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Prokaryotes play a fundamental role in global ocean biogeochemical cycles. However, how the abundance and metabolic activity of ecologically distinct subgroups (i.e., high nucleic acid (HNA) and low nucleic acid (LNA) cells), and their regulating factors, change in response to changing marine environmental conditions remains poorly understood. Here, we delved into the time-evolving dynamic responses of the HNA and LNA prokaryotic subgroups to declining resource availability and selective grazing by protozoa by conducting a 73-day incubation experiment in a large-volume (117,000 L) macrocosm that facilitates community-level exploration. We found that the metabolic activity of the HNA subgroup was higher than that of the LNA subgroup when the macrocosm was resource replete but that the HNA subgroup declined more rapidly than the LNA subgroup as the resources became increasingly scarce, leading to a steadily increasing contribution of LNA cells to prokaryotic activity. Meanwhile, as resources in the macrocosm became limited, protozoan grazing preference shifted from the HNA to the LNA subgroup and the contributions of the LNA subgroup to the carbon flow within the macrocosm increased. The findings highlight the resilience of LNA cells in resource-limited environments, illuminate the critical role of selective grazing by protozoa in balancing distinct prokaryotic subgroups under changing resource conditions, and demonstrate the complex and adaptive interactions between protozoa and prokaryotes across diverse environmental contexts.

Marine microbes are major drivers of marine biogeochemical cycles and play critical roles in the ecosystems. Aerobic anoxygenic phototrophic bacteria (AAPB) are an important bacterial functional group with capability of harvesting light energy and wide distribution, and appear to have a particular role in the ocean’s carbon cycling. Yet the global pattern of AAPB distribution was controversial at the beginning of the 21st century due to the defects of the AAPB enumeration methods. An advanced time-series observation-based infrared epifluorescence microscopy (TIREM) approach was established to amend the existing AAPB quantitative deviation and led to the accurate enumeration of AAPB in marine environments. The abundance of AAPB and AAPB% were higher in coastal and continental shelf waters than in oceanic waters, which does not support the idea that AAPB are specifically adapted to oligotrophic conditions due to photosynthesis in AAPB acting a supplement to their organic carbon respiration. Further investigation revealed that dependence of AAPB on dissolved organic carbon produced by phytoplankton (PDOC) may limit their competition and control AAPB distribution. So, the selection of carbon sources by AAPB indicated that they can effectively fractionate the carbon flow in the sea. Enlightened by these findings, the following studies on the interactions between marine microbes and DOC led to the discovery of a new mechanism of marine carbon sequestration— the Microbial Carbon Pump (MCP). The conceptual framework of MCP addresses the sources and mechanism of the vast DOC reservoir in the ocean and represents a breakthrough in the theory of ocean carbon sequestration.

The ocean has been a regulator of climate change throughout the history of Earth. One key mechanism is the mediation of the carbon reservoir by refractory dissolved organic carbon (RDOC), which can either be stored in the water column for centuries or released back into the atmosphere as CO2depending on the conditions. The RDOC is produced through a myriad of microbial metabolic and ecological processes known as the microbial carbon pump (MCP). Here, we review recent research advances in processes related to the MCP, including the distribution patterns and molecular composition of RDOC, links between the complexity of RDOC compounds and microbial diversity, MCP-driven carbon cycles across time and space, and responses of the MCP to a changing climate. We identify knowledge gaps and future research directions in the role of the MCP, particularly as a key component in integrated approaches combining the mechanisms of the biological and abiotic carbon pumps for ocean negative carbon emissions.

Migration is selective, resulting in inequalities between migrants and nonmigrants. However, investigating migration selection is empirically challenging because combined pre- and post-migration data are rarely available. We propose an alternative approach to assessing internal migration selection by integrating genetic data, enabling an investigation of migration selection with cross-sectional data collected post-migration. Using data from the UK Biobank, we utilized standard tools from statistical genetics to conduct a genome-wide association study (GWAS) for migration distance. We then calculated genetic correlations to compare GWAS results for migration with those for other characteristics. Given that individual genetics are determined at conception, these analyses allow a unique exploration of the association between pre-migration characteristics and migration. Results are generally consistent with the healthy migrant literature: genetics correlated with longer migration distance are associated with higher socioeconomic status and better health. We also extended the analysis to 53 traits and found novel correlations between migration and several physical health, mental health, personality, and sociodemographic traits.

This research note reinvestigates Abdellaoui et al.’s (2019) findings that genetically selective migration may lead to persistent and accumulating socioeconomic and health inequalities between types (coal mining or non–coal mining) of places in the United Kingdom. Their migration measure classified migrants who moved to the same type of place (coal mining to coal mining or non–coal mining to non–coal mining) into “stay” categories, preventing them from distinguishing migrants from nonmigrants. We reinvestigate the question of genetically selective migration by examining migration patterns between places rather than place types and find genetic selectivity in whether people migrate and where. For example, we find evidence of positive selection: people with genetic variants correlated with better education moved from non–coal mining to coal mining places with our measure of migration. Such findings were obscured in earlier work that could not distinguish nonmigrants from migrants.

• Heterogeneous lamella (HL) structures were obtained in fcc Ni 2 CoFeV 0.5 MEAs. • Most HL MEAs exhibited excellent strength and ductility synergy. • Annealing-induced yield strength increase occurred in the as-rolled sample. • The lattice friction stress (σ 0) and Hall-Petch coefficient (k) are 87.3 MPa and 722.8 MPa μm1/2, respectively. Single-phase face-centered cubic (fcc) medium- and high-entropy alloys (MEAs/HEAs) have high ductility but low yield strength. In this work, the microstructures of single-phase fcc Ni 2 CoFeV 0.5 MEAs were tailored by cold-rolling and subsequent annealing and typical heterogeneous lamella (HL) structures composed of recrystallized micro-grain lamellae (with an averaged grain size of ∼4 μm) and non-recrystallized nano-/ultrafine-grain lamellae were obtained. Tensile tests revealed that most HL samples exhibited excellent strength and ductility synergy. The HL sample with ∼23 vol% recrystallized grains annealed at 590 °C for 1 h had a high yield strength of 1120 MPa and a good fracture elongation of 12.3%, which increased by 5% and 46%, respectively compared with those of as-rolled sample. Annealing-induced yield strength increase is attributed to high-density annealing twin boundaries (TBs) in the recrystallized grains, the annihilation of mobile dislocations inside the non-recrystallized grains, and extra hetero-deformation-induced strengthening produced by the HL structure. Hall-Petch relationship of Ni 2 CoFeV 0.5 MEA can be reasonably described by counting both TBs and grain boundaries, with lattice friction stress of 87.3 MPa and coefficient of 722.8 MPa μm1/2. Our work provides optional and controllable solutions for preparing MEAs/HEAs with excellent mechanical properties by low-cost and high-efficiency thermo-mechanical treatments. [Display omitted] [ABSTRACT FROM AUTHOR]

Single-phase face-centered cubic (fcc) medium- and high-entropy alloys (MEAs/HEAs) have high ductility but low yield strength and hardness. In this work, the microstructures of single-phase fcc Ni2CoFe MEAs were tuned via thermo-mechanical treatment (cold-rolling plus annealing). Microhardness and tensile tests revealed that the as-rolled Ni2CoFe MEA had a high hardness of 331.2 HV and a high yield strength of 913 MPa but a poor fracture elongation of 7.9%, resulting from high-density lattice defects. With increasing annealing temperature, the hardness and strength gradually decreased and meanwhile the ductility gradually improved, due to the microstructural recovery, recrystallization and grain growth. The heterostructured sample annealed at 530 °C for 1 h exhibited simultaneous improvement in ultimate tensile strength and uniform elongation compared with those of as-rolled sample. For the heterostructured sample annealed at 550 °C for 1 h, a good fracture elongation of 13.6% and a decent ultimate tensile strength of 867 MPa were achieved. Extra hardening and strengthening were produced, benefiting from the construction of heterostructure. Moreover, the Ni2CoFe MEA exhibited more superior combination of strength and ductility compared to pure Ni. The severe lattice distortion existing in the Ni2CoFe MEA enhances the strain hardening and ductility by enhancing the dislocation accumulation capability.

A long‐standing enigma in oceanography is why terrestrial organic matter is “missing” in the global ocean, despite the considerable discharge into it every year. Although some explanations, such as mineralogical composition, hydrodynamic processes, and priming effect, have been proposed, we hypothesize that the essential mechanism behind the missing organic matter is microbial processing, for which the underlying coupled geochemical, molecular, and genetic evidence is unknown. An ultra‐large‐volume, long‐term river–seawater stratified simulation system was constructed to unravel the microbially driven fate of terrigenous particulate organic matter (POM) in oceans. Analysis of combining the molecular with POM chemical composition data suggests that Bacteroidetes could act as pioneers in the processing of terrigenous POM in oceans, degrading high‐molecular‐weight, high‐carbon compounds such as polysaccharides. Remaining low‐molecular‐weight nitrogenous organic matter is subsequently degraded by Planctomycetes and Proteobacteria. Isotopic signals show that this preferential degradation causes a distinct “aging” effect of POM, and along with nitrification enhanced by remineralization, causes a decrease in the POM C : N ratio. Degradation of terrigenous POM and bacterial biomass biosynthesis leads to positive deviations in δ15N and δ13C. Relatively refractory hydrocarbons, aromatic compounds, and phenols are accumulated by microbial processes in this system. This study provides mechanistic insights into the missing chemical and isotopic signals and microbially driven fate of terrigenous POM in the ocean, with important implications for how riverine material input affects marine carbon and nitrogen cycling.

An adaptive control method based on a fuzzy state observer is designed for air handling unit (AHU) systems, where the intensity of humidity source and heat load are considered to be uncertain, and approximated by fuzzy logics. Besides, the supply air temperature is unmeasurable, which is observed by a state observer. To avoid the system equilibrium point offset, the prediction errors generated by the system and serial-parallel estimation models are introduced into the controller design based on backstepping. Finally, the superiority of proposed adaptive fuzzy controller is analyzed by simulation comparison with feedback linearization and PID controllers in two cases.

Studying the stress propagation and damage mechanism for the mechanical environment of the gun bore is an important way to popularize and apply the new propellant. Taking rosette 19-hole gun propellant as the research object, transverse drop hammer impact tests for the propellant under low temperature were carried out. Electron microscope tests for the propellant interface were conducted before and after the drop hammer tests. Then, a simulation mechanical model of the propellant was established by using the discrete element method with the rosette shape and 19 inner holes taken into consideration. And a simulation of the transverse drop hammer impact on the propellant was carried out. Research results show that the discrepancy between the simulation and test results of the maximum drop hammer force is 3.16%; the amplitude and pulse width of the drop hammer force-time curves and the fracture damage in the simulation and test studies are also in good agreement. The results reveal that the established simulation model is able to well describe the stress propagation and fracture process of the rosette 19-hole gun propellant under low temperature when affected by transverse drop hammer impact, providing an effective theoretical model basis for studying the damage mechanism of the new propellant.

Improved oxygen saturation of asymmetric cortical veins detected using brain MRI with quantitative susceptibility mapping corresponded with better stroke outcomes for patients with asymmetric cortical veins that disappeared within 2 weeks.

Paeonia suffruticosaAndr. is a well-known landscape plant worldwide and also holds significant importance in China due to its medicinal and dietary properties. Previous studies have found that Cortex Moutan (CM), the dried root bark of P. suffruticosa, showed antiplatelet and cardioprotective effects, although the underlying mechanism and active compounds remain to be revealed. In this study, protein disulfide isomerase (PDI) inhibitors in CM were identified using a ligand-fishing method combined with the UHPLC-Q-TOF-MS assay. Further, their binding sites and inhibitory activities toward PDI were validated. The antiplatelet aggregation and antithrombotic activity were investigated. The results showed that two structurally similar compounds in CM were identified as the inhibitor for PDI with IC50at 3.22 μM and 16.73 μM; among them Mudanpioside C (MC) is the most effective PDI inhibitor. Molecular docking, site-directed mutagenesis, and MST assay unequivocally demonstrated the specific binding of MC to the b′-x domain of PDI (Kd= 3.9 μM), acting as a potent PDI inhibitor by interacting with key amino acids K263, D292, and N298 within the b′-x domain. Meanwhile, MC could dose-dependently suppress collagen-induced platelet aggregation and interfere with platelet activation, adhesion, and spreading. Administration of MC can significantly inhibit thrombosis formation without disturbing hemostasis in mice. These findings present a promising perspective on the antithrombotic properties of CM and highlight the potential application of MC as lead compounds for targeting PDI in thrombosis therapy.

Managing patients with refractory inflammatory bowel diseases (IBD) is a common clinical challenge. Galli Gigeriae Endothelium Corneum (GGEC), a chicken by-product, has been used for centuries in Asian countries as a functional food and supplement for the treatment of gastrointestinal disorders. In this study, a novel peptide (LNLYP, LP-5) with gastrointestinal stability that can enhance the intestinal barrier function that was first identified in GGEC. Our work demonstrated that aryl hydrocarbon receptor (AhR) activation by LP-5 could inhibit the Src kinase to increase tight junction protein levels and down-regulate the expression of inflammatory cytokines to protect the intestinal barrier and finally alleviate dextran sulfate sodium (DSS)-induced colitis. This study revealed that LP-5 had the potential to develop into a therapeutic agent for the treatment of colitis and provided new high-valued utilization of GGEC.

Background: The amyloid fibril formation in different tissues or organs is related to amyloidosis. The Ca2+, Zn2+ and heparan sulfate (HS) are important elements and compositions in human body, which play a key role in regulating various physiological activities. Recently, there are increasing evidence suggest that they are closely linked to the amyloid fibril formation. Objective: The effect of Ca2+ and Zn2+ on the amyloid fibril formation by β-casein was investigated in the absence and presence of HS, which was significantly to explore the relationship between the concentration changes of Ca2+ and Zn2+ and amyloid fibril formation. Methods: In this work, the influence of Ca2+ and Zn2+ on the β-casein fibril formation in the absence and presence of HS was investigated by various methods of Thioflavin T fluorescence assay, transmission electron microscopy and intrinsic fluorescence measure. Results: The results demonstrated that Ca2+ and Zn2+ promoted the β-casein fibril formation. The effect of Ca2+ was greater than that of Zn2+. Meanwhile, the both metal ions had stronger effects when β-casein was incubated with HS together. In addition, it was also observed that the microenvironment of β-casein was changed because the intrinsic fluorescence peaks were red-shifted on the influence of Ca2+ and Zn2+. Conclusion: Ca2+ and Zn2+ were capable of promoting the β-casein fibril formation in the both absence and presence of HS. This work set up the foundation for further researching of the amyloidosis pathogenesis and provided new insight for us to understand relationship between the inflammation and amyloidosis.

To explore the feasibility of diagnosing microvascular invasion (MVI) with radiomics, to compare the diagnostic performance of different models established by each method, and to determine the best diagnostic model based on radiomics. A retrospective analysis was conducted with 206 cases of hepatocellular carcinoma (HCC) confirmed through surgery and pathology in our hospital from June 2015 to September 2018. Among the samples, 88 were MVI-positive, and 118 were MVI-negative. The radiomics analysis process included tumor segmentation, feature extraction, data preprocessing, dimensionality reduction, modeling and model evaluation. A total of 1044 sets of texture feature parameters were extracted, and 21 methods were used for the radiomics analysis. All research methods could be used to diagnose MVI. Of all the methods, the LASSO+GBDT method had the highest accuracy, the LASSO+RF method had the highest sensitivity, the LASSO+BPNet method had the highest specificity, and the LASSO+GBDT method had the highest AUC. Through Z-tests of the AUCs, LASSO+GBDT, LASSO+K-NN, LASSO+RF, PCA + DT, and PCA + RF had Z-values greater than 1.96 (p<0.05). The DCA results showed that the LASSO + GBDT method was better than the other methods when the threshold probability was greater than 0.22. Radiomics can be used for the preoperative, noninvasive diagnosis of MVI, but different dimensionality reduction and modeling methods will affect the diagnostic performance of the final model. The model established with the LASSO+GBDT method had the optimal diagnostic performance and the greatest diagnostic value for MVI.

Fjords are representative marine ecosystems that play an important role in regulating coastal carbon cycling. As fingerprints of the dissolved organic matter (DOM) pool, fluorescent DOM (FDOM) is widely used to study the ocean carbon cycle. Here, we report on 1‐year of weekly observations of FDOM (from May 2018 to May 2019) in the Bedford Basin, a well‐studied northwestern Atlantic fjord. Results showed that differences in FDOM indices (biological index, fluorescence index, and humification indices) between the euphotic and aphotic layers changed during the investigation period, suggesting that classical definitions of these indices may not apply consistently. Spearman rank correlations showed that the surface FDOM was affected by physical and biological factors, while water mass renewal was the major control for the deeper layer. Humic‐like FDOM (FDOMH) changed following the Atlantic deep‐water intrusion, indicating that FDOMHmay be used to trace water mass movements in this region. FDOMHshows a significantly positive linear correlation with apparent oxygen utilization (AOU). Their slopes were higher than those from the open ocean, suggesting that the Bedford Basin is a hotspot of RDOM production. Hence, we proposed a possible carbon sequestration mechanism that fjords play as “RDOM producing hot spots” and that the produced RDOM is then transported to the open ocean via water mass movement and finally stored in the ocean for extended periods of time. The proposed biogeochemical processes may also occur, more generally, in the global coastal ocean. Fjords are representative marine systems and play an important role in regulating coastal carbon cycling; however, few high‐frequency long‐term time series observations of dissolved organic matter (DOM) have been reported to date. This study reports a 1‐year weekly observation of fluorescent DOM (FDOM) in the Bedford Basin, a 70‐m deep fjord located in Nova Scotia, Canada. The results suggested that FDOM indices are not reliable indicators as proposed originally, and the control factors of FDOM behaviors were different in the surface and bottom water, as well that humic‐like FDOM (FDOMH) have the potential to trace water mass movements. Significant positive linear relationships between apparent oxygen utilization and FDOMHwere observed in the aphotic zone, and their slopes were higher than those from the open ocean, suggesting that the Bedford Basin is a hotspot of RDOM production. Similar results are widely observed in dark marginal seas. Therefore, we propose a possible coastal carbon sequestration mechanism in which fjord systems (even coastal oceans) act as RDOM‐producing factories, and the produced RDOM is then transported to the open ocean via water mass movement and finally stored in the ocean at longer timescales. Weekly time series observations of fluorescent dissolved organic matter (FDOM) in the Bedford Basin are presentedFDOM signals trace deep seawater intrusionsFjords are potential hot spots of refractory dissolved organic matter (RDOM) production and serve as RDOM producing factories Weekly time series observations of fluorescent dissolved organic matter (FDOM) in the Bedford Basin are presented FDOM signals trace deep seawater intrusions Fjords are potential hot spots of refractory dissolved organic matter (RDOM) production and serve as RDOM producing factories

Polysulfides are newly discovered cellular contents, and they are involved in multiple intracellular processes, including redox homeostasis and protein sulfhydration. The dynamic changes of polysulfides inside the cell are directly related to these processes. To monitor the intracellular dynamics and subcellular levels of polysulfides, we developed green-fluorescent-protein (GFP)-based probes that are polysulfide-specific. A pair of cysteine residues was introduced near the GFP chromophore with the spatial distance between the cysteine residues designed to allow the formation of internal −Sn– (n≥ 3) bonds but not −S2– (disulfide) bonds. We tested these probes in model microorganisms and found that they displayed ratiometric changes to intracellular polysulfides that had clear variations associated with the growth phases. The distribution of polysulfides in subcellular organelles is heterogeneous, suggesting that polysulfides have multiple origins and functions in cells. These probes provided long-desired tools for polysulfide in vivo studies.

Mobile computing techniques have facilitated our life greatly, but it is rarely used in medical computing. The automatic diagnosis of benign and malignant pulmonary nodules is of great significance for the further treatment of patients. Therefore, taking the three-dimensional nature of clinical pulmonary nodules into account, in a mobile computing environment, an algorithm that combines three-dimensional deep and visual features (CTDDV) is proposed to achieve the classification of benign and malignant pulmonary nodules. In the new framework, deep features, visual features as well as shape descriptors were extracted using different three-dimensional algorithms. Then, Multiple Kernel Adaboost (MKAdaboost) classifiers were trained for each type of feature, and the results of the three classifiers were combined to distinguish lung nodules. We compared the four most advanced nodule classification methods on the LIDC-IDRI dataset. The results showed that our proposed CTDDV algorithm has achieved higher classification performance.

The China Seas include the South China Sea, East China Sea, Yellow Sea, and Bohai Sea. Located off the Northwestern Pacific margin, covering 4700000 km2from tropical to northern temperate zones, and including a variety of continental margins/basins and depths, the China Seas provide typical cases for carbon budget studies. The South China Sea being a deep basin and part of the Western Pacific Warm Pool is characterized by oceanic features; the East China Sea with a wide continental shelf, enormous terrestrial discharges and open margins to the West Pacific, is featured by strong cross-shelf materials transport; the Yellow Sea is featured by the confluence of cold and warm waters; and the Bohai Sea is a shallow semi-closed gulf with strong impacts of human activities. Three large rivers, the Yangtze River, Yellow River, and Pearl River, flow into the East China Sea, the Bohai Sea, and the South China Sea, respectively. The Kuroshio Current at the outer margin of the Chinese continental shelf is one of the two major western boundary currents of the world oceans and its strength and position directly affect the regional climate of China. These characteristics make the China Seas a typical case of marginal seas to study carbon storage and fluxes. This paper systematically analyzes the literature data on the carbon pools and fluxes of the Bohai Sea, Yellow Sea, East China Sea, and South China Sea, including different interfaces (land-sea, sea-air, sediment-water, and marginal sea-open ocean) and different ecosystems (mangroves, wetland, seagrass beds, macroalgae mariculture, coral reefs, euphotic zones, and water column). Among the four seas, the Bohai Sea and South China Sea are acting as CO2sources, releasing about 0.22 and 13.86–33.60 Tg C yr−1into the atmosphere, respectively, whereas the Yellow Sea and East China Sea are acting as carbon sinks, absorbing about 1.15 and 6.92–23.30 Tg C yr−1of atmospheric CO2, respectively. Overall, if only the CO2exchange at the sea-air interface is considered, the Chinese marginal seas appear to be a source of atmospheric CO2, with a net release of 6.01–9.33 Tg C yr−1, mainly from the inputs of rivers and adjacent oceans. The riverine dissolved inorganic carbon (DIC) input into the Bohai Sea and Yellow Sea, East China Sea, and South China Sea are 5.04, 14.60, and 40.14 Tg C yr−1, respectively. The DIC input from adjacent oceans is as high as 144.81 Tg C yr−1, significantly exceeding the carbon released from the seas to the atmosphere. In terms of output, the depositional fluxes of organic carbon in the Bohai Sea, Yellow Sea, East China Sea, and South China Sea are 2.00, 3.60, 7.40, and 5.92 Tg C yr−1, respectively. The fluxes of organic carbon from the East China Sea and South China Sea to the adjacent oceans are 15.25–36.70 and 43.93 Tg C yr−1, respectively. The annual carbon storage of mangroves, wetlands, and seagrass in Chinese coastal waters is 0.36–1.75 Tg C yr−1, with a dissolved organic carbon (DOC) output from seagrass beds of up to 0.59 Tg C yr−1. Removable organic carbon flux by Chinese macroalgae mariculture account for 0.68 Tg C yr−1and the associated POC depositional and DOC releasing fluxes are 0.14 and 0.82 Tg C yr−1, respectively. Thus, in total, the annual output of organic carbon, which is mainly DOC, in the China Seas is 81.72–104.56 Tg C yr−1. The DOC efflux from the East China Sea to the adjacent oceans is 15.00–35.00 Tg C yr−1. The DOC efflux from the South China Sea is 31.39 Tg C yr−1. Although the marginal China Seas seem to be a source of atmospheric CO2based on the CO2flux at the sea-air interface, the combined effects of the riverine input in the area, oceanic input, depositional export, and microbial carbon pump (DOC conversion and output) indicate that the China Seas represent an important carbon storage area.

Sulfur cycling in the biosphere is tightly interwoven with the cycling of carbon and nitrogen, through various biological and geochemical processes. Marine microorganisms, due to their high abundance, diverse metabolic activities, and tremendous adaptation potential, play an essential role in the functioning of global biogeochemical cycles and linking sulfur transformation to the cycling of carbon and nitrogen. Currently many coastal regions are severely stressed by hypoxic or anoxic conditions, leading to the accumulation of toxic sulfide. A number of recent studies have demonstrated that dissimilatory sulfur oxidation by heterotrophic bacteria can protect marine ecosystems from sulfide toxicity. Sulfur-oxidizing bacteria have evolved diverse phylogenetic and metabolic characteristics to fill an array of ecological niches in various marine habitats. Here, we review the recent findings on the microbial communities that are involved in the oxidation of inorganic sulfur compounds and address how the two elements of sulfur and carbon are interlinked and influence the ecology and biogeochemistry in the ocean. Delineating the metabolic enzymes and pathways of sulfur-oxidizing bacteria not only provides an insight into the microbial sulfur metabolism, but also helps us understand the effects of changing environmental conditions on marine sulfur cycling and reinforces the close connection between sulfur and carbon cycling in the ocean.

To achieve the Paris Agreement, China pledged to become “Carbon Neutral” by the 2060s. In addition to massive decarbonization, this would require significant changes in ecosystems toward negative CO2emissions. The ability of coastal blue carbon ecosystems (BCEs), including mangrove, salt marsh, and seagrass meadows, to sequester large amounts of CO2makes their conservation and restoration an important “nature-based solution (NbS)” for climate adaptation and mitigation. In this review, we examine how BCEs in China can contribute to climate mitigation. On the national scale, the BCEs in China store up to 118 Tg C across a total area of 1,440,377 ha, including over 75% as unvegetated tidal flats. The annual sedimental C burial of these BCEs reaches up to 2.06 Tg C year−1, of which most occurs in salt marshes and tidal flats. The lateral C flux of mangroves and salt marshes contributes to 1.17 Tg C year−1along the Chinese coastline. Conservation and restoration of BCEs benefit climate change mitigation and provide other ecological services with a value of $32,000 ha−1year−1. The potential practices and technologies that can be implemented in China to improve BCE C sequestration, including their constraints and feasibility, are also outlined. Future directions are suggested to improve blue carbon estimates on aerial extent, carbon stocks, sequestration, and mitigation potential. Restoring and preserving BCEs would be a cost-effective step to achieve Carbon Neutral by 2060 in China despite various barriers that should be removed.

China is the global leader in mariculture production. Increasing sequestered marine carbon (also known as blue carbon) via mariculture activities is a promising approach for mitigating climate change and promoting the development of a low-carbon economy. Mariculture blue carbon is also considered an important component of China’s “sea granary”. In addition to shellfish and macroalgae yields, which represent carbon removed from mariculture environment, blue carbon also includes other important components, which have been largely neglected in the past, such as the carbon transformed by microbes, dissolved organic carbon (mainly referred to as recalcitrant dissolved organic carbon), and sedimentary particulate carbon. Hence, from different aspects, a comprehensive study on the formation processes and mechanisms of carbon sequestration is of great significance for comprehensively unveiling the carbon sequestration capability in coastal mariculture environment, which will contribute to the sustainable development of the fishery economy and construction of an ecological civilization. Moreover, it may add significant economic benefits to the future carbon-trading market.

Sulfide (H2S, HS-and S2-) oxidation to sulfite and thiosulfate by heterotrophic bacteria, using sulfide:quinone oxidoreductase (SQR) and persulfide dioxygenase (PDO), has recently been reported as a possible detoxification mechanism for sulfide at high levels. Bioinformatic analysis revealed that the sqrand pdogenes were common in sequenced bacterial genomes, implying the sulfide oxidation may have other physiological functions. SQRs have previously been classified into six types. Here we grouped PDOs into three types and showed that some heterotrophic bacteria produced and released H2S from organic sulfur into the headspace during aerobic growth, and others, for example, Pseudomonas aeruginosaPAO1, with sqrand pdodid not release H2S. When the sqrand pdogenes were deleted, the mutants also released H2S. Both sulfide-oxidizing and non-oxidizing heterotrophic bacteria were readily isolated from various environmental samples. The sqrand pdogenes were also common in the published marine metagenomic and metatranscriptomic data, indicating that the genes are present and expressed. Thus, heterotrophic bacteria actively produce and consume sulfide when growing on organic compounds under aerobic conditions. Given their abundance on Earth, their contribution to the sulfur cycle should not be overlooked.

Sulfide (H2S, HS−and S2−) oxidation to sulfite and thiosulfate by heterotrophic bacteria, using sulfide:quinone oxidoreductase (SQR) and persulfide dioxygenase (PDO), has recently been reported as a possible detoxification mechanism for sulfide at high levels. Bioinformatic analysis revealed that the sqr and pdo genes were common in sequenced bacterial genomes, implying the sulfide oxidation may have other physiological functions. SQRs have previously been classified into six types. Here we grouped PDOs into three types and showed that some heterotrophic bacteria produced and released H2S from organic sulfur into the headspace during aerobic growth, and others, for example, Pseudomonas aeruginosa PAO1, with sqr and pdo did not release H2S. When the sqr and pdo genes were deleted, the mutants also released H2S. Both sulfide-oxidizing and non-oxidizing heterotrophic bacteria were readily isolated from various environmental samples. The sqr and pdo genes were also common in the published marine metagenomic and metatranscriptomic data, indicating that the genes are present and expressed. Thus, heterotrophic bacteria actively produce and consume sulfide when growing on organic compounds under aerobic conditions. Given their abundance on Earth, their contribution to the sulfur cycle should not be overlooked.

Introduction:Stroke due to sickle cell disease is often attributed to large vessel involvement in the disorder. The role of cerebral microvascular disease in sickle cell disease has received little attention. In this study, we examined development of cerebral microvascular lesions in a mouse model of sickle cell disease. We focused on cerebral microhemorrhages, the neuropathologic substrate of cerebral microbleeds.Methods:We studied microvascular disease in a well-characterized mouse model of humanized transgenic sickle (HbSS-BERK) and control (HbAA-BERK) mice expressing >99% human sickle hemoglobin (Hb) and normal human HbA, respectively. HbSS-BERK express human α and βS globins on a mixed genetic background. HbAA-BERK mice express normal human α and βA globin thus producing only normal human hemoglobin A, on the same mixed genetic background as HbSS-BERK. Seven- to nine-month-old mice (N=18 HbSS, N=12 HbAA) were examined. We collected mouse brains and performed standard histology using Prussian blue staining to detect CMH formation at 20x magnification. The average number, total area, and size of Prussian blue-positive deposits were quantified. In separate studies, Toluidine Blue staining was used to identify mast cells.Results:HbSS mice showed approximately 70% more cerebral microhemorrhages than controls (mean±SE of 1.17± 0.22 vs 0.69±0.13 number/cm2,p=0.04). Lesion size did not differ between HbSS and control mice. Activated mast cells were identified in HbSS mouse brain but not in control mice.Conclusions:In this mouse model of sickle cell disease, HbSS mice demonstrated significantly increased development of cerebral microhemorrhages. These findings emphasize the potential importance of cerebral microvascular disease in sickle cell disease. Cerebral mast cell activation in sickle cell disease may be a novel target for investigation.

Introduction:Periodontitis is a highly prevalent disorder that is increasingly recognized as a risk factor for cerebrovascular disease. In this study we examined the role of periodontitis in the development of cerebral microvascular disease.Methods:Hypertension was induced in aged (17 months old) male C57BL/6J mice via infusion of angiotensin II (ATII) at 1000 ng/kg/min via Alzet pump over 4 weeks. Periodontitis was induced by giving P. gingivalis-LPS (20 μg in 2 μL) injections between the first and second maxillary molars on both the right and left sides twice a week for six weeks. At end of six weeks, we collected mouse brains (N=5 each for Hypertension, Periodontitis, Hypertension + Periodontitis, and Control) and performed standard histology using Prussian blue staining to detect cerebral microhemorrhages (CMH) formation at 20x magnification. The average number, total area, and size of Prussian blue-positive deposits were quantified.Results:ATII-induced hypertension in animals (Systolic blood pressure: 113±2 mmHg to 156±3 mmHg, mean+SE, p<0.0001; Diastolic blood pressure: 82±2 mmHg to 119±3 mmHg, p<0.0001). Presence of hypertension produced significant increase in number of CMH compared to controls (1.97±0.29 per cm2vs. 1.24±0.20 per cm2, p<0.05). Presence of periodontitis did not alter the number of microhemorrhages (1.68±0.13 per cm2vs.1.97±0.29 per cm2). However, size of microhemorrhages doubled in the presence of periodontitis with hypertension (10.58±2.55 μm2per cm2vs. 5.05±1.15 μm2per cm2, p<0.05).Conclusions:In this mouse model of ATII-induced hypertension, periodontitis appears to increase size of CMH rather than induce development of new lesions. These findings suggest a role for periodontitis in cerebrovascular disease by modifying and exacerbating pre-existing stroke risk factors rather than acting as an independent risk factor.

Introduction:Chronic kidney disease (CKD) is increasingly recognized as a risk factor of cerebral microvascular disease, but its association with common neuropathologic changes is not well understood. We investigated the relationship between CKD and development of cerebral microhemorrhages (CMH) in a mouse model of aging. We also examined the effect of CKD on endothelial cell function in an in vitroblood-brain barrier (BBB) model.Methods:CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We performed standard histology using Prussian blue staining to examine CMH formation. Correlations between CMH burden and serum creatinine levels were assessed. In cell culture studies, human brain microvascular endothelial cells (ihBMECs) derived from induced pluripotent stem cell line IMR90-4 were treated with serum from healthy or CKD patient donors for up to 3 days. Transendothelial electrical resistance (TEER) and tracer (sodium fluorescein) permeability across the ihBMEC monolayer were measured to assess the integrity of the in vitroBBB.Results:CKD induction in aged C57BL/6J mice caused a significant increase in both serum creatinine level (0.09±0.01 mg/dL to 0.43±0.03 mg/dL, p<0.001) and CMH number (p<0.05), without alteration of systolic or diastolic blood pressure. Number of CMH was positively correlated with serum creatinine level (r=0.41, p<0.001). Incubation of CKD serum with ihBMECs significantly reduced TEER by 26% (p<0.05) and increased sodium fluorescein permeability by 100% (p<0.01) across the ihBMEC monolayer.Conclusions:Adenine-induced CKD promotes the development of CMH in aged C57BL/6J mice independent of blood pressure, and extent of CMH development is directly proportional to degree of renal insufficiency. Moreover, serum-derived factors in CKD disrupt BBB integrity in vitro.These findings suggest CKD provokes microvascular injury at the capillary level, leading to CMH formation in this model.

Introduction:Cerebral microhemorrhages (CMH) are the pathologic substrate of MRI-demonstrable cerebral microbleeds, and are thought to occur when integrity of cerebral microvessels is compromised, leading to deposits of hemosiderin/iron accumulating within brain tissue. The presence of CMH is associated with cognitive decline and ischemic and hemorrhagic stroke. Hypertension (HTN) is a major risk factor for cerebral microbleeds and has been linked to a more significant microbleed burden in patients. Despite the clinical significance of HTN and cerebral microbleeds, our understanding of HTN-induced microbleed formation remains limited, and the vascular origin of CMH remains obscure.Methods:We used a perfusion-based vascular label with tissue clearing to enable three-dimensional visualization of CMH with the surrounding microvascular network. Adult (18-month-old) C57BL/6J mice were administered angiotensin II to induce HTN (n=10) or PBS (n=10). Lectin-DyLight-649 was injected retro-orbitally to bind to the endothelial walls of all blood vessels in a mouse. Brains were cut into 1-mm thick sections, stained with Prussian blue to label CMH, cleared using iDISCO, and imaged via confocal microscopy. MATLAB and neuTube were used to quantify vessel diameters.Results:Using this methodology, we were able to collect three-dimensional transmission images of CMH that were colocalized with three-dimensional fluorescence images of the surrounding microvasculature. The average vessel diameter of the 5 nearest vessels to 17 different CMH was found to be 4.22±0.81 μm, which corresponds to capillary-size vessels.Conclusions:These data support a capillary origin for cerebral microhemorrhages in this mouse model. The capillary origin implies a role for the blood-brain barrier in the development of CMH and cerebral microbleeds in this model of HTN and aging. Three-dimensional imaging has substantial utility for improved understanding of CMH origin.

Introduction:Cerebral microhemorrhages (CMH) are the pathological substrate for cerebral microbleeds, represent focal hemosiderin deposits on MRI, and are associated with increased risk of cognitive impairment and ischemic and hemorrhagic stroke. Aging and hypertension are the most common risk factors for cerebral microbleeds. In this study, we analyzed the effect of hypertension on the development of CMH in a mouse model of aging.Methods:Hypertension was induced in aged (17 months old) female and male C57BL/6J mice, via infusion of angiotensin II (ATII) at 1000 ng/kg/min via Alzet pump over four weeks. We further examined underlying mechanism by inhibiting ATII type 1 receptor (AT1R) with telmisartan, via drinking water for 4 weeks. We collected mouse brains and performed standard histology using Prussian blue staining to detect CMH formation at 20x magnification. We also examined correlations between CMH burden and systolic (SBP) and diastolic (DPB) blood pressures.Results:ATII infusion induced significant increases in SBP (121±4 mmHg to 159±6 mmHg; p<0.001) and DBP (94±4 mmHg to 129±7 mmHg; p<0.001). Telmisartan completely blocked ATII-induced blood pressure elevation. Hypertension increased the number of CMH (p=0.01) in male and female mice. In animals with ATII infusion, number of CMH were positively correlated with SBP (r=0.45, p=0.02) and DBP (r=0.47, p=0.01). Telmisartan reduced by 55% the number of ATII-induced CMH, but compared to controls, CMH number remained elevated (p=0.03) in telmisartan-treated animals.Conclusions:ATII-induced hypertension promotes the development of CMH in aged mice in a manner that appears dependent on the extent of hypertension. However, in the presence of ATII with ATIR blockade, CMH develops even in the absence of hypertension. These findings emphasize the importance of presence and extent of hypertension in development of CMH in aging, as well as the significance of non-AT1R-mediated pathways independent of hypertension in ATII-induced CMH.

Large amounts of terrigenous organic matter (TOM) are delivered to the ocean every year. However, removal processes of TOM in the ocean are still poorly constrained. Here, we report results from a 339-day dark incubation experiment with a unique system holding a vertically stratified freshwater–seawater column. The quality and quantity of dissolved organic matter (DOM), RNA-based size-fraction microbial communities, and environmental factors were high-frequency-monitored. Microbial processes impacted TOM composition, including an increased DOM photobleaching rate with incubation time. The mixed layer had changed the bacterial community structure, diversity, and higher oxygen consumption rate. A two-end member modeling analysis suggested that estimated nutrient concentrations and prokaryotic abundance were lower, and total dissolved organic carbon was higher than that of the measured values. These results imply that DOM biodegradation was stimulated during freshwater–seawater mixing. In the bottom layer, fluorescent DOM components increased with the incubation time and were significantly positively related to highly unsaturated, oxygenated, and presumably aromatic compound molecular formulas. These results suggest that surfaced-derived TOM sinking leads to increased DOM transformation and likely results in carbon storage in the bottom water. Overall, these results suggest that microbial transforming TOM plays more important biogeochemical roles in estuaries and coastal oceans than what we know before.

Bacterial outer membrane vesicles (OMVs) are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine. In this study, OMVs are demonstrated as promising antitumor therapeutics. OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity, but the therapeutic window of OMVs is narrow for its toxicity. We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) into OMVs as a therapeutic platform. We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform, providing combinational photodynamic/chemo-/immunotherapy, eradicates triple-negative breast tumors in mice without side effects. Importantly, this strategy also effectively prevents tumor metastasis to the lung. This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.