Self-limiting multimerization of α-synuclein on membrane and its implication in Parkinson's diseases.

α-Synuclein (α-syn), a crucial molecule in Parkinson's disease (PD), is known for its interaction with lipid membranes, which facilitates vesicle trafficking and modulates its pathological aggregation. Deciphering the complexity of the membrane-binding behavior of α-syn is crucial to understand its functions and the pathology of PD. Here, we used single-molecule imaging to show that α-syn forms multimers on lipid membranes with huge intermultimer distances. The multimers are characterized by self-limiting growth, manifesting in concentration-dependent exchanges of monomers, which are fast at micromolar concentrations and almost stop at nanomolar concentrations. We further uncovered movement patterns of α-syn's occasional trapping on membranes, which may be attributed to sparse lipid packing defects. Mutations such as E46K and E35K may disrupt the limit on the growth, resulting in larger multimers and accelerated amyloid fibril formation. This work emphasizes sophisticated regulation of α-syn multimerization on membranes as a critical underlying factor in the PD pathology.

[Study on the clinical effect of initiating continuous blood purification at different times for severe acute pancreatitis].

OBJECTIVE: To observe the clinical effect of initiating continuous blood purification (CBP) treatment at different times for patients with severe acute pancreatitis (SAP), and to explore the optimal timing for starting CBP treatment for SAP, so as to provide evidence for clinicians to start CBP treatment. METHODS: A retrospective cohort study was used to select patients with SAP who received CBP treatment in People's Hospital of Hunan Province from January 2020 to December 2023. According to the timing of CBP initiation, the patients were divided into early initiation group (diagnosis of SAP to the first CBP treatment time < 24 hours) and late initiation group (diagnosis of SAP to the first CBP treatment time of 24-48 hours). The general data, acute physiology and chronic health evaluation II (APACHE II), bedside index for severity in acute pancreatitis (BISAP) score and laboratory indicators, local complications and systemic complications, intensive care unit (ICU) treatment time, hospital stay, treatment cost, and clinical outcome of the two groups were collected and compared. RESULTS: A total of 130 patients with SAP who received CBP treatment were enrolled, including 90 patients in the early initiation group and 40 patients in the late initiation group. Before treatment, there were no significant differences in gender, age, APACHE II score, BISAP score, etiology and laboratory examination indexes between the early initiation group and late initiation group. At 48, 72, 96 hours after treatment, the blood calcium level of the two groups was significantly higher than that before treatment, and the levels of white blood cell count (WBC), C-reactive protein (CRP), lactic acid, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), APACHE II score and BISAP score were significantly lower than those before treatment. The WBC level, APACHE II score and BISAP score of the late initiation group were significantly lower than those of the early initiation group at 72 hours and 96 hours after treatment [WBC (×109/L): 10.96 (8.68, 13.04) vs. 12.45 (8.93, 16.30) at 72 hours after treatment, and 10.18 (8.68, 12.42) vs. 11.96 (8.81, 16.87) at 96 hours after treatment; APACHE II score: 9.50 (5.75, 12.00) vs. 11.00 (6.25, 14.00) at 72 hours after treatment, and 10.00 (4.00, 12.00) vs. 12.00 (7.00, 14.75) at 96 hours after treatment; BISAP score: 2.35±1.03 vs. 2.76±1.10 at 72 hours after treatment, and 2.08±1.21 vs. 2.70±1.11 at 96 hours after treatment], the differences were statistically significant (all P < 0.05). In terms of complications, the incidence of pancreatic abscess in the late initiation group was significantly lower than that in the early initiation group [5.00% (2/40) vs. 20.00% (18/90)], but the incidence of abdominal compartment syndrome was significantly higher than that in the early initiation group [42.50% (17/40) vs. 13.33% (12/90)], the differences were statistically significant (all P < 0.05). In addition, the ICU treatment time in the early initiation group was significantly shorter than that in the late initiation group [days: 11.00 (6.00, 20.00) vs. 15.00 (9.75, 25.00), P < 0.05], and there were no statistically significant differences in hospitalization costs, length of stay and mortality between the two groups. CONCLUSIONS: CBP can effectively increase the level of blood calcium and decrease the level of lactic acid and inflammatory factors. Starting CBP within 24-48 hours after diagnosis of SAP can reduce WBC level and disease severity score faster, and reduce the occurrence of pancreatic abscess. Initiation of CBP within 24 hours after diagnosis of SAP can reduce the incidence of abdominal compartment syndrome and shorten the duration of ICU treatment.

Multiple Non-Destructive Approaches to Analysis of the Early Silurian Chain Coral Halysites from South China.

Cnidarians are among the most important diploblastic organisms, elucidating many of the early stages of Metazoan evolution. However, Cnidarian fossils from Cambrian deposits have been rarely documented, mainly due to difficulties in identifying early Cnidarian representatives. Halysites, a tabulate coral from Silurian reef systems, serves as a crucial taxon for interpreting Cambrian cnidarians. Traditionally, the biological characteristics of Halysites have been analyzed using methods limited by pretreatment requirements (destructive testing) and the chamber size capacity of relevant analytical instruments. These constraints often lead to irreversible information loss and inadequate data extraction. This means that, to date, there has been no high-resolution three-dimensional mineralization analysis of Halysites. This study aims to introduce novel, non-destructive techniques to analyze the internal structure and chemical composition of Halysites. Furthermore, it seeks to elucidate the relationship between coral organisms and biomineralization in reef settings and to compare Silurian Tabulata with putative Cambrian cnidarians. Techniques such as micro-X-ray fluorescence spectrometry (micro-XRF), micro-X-ray computed tomography (micro-CT), and scanning electron microscopy (SEM) were employed in this research. With the help of high-resolution micro-CT scanning, we identify the growth pattern of Halysites, showing both lateral and vertical development. The lateral multiple-branching growth pattern of Halysites corals is first established herein. The flaggy corallite at the initial stage of branching is also observed. The micro-XRF mapping results reveal the occurrence of septa spines for Halysites, a trait previously thought rare or absent. Additionally, the ratio of coral volume to the surrounding rock was assessed, revealing that Halysites reefs were relatively sparse (volume ratio = ~30%). The cavities between Halysites likely provided more space for other organisms (e.g., rugose corals and bryozoans) when compared to other coral reef types. Additionally, we provide a comparative analysis of post-Cambrian colonial calcareous skeletons, offering insights into the structural features and growth patterns of early skeletal metazoans across the Ediacaran-Cambrian boundary.

Microplastics promote methane emission in estuarine and coastal wetlands.

Increasing microplastic (MP) pollution poses significant threats to estuarine and coastal ecosystems. However, the effects of MPs on the emission of methane (CH4), a potent greenhouse gas, within these ecosystems and the underlying regulatory mechanisms have not been elucidated. Here, a combination of 13C stable isotope-based method and molecular techniques was applied to investigate how conventional petroleum-based MPs [polyethylene (PE) and polyvinyl chloride (PVC)] and biodegradable MPs [polylactic acid (PLA) and polyadipate/butylene terephthalate (PBAT)] regulate CH4 production and consumption and thus affect CH4 emission dynamics in estuarine and coastal wetlands. Results indicated that both conventional and biodegradable MPs enhanced the emission of CH4 (P < 0.05), with the promoting effect being more significant for biodegradable MPs. However, the mechanisms by which conventional and biodegradable MPs promote CH4 emissions were different. Specifically, conventional MPs stimulated the emission of CH4 by inhibiting the processes of CH4 consumption, but had no significant effect on CH4 production rate. Nevertheless, biodegradable MPs promoted CH4 emissions via accelerating the activities the methanogens while inhibiting the oxidation of CH4, thus resulting in a higher degree of promoting effect on CH4 emissions than conventional MPs. Consistently, quantitative PCR further revealed a significant increase in the abundance of methyl-coenzyme M reductase gene (mcrA) of methanogens under the exposure of biodegradable MPs (P < 0.05), but not conventional MPs. Furthermore, the relative abundance of most genes involved in CH4 oxidation exhibited varying degrees of reduction after exposure to all types of MPs, based on metagenomics data. This study reveals the effects of MPs on CH4 emissions in estuarine and coastal ecosystems and their underlying mechanisms, highlighting that the emerging biodegradable MPs exhibited a greater impact than conventional MPs on promoting CH4 emissions in these globally important ecosystems, thereby accelerating global climate change.

Biomechanical analysis of a new cannulated screw for unstable femoral neck fractures.

Background: The treatment of unstable femoral neck fractures (FNFs) remains a challenge. In this study, a new cannulated screw for unstable FNFs was designed to provide a new approach for the clinical treatment of these injuries, and its biomechanical stability was analyzed using finite element analysis and mechanical tests. Methods: An unstable FNF model was established. An internal fixation model with parallel inverted triangular cannulated screws (CSs) and a configuration with two superior cannulated screws and one inferior new cannulated screw (NCS) were used. The biomechanical properties of the two fixation methods were compared and analyzed by using finite element analysis and mechanical tests. Results: The NCS model outperformed the CSs model in terms of strain and stress distribution in computer-simulated reconstruction of the inverted triangular cannulated screw fixation model for unstable FNFs. In the biomechanical test, the NCS group showed significantly smaller average femoral deformation (1.08 ± 0.15 mm vs. 1.50 ± 0.37 mm) and fracture line displacement (1.43 ± 0.30 mm vs. 2.01 ± 0.47 mm). In the NCS group, the mean stiffness was significantly higher than that in the CSs group (729.37 ± 82.20 N/mm vs. 544.83 ± 116.07 N/mm), and the mean compression distance was significantly lower than that in the CSs group (2.87 ± 0.30 mm vs. 4.04 ± 1.09 mm). Conclusion: The NCS combined with two ordinary cannulated screws in an inverted triangle structure to fix unstable FNFs can provide better biomechanical stability than CSs and exhibit a length- and angle-stable construct to prevent significant femoral neck shortening.

Triggered Release of Ampicillin from Metallic Implant Coatings for Combating Periprosthetic Infections.

Periprosthetic infections caused by Staphylococcus aureus (S. aureus) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin ß-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the ß-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus, it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli (E. coli) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the ß-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.

Bimetallic sulfide/N-doped carbon composite derived from Prussian blue analogues/cellulose nanofibers film toward enhanced oxygen evolution reaction.

Exploiting effective, stable, and cost-efficient electrocatalysts for the water oxidation reaction is highly desirable for renewable energy conversion techniques. Constructional design and compositional manipulation are widely used approaches to efficaciously boost the electrocatalytic performance. Herein, we designed a NiFe-bimetallic sulfide/N-doped carbon composite via a two-step thermal treatment of Prussian blue analogues/cellulose nanofibers (PBA/CNFs) film. The NiFe-bimetallic sulfide/N-doped carbon composite displayed enhanced OER performance in an alkaline environment, with an overpotential of 282 mV at 10 mA cm-2, a Tafel slope of 59.71 mV dec-1, and good stability, making the composite a candidate electrocatalyst for OER-related energy equipment. The introduction of CNFs in the precursor prevented the aggregation of PBA nanoparticles (NPs), exposed more active sites, and the resulting carbon substrate enhanced the electroconductivity of the composite. Moreover, the synergistic effect of Ni and Fe in the bimetallic sulfide could modulate the configuration of electrons, enrich the catalytically active sites, and augment the electric conductivity, thus ameliorating the OER performance. This study broadens the application of MOF-CNF composites to construct hierarchical structures of metal compounds and provides some thoughts for the development of cost-effective precious-metal-free catalysts for electrocatalysis.

Active dark carbon fixation evidenced by 14C isotope assimilation and metagenomic data across the estuarine-coastal continuum.

Estuaries, as important land-ocean transitional zones across the Earth's surface, are hotspots of microbially driven dark carbon fixation (DCF), yet understanding of DCF process remains limited across the estuarine-coastal continuum. This study explored DCF activities and associated chemoautotrophs along the estuarine and coastal environmental gradients, using radiocarbon labelling and molecular techniques. Significantly higher DCF rates were observed at middle- and high-salinity regions (0.65-2.31 and 0.66-2.82 mmol C m-2 d-1, respectively), compared to low-salinity zone (0.07-0.19 mmol C m-2 d-1). Metagenomic analysis revealed relatively stable DCF pathways along the estuarine-coastal continuum, primarily dominated by Calvin-Benson-Bassham (CBB) cycle and Wood-Ljungdahl (WL) pathway. Nevertheless, chemoautotrophic communities driving DCF exhibited significant spatial variations. It is worth noting that although CBB cycle played an important role in DCF in estuarine sediments, WL pathway might play a more significant role, which has not been previously recognized. Overall, this study highlights that DCF activities coincide with the genetic potential of chemoautotrophy and the availability of reductive substrates across the estuarine-coastal continuum, and provides an important scientific basis for accurate quantitative assessment of global estuarine carbon sink.

Role of n-DAMO in Mitigating Methane Emissions from Intertidal Wetlands Is Regulated by Saltmarsh Vegetations.

Coastal wetlands are hotspots for methane (CH4) production, reducing their potential for global warming mitigation. Nitrite/nitrate-dependent anaerobic methane oxidation (n-DAMO) plays a crucial role in bridging carbon and nitrogen cycles, contributing significantly to CH4 consumption. However, the role of n-DAMO in reducing CH4 emissions in coastal wetlands is poorly understood. Here, the ecological functions of the n-DAMO process in different saltmarsh vegetation habitats as well as bare mudflats were quantified, and the underlying microbial mechanisms were explored. Results showed that n-DAMO rates were significantly higher in vegetated habitats (Scirpus mariqueter and Spartina alterniflora) than those in bare mudflats (P < 0.05), leading to an enhanced contribution to CH4 consumption. Compared with other habitats, the contribution of n-DAMO to the total anaerobic CH4 oxidation was significantly lower in the Phragmites australis wetland (15.0%), where the anaerobic CH4 oxidation was primarily driven by ferric iron (Fe3+). Genetic and statistical analyses suggested that the different roles of n-DAMO in various saltmarsh wetlands may be related to divergent n-DAMO microbial communities as well as environmental parameters such as sediment pH and total organic carbon. This study provides an important scientific basis for a more accurate estimation of the role of coastal wetlands in mitigating climate change.

DMFF: An Open-Source Automatic Differentiable Platform for Molecular Force Field Development and Molecular Dynamics Simulation.

In the simulation of molecular systems, the underlying force field (FF) model plays an extremely important role in determining the reliability of the simulation. However, the quality of the state-of-the-art molecular force fields is still unsatisfactory in many cases, and the FF parameterization process largely relies on human experience, which is not scalable. To address this issue, we introduce DMFF, an open-source molecular FF development platform based on an automatic differentiation technique. DMFF serves as a powerful tool for both top-down and bottom-up FF development. Using DMFF, both energies/forces and thermodynamic quantities such as ensemble averages and free energies can be evaluated in a differentiable way, realizing an automatic, yet highly flexible FF optimization workflow. DMFF also eases the evaluation of forces and virial tensors for complicated advanced FFs, helping the fast validation of new models in molecular dynamics simulation. DMFF has been released as an open-source package under the LGPL-3.0 license and is available at https://github.com/deepmodeling/DMFF.

Visualizing the Interfacial Chemistry in Multivalent Metal Anodes by Transmission Electron Microscopy.

Multivalent metal batteries (MMBs) have been considered potentially high-energy and low-cost alternatives to commercial Li-ion batteries, thus attracting tremendous research interest for energy-storage applications. However, the plating and stripping of multivalent metals (i.e., Zn, Ca, Mg) suffer from low Coulombic efficiencies and short cycle life, which are largely rooted in the unstable solid electrolyte interphase. Apart from exploring new electrolytes or artificial layers for robust interphases, fundamental works on deciphering interfacial chemistry have also been conducted. This work is dedicated to summarizing the state-of-the-art advances in understanding the interphases for multivalent metal anodes revealed by transmission electron microscopy (TEM) methods. Operando and cryogenic TEM with high spatial and temporal resolutions realize the dynamic visualization of the vulnerable chemical structures in interphase layers. Following a scrutinization of the interphases on different metal anodes, we elucidate their features for appealing multivalent metal anodes. Finally, perspectives are proposed for the remaining issues on analyzing and regulating interphases for practical MMBs.

Modulating On-Demand Release of Vancomycin from Implant Coatings via Chemical Modification of a Micrococcal Nuclease-Sensitive Oligonucleotide Linker.

Periprosthetic infections are one of the most serious complications in orthopedic surgeries, and those caused by Staphylococcus aureus (S. aureus) are particularly hard to treat due to their tendency to form biofilms on implants and their notorious ability to invade the surrounding bones. The existing prophylactic local antibiotic deliveries involve excessive drug loading doses that could risk the development of drug resistance strains. Utilizing an oligonucleotide linker sensitive to micrococcal nuclease (MN) cleavage, we previously developed an implant coating capable of releasing covalently tethered vancomycin, triggered by S. aureus-secreted MN, to prevent periprosthetic infections in the mouse intramedullary (IM) canal. To further engineer this exciting platform to meet broader clinical needs, here, we chemically modified the oligonucleotide linker by a combination of 2'-O-methylation and phosphorothioate modification to achieve additional modulation of its stability/sensitivity to MN and the kinetics of MN-triggered on-demand release. We found that when all phosphodiester bonds within the oligonucleotide linker 5'-carboxy-mCmGTTmCmG-3-acrydite, except for the one between TT, were replaced by phosphorothioate, the oligonucleotide (6PS) stability significantly increased and enabled the most sustained release of tethered vancomycin from the coating. By contrast, when only the peripheral phosphodiester bonds at the 5'- and 3'-ends were replaced by phosphorothioate, the resulting oligonucleotide (2PS) linker was cleaved by MN more rapidly than that without any PS modifications (0PS). Using a rat femoral canal periprosthetic infection model where 1000 CFU S. aureus was inoculated at the time of IM pin insertion, we showed that the prophylactic implant coating containing either 0PS- or 2PS-modified oligonucleotide linker effectively eradicated the bacteria by enabling the rapid on-demand release of vancomycin. No bacteria were detected from the explanted pins, and no signs of cortical bone changes were detected in these treatment groups throughout the 3 month follow-ups. With an antibiotic tethering dose significantly lower than conventional antibiotic-bearing bone cements, these coatings also exhibited excellent biocompatibility. These chemically modified oligonucleotides could help tailor prophylactic anti-infective coating strategies to meet a range of clinical challenges where the risks for S. aureus prosthetic infections range from transient to long-lasting.

Tidal dynamics regulates potential coupling of carbon­nitrogen­sulfur cycling microbes in intertidal flats.

Tide-driven hydrodynamic process causes significant geochemical gradients that influence biogeochemical cycling and ecological functioning of estuarine and coastal ecosystems. However, the effects of tidal dynamics on microbial communities, particularly at the functional gene level, remain unclear even though microorganisms play critical roles in biogeochemical carbon (C), nitrogen (N) and sulfur (S) cycling. Here, we used 16S rRNA gene amplicon sequencing and microarray-based approach to reveal the stratification of microorganisms related to C, N and S cycles along vertical redox gradients in intertidal wetlands. Alpha-diversity of bacteria and archaea was generally higher at the deep groundwater-sediment interface. Microbial compositions were markedly altered along the sediment profile, and these shifts were largely due to changes in nutrient availability and redox potential. Furthermore, functional genes exhibited redox partitioning between interfaces and transition layer, with abundant genes involved in C decomposition, methanogenesis, heterotrophic denitrification, sulfite reduction and sulfide oxidation existed in the middle anoxic zone. The influence of tidal dynamics on sediment function was highly associated with redox state, sediment texture, and substrates availability, leading to distinct distribution pattern of metabolic coupling of microbes involved in energy flux and elemental cycling in intertidal wetlands. These results indicate that tidal cycles are critical in determining microbial community and functional structure, and they provide new insights into sediment microbe-mediated biogeochemical cycling in intertidal habitats.

Recent advances in proton exchange membrane water electrolysis.

Proton exchange membrane water electrolyzers (PEMWEs) are an attractive technology for renewable energy conversion and storage. By using green electricity generated from renewable sources like wind or solar, high-purity hydrogen gas can be produced in PEMWE systems, which can be used in fuel cells and other industrial sectors. To date, significant advances have been achieved in improving the efficiency of PEMWEs through the design of stack components; however, challenges remain for their large-scale and long-term application due to high cost and durability issues in acidic conditions. In this review, we examine the latest developments in engineering PEMWE systems and assess the gap that still needs to be filled for their practical applications. We provide a comprehensive summary of the reaction mechanisms, the correlation among structure-composition-performance, manufacturing methods, system design strategies, and operation protocols of advanced PEMWEs. We also highlight the discrepancies between the critical parameters required for practical PEMWEs and those reported in the literature. Finally, we propose the potential solution to bridge the gap and enable the appreciable applications of PEMWEs. This review may provide valuable insights for research communities and industry practitioners working in these fields and facilitate the development of more cost-effective and durable PEMWE systems for a sustainable energy future.

Fast degradation of macro alkanes through activating indigenous bacteria using biosurfactants produced by Burkholderia sp.

Soil bacteria that produce biosurfactants can use total petroleum hydrocarbons (TPHs) as a carbon source. This study demonstrated that biosurfactants produced by Burkholderia sp. enhanced the recovery and synergism of soil microbial community, resulting in fast degradation of macro alkanes. Experiments were carried out by applying bio-stimulation after pre-oxidation to investigate the effects of nutrient addition on biosurfactant production, TPH degradation, and microbial community succession in the soil. The results presented that bio-stimulation could produce biosurfactants in high C/N (32.6) and C/H (13.3) conversion after pre-oxidation and increased the total removal rate of TPH (10.59-46.71%). The number of total bacteria had a rapid increase trend (2.94-8.50 Log CFU/g soil). The degradation rates of macro alkanes showed a 4.0-fold (48.07 mg/kg·d-1 versus 186.48 mg/kg·d-1) increase, and the bioremediation time of degrading macro alkanes saved 166 days. Further characterization revealed that the biosurfactants produced by Burkholderia sp. could activate indigenous bacteria to degrade macro alkanes rapidly. A shift in phylum from Actinomycetes to Proteobacteria was observed during bioremediation. The average relative abundance of the microbial community increased from 36.24 to 64.96%, and the predominant genus tended to convert from Allorhizobium (8.57%) to Burkholderia (15.95%) and Bacillus (15.70%). The co-occurrence network and Pearson correlation analysis suggested that the synergism of microbial community was the main reason for the fast degradation of macro alkanes in petroleum-contaminated soils. Overall, this study indicated the potential of the biosurfactants to activate and enhance the recovery of indigenous bacteria after pre-oxidation, which was an effective method to remediate petroleum-contaminated soils.

Potential response of dark carbon fixation to global warming in estuarine and coastal waters.

Dark carbon fixation (DCF), through which chemoautotrophs convert inorganic carbon to organic carbon, is recognized as a vital process of global carbon biogeochemical cycle. However, little is known about the response of DCF processes in estuarine and coastal waters to global warming. Using radiocarbon labelling method, the effects of temperature on the activity of chemoautotrophs were investigated in benthic water of the Yangtze estuarine and coastal areas. A dome-shaped thermal response pattern was observed for DCF rates (i.e., reduced rates at lower or higher temperatures), with the optimum temperature (Topt ) varying from about 21.9 to 32.0°C. Offshore sites showed lower Topt values and were more vulnerable to global warming compared with nearshore sites. Based on temperature seasonality of the study area, it was estimated that warming would accelerate DCF rate in winter and spring but inhibit DCF activity in summer and fall. However, at an annual scale, warming showed an overall promoting effect on DCF rates. Metagenomic analysis revealed that the dominant chemoautotrophic carbon fixation pathways in the nearshore area were Calvin-Benson-Bassham (CBB) cycle, while the offshore sites were co-dominated by CBB and 3-hydroxypropionate/4-hydroxybutyrate cycles, which may explain the differential temperature response of DCF along the estuarine and coastal gradients. Our findings highlight the importance of incorporating DCF thermal response into biogeochemical models to accurately estimate the carbon sink potential of estuarine and coastal ecosystems in the context of global warming.

Oxygen-Generating Biomaterials for Translational Bone Regenerative Engineering.

Successful regeneration of critical-size defects remains one of the significant challenges in regenerative engineering. These large-scale bone defects are difficult to regenerate and are often reconstructed with matrices that do not provide adequate oxygen levels to stem cells involved in the regeneration process. Hypoxia-induced necrosis predominantly occurs in the center of large matrices since the host tissue's local vasculature fails to provide sufficient nutrients and oxygen. Indeed, utilizing oxygen-generating materials can overcome the central hypoxic region, induce tissue in-growth, and increase the quality of life for patients with extensive tissue damage. This article reviews recent advances in oxygen-generating biomaterials for translational bone regenerative engineering. We discussed different oxygen-releasing and delivery methods, fabrication methods for oxygen-releasing matrices, biology, oxygen's role in bone regeneration, and emerging new oxygen delivery methods that could potentially be used for bone regenerative engineering.

Effects of acidification on nitrification and associated nitrous oxide emission in estuarine and coastal waters.

In the context of an increasing atmospheric carbon dioxide (CO2) level, acidification of estuarine and coastal waters is greatly exacerbated by land-derived nutrient inputs, coastal upwelling, and complex biogeochemical processes. A deeper understanding of how nitrifiers respond to intensifying acidification is thus crucial to predict the response of estuarine and coastal ecosystems and their contribution to global climate change. Here, we show that acidification can significantly decrease nitrification rate but stimulate generation of byproduct nitrous oxide (N2O) in estuarine and coastal waters. By varying CO2 concentration and pH independently, an expected beneficial effect of elevated CO2 on activity of nitrifiers ("CO2-fertilization" effect) is excluded under acidification. Metatranscriptome data further demonstrate that nitrifiers could significantly up-regulate gene expressions associated with intracellular pH homeostasis to cope with acidification stress. This study highlights the molecular underpinnings of acidification effects on nitrification and associated greenhouse gas N2O emission, and helps predict the response and evolution of estuarine and coastal ecosystems under climate change and human activities.

Effects of periodic drying-wetting on microbial dynamics and activity of nitrite/nitrate-dependent anaerobic methane oxidizers in intertidal wetland sediments.

Nitrite/nitrate-dependent anaerobic methane oxidation (n-DAMO) plays an important role in methane (CH4) consumption in intertidal wetlands. However, little is known about the responses of n-DAMO in intertidal wetlands to periodic drying-wetting caused by tidal cycling. Here, comparative experiments (waterlogged, desiccated, reflooded) with the Yangtze estuarine intertidal sediments were performed to examine the effects of periodic tidal changes on n-DAMO microbial communities, abundances, and potential activities. Functional gene sequencing indicated the coexistence of n-DAMO bacteria and archaea in the tide-fluctuating environments and generally higher biodiversity under reflooded conditions than consecutive inundation or emersion. The n-DAMO microbial abundance and associated activity varied significantly during alternative exposure and inundation, with higher abundance and activity under the waterlogged than desiccated conditions. Reflooding of intertidal wetlands might intensify n-DAMO activities, indicating the resilience of n-DAMO microbial metabolisms to the wetting-drying events. Structural equation modeling and correlation analysis showed that n-DAMO activity was highly related to n-DAMO microbial abundance and substrate availability under inundation, whereas salt accumulation in sediment was the primary factor restraining n-DAMO activity under the desiccation. Overall, this study reveals tidal-induced shifts of n-DAMO activity and associated contribution to mitigating CH4, which may help accurately project CH4 emission from intertidal wetlands under different tidal scenarios.

Dysregulation of AMPK-mTOR signaling leads to comorbid anxiety in Dip2a KO mice.

Autism is often comorbid with other psychiatric disorders. We have previously shown that Dip2a knockout (KO) induces autism-like behaviors in mice. However, the role of Dip2a in other psychiatric disorders remains unclear. In this paper, we revealed that Dip2a KO mice had comorbid anxiety. Dip2a KO led to a reduction in the dendritic length of cortical and hippocampal excitatory neurons. Molecular mechanism studies suggested that AMPK was overactivated and suppressed the mTOR cascade, contributing to defects in dendritic morphology. Deletion of Dip2a in adult-born hippocampal neurons (Dip2a conditional knockout (cKO)) increased susceptibility to anxiety upon acute stress exposure. Application of (2R,6R)-hydroxynorketamine (HNK), an inhibitor of mTOR, rescued anxiety-like behaviors in Dip2a KO and Dip2a cKO mice. In addition, 6 weeks of high-fat diet intake alleviated AMPK-mTOR signaling and attenuated the severity of anxiety in both Dip2a KO mice and Dip2a cKO mice. Taken together, these results reveal an unrecognized function of DIP2A in anxiety pathophysiology via regulation of AMPK-mTOR signaling.