Artemisia argyi polyphenols Attenuates DSS-induced colitis in mice by regulating the structural composition of gut microbiota.

BACKGROUND: Intestinal health is affected by heredity, lifestyle, and structure of gut microbiota. The imbalance of symbiotic and harmful bacteria in gut microbiota may increase the occurrence of colonic inflammation. Supplementary A. muciniphila can improve the survival rate of colitis mice, reduce colon tissue injury, and the expression of anti-inflammatory factors was upregulated. Artemisia argyi has been reported to have anti-inflammatory, antioxidant, bactericidal, and immunomodulatory effects. However, its anti-inflammatory effect and mechanism, and its influence on gut microbiota and metabolites are still unclear yet. PURPOSE: To explore whether Artemisia argyi Polyphenols(AAPs) can alleviate ulcerative colitis (UC) by changing gut microbiota. METHODS: The therapeutic effect of AAPs on colitis was investigated by inducing ulcerative colitis in mice using dextran sodium sulfate (DSS) and administering different doses of AAPs orally to mice. Exploring the levels of inflammatory proteins, oxidative stress proteins, and barrier proteins using western blotting and immunofluorescence, and explored the structural changes of gut microbiota and its metabolites. Meanwhile, in order to explore whether the role of AAPs in alleviating colitis is based on the regulation of gut microbiota structure, we conducted fecal microbiota transplantation (FMT). RESULTS: It showed that AAPs and FMT trial alleviated DSS-induced colonic injury, including clinical parameters and pathological injury of colon tissue, reduction in the expression of inflammatory proteins: IL-6, TNF-α, p-p65, p-IκBα, and increase in the expression of antioxidant proteins: Nrf2, NQO-1 and HO-1 and barrier proteins: Claudin-1, Occludin, ZO-1 and MUC2. AAPs and FMT promoted the content of beneficial bacteria, such as Butyricimonas and Lactobacillus, and the content of beneficial metabolites for instance acetic acid, butyric acid, and valeric acid has also increased. CONCLUSION: These results suggested that AAPs might improve DSS-induced colonic injury by changing the structural of gut microbiota while promoting the synthesis of fatty acids in the intestine, thereby providing a theoretical basis for using AAPs to treat ulcerative colitis.

Evaluation of the horizontal approach to the medial malleolar facet in sagittal talar fractures through dorsiflexion and plantarflexion positions.

BACKGROUND: Talar fractures often require osteotomy during surgery to achieve reduction and screw fixation of the fractured fragments due to limited visualization and operating space of the talar articular surface. The objective of this study was to evaluate the horizontal approach to the medial malleolus facet by maximizing exposure through dorsiflexion and plantarflexion positions. METHODS: In dorsiflexion, plantarflexion, and functional foot positions, we respectively obtained the anterior and posterior edge lines of the projection of the medial malleolus on the medial malleolar facet. The talar model from Mimics was imported into Geomagic software for image refinement. Then Solidworks software was used to segment the medial surface of the talus and extend the edge lines from the three positions to project them onto the "semicircular" base for 2D projection. The exposed area in different positions, the percentage of total area it represents, and the anatomic location of the insertion point at the groove between the anteroposternal protrusions of the medial malleolus were calculated. RESULTS: The mean total area of the "semicircular" region on the medial malleolus surface of the talus was 542.10 ± 80.05 mm2. In the functional position, the exposed mean area of the medial malleolar facet around the medial malleolus both anteriorly and posteriorly was 141.22 ± 24.34 mm2, 167.58 ± 22.36mm2, respectively. In dorsiflexion, the mean area of the posterior aspect of the medial malleolar facet was 366.28 ± 48.12 mm2. In plantarflexion, the mean of the anterior aspect of the medial malleolar facet was 222.70 ± 35.32 mm2. The mean overlap area of unexposed area in both dorsiflexion and plantarflexion was 23.32 ± 5.94 mm2. The mean percentage of the increased exposure area in dorsiflexion and plantarflexion were 36.71 ± 3.25% and 15.13 ± 2.83%. The mean distance from the insertion point to the top of the talar dome was 10.69 ± 1.24 mm, to the medial malleolus facet border of the talar trochlea was 5.61 ± 0.96 mm, and to the tuberosity of the posterior tibiotalar portion of the deltoid ligament complex was 4.53 ± 0.64 mm. CONCLUSIONS: Within the 3D model, we measured the exposed area of the medial malleolus facet in different positions and the anatomic location of the insertion point at the medial malleolus groove. When the foot is in plantarflexion or dorsiflexion, a sufficiently large area and operating space can be exposed during surgery. The data regarding the exposed visualization area and virtual screws need to be combined with clinical experience for safer reduction and fixation of fracture fragments. Further validation of its intraoperative feasibility will require additional clinical research.

Endothelial POFUT1 controls injury-induced liver fibrosis by repressing fibrinogen synthesis.

BACKGROUND & AIMS: NOTCH signaling in liver sinusoidal endothelial cells (LSECs) regulates liver fibrosis, a pathological feature of chronic liver diseases. POFUT1 is an essential regulator of NOTCH signaling. Here, we investigated the role of LSEC-expressed POFUT1 in liver fibrosis. METHODS: Endothelial-specific Pofut1 knockout mice were generated and experimental liver fibrosis was induced by chronic carbon tetrachloride exposure or common bile duct ligation. Liver samples were assessed by ELISA, histology, electron microscopy, immunostaining and RNA in situ hybridization. LSECs and hepatic stellate cells (HSCs) were isolated for gene expression analysis by RNA sequencing, qPCR, and western blotting. Signaling crosstalk between LSECs and HSCs was investigated by treating HSCs with supernatant from LSEC cultures. Liver single-cell RNA sequencing datasets from patients with cirrhosis and healthy individuals were analyzed to evaluate the clinical relevance of gene expression changes observed in mouse studies. RESULTS: POFUT1 loss promoted injury-induced LSEC capillarization and HSC activation, leading to aggravated liver fibrosis. RNA sequencing analysis revealed that POFUT1 deficiency upregulated fibrinogen expression in LSECs. Consistently, fibrinogen was elevated in LSECs of patients with cirrhosis. HSCs treated with supernatant from LSECs of Pofut1 null mice showed exacerbated activation compared to those treated with supernatant from control LSECs, and this effect was attenuated by knockdown of fibrinogen or by pharmacological inhibition of fibrinogen receptor signaling, altogether suggesting that LSEC-derived fibrinogen induced the activation of HSCs. Mechanistically, POFUT1 loss augmented fibrinogen expression by enhancing NOTCH/HES1/STAT3 signaling. CONCLUSIONS: Endothelial POFUT1 prevents injury-induced liver fibrosis by repressing the expression of fibrinogen, which functions as a profibrotic paracrine signal to activate HSCs. Therapies targeting the POFUT1/fibrinogen axis offer a promising strategy for the prevention and treatment of fibrotic liver diseases. IMPACT AND IMPLICATIONS: Paracrine signals produced by liver vasculature play a major role in the development of liver fibrosis, which is a pathological hallmark of most liver diseases. Identifying those paracrine signals is clinically relevant in that they may serve as therapeutic targets. In this study, we discovered that genetic deletion of Pofut1 aggravated experimental liver fibrosis in mouse models. Moreover, fibrinogen was identified as a downstream target repressed by Pofut1 in liver endothelial cells and functioned as a novel paracrine signal that drove liver fibrosis. In addition, fibrinogen was found to be relevant to cirrhosis and may serve as a potential therapeutic target for this devastating human disease.

Sulforaphane inhibits the migration and invasion of BPDE-induced lung adenocarcinoma cells by regulating NLRP12.

This study aims to explore the impact and underlying mechanism of sulforaphane (SFN) intervention on the migration and invasion of lung adenocarcinoma induced by 7, 8-dihydroxy-9, 10-epoxy-benzo (a) pyrene (BPDE). Human lung adenocarcinoma A549 cells were exposed to varying concentrations of BPDE (0.25, 0.50, and 1.00 µM) and subsequently treated with 5 µM SFN. Cell viability was determined using CCK8 assay, while migration and invasion were assessed using Transwell assays. Lentivirus transfection was employed to establish NLRP12 overexpressing A549 cells. ELISA was utilized to quantify IL-33, CXCL12, and CXCL13 levels in the supernatant, while quantitative real-time PCR (qRT-PCR) and Western Blot were used to analyze the expression of NLRP12 and key factors associated with canonical and non-canonical NF-κB pathways. Results indicated an increase in migratory and invasive capabilities, concurrent with heightened expression of IL-33, CXCL12, CXCL13, and factors associated with both canonical and non-canonical NF-κB pathways. Moreover, mRNA and protein levels of NLRP12 were decreased in BPDE-stimulated A549 cells. Subsequent SFN intervention attenuated BPDE-induced migration and invasion of A549 cells. Lentivirus-mediated NLRP12 overexpression not only reversed the observed phenotype in BPDE-induced cells but also led to a reduction in the expression of critical factors associated with both canonical and non-canonical NF-κB pathways. Collectively, we found that SFN could inhibit BPDE-induced migration and invasion of A549 cells by upregulating NLRP12, thereby influencing both canonical and non-canonical NF-κB pathways.

Single-cell RNA sequencing analysis to evaluate antimony exposure effects on cell-lineage communications within the Drosophila testicular niche.

The increasing production and prevalence of antimony (Sb)-related products raise concerns regarding its potential hazards to reproductive health. Upon environmental exposure, Sb reportedly induces testicular toxicity during spermatogenesis; moreover, it is known to affect various testicular cell populations, particularly germline stem cell populations. However, the cell-cell communication resulting from Sb exposure within the testicular niche remains poorly understood. To address this gap, herein we analyzed testicular single-cell RNA sequencing data from Sb-exposed Drosophila. Our findings revealed that the epidermal growth factor receptor (EGFR) and WNT signaling pathways were associated with the stem cell niche in Drosophila testes, which may disrupt the homeostasis of the testicular niche in Drosophila. Furthermore, we identified several ligand-receptor pairs, facilitating the elucidation of intercellular crosstalk involved in Sb-mediated reproductive toxicology. We employed scRNA-seq analysis and conducted functional verification to investigate the expression patterns of core downstream factors associated with EGFR and WNT signatures in the testes under the influence of Sb exposure. Altogether, our results shed light on the potential mechanisms of Sb exposure-mediated testicular cell-lineage communications.

Dietary Flavonoid Intake and Carotid Calcification in Patients with Ischemic Stroke.

INTRODUCTION: Owing to the antioxidant and anti-inflammatory effects, flavonoids can influence the initiation and development of atherosclerosis, but the underlying mechanisms remain largely undetermined. This study aimed to evaluate the associations between dietary flavonoids and carotid calcification in patients with ischemic stroke. METHODS: This study screened consecutive patients with ischemic stroke via Nanjing Stroke Registry Program from February 2016 to April 2021. A semiquantitative food frequency questionnaire was used to evaluate dietary consumption of flavonoids and other nutritional components. Presence and degree of carotid calcification were determined according to Agatston scores on computer tomography angiography. Logistic regression was performed to evaluate the association between dietary flavonoids (total flavonoids, flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and isoflavones) and carotid calcification. RESULTS: Of the 601 enrolled patients, 368 (61.2%) were detected with carotid calcification. Patients with high intake of total flavonoids (the fifth quintile) had a 52% lower carotid calcification risk than those with low intake (the first quintile; odds ratio [OR] = 0.48; 95% confidence interval [CI], 0.26-0.90; p = 0.007 for trends) after adjusting for major confounders. Patients with high intake of flavan-3-ols (the fifth quintile) had a 51% lower carotid calcification risk than those with low intake (the first quintile; OR = 0.49; 95% CI, 0.25-0.97; p = 0.016 for trends). CONCLUSION: Dietary flavonoid intake is associated with carotid calcification, and, therefore, may influence the risk of stroke occurrence and recurrence.

A Drosophila model of gestational antimony exposure uncovers growth and developmental disorders caused by disrupting oxidative stress homeostasis.

The toxic heavy metal antimony (Sb) is ubiquitous in our daily lives. Various models have shown that Sb induces neuronal and reproductive toxicity. However, little is known about the developmental toxicity of Sb exposure during gestation and the underlying mechanisms. To study its effects on growth and development, Drosophila stages from eggs to pupae were exposed to different Sb concentrations (0, 0.3, 0.6 and 1.2 mg/mL Sb); RNA sequencing was used to identify the underlying mechanism. The model revealed that prenatal Sb exposure significantly reduced larval body size and weight, the pupation and eclosion rates, and the number of flies at all stages. With 1.2 mg/mL Sb exposure in 3rd instar larvae, 484 genes were upregulated and 694 downregulated compared to controls. Biological analysis showed that the disrupted transcripts were related to the oxidative stress pathway, as verified by reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and glutathione (GSH) intervention experiments. Sb exposure induced oxidative stress imbalance could be rectified by chelation and antioxidant effects of NAC/GSH. The Drosophila Schneider 2 (S2) model further demonstrated that NAC and GSH greatly ameliorated cell death induced by Sb exposure. In conclusion, gestational Sb exposure disrupted oxidative stress homeostasis, thereby impairing growth and development.

Partition of phthalates among air, PM2 .5 , house dust and skin in residential indoor environments.

As a group of typical endocrine disrupters, phthalates are simultaneously present in a variety of environmental media and enter human body through multiple exposure pathways. In this study, field monitoring data were used to characterize the skin-air (Klg ), dust-air (Kd ), and PM2.5 -air (Kp ) partition coefficients of DiBP, DnBP, and DEHP. The median values of log(Klg ) in the summer and winter were 7.654 and 7.932, 7.265 and 7.902, 9.419 and 9.015 for DiBP, DnBP, and DEHP, respectively, and Klg was significantly higher in the winter. The median Kd (m3 /mg) in the summer (0.036-0.151 for DiBP, 0.021-0.036 for DnBP and 1.479-4.069 for DEHP) were significantly higher than the counterparts in the winter (0.027-0.065 for DiBP, 0.022-0.245 for DnBP, and 0.140-3.250 for DEHP). In addition, Kd was associated with material of surface and residence time of dust. The Kp values (m3 /µg) of DiBP, DnBP, and DEHP in the summer (0.053, 0.015, and 0.021) were also significantly higher than the counterparts in the winter (0.011, 0.004, and 0.025). The partition of phthalates was influenced by built environment, such as temperature, humidity, ventilation, indoor chemistry, smoking, and building age. Except Klg , there was substantial discrepancy between the estimates of K with empirical equations and the values of K based on field monitoring data in our study.

miR-223-3p Regulates NLRP3 to Inhibit Proliferation and Promote Apoptosis of ONG Cells.

Objective: Optic nerve glioma (ONG) is a rare disease, defined as a WHO grade I tumor, which affects the visual pathway. The objective of this study was to investigate the expression of miR-223-3p in ONG as well as its function and regulation in ONG cell lines. Methods: qRT-PCR assays were used to measure miR-223-3p expression in ONG tissues and cell lines. After overexpression of miR-223-3p in Hs683 and WERI-Rb-1 cell lines, CCK-8 and EdU assays were performed to examine cell proliferation, and flow cytometry was used to assess apoptosis. Dual luciferase assays were utilized to identify the target binding to miR-223-3p and NLRP3. Rescue assays were carried out to investigate the regulatory mechanism of miR-223-3p acting through NLRP3. Nude mouse tumorigenesis assays were established to verify the effect of miR-223-3p on ONG growth. Results: miR-223-3p was weakly expressed in both ONG tissues and cell lines. miR-223-3p inhibited the proliferative ability of Hs683 and WERI-Rb-1 cell lines and promoted apoptosis. In addition, there was binding between miR-223-3p and NLRP3. Simultaneous overexpression of NLRP3 and miR-223-3p partially counteracted the role of miR-223-3p in the cell lines. Lastly, miR-223-3p inhibited ONG growth. Conclusion: miR-223-3p plays an inhibitory role in ONG development by regulating NLRP3 to inhibit the proliferation of ONG cells and promote apoptosis.

Acute ischemic Stroke combined with Stanford type A aortic dissection: A case report and literature review.

BACKGROUND: Acute aortic dissection (AAD) is a high mortality disease that can lead to acute ischemic strokes (AIS). Some of the patients with AAD combined with AIS initially present with neurological symptoms, which can easily lead to missed or delayed AAD diagnosis. This is attributed to the lack of physician awareness or the urgency of patient thrombolysis. Intravenous administration of thrombolytic therapy (IVT) for AAD is associated with poor prognostic outcomes. We report a patient with AIS combined with AAD who developed a massive cerebral infarction after receiving IVT for a missed AAD diagnosis. CASE SUMMARY: A 49-year-old man was admitted to a local hospital with an acute onset of left-sided limb weakness accompanied by slurred speech. The patient had a history of hypertension that was not regularly treated with medication. Physical examination revealed incomplete mixed aphasia and left limb hemiparesis. Cranial computed tomography (CT) scan showed bilateral basal ganglia and lateral ventricular paraventricular infarct lesions. The patient was diagnosed with AIS and was administered with IVT. After IVT, patient's muscle strength and consciousness deteriorated. From the local hospital, he was referred to our hospital for further treatment. Emergency head and neck CT angiography (CTA) scans were performed. Results showed multiple cerebral infarctions, and aortic dissection in the ascending aorta, innominate artery, as well as in the right common carotid artery. Then, the CTA of thoracoabdominal aorta was performed, which revealed a Stanford type A aortic dissection and aortic dissection extending from the aortic root to the left external iliac artery. Laceration was located in the lesser curvature of the aortic arch. AAD complicated with AIS was considered, and the patient was immediately subjected to cardiovascular surgery for treatment. The next day, the patient underwent aortic arch and ascending aortic replacement and aortic valvuloplasty. CONCLUSION: Clinical manifestations for AAD combined with AIS are diverse. Some patients may not exhibit typical chest or back pains. Therefore, patients should be carefully evaluated to exclude AAD before administering IVT in order to avoid adverse consequences.

Extracellular vesicles carrying proinflammatory factors may spread atherosclerosis to remote locations.

Most cells involved in atherosclerosis release extracellular vesicles (EVs), which can carry bioactive substances to downstream tissues via circulation. We hypothesized that EVs derived from atherosclerotic plaques could promote atherogenesis in remote locations, a mechanism that mimics the blood metastasis of cancer. Ldlr gene knockout (Ldlr KO) rats were fed on a high cholesterol diet and underwent partial carotid ligation to induce local atherosclerosis. EVs were separated from carotid artery tissues and downstream blood of carotid ligation by centrifugation. MiRNA sequencing and qPCR were then performed to detect miRNA differences in EVs from rats with and without induced carotid atherosclerosis. Biochemical analyses demonstrated that EVs derived from atherosclerosis could increase the expression of ICAM-1, VCAM-1, and E-selectin in endothelial cells in vitro. EVs derived from atherosclerosis contained a higher level of miR-23a-3p than those derived from controls. MiR-23a-3p could promote endothelial inflammation by targeting Dusp5 and maintaining ERK1/2 phosphorylation in vitro. Inhibiting EV release could attenuate atherogenesis and reduce macrophage infiltration in vivo. Intravenously administrating atherosclerotic plaque-derived EVs could induce intimal inflammation, arterial wall thickening and lumen narrowing in the carotids of Ldlr KO rats, while simultaneous injection of miR-23a-3p antagomir could reverse this reaction. The results suggested that EVs may transfer atherosclerosis to remote locations by carrying proinflammatory factors, particularly miR-23a-3p.

GAP-43 Induces the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Retinal Ganglial-Like Cells.

Optic neuritis (ON) is a common neurological disease, and the transplant of retinal ganglion cells (RGCs) has been thought as a promising strategy for improving the injury of the optic nerve system. Bone mesenchymal stem cells (BMSCs) have the potential to differentiate into neural cells. Several studies have indicated that GAP-43 is related with the regeneration of nerve cells, while the effect of GAP-43 on inducing BMSC differentiation remains unclear. In this study, the BMSCs were separated from the rats and identified with flow cytometry assay. The GAP-43 expressed vectors were transfected into the BMSCs, and the biomarkers of RGCs such as PAX6, LHX2, and ATOH7 were used to observe by qRT-PCR. Moreover, the effect of GAP-43-induced BMSCs (G-BMSCs) on ON improvement was also verified with rat models, and the activity of MAPK pathway was measured with western blot. Here, it was found that GAP-43 could obviously promote the differentiation of BMSCs, and increased PAX6, LHX2, ATOH7, BRN3A, and BRN3B were observed in the process of cell differentiation. Moreover, it was also found that G-BMSCs significantly increased the abundances of NFL and NFM in G-BMSCs, and GAP-43 could also enhance the activity of MAPK pathways in BMSCs. Therefore, this study suggested that GAP-43 could induce the differentiation of bone marrow-derived mesenchymal stem cells into retinal ganglial cells.

Ether-Water Hybrid Electrolyte Contributing to Excellent Mg Ion Storage in Layered Sodium Vanadate.

Magnesium ion batteries have potential for large-scale energy storage. However, the high charge density of Mg2+ ions establishes a strong intercalation energy barrier in host materials, causing sluggish diffusion kinetics and structural degradation. Here, we report that the kinetic and dissolution issues connected to cathode materials can be resolved simultaneously using a tetraethylene glycol dimethyl ether (TEGDME)-water hybrid electrolyte. The lubricating and shielding effect of water solvent could boost the swift transport of Mg2+, contributing to a high diffusion coefficient within the sodium vanadate (NaV8O20·nH2O) cathode. Meanwhile, the organic TEGDME component can coordinate with water to diminish its activity, thus providing the hybrid electrolyte with a broad electrochemical window of 3.9 V. More importantly, the TEGDME preferentially amassed at the interface, leading to a robust cathode electrolyte interface layer that suppresses the dissolution of vanadium species. Consequently, the NaV8O20·nH2O cathode achieved a specific capacity of 351 mAh g-1 at 0.3 A g-1 and a long cycle life of 1000 cycles in this hybrid electrolyte. A mechanism study revealed the reversible interaction of Mg2+ during cycles. This organic water hybrid electrolyte is effective for overcoming the difficulty of multivalent ion storage.

Improvement of nickel-cobalt-based supercapacitors energy storage performance by modification of elements.

Hybrid supercapacitors have the advantages of fast charging and discharging and long service life, which are an efficient and practical energy storage device. Therefore, the design of hybrid supercapacitors is the focus of current research. In this paper, the silver modified spinel NiCo2S4 nanorods (Ag2S-NiCo2S4/CF) are synthesized by an efficient and economical method, which has excellent electrochemical performance. The Ag2S-NiCo2S4/CF shows a high specific capacity of 179.7 mAh g-1 at current density of 1 A g-1, and excellent rate capability (capacitance retention of ~87% at 20 A g-1). The corresponding Ag2S-NiCo2S4/CF//AC/CF hybrid supercapacitor is assembled by Ag2S-NiCo2S4/CF as the positive electrode, which can provide an energy density of 35.978 Wh kg-1 at a high-power density of 800 W kg-1 and has significant cyclic stability (~80% of the initial capacitor after ~9600 cycles). Therefore, Ag2S-NiCo2S4/CF material is a promising electrode material that can be applied to hybrid supercapacitors.

Design of nickel cobalt molybdate regulated by boronizing for high-performance supercapacitor applications.

Nickel-cobalt-based molybdates have been intensively investigated because of their high theoretical specific capacitance and multifarious oxidation states. Here, we have successfully synthesized hierarchical structures (Ni3B/Ni(BO2)2@NixCoyMoO4) by boronizing NixCoyMoO4 nanosheets on flexible carbon cloth substrates. Benefitting from the synergistic effect among Ni3B, Ni(BO2)2 and NixCoyMoO4 in hybrid architectures, the electrode material possesses higher capacity of 394.7 mA h g-1 at 1 A g-1 and a good rate performance (309.5 mA h g-1 maintained at 20 A g-1). Then, a hybrid supercapacitor assembled with Ni3B/Ni(BO2)2@NixCoyMoO4 and activated carbon as the positive and the negative electrode, displays a high specific capacitance of 370.7 F g-1 at 1 A g-1 (210 F g-1 at 10 A g-1), a high voltage of 1.7 V, and a high energy density of 131.8 W h kg-1 at the power density of 800 W kg-1 (still 74.7 W h kg-1 maintained at 8000 W kg-1). This study widens the research scope of boronizing pseudocapacitance materials and reveals a high application potential of Ni3B/Ni(BO2)2@NixCoyMoO4 for energy storage devices in the future.

Increased greenhouse gas emissions intensity of major croplands in China: Implications for food security and climate change mitigation.

Balancing crop production and greenhouse gas (GHG) emissions from agriculture soil requires a better understanding and quantification of crop GHG emissions intensity, a measure of GHG emissions per unit crop production. Here we conduct a state-of-the-art estimate of the spatial-temporal variability of GHG emissions intensities for wheat, maize, and rice in China from 1949 to 2012 using an improved agricultural ecosystem model (Dynamic Land Ecosystem Model-Agriculture Version 2.0) and meta-analysis covering 172 field-GHG emissions experiments. The results show that the GHG emissions intensities of these croplands from 1949 to 2012, on average, were 0.10-1.31 kg CO2 -eq/kg, with a significant increase rate of 1.84-3.58 × 10-3  kg CO2 -eq kg-1  year-1 . Nitrogen fertilizer was the dominant factor contributing to the increase in GHG emissions intensity in northern China and increased its impact in southern China in the 2000s. Increasing GHG emissions intensity implies that excessive fertilizer failed to markedly stimulate crop yield increase in China but still exacerbated soil GHG emissions. This study found that overfertilization of more than 60% was mainly located in the winter wheat-summer maize rotation systems in the North China Plain, the winter wheat-rice rotation systems in the middle and lower reaches of the Yangtze River and southwest China, and most of the double rice systems in the South. Our simulations suggest that roughly a one-third reduction in the current N fertilizer application level over these "overfertilization" regions would not significantly influence crop yield but decrease soil GHG emissions by 29.60%-32.50% and GHG emissions intensity by 0.13-0.25 kg CO2 -eq/kg. This reduction is about 29% and 5% of total agricultural soil GHG emissions in China and the world, respectively. This study suggests that improving nitrogen use efficiency would be an effective strategy to mitigate GHG emissions and sustain China's food security.

Necroptosis Mediates Cigarette Smoke-Induced Inflammatory Responses in Macrophages.

Introduction: Cigarette smoke (CS)-induced inflammation in macrophages is involved in the pathological process of chronic obstructive pulmonary disease (COPD). Necroptosis, which is a form of programmed necrosis, has a close relationship with robust inflammation, while its roles in COPD are unclear. Materials and Methods: Necroptosis markers were measured in mouse alveolar macrophages and cultured bone marrow-derived macrophages (BMDMs). Necroptosis inhibitors were used to block necroptosis in BMDMs, and inflammatory cytokines were detected. We further explored the related signaling pathways. Results: In this study, we demonstrated the way in which necroptosis, in addition to its upstream and downstream signals, regulates CS-induced inflammatory responses in macrophages. We observed that CS exposure caused a significant increase in the levels of necroptosis markers (receptor interacting kinases [RIPK] 1 and 3) in mouse alveolar macrophages and BMDMs. Pharmacological inhibition of RIPK1 or 3 caused a significant suppression in CS extract (CSE)-induced inflammatory cytokines, chemokine ligands (CXCL) 1 and 2, and interleukin (IL)-6 in BMDMs. CSE-induced necroptosis was regulated by mitochondrial reactive oxygen species (mitoROS), which also promoted inflammation in BMDMs. Furthermore, necroptosis regulated CSE-induced inflammatory responses in BMDMs, most likely through activation of the nuclear factor-κB pathway. Conclusion: Taken together, our results demonstrate that mitoROS-dependent necroptosis is essential for CS-induced inflammation in BMDMs and suggest that inhibition of necroptosis in macrophages may represent effective therapeutic approaches for COPD patients.

Combined gadoxetic acid and gadobenate dimeglumine enhanced liver MRI: a parameter optimization study.

PURPOSE: To demonstrate the feasibility of combined delayed-phase gadoxetic acid (GA) and gadobenate dimeglumine (GD) enhanced liver MRI for improved detection of liver metastases, and to optimize contrast agent dose, timing, and flip angle (FA). METHODS: Fourteen healthy volunteers underwent liver MRI at 3.0T at two visits during which they received two consecutive injections: 1. GA (Visit 1 = 0.025 mmol/kg; Visit 2 = 0.05 mmol/kg) and 2. GD (both visits = 0.1 mmol/kg) 20 min after GA administration. Two sub-studies were performed: Experiment-1 Eight subjects underwent multi-phase breath-held 3D-fat-saturated T1-weighted spoiled gradient echo (SGRE) imaging to determine the optimal imaging window for the combined GA + GD protocol to create a homogeneously hyperintense liver and vasculature ("plain-white-liver") with maximum contrast to muscle which served as a surrogate for metastatic lesions in both experiments. Experiment-2 Six subjects underwent breath-held 3D-fat-saturated T1-weighted SGRE imaging at three different FA to determine the optimal FA for best image contrast. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated. RESULTS: Experiment-1 The combined GA + GD protocol created a homogeneously hyperintense liver and vasculature with maximum CNR liver/muscle at approximately 60-120 s after automatic GD-bolus detection. Experiment-2 Flip angles between 25° and 35° at a dose of 0.025 mmol/kg GA provided the best combination that minimized liver/vasculature CNR, while maximizing liver/muscle CNR. CNR performance to achieve a "plain-white-liver" was superior with 0.025 mmol/kg GA compared to 0.05 mmol/kg. CONCLUSION: Combined GA + GD enhanced T1-weighted MRI is feasible to achieve a homogeneously "plain-white-liver". Future studies need to confirm that this protocol can improve sensitivity of liver lesion detection in patients with metastatic liver disease.

Novel mulberry silkworm cocoon-derived carbon dots and their anti-inflammatory properties.

Mulberry silkworm cocoon (MSC) carbonisata has been used for the treatment of inflammatory diseases for hundreds of years; however, after years of research efforts, little information is available on its anti-inflammatory components and underlying mechanism. We developed novel carbon dots (CDs) derived from MSC carbonisata (MSC-CDs), for the first time, with an average diameter of 2.26-9.35 nm and a quantum yield (QY) of 6.32%. The MSC-CDs were prepared using a modified pyrolysis method, and no further modification and external surface passivation agent was required. With abundant surface groups, MSC-CDs showed distinct solubility and bioactivity. In this study, we innovatively used three classical experimental models of inflammation to evaluate the anti-inflammatory bioactivity of MSC-CDs. The results indicated that MSC-CDs exhibited marked anti-inflammatory bioactivity which was likely mediated by inhibition of the expression of interleukin-6 and tumour necrosis factor-α. These results suggest that MSC-CDs possess a remarkable anti-inflammatory property, which provides evidence to support further investigation of the considerable potential and effective material basis of this traditional Chinese medicine.

Novel Carbon Dots Derived from Puerariae lobatae Radix and Their Anti-Gout Effects.

Gout is a disease with a high incidence and causing great harm, and the current treatment drugs are not satisfactory. In this study, novel water-soluble carbon dots (CDs) with anti-gout effect, named Puerariae lobatae Radix CDs (PLR-CDs), are reported. PLR-CDs were synthesized with an improved pyrolysis method at 300 °C, and their characterization was performed with multifaceted approaches, such as transmission electron microscopy (TEM) and ultraviolet-visible (UV-vis) and Fourier-transform infrared (FTIR) spectroscopy. In addition, the biocompatibility of PLR-CDs was studied using the cell counting kit (CCK)-8 in LO2 cells and RAW264.7 cells, and the anti-gout activity of PLR-CDs was examined on animal models of hyperuricemia and gouty arthritis. The characterization of PLR-CDs indicated that they were nearly spherical, with diameters ranging from 3.0 to 10.0 nm, and the lattice spacing was 0.283 nm. The toxicity experiment revealed that PLR-CDs were non-poisonous for LO2 cells and RAW264.7 cells at concentrations below 250 µg/mL. The results of pharmacodynamic experiments showed that PLR-CDs could lower the blood uric acid level in model rats by inhibiting the activity of xanthine oxidase and reduce the degree of swelling and pathological damage of gouty arthritis. Thus, PLR-CDs with anti-gout biological activity and good biocompatibility have the prospect of clinical application for the treatment of gout.