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Abstract Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor‐specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects.

Abstract Objective Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. Methods Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. Results Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0–151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. Conclusions Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

Abstract Chronic rhinosinusitis (CRS) can be traditionally classified as CRSwNP [with nasal polyps (NPs)] and CRSsNP (without NPs) based on the clinical phenotypes but recently suggested to be classified by the endotypes. We have identified overexpression of the cyclooxygenase-2 (COX-2) gene in NP tissues of Taiwanese CRSwNP patients. Therefore, in this study, we sought to investigate its protein expression/location/distribution in NP specimens and explore its roles in nasal polyposis. The COX-2 protein and mRNA expression was found higher in NPs than that in the control and CRSsNP patients’ nasal tissues, mainly located at the epithelium and subepithelial stroma. Consistently, the CRS-related peptidoglycan (PGN) and bradykinin provoked COX-2 mRNA and protein upregulation in the human NP-derived fibroblasts and caused PGE2, thromboxane A2 (TXA2), and interleukin (IL-6) secretion in culture medium. Further analysis revealed that the PI3K/Akt activation and COX-2 induction were necessarily required for PGN-induced IL-6 production/secretion and the induced PGE2, but not TXA2, was speculated to affect IL-6 protein trafficking and production. Finally, the IL-6 increase observed in vitro could also be detected in NP tissues. Collectively, we demonstrated here that COX-2 protein and IL-6 are overexpressed in human NP tissues. In response to PGN challenge, the PI3K/Akt activation and COX-2-mediated PGE2 autacoid correlates with extracellular IL-6 protein trafficking/production in NP-derived fibroblasts, which can additionally contribute to the production of Th17-related cytokines such as IL-17 and TNF-α. This study also suggests COX-2 as a special biomarker for CRSwNP endotyping and may highlight the importance of COX-2 inhibitors in treating CRSwNP.

Abstract Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

The purpose of this study is to clarify the role of IL-33 in the immune response to angiostrongyliasis, especially in terms of antibody production and isotype switching. In our experiment, C57BL/6 mice were each infected with 35 infectious larvae and were divided into groups that received an intraperitoneal injection of IL-33, anti-IL-33 monoclonal antibody (mAb), or anti-ST2 mAb 3 days post-infection (dpi) and were subsequently administered booster shots at 5-day intervals with the same dose. Serum samples from each group were collected weekly for ELISA assays. The levels of total IgG, IgG1, and IgG3 were significantly increased in A. cantonensis-infected mice that were treated with IL-33, and the levels decreased significantly in infected groups treated with anti-IL-33 or anti-ST2 mAb. These results suggest that IL-33 may play a critical role in the pathogenesis of human angiostrongyliasis and could be useful for understanding protective immunity against this parasitic infection.

Abstract Muscular dystrophy (MD) is a genetic disorder that causes progressive muscle weakness and degeneration. Limb‐girdle muscular dystrophy (LGMD) is a type of MD that mainly causes muscle atrophy within the shoulder and pelvic girdles. LGMD is classified into autosomal dominant (LGMD‐D) and autosomal recessive (LGMD‐R) inheritance patterns. Mutations in the Dysferlin gene (DYSF) are common causes of LGMD‐R. However, genetic screening of DYSF mutations is rare in Taiwan. Herein, we identified a novel c.2867_2871del ACCAG deletion and a previously reported c.937+1G>A mutation in DYSF from a Taiwanese family with LGMD. The primary symptoms of both siblings were difficulty climbing stairs, walking on the toes, and gradually worsening weakness in the proximal muscles and increased creatine kinase level. Through pedigree analysis and sequencing, two siblings from this family were found to have compound heterozygous DYSF mutations (c. 937+1G>A and c. 2867_2871del ACCAG) within the separated alleles. These mutations induced early stop codons; if translated, truncated DYSF proteins will be expressed. Or, the mRNA products of these two mutations will merit the nonsense‐mediated decay, might result in no dysferlin protein expressed. To our knowledge, this is the first report of a novel c.2867_2871del ACCAG deletion in DYSF. Further research is required to examine the effects of the novel DYSF mutation in Taiwanese patients with LGMD.

BackgroundAngiogenesis in folliculogenesis contributes to oocyte developmental competence in natural and in vitro fertilization (IVF) cycles. Therefore, the identification of key angiogenic factors in follicular fluid (FF) during folliculogenesis is clinically significant and important for in vitro fertilization. This study aims to identify the key angiogenic factors in FF for predicting oocyte maturity during in vitro fertilization.Materials and methodsForty participants who received ovarian stimulation using a GnRH antagonist protocol in their first in vitro fertilization treatment were recruited. From each patient, two follicular samples (one preovulatory follicle, > 18 mm; one mid-antral follicle, < 14 mm) were collected without flushing during oocyte retrieval. In total, 80 FF samples were collected from 40 patients. The expression profiles of angiogenesis-related proteins in FF were analyzed via Luminex high-performance assays. Recorded patient data included antral follicle count, anti-müllerian hormone, age, and BMI. Serum samples were collected on menstrual cycle day 2, the trigger day, and the day of oocyte retrieval. Hormone concentrations including day 2 FSH/LH/E2/P4, trigger day E2/LH/P4, and retrieval day E2/LH/P4 were measured by chemiluminescence assay.ResultsTen angiogenic factors were highly expressed in FF: eotaxin, Gro-α, IL-8, IP-10, MCP-1, MIG, PAI-1 (Serpin), VEGF-A, CXCL-6, and HGF. The concentrations of eotaxin, IL-8, MCP1, PAI-1, and VEGF-A were significantly higher in preovulatory follicles than those in mid-antral follicles, while the Gro-α and CXCL-6 expressional levels were lower in preovulatory than in mid-antral follicles (p < 0.05). Logistic regression and receiver operating characteristic (ROC) analysis revealed that VEGF-A, eotaxin, and CXCL-6 were the three strongest predictors of oocyte maturity. The combination of VEGF-A and CXCL-6 predicted oocyte maturity with a higher sensitivity (91.7%) and specificity (72.7%) than other combinations.ConclusionOur findings suggest that VEGF-A, eotaxin, and CXCL-6 concentrations in FF strongly correlate with oocyte maturity from the mid-antral to preovulatory stage. The combination of VEGF-A and CXCL-6 exhibits a relatively good prediction rate of oocyte maturity during in vitro fertilization.

Crop planting patterns are an important component of agricultural land systems. These patterns have been significantly changed due to the combined impacts of climatic changes and socioeconomic developments. However, the extent of these changes and their possible impacts on the environment, terrestrial landscapes and rural livelihoods are largely unknown due to the lack of spatially explicit datasets including crop planting patterns. To fill this gap, this study proposes a new method for spatializing statistical data to generate multitemporal crop planting pattern datasets. This method features a two-level model that combines a land-use simulation and a crop pattern simulation. The output of the first level is the spatial distribution of the cropland, which is then used as the input for the second level, which allocates crop censuses to individual gridded cells according to certain rules. The method was tested using data from 2000 to 2019 from Heilongjiang Province, China, and was validated using remote sensing images. The results show that this method has high accuracy for crop area spatialization. Spatial crop pattern datasets over a given time period can be important supplementary information for remote sensing and thus support a wide range of application in agricultural land systems.

The use of manufactured silica nanoparticles (SiNPs) has become widespread in everyday life, household products, and various industrial applications. While the harmful effects of crystalline silica on the lungs, known as silicosis or chronic pulmonary diseases, are well understood, the impact of SiNPs on the airway is not fully explored. This study aimed to investigate the potential effects of SiNPs on human tracheal smooth muscle cells (HTSMCs). Our findings revealed that SiNPs induced the expression of cyclooxygenase-2 (COX-2) mRNA/protein and the production of prostaglandin E2 (PGE2) without causing cytotoxicity. This induction was transcription-dependent, as confirmed by cell viability assays and COX-2 luciferase reporter assays. Further analysis, including Western blot with pharmacological inhibitors and siRNA interference, showed the involvement of receptor tyrosine kinase (RTK) EGF receptor (EGFR), non-RTK Pyk2, protein kinase Cα (PKCα), and p42/p44 MAPK in the induction process. Notably, EGFR activation initiated cellular signaling that led to NF-κB p65 phosphorylation and translocation into the cell nucleus, where it bound and stimulated COX-2 gene transcription. The resulting COX-2 protein triggered PGE2 production and secretion into the extracellular space. Our study demonstrated that SiNPs mediate COX-2 up-regulation and PGE2 secretion in HTSMCs through the sequential activation of the EGFR/Pyk2/PKCα/p42/p44MAPKs-dependent NF-κB signaling pathway. Since PGE2 can have both physiological bronchodilatory and anti-inflammatory effects, as well as pathological pro-inflammatory effects, the increased PGE2 production in the airway might act as a protective compensatory mechanism and/or a contributing factor during airway exposure to SiNPs.

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. Here, the authors show that also presynaptic NMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner.

The risk of lung exposure to silica nanoparticles (SiNPs) and related lung inflammatory injury is increasing with the wide application of SiNPs in a variety of industries. A growing body of research has revealed that cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) up-regulated by SiNP toxicity has a role during pulmonary inflammation. The detailed mechanisms underlying SiNP-induced COX-2 expression and PGE2 synthesis remain unknown. The present study aims to dissect the molecular components involved in COX-2/PGE2 up-regulated by SiNPs in human pulmonary alveolar epithelial cells (HPAEpiCs) which are one of the major targets while SiNPs are inhaled. In the present study, we demonstrated that SiNPs induced COX-2 expression and PGE2 release, which were inhibited by pretreatment with a reactive oxygen species (ROS) scavenger (edaravone) or the inhibitors of proline-rich tyrosine kinase 2 (Pyk2, PF-431396), epidermal growth factor receptor (EGFR, AG1478), phosphatidylinositol 3-kinase (PI3K, LY294002), protein kinase B (Akt, Akt inhibitor VIII), p38 mitogen-activated protein kinase (MAPK) (p38 MAPK inhibitor VIII), c-Jun N-terminal kinases (JNK)1/2 (SP600125), Forkhead Box O1 (FoxO1, AS1842856), and activator protein 1 (AP-1, Tanshinone IIA). In addition, we also found that SiNPs induced ROS-dependent Pyk2, EGFR, Akt, p38 MAPK, and JNK1/2 activation in these cells. These signaling pathways induced by SiNPs could further cause c-Jun and FoxO1 activation and translocation from the cytosol to the nucleus. AP-1 and FoxO1 activation could increase COX-2 and PGE2 levels induced by SiNPs. Finally, the COX-2/PGE2 axis might promote the inflammatory responses in HPAEpiCs. In conclusion, we suggested that SiNPs induced COX-2 expression accompanied by PGE2 synthesis mediated via ROS/Pyk2/EGFR/PI3K/Akt/p38 MAPK- and JNK1/2-dependent FoxO1 and AP-1 activation in HPAEpiCs.

Abstract Background The optimal sequence of pulmonary vessel interruption during lung cancer resection remains controversial. This review aimed to elucidate the association of vein-first versus artery-first ligation and survival of the patients. Methods We searched PubMed, Web of Science, Scopus, Embase, Cochrane Library and Google Scholar from their inception to September 2021 for published articles that compared vein-first (the pulmonary vein was interrupted first) and artery-first procedure (the pulmonary artery was ligated first) during lung cancer surgery. Results Finally, a total of 13 full articles were obtained. First, 7 studies with survival information were included for meta-analyses. As compared with the artery-first ligation, vein-first approach did not decrease the risk of local recurrence (risk ratio [RR] 0.92 in favour of vein-first; 95% confidence interval [CI] 0.61–1.39, p = 0.68) or distant metastasis (RR 0.92; 95% CI 0.30–2.85, p = 0.89); but it was associated with better disease-free survival (RR 0.52; 95% CI 0.37–0.73, p

ABSTRACT Cefoperazone-sulbactam (SCF)-resistant Pseudomonas aeruginosa poses a big challenge in the use of SCF to treat infection caused by the pathogen. We have recently shown exogenous nitrite-enabled killing of naturally and artificially evolved Pseudomonas aeruginosa strains (AP-RCLIN-EVO and AP-RLAB-EVO, respectively) by SCF. However, the underlying mechanism is unknown. Here, reprogramming metabolomics was adopted to investigate how nitrite enhanced the SCF-mediated killing efficacy. Nitrite-reprogrammed metabolome displayed an activated pyruvate cycle (P cycle), which was confirmed by elevated activity of pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. The activated P cycle provided NADH for the electron transport chain and thereby increased reactive oxygen species (ROS), which potentiated SCF to kill AP-RCLIN-EVO and AP-RLAB-EVO. The nitrite-enabled killing of AP-RCLIN-EVO and AP-RLAB-EVO by SCF was inhibited by PDH inhibitor furfural and ROS scavenger N-Acetyl-L-cysteine but promoted by ROS promoter Fe3+. SCF alone could not induce ROS, but SCF-mediated killing efficacy was enhanced by ROS. In addition, the present study demonstrated that nitrite repressed antioxidants, which were partly responsible for the elevated ROS. These results reveal a nitrite-reprogrammed metabolome mechanism by which AP-RCLIN-EVO and AP-RLAB-EVO sensitivity to SCF is elevated. IMPORTANCE Antibiotic-resistant Pseudomonas aeruginosa has become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. Understanding antibiotic resistance mechanisms and developing novel control measures are highly appreciated. We have recently shown that a reduced nitrite-dependent NO biosynthesis contributes to cefoperazone-sulbactam (SCF) resistance, which is reverted by exogenous nitrite, in both naturally and artificially evolved P. aeruginosa strains (AP-RCLIN-EVO and AP-RLAB-EVO, respectively). However, the mechanism is unknown. The present study reports that the nitrite-enabled killing of AP-RCLIN-EVO and AP-RLAB-EVO by SCF is attributed to the promoted production of reactive oxygen species (ROS). Nitrite activates the pyruvate cycle to generate NADH for the electron transport chain, which in turn promotes ROS generation. Nitrite-potentiated SCF-mediated killing is decreased by pyruvate dehydrogenase inhibitor furfural and ROS scavenger N-Acetyl-L-cysteine but increased by ROS promoter Fe3+. Furthermore, SCF-mediated killing is promoted by H2O2 in a dose-dependent manner. In addition, the combination of nitrite and H2O2 greatly enhances SCF-mediated killing. These results not only disclose a nitrite-ROS-potentiated SCF-mediated killing, but also show SCF-mediated killing is dependent upon ROS.

Structural degradation in manganese oxides leads to unstable activity during long-term cycles. Herein, authors demonstrated that reduced unstable O 2p holes and the short interlayer distance of layered lithium manganese oxide are favorable for excellent electrocatalytic stability and activity.

BackgroundAs an age-related syndrome, frailty may play a central role in poor health among older adults. Sarcopenia overlaps with the physical domain of frailty, and most existing studies have analyzed the associated factors of frailty and sarcopenia as an isolated state. Perturbations in metabolism may play an important role in the presence of frailty or sarcopenia; however, the metabolites associated with frailty, especially overlapping with sarcopenia remain unclear. In this study, we aimed to explore whether amino acids, carnitines, acylcarnitines and lysophosphatidylcholines, as specific panels, are significantly correlated with frailty, especially overlapping with sarcopenia, to gain insight into potential biomarkers and possible biological mechanisms and to facilitate their management.MethodsWe applied a targeted high-performance liquid chromatography-tandem mass spectrometry approach in serum samples from 246 Chinese older men (age 79.2 ± 7.8 years) with frailty (n = 150), non-frailty (n = 96), frailty and sarcopenia (n = 52), non-frail and non-sarcopenic control (n = 85). Frailty was evaluated using Freid phenotype criteria, sarcopenia was defined by diagnostic algorithm of Asian Working Group on Sarcopenia, and the participants were diagnosed as frailty and sarcopenia when they met the evaluation criteria of both frailty and sarcopenia. A panel of 29 metabolomic profiles was assayed and included different classes of amino acids, carnitines, acylcarnitines, and lysophosphatidylcholines (LPCs). Multivariate logistic regression was used to screen the metabolic factors contributing to frailty status, and orthogonal partial least squares discriminant analysis was used to explore important factors and distinguish different groups.ResultsIn older men demonstrating the frail phenotype, amino acid perturbations included lower tryptophan and higher glycine levels. With regard to lipid metabolism, the frailty phenotype was characterized by lower concentrations of isovalerylcarnitine (C5), LPC16:0 and LPC18:2, while higher levels of octanoyl-L-carnitine (C8), decanoyl-L-carnitine (C10), dodecanoyl-L-carnitine (C12) and tetradecanoyl-L-carnitine (C14). After adjusting for several clinical confounders, tryptophan, LPC18:2, LPC 16:0 and C5 were negatively correlated with frailty, and C8 and C12 were positively related to frailty. We preliminarily identified metabolic profiles (LPC16:0, LPC18:2, glycine and tryptophan) that may distinguish older men with frailty from those without frailty. Importantly, a set of serum amino acids and LPCs (LPC16:0, LPC18:2, and tryptophan) was characterized in the metabotype of older adults with an overlap of frailty and sarcopenia. The metabolites that were most discriminating of frailty status implied that the underlying mechanism might be involved in antioxidation and mitochondrial dysfunction.ConclusionsThese present metabolic analyses may provide valuable information on the potential biomarkers and possible biological mechanisms of frailty, and overlapping sarcopenia. The findings obtained may offer insight into their management in older adults.

Background: Hospital-acquired pneumonia (HAP) remains an important cause of morbidity and mortality despite advances in antimicrobial therapy. The emergence of Gram-negative bacteria (GNB) is of major concern. The objective of this study was to describe the epidemiology, microbiology, and predictors of infection-related 30-day mortality in HAP with GNB. Methods: We performed a retrospective, single-center analysis of HAP patients with GNB occurring from January 2014 and December 2017. Univariate and multivariate analyses were performed to identify the risk factors for mortality. Results: During the observational period, there were 1472 cases of HAP; 314 cases were bacterial culture-positive, 269 cases were caused by GNB, with a predominance of Acinetobacter baumannii and Pseudomonas aeruginosa. The mortality related to GNB was 14.5% (39 deaths).In the multivariate logistic regression analysis, the risk factors for mortality were age >70 years, intensive care unit (ICU) admission, blood lymphocyte count

AIM: To investigate the expression of TWIK-related arachidonic acid-stimulated K+ channel (TRAAK) in retinal degeneration mice (rd1) and further evaluate how TRAAK affect photoreceptor cell apoptosis. METHODS: The rd1 mice were distributed into blank (no treatment), control (1.4% DMSO, intraperitoneal injection) and riluzole groups (4 mg/kg·d, intraperitoneal injection) from postnatal 7d to 10, 14 and 18d; C57 group (no treatment), as age-matched wild-type control. The thickness of the outer nuclear layer (ONL) of retina was detected by paraffin section hematoxylin and eosin staining. The expression of TRAAK and the apoptosis of the ONL cells were detected by immunostaining, Western blotting, and real-time polymerase chain reaction. RESULTS: The channel agonist riluzole activated TRAAK and delayed the apoptosis of photoreceptor cells in ONL layer of rd1 mice. Both at mRNA and protein levels, after riluzole treatment, TRAAK expression was significantly upregulated, when compared with the control and blank group. Then we detected a series of apoptosis related mRNA and protein. The anti-apoptotic factor Bcl-2 downregulated and the pro-apoptotic factors Bax and cleaved-caspase-3 upregulated significantly. CONCLUSION: Riluzole elevates the expression of TRAAK and inhibits the development of apoptosis. Activation of TRAAK may have some potential effects to put off photoreceptor apoptosis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complicated inflammatory disease, and the underlying mechanism remains unclear. While some reactive oxygen/nitrogen species-related gene products are reported to participate in CRSwNP, a systemic and full analysis of oxidative-stress-associated genes in CRSwNP has not been extensively studied. Therefore, this study sought to catalog the gene-expression patterns related to oxidative stress and antioxidant defense in control and CRSwNP patients. In total, 25 control and 25 CRSwNP patients were recruited. The distribution and expression of 4-hydroxynonenal and 3-nitrotyrosine as markers of oxidative stress—which is represented by lipid peroxidation and the protein nitration of tyrosine residues in CRSwNP nasal polyps (NPs)—were more apparently increased than those found in the control nasal mucosae, as determined by immunohistochemistry (IHC). The expression of 84 oxidative-stress-related genes in nasal mucosae and NP tissues was analyzed via real-time PCR, which showed that 19 genes and 4 genes were significantly up- and downregulated, respectively; among them, inducible nitric oxide synthase (iNOS) and heme oxygenase 1 (HO-1) were notably upregulated, whereas lactoperoxidase (LPO), myeloperoxidase (MPO), and superoxide dismutase 3 (SOD3) were highly downregulated. Changes in the mRNA and protein levels of these redox proteins were confirmed with a customized, real-time PCR array and RT-PCR analysis, as well as Western blotting and IHC assays. A receiver operating characteristic curve analysis further suggested that LPO, MPO, SOD3, HO-1, and iNOS are possible endotype predictors of CRSwNP development. Collectively, we present an oxidative-stress-related gene profile of CRSwNP NP tissues, providing evidence that the systemic changes in oxidative stress and the antioxidative defense system, including novel iNOS, heme peroxidases, and other genes, are closely linked to CRSwNP pathology, development, and progression.

Hydrogen sulfide (H2S) was the third gasotransmitter to be recognized as a cytoprotectant. A recent study demonstrated that exogenous supplementation of H2S ameliorates functional insufficiency in chronic kidney disease (CKD). However, how the H2S system is impaired by CKD has not been elucidated. The uremic toxin indoxyl sulfate (IS) is known to accumulate in CKD patients and harm the renal tubular cells. This study therefore treated the proximal tubular cells, LLC-PK1, with IS to see how IS affects H2S formation. Our results showed that H2S release from LLC-PK1 cells was markedly attenuated by IS when compared with control cells. The H2S donors NaHS and GYY-4137 significantly attenuated IS-induced tubular damage, indicating that IS impairs H2S formation. Interestingly, IS downregulated the H2S-producing enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), and these effects could be reversed by inhibition of the IS receptor, aryl hydrocarbon receptor (AhR). As transcription factor specificity protein 1 (Sp1) regulates the gene expression of H2S-producing enzymes, we further showed that IS significantly decreased the DNA binding activity of Sp1 but not its protein expression. Blockade of AhR reversed low Sp1 activity caused by IS. Moreover, exogenous H2S supplementation attenuated IS-mediated superoxide formation and depletion of the cellular glutathione content. These results clearly indicate that IS activates AhR, which then attenuates Sp1 function through the regulation of H2S-producing enzyme expression. The attenuation of H2S formation contributes to the low antioxidant defense of glutathione in uremic toxin-mediated oxidative stress, causing tubular cell damage.

Abstract: Rice planting patterns have changed dramatically over the past several decades in northeast China (NEC) due to the combined influence of global change and agricultural policy. Except for its great implications for environmental protection and climate change adaption, the spatio-temporal changes of rice cultivation in NEC are not clear. In this study, we conducted spatio-temporal analyses of NEC's major rice production region, Heilongjiang Province, by using satellite-derived rice cultivation maps. We found that the total cultivated area of rice in Heilongjiang Province increased largely from 1993 to 2011 and it expanded spatially to the northern and eastern part of the Sanjiang Plain. The results also showed that rice cultivation areas experienced a larger increase in the region managed by the Reclamation Management Bureau (RMB) than that managed by the local provincial government. Rice cultivation changes were closely related with those geographic factors over the investigated periods, represented by the geomorphic (slope), climatic (accumulated temperature), and hydrological (watershed) variables. These findings provide clear evidence that crop cultivation in NEC has been modified to better cope with the global change.

The successful launched Gaofen satellite no. 1 wide field-of-view (GF-1 WFV) camera is characterized by its high spatial resolution and may provide some potential for regional crop mapping. This study, taking the Bei'an City, Northeast China as the study area, aims to investigate the potential of GF-1 WFV images for crop identification and explore how to fully use its spectral, textural and temporal information to improve classification accuracy. In doing so, an object-based and Random Forest (RF) algorithm was used for crop mapping. The results showed that classification based on an optimized single temporal GF-1 image can achieve an overall accuracy of about 83%, and the addition of textural features can improve the accuracy by 8.14%. Moreover, the multi-temporal GF-1 data can produce a classification map of crops with an overall accuracy of 93.08% and the introduction of textural variables into multi-temporal GF-1 data can only increase the accuracy by about 1%, which suggests the importance of temporal information of GF-1 for crop mapping in comparison with single temporal data. By comparing classification results of GF-1 data with different feature inputs, it is concluded that GF-1 WFV data in general can meet the mapping efficiency and accuracy requirements of regional crop. But given the unique spectral characteristics of the GF-1 WFV imagery, the use of textual and temporal information is needed to yield a satisfactory accuracy.

By employing the unique phenological feature of winter wheat extracted from peak before winter (PBW) and the advantages of moderate resolution imaging spectroradiometer (MODIS) data with high temporal resolution and intermediate spatial resolution, a remote sensing-based model for mapping winter wheat on the North China Plain was built through integration with Landsat images and land-use data. First, a phenological window, PBW was drawn from time-series MODIS data. Next, feature extraction was performed for the PBW to reduce feature dimension and enhance its information. Finally, a regression model was built to model the relationship of the phenological feature and the sample data. The amount of information of the PBW was evaluated and compared with that of the main peak (MP). The relative precision of the mapping reached up to 92% in comparison to the Landsat sample data, and ranged between 87 and 96% in comparison to the statistical data. These results were sufficient to satisfy the accuracy requirements for winter wheat mapping at a large scale. Moreover, the proposed method has the ability to obtain the distribution information for winter wheat in an earlier period than previous studies. This study could throw light on the monitoring of winter wheat in China by using unique phenological feature of winter wheat.

High-resolution satellite data have been playing an important role in agricultural remote sensing monitoring. However, the major data sources of high-resolution images are not owned by China. The cost of large scale use of high resolution imagery data becomes prohibitive. In pace of the launch of the Chinese “High Resolution Earth Observation Systems”, China is able to receive superb high-resolution remotely sensed images (GF series) that equalizes or even surpasses foreign similar satellites in respect of spatial resolution, scanning width and revisit period. This paper provides a perspective of using high resolution remote sensing data from satellite GF-1 for agriculture monitoring. It also assesses the applicability of GF-1 data for agricultural monitoring, and identifies potential applications from regional to national scales. GF-1's high resolution (i.e., 2 m/8 m), high revisit cycle (i.e., 4 days), and its visible and near-infrared (VNIR) spectral bands enable a continuous, efficient and effective agricultural dynamics monitoring. Thus, it has gradually substituted the foreign data sources for mapping crop planting areas, monitoring crop growth, estimating crop yield, monitoring natural disasters, and supporting precision and facility agriculture in China agricultural remote sensing monitoring system (CHARMS). However, it is still at the initial stage of GF-1 data application in agricultural remote sensing monitoring. Advanced algorithms for estimating agronomic parameters and soil quality with GF-1 data need to be further investigated, especially for improving the performance of remote sensing monitoring in the fragmented landscapes. In addition, the thematic product series in terms of land cover, crop allocation, crop growth and production are required to be developed in association with other data sources at multiple spatial scales. Despite the advantages, the issues such as low spectrum resolution and image distortion associated with high spatial resolution and wide swath width, might pose challenges for GF-1 data applications and need to be addressed in future agricultural monitoring.

Rice area has been expanding rapidly during the past 30 years under the influence of global change in northeastern China, which is the northernmost region of rice cultivation in China. However, the spatio-temporal dynamic changes in rice area are still unclear, although they may have important policy implications for environmental protection and adaptation to climate change. In this study, we aimed to identify the dynamic changes of the rice area in Heilongjiang Province of northeastern China by extracting data from multiple Landsat images. The study used ground quadrats selected from Google Earth and the extraction of a confusion matrix to verify the accuracy of extraction. The overall accuracy of the extracted rice area was higher than 95% as a result of using the artificial neural network (ANN) classification method. The results showed that the rice area increased by approximately 2.4×106 ha during the past 30 years at an annual rate of 8.0×104 ha, and most of the increase occurred after 2000. The central latitude of the rice area shifted northwards from 46 to 47°N during the study period, and moved eastwards from 130 to 133°E. The rice expansion area accounted for 98% of the total change in rice area, and rice loss was notably rare. The rice expansion was primarily from dryland. In addition, rice cultivation in marshland and grassland played a minor role in the rice expansion in this region.

How to fully use spectral and temporal information for efficient identification of crops becomes a crucial issue since each crop has its specific seasonal dynamics. A thorough understanding on the relative usefulness of spectral and temporal features is thus essential for better organization of crop classification information. This study, taking Heilongjiang Province as the study area, aims to use time-series moderate resolution imaging spectroradiometer (MODIS) surface reflectance product (MOD09A1) data to evaluate the importance of spectral and temporal features for crop classification. In doing so, a feature selection strategy based on separability index (SI) was first used to rank the most important spectro-temporal features for crop classification. Ten feature scenarios with different spectral and temporal variable combinations were then devised, which were used for crop classification using the support vector machine and their accuracies were finally assessed with the same crop samples. The results show that the normalized difference tillage index (NDTI), land surface water index (LSWI) and enhanced vegetation index (EVI) are the most informative spectral features and late August to early September is the most informative temporal window for identifying crops in Heilongjiang for the observed year 2011. Spectral diversity and time variety are both vital for crop classification, and their combined use can improve the accuracy by about 30% in comparison with single image. The feature selection technique based on SI analysis is superior for achieving high crop classification accuracy (producers' accuracy of 94.03% and users' accuracy of 93.77%) with a small number of features. Increasing temporal resolution is not necessarily important for improving the classification accuracies for crops, and a relatively high classification accuracy can be achieved as long as the images associated with key phenological phrases are retained.

Using simultaneously collected remote sensing data and field measurements, this study firstly assessed the consistency and applicability of China high-resolution earth observation system satellite 1 (GF-1) wide field of view (WFV) camera, environment and disaster monitoring and forecasting satellite (HJ-1) charge coupled device (CCD), and Landsat-8 operational land imager (OLI) data for estimating the leaf area index (LAI) of winter wheat via reflectance and vegetation indices (VIs). The accuracies of these LAI estimates were then assessed through comparison with an empirical model and the PROSAIL radiative transfer model. The effects of radiation calibration, spectral response functions, and spatial resolution on discrepancies in the LAI estimates between the different sensors were also analyzed. The results yielded the following observations: (1) The correlation between reflectance from different sensors is relative good, with the adjusted coefficients of determination (R2) between 0.375 to 0.818. The differences in reflectance are ranging from 0.002 to 0.054. The correlation between VIs from different sensors is high with the R2 between 0.729 and 0.933. The differences in the VIs are ranging from 0.07 to 0.156. These results show the three sensors' images can all be used for cross calibration of the reflectance and VIs. (2) The four VIs from the three sensors are all demonstrated to be highly correlated with LAI (R2 between 0.703 and 0.849). The linear models associated with the 2-band enhanced vegetation index (EVI2), which feature the highest R2 (higher than 0.746) and the lowest root mean square errors (RMSE) (less than 0.21), were selected to estimate the winter wheat LAI. The accuracy of the estimated LAI from Landsat-8 was the highest, with the relative errors (RE) of 2.18% and an RMSE of 0.13, while the HJ-1 was the lowest, with the RE of 2.43% and the RMSE of 0.15. (3) The inversion errors in the different sensors' LAI estimates using the PROSAIL model are small. The accuracy of the GF-1 is the highest with the RE of 3.44%, and the RMSE of 0.22, whereas that of the HJ-1 is the lowest with the RE of 4.95%, and the RMSE of 0.26. (4) The effects of the spectral response function and radiation calibration for the different sensors are small and can be ignored, but the effects of spatial resolution are significant and must be taken into consideration in practical applications.

Due to the limitations of current extraction methods, extracellular DNA (eDNA) is rarely discerned from intracellular DNA (iDNA) despite having unique contributions to antibiotic resistance genes (ARGs) propagation. Furthermore, eDNA may be free (f-eDNA) or adsorbed to or suspended solids, including cells (a-eDNA), which affects ARG persistence and transmissivity. We developed a novel method using magnetic beads to separate iDNA, a-eDNA, and f-eDNA to assess how these physical states of ARGs change across a wastewater treatment plant. This method efficiently extracted eDNA (>85.3%) with higher recovery than current methods such as alcohol precipitation, CTAB-based extraction, and DNA extraction kits (

Abstract: The leaf area index (LAI) is an important vegetation parameter, which is used widely in many applications. Remote sensing techniques are known to be effective but inexpensive methods for estimating the LAI of crop canopies. During the last two decades, hyperspectral remote sensing has been employed increasingly for crop LAI estimation, which requires unique technical procedures compared with conventional multispectral data, such as denoising and dimension reduction. Thus, we provide a comprehensive and intensive overview of crop LAI estimation based on hyperspectral remote sensing techniques. First, we compare hyperspectral data and multispectral data by highlighting their potential and limitations in LAI estimation. Second, we categorize the approaches used for crop LAI estimation based on hyperspectral data into three types: approaches based on statistical models, physical models (i.e., canopy reflectance models), and hybrid inversions. We summarize and evaluate the theoretical basis and different methods employed by these approaches (e.g., the characteristic parameters of LAI, regression methods for constructing statistical predictive models, commonly applied physical models, and inversion strategies for physical models). Thus, numerous models and inversion strategies are organized in a clear conceptual framework. Moreover, we highlight the technical difficulties that may hinder crop LAI estimation, such as the “curse of dimensionality” and the ill-posed problem. Finally, we discuss the prospects for future research based on the previous studies described in this review.

BACKGROUND:Adenomyosis is a medical condition defined by the abnormal presence of endometrial tissue within the myometrium, in which fibrosis occurs with new collagen deposition and myofibroblast differentiation. In this study, the effect of several mediators and growth factors on collagen expression was investigated on human endometrial stromal cells (fibroblasts) derived from adenomyotic endometrium. EXPERIMENTAL APPROACH:RT-PCR, Western blot analysis, pharmacological interventions and siRNA interference were applied to primary cultured human endometrial stromal cells (fibroblasts). Immunohistochemistry was used to analyze protein expression in adenomyotic endometrium tissue specimens. RESULTS:Of the tested mediators, transforming growth factor β1 (TGFβ1) and its isoforms were effective to induce collagen and connective tissue growth factor (CTGF) expression. Collagen and CTGF induction by TGFβ1 could be reduced by the inhibitors targeting DNA transcription, protein translation, and Smad2/3 signaling. Interestingly, TGFβ1 induced Smad2/3 phosphorylation and CTGF mRNA expression, but not collagen mRNA expression, suggesting that TGFβ1 mediates collagen expression through CTGF induction and Smad2/3 activation. In parallel, TGFβ1 and CTGF also induced expression of heat shock protein (HSP) 47, a protein required for the synthesis of several types of collagens. However, only CTGF siRNA knockdown, could compromise TGFβ1-induced collagen expression. Finally, the immunohistochemistry revealed vimentin- and α-SMA-positive staining for (myo)fibroblasts, TGFβ1, collagen, and CTGF in the subepithelial stroma region of human adenomyotic endometria. CONCLUSION AND IMPLICATIONS:We reveal here that TGFβ1, collagen, and CTGF are expressed in the stroma of adenomyotic endometria and demonstrate that TGFβ1 can induce collagen production in endometrium-derived fibroblasts through cellular Smad2/3-dependent signaling pathway and CTGF expression, suggesting that endometrial TGFβ may take part in the pathogenesis of adenomyosis and ectopic endometrium may participate in uterine adenomyosis.

Background/Aims: The chemokine CXCL1 has been reported to be expressed in lung airway epithelium and non-small cell lung cancer biopsy specimens. In this study, we investigated the effects of TNF-α, an abundant cytokine detected in inflammation and various cancers, on CXCL1 release by human A549 lung carcinoma epithelial cells. Methods: CXCL1 expression was determined by ELISA and RT-PCR. TNF-α signaling was examined by western blotting. Monocyte migration was assayed by a Transwell migration system. Results: TNF-α stimulated CXCL1 release and mRNA expression, and this release was inhibited by inhibitors of JNK, p38 MAPK, PI-3K/Akt and AP-1 transcription factor. TNF-α treatment was followed by JNK, p38 MAPK and PI3K/Akt activation. However, only the JNK inhibitor could reduce the CXCL1 mRNA level, suggesting that JNK is required mainly for CXCL1 mRNA synthesis, whereas p38 MAPK and PI-3K/Akt might be responsible for CXCL1 secretion. Dexamethasone (dex) and TGF-β reduced CXCL1 secretion, with dex upregulating the expression of MAP kinase phosphatase-1 and TGF-β causing smad2/3 activation and nuclear translocation. A functional analysis showed that the released CXCL1 enhanced monocyte migration and could be abolished by a CXCL1 neutralizing antibody and CXCR antagonist. Conclusion: We demonstrate that TNF-α induces CXCL1 expression through the JNK, p38 MAPK and PI-3K/Akt signaling pathways in human pulmonary epithelial cells.

To feed the increasing world population, more food needs to be produced from agricultural land systems. Solutions to produce more food with fewer resources while minimizing adverse environmental and ecological consequences require sustainable agricultural land use practices as supplementary to advanced biotechnology and agronomy. This review paper, from a land system perspective, systematically proposed and analyzed three interactive strategies that could possibly raise future food production under global change. By reviewing the current literatures, we suggest that cropland expansion is less possible amid fierce land competition, and it is likely to do less in increasing food production. Moreover, properly allocating crops in space and time is a practical way to ensure food production. Climate change, dietary shifts, and other socio-economic drivers, which would shape the demand and supply side of food systems, should be taken into consideration during the decision-making on rational land management in respect of sustainable crop choice and allocation. And finally, crop-specific agricultural intensification would play a bigger role in raising future food production either by increasing the yield per unit area of individual crops or by increasing the number of crops sown on a particular area of land. Yet, only when it is done sustainably is this a much more effective strategy to maximize food production by closing yield and harvest gaps.

Remote sensing, in particular satellite imagery, has been widely used to map cropland, analyze cropping systems, monitor crop changes, and estimate yield and production. However, although satellite imagery is useful within large scale agriculture applications (such as on a national or provincial scale), it may not supply sufficient information with adequate resolution, accurate geo-referencing, and specialized biological parameters for use in relation to the rapid developments being made in modern agriculture. Information that is more sophisticated and accurate is required to support reliable decision-making, thereby guaranteeing agricultural sustainability and national food security. To achieve this, strong integration of information is needed from multi-sources, multi-sensors, and multi-scales. In this paper, we propose a new framework of satellite, aerial, and ground-integrated (SAGI) agricultural remote sensing for use in comprehensive agricultural monitoring, modeling, and management. The prototypes of SAGI agriculture remote sensing are first described, followed by a discussion of the key techniques used in joint data processing, image sequence registration and data assimilation. Finally, the possible applications of the SAGI system in supporting national food security are discussed.

For the scientific management of farmland, it is significant to understand the spatio-temporal variability of soil organic matter and to study the influences of related factors. Using geostatistical theory, GIS spatial analysis, trend analysis and a Geographically Weighted Regression (GWR) model, this study analyzed the response of soil organic matter to climate and socio-economic factors in central Heilongjiang Province during the past 25 years. Second soil survey data of China for 1979–1985, 2005 field sampling data, climate observations and socio-economic data for 1980–2005 were analyzed. First, soil organic matter in 2005 was spatially interpolated using the Co-Kriging method along with auxiliary data sets of soil type and pH. The spatio-temporal variability was then studied by comparison with the 1980s second soil census data. Next, the temporal trends in climate and socio-economic factors over the past 25 years were investigated. Finally, we examined the variation of the response of soil organic matter to climate and socio-economic factors using the GWR model spatially and temporally. The model showed that 53.82% area of the organic matter content remained constant and 29.39% has decreased during the past 25 years. The impact of precipitation on organic matter content is mainly negative, with increasing absolute values of the regression coefficient. The absolute value of regression coefficient of annual average temperature has decreased, and more areas are now under its negative effects. In addition, the areas of positive regression coefficient of annual sunshine hours have northward shifted, with the increasing absolute value of positive coefficient and decreasing absolute value of negative coefficient. The areas of positive regression coefficient of mechanized farming as a socio-economic factor have westward shifted, with the increasing absolute value of negative coefficient and decreasing absolute value of positive coefficient. The area of regions with the positive regression coefficient of irrigation has expanded. The regions with positive regression coefficient of fertilizer use have shrinked. The positive regression coefficient of mulch film consumption has significantly increased. The regression coefficient of pesticide consumption was mainly positive in the west of the study area, while it was negative to the east. Generally, GWR model is capable to investigate the influence of both climatic and socio-economic factors, avoided the insufficiency of other research based on the single perspective of climatic or socio-economic factors. Therefore, we can conclude that GWR model could provide methodological support for global change research and serve as basic reference for cultivated land quality improvement and agricultural decision making.