Accurate estimation of regional and global patterns of ecosystem respiration (ER) is crucial to improve the understanding of terrestrial carbon cycles and the predictive ability of the global carbon ...budget. However, large uncertainties still exist in regional and global ER estimation due to the drawbacks of modeling methods. Based on eddy covariance ER data from 132 sites in China from 2002 to 2020, we established Intelligent Random Forest (IRF) models that integrated ecological understanding with machine learning techniques to estimate ER. The results showed that the IRF models performed better than semiempirical models and machine learning algorithms. The observed data revealed that gross primary productivity (GPP), living plant biomass, and soil organic carbon (SOC) were of great importance in controlling the spatiotemporal variability of ER across China. An optimal model governed by annual GPP, living plant biomass, SOC, and air temperature (IRF‐04 model) matched 93% of the spatiotemporal variation in site‐level ER, and was adopted to evaluate the spatiotemporal pattern of ER in China. Using the optimal model, we obtained that the annual value of ER in China ranged from 5.05 to 5.84 Pg C yr−1 between 2000 and 2020, with an average value of 5.53 ± 0.22 Pg C yr−1. In this study, we suggest that future models should integrate process‐based and data‐driven approaches for understanding and evaluating regional and global carbon budgets.
Plain Language Summary
With China already committing to achieve carbon neutrality before 2060, an accurate assessment of land carbon sink and its flux rate in China is an increasingly important area in global change ecology. In this essay, a high‐efficiency and accurate simulation method was introduced in this field; This method is particularly useful in the assessment of carbon sink and its flux rate in China by combining with reliable observation flux data. Using this new method, a reliable and reasonable value of carbon flux (ecosystem respiration) was obtained. Meanwhile, that method provides a better understanding of the mechanism governing the spatiotemporal variability of carbon flux. Therefore, this present study has gone some way toward enhancing our understanding of a comprehensive assessment and analysis of land carbon sink in China.
Key Points
A model integrating ecological knowledge and machine learning was established to estimate ecosystem respiration (ER) in China
The spatiotemporal patterns of ER are significantly affected by productivity, plant biomass, soil organic carbon, and air temperature
China's ER was estimated to be 5.53 ± 0.22 petagrams of carbon per year (Pg C yr−1) on average for the years 2000–2020
Single-cell RNA-seq (scRNA-seq) is being used widely to resolve cellular heterogeneity. With the rapid accumulation of public scRNA-seq data, an effective and efficient cell-querying method is ...critical for the utilization of the existing annotations to curate newly sequenced cells. Such a querying method should be based on an accurate cell-to-cell similarity measure, and capable of handling batch effects properly. Herein, we present Cell BLAST, an accurate and robust cell-querying method built on a neural network-based generative model and a customized cell-to-cell similarity metric. Through extensive benchmarks and case studies, we demonstrate the effectiveness of Cell BLAST in annotating discrete cell types and continuous cell differentiation potential, as well as identifying novel cell types. Powered by a well-curated reference database and a user-friendly Web server, Cell BLAST provides the one-stop solution for real-world scRNA-seq cell querying and annotation.
Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC ...progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed. Perineural invasion was associated with impaired immune responses characterized by decreased CD8
T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe perineural invasion. Acetylcholine impaired the ability of PDAC cells to recruit CD8
T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFNγ production by CD8
T cells in a dose-dependent manner and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T-cell response in an orthotopic PDAC model. Conversely, blocking perineural invasion with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8
T cells, an elevated Th1/Th2 ratio, and improved survival. In conclusion, perineural invasion-triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8
T-cell infiltration and a reduced Th1/Th2 ratio. SIGNIFICANCE: These findings provide a promising therapeutic strategy to modulate the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma with severe perineural invasion.
• Root hair development is crucial for phosphate absorption, but how phosphorus deficiency affects root hair initiation and elongation remains unclear.
• We demonstrated the roles of auxin efflux ...carrier PIN-FORMED2 (PIN2) and phospholipase D (PLD)-derived phosphatidic acid (PA), a key signaling molecule, in promoting root hair development in Arabidopsis thaliana under a low phosphate (LP) condition.
• Root hair elongation under LP conditions was greatly suppressed in pin2 mutant or under treatment with a PLDζ2-specific inhibitor, revealing that PIN2 and polar auxin transport and PLDζ2-PA are crucial in LP responses. PIN2 was accumulated and degraded in the vacuole under a normal phosphate (NP) condition, whereas its vacuolar accumulation was suppressed under the LP or NP plus PA conditions. Vacuolar accumulation of PIN2 was increased in pldζ2 mutants under LP conditions. Increased or decreased PIN2 vacuolar accumulation is not observed in sorting nexin1 (snx1) mutant, indicating that vacuolar accumulation of PIN2 is mediated by SNX1 and the relevant trafficking process. PA binds to SNX1 and promotes its accumulation at the plasma membrane, especially under LP conditions, and hence promotes root hair development by suppressing the vacuolar degradation of PIN2.
• We uncovered a link between PLD-derived PA and SNX1-dependent vacuolar degradation of PIN2 in regulating root hair development under phosphorus deficiency.
Brassinosteroids (BRs) play essential roles in modulating plant growth, development and stress responses. Here, involvement of BRs in plant systemic resistance to virus was studied. Treatment of ...local leaves in Nicotiana benthamiana with BRs induced virus resistance in upper untreated leaves, accompanied by accumulations of H₂O₂ and NO. Scavenging of H₂O₂ or NO in upper leaves blocked BR‐induced systemic virus resistance. BR‐induced systemic H₂O₂ accumulation was blocked by local pharmacological inhibition of NADPH oxidase or silencing of respiratory burst oxidase homolog gene NbRBOHB, but not by systemic NADPH oxidase inhibition or NbRBOHA silencing. Silencing of the nitrite‐dependent nitrate reductase gene NbNR or systemic pharmacological inhibition of NR compromised BR‐triggered systemic NO accumulation, while local inhibition of NR, silencing of NbNOA1 and inhibition of NOS had little effect. Moreover, we provide evidence that BR‐activated H₂O₂ is required for NO synthesis. Pharmacological scavenging or genetic inhibiting of H₂O₂ generation blocked BR‐induced systemic NO production, but BR‐induced H₂O₂ production was not sensitive to NO scavengers or silencing of NbNR. Systemically applied sodium nitroprusside rescued BR‐induced systemic virus defense in NbRBOHB‐silenced plants, but H₂O₂ did not reverse the effect of NbNR silencing on BR‐induced systemic virus resistance. Finally, we demonstrate that the receptor kinase BRI1(BR insensitive 1) is an upstream component in BR‐mediated systemic defense signaling, as silencing of NbBRI1 compromised the BR‐induced H₂O₂ and NO production associated with systemic virus resistance. Together, our pharmacological and genetic data suggest the existence of a signaling pathway leading to BR‐mediated systemic virus resistance that involves local Respiratory Burst Oxidase Homolog B (RBOHB)‐dependent H₂O₂ production and subsequent systemic NR‐dependent NO generation.
Lung cancer, the leading cause of cancer deaths worldwide, is characterized with malignant cell growth. Advances in next-generation sequencing has helped us further understand RNA and identify novel ...circular RNAs (circRNAs) that may be useful in the early diagnosis and treatment of lung cancer. Similar to other noncoding RNAs, circRNAs present diverse biological functions in normal and disease states, including various types of cancers. This review focuses mainly on the poorly understood functions of circRNA in lung cancer. This paper also summarizes the recent advances in circRNA biogenesis, analyzes the role of circRNAs in cancers, and discusses the potential mechanisms of circRNAs in lung cancer.
•Classification and underlying mechanisms of circRNA formation.•CircRNA profiles, their cellular effects and corresponding mechanisms in lung cancer.•Possible mechanisms of circRNAs in lung cancer.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus responsible for the ongoing COVID-19 pandemic. SARS-CoV-2 binds to the human cell receptor angiotensin-converting ...enzyme 2 (ACE2) through its receptor-binding domain in the S1 subunit of the spike protein (S1-RBD). The serum levels of autoantibodies against ACE2 are significantly higher in patients with COVID-19 than in controls and are associated with disease severity. However, the mechanisms through which these anti-ACE2 antibodies are induced during SARS-CoV-2 infection are unclear. In this study, we confirmed the increase in antibodies against ACE2 in patients with COVID-19 and found a positive correlation between the amounts of antibodies against ACE2 and S1-RBD. Moreover, antibody binding to ACE2 was significantly decreased in the sera of some COVID-19 patients after preadsorption of the sera with S1-RBD, which indicated that antibodies against S1-RBD can cross-react with ACE2. To confirm this possibility, two monoclonal antibodies (mAbs 127 and 150) which could bind to both S1-RBD and ACE2 were isolated from S1-RBD-immunized mice. Measurement of the binding affinities by Biacore showed these two mAbs bind to ACE2 much weaker than binding to S1-RBD. Epitope mapping using synthetic overlapping peptides and hydrogen deuterium exchange mass spectrometry (HDX-MS) revealed that the amino acid residues P463, F464, E465, R466, D467 and E471 of S1-RBD are critical for the recognition by mAbs 127 and 150. In addition, Western blotting analysis showed that these mAbs could recognize ACE2 only in native but not denatured form, indicating the ACE2 epitopes recognized by these mAbs were conformation-dependent. The protein-protein interaction between ACE2 and the higher affinity mAb 127 was analyzed by HDX-MS and visualized by negative-stain transmission electron microscopy imaging combined with antigen-antibody docking. Together, our results suggest that ACE2-cross-reactive anti-S1-RBD antibodies can be induced during SARS-CoV-2 infection due to potential antigenic cross-reactivity between S1-RBD and its receptor ACE2.
Dye-doped nematic liquid crystal refilled gradient-pitched enantiomorphic cholesteric liquid crystal polymer templates are demonstrated. The enantiomorphic device has high reflectivity and wide ...spectral tunability throughout the entire visible region. This device can also provide low threshold lasing emission with both right- and left-circular polarizations from the blue to the red region.
Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple‐negative breast cancer (TNBC). Epithelial–mesenchymal transition (EMT) is thought to contribute to ...chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal‐like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA‐MB‐231 cells gradually increases in a time‐dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatin‐resistant MDA‐MB‐231 cells are significantly higher than wild‐type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC.
What's new?
Epithelial‐mesenchymal transition (EMT) likely contributes to chemoresistance in triple‐negative breast cancers (TNBC), but the underlying mechanisms remain unclear. Here, the expression of Notch1 positively associated with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples. High expression of Notch1 and MCAM predicted poor survival, particularly in patients treated with chemotherapy. Notch1 and MCAM levels were significantly higher in cisplatin‐resistant than wild‐type TNBC cells. The findings suggest that Notch1 regulates MCAM in EMT and contributes to cisplatin resistance in TNBC. Targeting the Notch1/MCAM axis might be a potential avenue to enhance therapeutic efficacy in patients with TNBC.
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