Airborne observations over the North Atlantic Ocean reveal the importance of gas-phase urea in the atmosphere.

Reduced nitrogen (N) is central to global biogeochemistry, yet there are large uncertainties surrounding its sources and rate of cycling. Here, we present observations of gas-phase urea (CO(NH2)2) in the atmosphere from airborne high-resolution mass spectrometer measurements over the North Atlantic Ocean. We show that urea is ubiquitous in the lower troposphere in the summer, autumn, and winter but was not detected in the spring. The observations suggest that the ocean is the primary emission source, but further studies are required to understand the responsible mechanisms. Urea is also observed aloft due to long-range transport of biomass-burning plumes. These observations alongside global model simulations point to urea being an important, and currently unaccounted for, component of reduced-N to the remote marine atmosphere. Airborne transfer of urea between nutrient-rich and -poor parts of the ocean can occur readily and could impact ecosystems and oceanic uptake of carbon dioxide, with potentially important climate implications.

Electrical feedback system for enhancing the RF power of photodetector.

In this paper, we propose a system for enhancing the RF output power of the photodetector, especially the power of fundamental tune and second-order harmonic, by feeding back part of the RF signal through an electrical feedback circuit. As a result of bias modulation and opto-electric mixing, the RF output power can be effectively enhanced. The structure of uni-traveling carrier photodetector (UTC-PD) is employed in this work. With the RF enhancement system, the power of fundamental tune and second-order harmonic improve by 6.4 dB and 9.9 dB respectively, under the condition of 26 dBm input optical power, 3 V bias voltage, and 14 GHz input optical signal. Further, it was observed that third-order harmonic appeared under the influence of this system.

Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma.

BACKGROUND: Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. RESULTS: Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T2-weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. CONCLUSIONS: Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma.

Finale: impact of the ORCHESTRA/ENCORE programmes on Southern Ocean heat and carbon understanding.

The 5-year Ocean Regulation of Climate by Heat and Carbon Sequestration and Transports (ORCHESTRA) programme and its 1-year extension ENCORE (ENCORE is the National Capability ORCHESTRA Extension) was an approximately 11-million-pound programme involving seven UK research centres that finished in March 2022. The project sought to radically improve our ability to measure, understand and predict the exchange, storage and export of heat and carbon by the Southern Ocean. It achieved this through a series of milestone observational campaigns in combination with model development and analysis. Twelve cruises in the Weddell Sea and South Atlantic were undertaken, along with mooring, glider and profiler deployments and aircraft missions, all contributing to measurements of internal ocean and air-sea heat and carbon fluxes. Numerous forward and adjoint numerical experiments were developed and supported by the analysis of coupled climate models. The programme has resulted in over 100 peer-reviewed publications to date as well as significant impacts on climate assessments and policy and science coordination groups. Here, we summarize the research highlights of the programme and assess the progress achieved by ORCHESTRA/ENCORE and the questions it raises for the future. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy.

BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.

Simulation and design of a high-speed and high-power modified uni-traveling carrier photodiode based on the electric field distribution in the depletion region.

A modified uni-traveling carrier photodiode with an electric field control layer is proposed to achieve high-speed and high-power performance at a lower bias voltage. By inserting the 10 nm p-type InGaAs electric field control layer between the intrinsic absorption layer and space layer, the electric field distribution in the depleted absorption layer and depleted non-absorption layer can be changed. It is beneficial for reducing power consumption and heat generation, meanwhile suppressing the space-charge effect. Compared with the original structure without the electric field control layer, the 3 dB bandwidth of the 20 µm diameter novel structure, to the best of our knowledge, is improved by 27.1% to 37.5 GHz with a reverse bias of 2 V, and the RF output power reaches 23.9 dBm at 30 GHz. In addition, under 8 V bias voltage, the bandwidth reaches 47.3 GHz.

Evaluation of the safety and protection efficacy of an attenuated genotype vii newcastle disease virus strain as a candidate vaccine.

Newcastle disease (ND) is a serious avian infectious disease, causing severe economic loss worldwide. Its prevention depends on comprehensive vaccination scheme against Newcastle disease virus (NDV). However, current vaccine strains are of different genotypes with prevalent circulating strains (genotype VII), with significant genetic distance. Our team previously generated a genotype matched attenuated NDV strain (rmNA-1). In this study, its safety and immunization efficacy were evaluated. Its lentogenic characteristic was stable for 25 generations in embryonated chicken eggs and for six generations in SPF chickens. Overdosed administration did not cause any clinical signs or pathogenic changes in chickens. As to its immunization effect, rmNA-1 stimulated a comparable serum NDV specific antibody level to a LaSota (genotype II) strain based commercial vaccine, and provided full protection against virulent genotype VII strain challenge, with significantly reduced virus shedding period.

Characterizing the Particle Composition and Cloud Condensation Nuclei from Shipping Emission in Western Europe.

Commercial shipping is considered as an important source of air pollution and cloud condensation nuclei (CCN). To assess the climatic and environmental impacts of shipping, detailed characterization of ship plumes near the point of emission and understanding of ship plume evolution further downwind are essential. This airborne measurement study presents the online characterization of particulate phase ship emissions in the region of Western Europe in 2019 prior to new international sulfur emission controls becoming enacted. More than 30 ships from both the sulfur emission control area (SECA) in the English Channel and the open sea (OS) are measured and compared. Ships within the SECA emitted much less sulfate (SO4) compared with those at OS. When shifted to a lower apparent fuel sulfur content (FSC) at similar engine loads, the peak of the fresh ship emitting the particle number size distribution shifted from around 60-80 nm in diameter to below 40 nm in diameter. The emission factors (EFs) of sulfate are predicted to decrease by around 94% after the 2020 regulation on ship sulfur emission in the open ocean. The EFs of refractory black carbon (rBC) and organic compounds (Org) do not appear to be directly affected by the lower sulfur contents. The total number concentration for condensation nuclei (CN) >2.5 nm and >0.1 µm are predicated to be reduced by 69 and 56%, respectively. Measured plume evolution results indicate that the S(IV) to S(VI) conversion rate was around 23.4% per hour at the beginning of plume evolution, and the CCN and CN >2.5 nm ratio increased with plume age primarily due to condensation and coagulation. We estimate that the new sulfur emission regulation will lead to a reduction of more than 80% in CCN from fresh ship emissions. The ship-emitted EFs results presented here will also inform emission inventories, policymaking, climate, and human health studies.

One-Step Hydrothermal Synthesis of Nitrogen-Doped Conjugated Carbonized Polymer Dots with 31% Efficient Red Emission for In Vivo Imaging.

Carbon dots with long-wavelength emissions, high quantum yield (QY) and good biocompatibility are highly desirable for biomedical applications. Herein, a green, facile hydrothermal synthesis of highly efficient red emissive nitrogen-doped carbonized polymer dots (CPDs) with optimal emission at around 630 nm are reported. The red emissive CPDs possess a variety of superior properties including excellent water dispersibility, good biocompatibility, narrow bandwidth emission, an excitation-independent emission, and high QY (10.83% (in water) and 31.54% (in ethanol)). Further studies prove that such strong red fluorescence is ascribed to the efficient conjugated aromatic π systems and hydrogen bonds of CPDs. And the fluorescence properties of CPDs can be regulated by adjusting the dosage of HNO3 before the reaction. Additionally, the as-prepared CPDs are successfully used as a fluorescent probe for bioimaging, both in vitro and in vivo. More importantly, biodistribution results demonstrate that most CPDs and their metabolites are not only excreted in urine but also excreted by hepatobiliary system in a rapid manner. Besides, the CPDs could easily cross the blood brain barrier, which may provide a valuable strategy for the theranostics of some brain diseases through real-time tracking.

Reversible "Off-On" Fluorescence of Zn2+-Passivated Carbon Dots: Mechanism and Potential for the Detection of EDTA and Zn2.

Zn2+-passivated carbon dots (named Z-CDs) were synthesized from zinc gluconate for the first time through a one-step pyrolysis treatment. The mechanism of Zn2+-enhanced fluorescence was carefully investigated, and a new strategy to passivate the surfaces of CDs by Zn2+ was proposed. Inspired by the complexation reaction between Zn2+ and ethylenediaminetetraacetic acid (EDTA), a reversible "off-on" fluorescent nanosensor for the detection of EDTA and Zn2+ was constructed based on the depassivation and repassivation of Z-CDs, with a limit of detection as low as 3.2 × 10-7 M and 5.1 × 10-7 M, respectively. The proposed Z-CD-based nanosensor had been further utilized for EDTA and Zn2+ monitoring in tap water with excellent recovery. To the best of our knowledge, this was the first report of a fluorescence-based sensor of EDTA and a turn-on sensor of Zn2+ based on CDs with reversible detection capability. Also, benefiting from the low toxicity of zinc, Z-CDs were applied for multicolor bioimaging and in vitro detection in cells.

Modern pollen distribution in the northeastern Indian Ocean and its significance.

In order to provide a reference for reconstructing the paleoclimate of the northeastern Indian Ocean, 36 airborne pollen samples were analyzed using methods for airborne pollen, and 26 surface water samples were analyzed using a lab method for surface water. We found that little pollen is airborne over the Indian Ocean in spring, but airborne pollen types and concentrations can help to deduce paleomonsoon strength and direction. The conclusions included the following: (1) Pollen in the sediment was transported mainly via ocean currents instead of the early summer or spring wind. (2) Airborne pollen types and concentrations are proportional to the wind speed and inversely proportional to the pollen distance transported and depend on whether the wind is from the land or from the sea. If the wind is from the land, the pollen concentration is proportional to the angle between the wind direction and the coastline. (3) The pollen concentration in the sample collected from a water depth of 30-45 m is higher than in the samples collected from a depth of 5 m. The pollen concentration and salinity are higher in the equatorial area than in the Northern Hemisphere.

Genetic diversity of the genotype VII Newcastle disease virus: identification of a novel VIIj sub-genotype.

Newcastle disease (ND) is a highly contagious disease of poultry caused by Newcastle disease virus (NDV). Multiple genotypes of NDV have been circulating worldwide and NDV is continuously evolving, resulting into more diversity. Of multiple viral genotypes, VII is particularly important given that it had been associated with most recent ND outbreaks worldwide. In this study, an epidemiological investigation performed in northeastern China during 2014-2015 showed that 11 genotype VII isolates amounted to 55 percent in a total number of NDV isolates. Therefore, to evaluate the genetic diversity worldwide and epidemiological distribution in China of genotype VII NDV, a phylogenetic analysis based on the 1255 complete F gene sequences showed that VII is the most predominant genotype worldwide. A further detailed characterization on genotype VII was conducted based on the 477 complete F gene sequences from 11 isolates and 466 reference viruses available in GenBank. The results demonstrated that VII can be further divided into 8 sub-genotypes (VIIb, VIId-VIIj), indicating its complex genetic diversity. It is worthy of note that the isolation rate of VIIj is increasing recently. It emphasizes the necessity to pay close attention to the epidemiological dynamic of genotype VII NDV and highlights the importance of vaccination program.

Atmospheric deposition of methanol over the Atlantic Ocean.

In the troposphere, methanol (CH3OH) is present ubiquitously and second in abundance among organic gases after methane. In the surface ocean, methanol represents a supply of energy and carbon for marine microbes. Here we report direct measurements of air-sea methanol transfer along a ∼10,000-km north-south transect of the Atlantic. The flux of methanol was consistently from the atmosphere to the ocean. Constrained by the aerodynamic limit and measured rate of air-sea sensible heat exchange, methanol transfer resembles a one-way depositional process, which suggests dissolved methanol concentrations near the water surface that are lower than what were measured at ∼5 m depth, for reasons currently unknown. We estimate the global oceanic uptake of methanol and examine the lifetimes of this compound in the lower atmosphere and upper ocean with respect to gas exchange. We also constrain the molecular diffusional resistance above the ocean surface-an important term for improving air-sea gas exchange models.

A Co-MOF encapsulated microneedle patch activates hypoxia induction factor-1 to pre-protect transplanted flaps from distal ischemic necrosis.

Avoiding ischemic necrosis after flap transplantation remains a significant clinical challenge. Developing an effective pretreatment method to promote flap survival postoperatively is crucial. Cobalt chloride (CoCl2) can increase cell tolerance to ischemia and hypoxia condition by stimulating hypoxia-inducible factor-1 (HIF-1) expression. However, the considerable toxic effects severely limit the clinical application of CoCl2. In this study, cobalt-based metal-organic frameworks (Co-MOF) encapsulated in a microneedle patch (Co-MOF@MN) was developed to facilitate the transdermal sustained release of Co2+ for rapid, minimally invasive rapid pretreatment of flap transplantation. The MN patch was composed of a fully methanol-based two-component cross-linked polymer formula, with a pyramid structure and high mechanical strength, which satisfied the purpose of penetrating the skin stratum corneum of rat back to achieve subcutaneous vascular area administration. Benefiting from the water-triggered disintegration of Co-MOF and the transdermal delivery via the MN patch, preoperative damage and side effects were effectively mitigated. Moreover, in both the oxygen-glucose deprivation/recovery (OGD/R) cell model and the rat dorsal perforator flap model, Co-MOF@MN activated the HIF-1α pathway and its associated downstream proteins, which reduced reperfusion oxidative damage, improved blood supply in choke areas, and increased flap survival rates post-transplantation. This preprotection strategy, combining MOF nanoparticles and the MN patch, meets the clinical demands for trauma minimization and uniform administration in flap transplantation. STATEMENT OF SIGNIFICANCE: Cobalt chloride (CoCl2) can stimulate the expression of hypoxia-inducible factor (HIF-1) and improve the tolerance of cells to ischemia and hypoxia conditions. However, the toxicity and narrow therapeutic window of CoCl2 severely limit its clinical application. Herein, we explored the role of Co-MOF as a biocompatible nanocage for sustained release of Co2+, showing the protective effect on vascular endothelial cells in the stress model of oxygen-glucose deprivation. To fit the clinical needs of minimal trauma in flap transplantation, a Co-MOF@MN system was developed to achieve local transdermal delivery at the choke area, significantly improving blood supply opening and flap survival rate. This strategy of two-step delivery of Co2+ realized the enhancement of biological functions while ensuring the biosafety.

S-Doped carbonized polymer dots inhibit early myocardial fibrosis by regulating mitochondrial function.

Myocardial fibrosis (MF) is a critical pathological lesion in the progression of various acute and chronic cardiovascular diseases. However, there is still a lack of clinically effective drugs and treatments for MF therapies. Herein, for the first time, we developed fluorescent sulfur-doped carbonized polymer dots (S-CPDs) as new nano-antioxidants to reduce the cardiomyocyte damage caused by reactive oxygen species (ROS) in the early stage of fibrotic lesions. In vitro results suggested that the pre-protection of S-CPDs significantly increased the survival rate of H9c2 cells under severe oxidative stress, inhibited the isoproterenol (ISO)-induced hypertrophy of myocardial cells through improving the content of mitochondria related proteins and adenosine triphosphate (ATP) in cells. Moreover, S-CPD administration could effectively decrease cardiac hypertrophy and promote heart function in MF rat models. The rapid internalization, high biocompatibility and fluorescence imaging potential of S-CPDs revealed their promising application prospects in the diagnoses and treatments of cardiovascular diseases.

Brain-targeted ginkgolide B-modified carbonized polymer dots for alleviating cerebral ischemia reperfusion injury.

Ischemic stroke (IS) is a leading cause of death in the world, and there is still a lack of effective treatments. Ginkgolide B (GB) can antagonize the platelet activating factor receptor and has shown a significant curative effect on cerebral ischemia. However, GB and other drugs for IS have shown poor clinical efficacy due to their inability to cross the blood-brain barrier (BBB). Herein, red fluorescent carbonized polymer dots (CPDs) were developed as biocompatible nanocarriers to deliver GB to the brain tissue. Both in vivo and in vitro experiments verified the ability of GB-CPDs to penetrate the BBB, and GB-CPDs remained in the brain significantly longer than unmodified CPDs. In a rat model of middle cerebral artery occlusion (MCAO), circulatory administration of GB-CPDs effectively reduced cerebral infarct size and neuronal apoptosis, with a significantly better therapeutic effect compared to GB. This study provided a novel GB-based nanodrug that could target the brain with improved efficacy, showing great application potential in central nervous system diseases.

Nerve trunk healing and neuroma formation after nerve transection injury.

The nerve trunk healing process of a transected peripheral nerve trunk is composed of angiogenesis, nerve fiber regeneration, and scarring. Nerve trunk healing and neuroma formation probably share identical molecular mediators and similar regulations. At the nerve transection site, angiogenesis is sufficient and necessary for nerve fiber regeneration. Angiogenesis and nerve fiber regeneration reveal a positive correlation in the early time. Scarring and nerve fiber regeneration show a negative correlation in the late phase. We hypothesize that anti-angiogenesis suppresses neuromas. Subsequently, we provide potential protocols to test our hypothesis. Finally, we recommend employing anti-angiogenic small-molecule protein kinase inhibitors to investigate nerve transection injuries.

N-Acetyl-l-cysteine-Derived Carbonized Polymer Dots with ROS Scavenging via Keap1-Nrf2 Pathway Regulate Alveolar Bone Homeostasis in Periodontitis.

Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption. As oxidative stress is the key cause of periodontitis in the early periodontal microenvironment, antioxidative therapy has been considered a viable treatment for periodontitis. However, more stable and effective reactive oxygen species (ROS)-scavenging nanomedicines are still highly needed due to the instability of traditional antioxidants. Herein, a new type of N-acetyl-l-cysteine (NAC)-derived red fluorescent carbonized polymer dots (CPDs) has been synthesized with excellent biocompatibility, which can serve as an extracellular antioxidant to scavenge ROS effectively. Moreover, NAC-CPDs can promote osteogenic differentiation in human periodontal ligament cells (hPDLCs) under H2 O2 stimulation. In addition, NAC-CPDs are capable of targeted accumulation in alveolar bone in vivo, reducing the level of alveolar bone resorption in periodontitis mice, as well as performing fluorescence imaging in vitro and in vivo. In terms of mechanism, NAC-CPDs may regulate redox homeostasis and promote bone formation in the periodontitis microenvironment by modulating the kelch-like ECH-associated protein l (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This study provides a new strategy for the application of CPDs theranostic nanoplatform for periodontitis.

Renal-friendly Li+-doped carbonized polymer dots activate Schwann cell autophagy for promoting peripheral nerve regeneration.

Activation of autophagy in Schwann cells (SCs) has emerged as a powerful trigger for peripheral nerve injury (PNI) repair. Lithium ion (Li+) is a classical autophagy activator that plays an important role in promoting axonal extension and remyelination. However, the therapeutic window of existing lithium drugs is extremely narrow, and the adverse side effects, especially nephrotoxicity, severely limit their therapeutic value. Herein, Li+-doped carbonized polymer dots (Li-CPDs) was synthesized for the first time to change the pharmacokinetics of Li+ from occupying epithelial sodium channels to lipid raft-mediated endocytosis. The in-vivo results confirmed that Li-CPDs could accelerate the removal of myelin debris and promote nerve regeneration via activating autophagy of SCs. Moreover, Li-CPDs exhibited almost no renal toxicity compared to that of raw lithium drugs. Thus, Li-CPDs could serve as a promising Li+-based nanomedicine for PNI regeneration with improved biosafety. STATEMENT OF SIGNIFICANCE: Regardless of the fact that lithium drugs have been used in treatment of mental illness such as manic depression, the systemic side effects and renal metabolic toxicity still seriously restrict their clinical application. Since Li+ and Na+ compete for ion channels of cell membrane, the cell entry efficiency is extremely low and easily affected by body fluctuations, which seems to be an unsolvable problem. Herein, we rationally exploited the endocytotic features of CPDs to develop Li-CPDs. The Li-CPDs improved the entry pathway, greatly reduced nephrotoxicity, and inherited the biological function of Li+ to activate autophagy for promoting peripheral nerve regeneration. Due to the BBB-crossing property of Li-CPDs, it also showed application prospects in future research on central nervous system diseases.