT to highly diverse grassland soil microbial communities in response to climate warming showed that the iDIRECT-processed networks were significantly different from the original networks, with considerably fewer nodes, links, and connectivity, but higher relative modularity. Further analysis revealed that the iDIRECT-processed network was more complex under warming than the control and more robust to both random and target species removal (P < 0.001). As a general approach, iDIRECT has great advantages for network inference, and it should be widely applicable to infer direct relationships in association networks across diverse disciplines in science and engineering.

Macroecological distributions of gene variants highlight the functional organization of soil microbial systems.

The recent application of macroecological tools and concepts has made it possible to identify consistent patterns in the distribution of microbial biodiversity, which greatly improved our understanding of the microbial world at large scales. However, the distribution of microbial functions remains largely uncharted from the macroecological point of view. Here, we used macroecological models to examine how the genes encoding the functional capabilities of microorganisms are distributed within and across soil systems. Models built using functional gene array data from 818 soil microbial communities showed that the occupancy-frequency distributions of genes were bimodal in every studied site, and that their rank-abundance distributions were best described by a lognormal model. In addition, the relationships between gene occupancy and abundance were positive in all sites. This allowed us to identify genes with high abundance and ubiquitous distribution (core) and genes with low abundance and limited spatial distribution (satellites), and to show that they encode different sets of microbial traits. Common genes encode microbial traits related to the main biogeochemical cycles (C, N, P and S) while rare genes encode traits related to adaptation to environmental stresses, such as nutrient limitation, resistance to heavy metals and degradation of xenobiotics. Overall, this study characterized for the first time the distribution of microbial functional genes within soil systems, and highlight the interest of macroecological models for understanding the functional organization of microbial systems across spatial scales.

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.

Ischaemia-free liver transplantation in humans: a first-in-human trial.

Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context.

Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes.

BACKGROUND: Canonical nonsense-mediated decay (NMD) is an important splicing-dependent process for mRNA surveillance in mammals. However, processed pseudogenes are not able to trigger NMD due to their lack of introns. It is largely unknown whether they have evolved other surveillance mechanisms. RESULTS: Here, we find that the RNAs of pseudogenes, especially processed pseudogenes, have dramatically higher m6A levels than their cognate protein-coding genes, associated with de novo m6A peaks and motifs in human cells. Furthermore, pseudogenes have rapidly accumulated m6A motifs during evolution. The m6A sites of pseudogenes are evolutionarily younger than neutral sites and their m6A levels are increasing, supporting the idea that m6A on the RNAs of pseudogenes is under positive selection. We then find that the m6A RNA modification of processed, rather than unprocessed, pseudogenes promotes cytosolic RNA degradation and attenuates interference with the RNAs of their cognate protein-coding genes. We experimentally validate the m6A RNA modification of two processed pseudogenes, DSTNP2 and NAP1L4P1, which promotes the RNA degradation of both pseudogenes and their cognate protein-coding genes DSTN and NAP1L4. In addition, the m6A of DSTNP2 regulation of DSTN is partially dependent on the miRNA miR-362-5p. CONCLUSIONS: Our discovery reveals a novel evolutionary role of m6A RNA modification in cleaning up the unnecessary processed pseudogene transcripts to attenuate their interference with the regulatory network of protein-coding genes.

Seasonal dynamics of the microbial community in two full-scale wastewater treatment plants: Diversity, composition, phylogenetic group based assembly and co-occurrence pattern.

The optimal operation and functional stability of a wastewater treatment plant (WWTP) strongly depend on the properties of its microbial community. However, a knowledge gap remains regarding the seasonal dynamics of microbial community properties, especially phylogenetic group based assembly and co-occurrence patterns. Accordingly, in this study, influent and activated sludge (AS) samples were weekly collected from 2 full-scale WWTPs for one year (89 influent and 103 AS samples in total) and examined by high-throughput Illumina-MiSeq sequencing. The results suggested that the microbial community diversity and composition in the influent fluctuated substantially with season, while those in the AS had a relatively more stable pattern throughout the year. The phylogenetic group based assembly mechanisms of AS community were identified by using "Infer Community Assembly Mechanisms by Phylogenetic-bin-based null model (iCAMP)". The results showed that drift accounted for the largest proportion (52.8%), while homogeneous selection (18.2%) was the most important deterministic process. Deterministic processes dominated in 47 microbial groups (bins), which were also found (~40%) in the AS core taxa dataset. Moreover, the results suggested that Nitrospira were more susceptible to stochastic processes in winter, which may provide a possible explanation for nitrification failure in winter. Network analysis results suggested that the network structure of the AS community could be more stable in summer and autumn. In addition, there were no identical keystone taxa found in different networks (constructed from different plants, sources, and seasons), which supported the context dependency theory. The results of this study deepened our understanding of the microbial ecology in AS systems and provided a foundation for further studies on the community regulation strategy of WWTPs.

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.

A conductive dual-network hydrogel composed of oxidized dextran and hyaluronic-hydrazide as BDNF delivery systems for potential spinal cord injury repair.

Spinal cord injury (SCI) often causes neuronal death and axonal degeneration. In this study, we report a new strategy for preparing injectable and conductive polysaccharides-based hydrogels that could sustainably deliver brain-derived neurotrophic factor (BDNF) for SCI repair. We used poly(lactic-co-glycolic acid) (PLGA) as a carrier to encapsulate BDNF. The resulting microspheres were then modified with tannic acid (TA). The polysaccharides-based hydrogel composed of oxidized dextran (Dex) and hyaluronic acid-hydrazide (HA) was mixed with TA-modified microspheres to form the ultimate BDNF@TA-PLGA/Dex-HA hydrogel. Our results showed that the hydrogel had properties similar to natural spinal cords. Specifically, the hydrogel had soft mechanical properties and high electrical conductivity. The cross-sectional morphology of the hydrogel exhibited a continuous and porous structure. The swelling and degradation behaviors of the Dex-HA hydrogel in vitro indicated the incorporation of TA into hydrogel matrix could improve the stability of the hydrogel matrix as well as extend the release time of BDNF from the matrix. Furthermore, results from immunostaining and real-time PCR demonstrated that BDNF@TA-PLGA/Dex-HA hydrogel could promote the differentiation of neural stem cells (NSCs) into neurons and inhibit astrocyte differentiation in vitro. These results show the great potential of this hydrogel as a biomimetic material in SCI regeneration.