Publications by authors named "Kai Wang"

4,840 Publications

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Association Between Dopaminergic Medications and the Evolution of REM Sleep Behavior Disorder in Parkinson's Disease.

Front Neurol 2022 10;13:880583. Epub 2022 Jun 10.

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

REM sleep behavior disorder (RBD) is closely associated with Parkinson's disease (PD), however, the influence of dopaminergic replacement therapy (DRT) on the clinical course of RBD in PD remains less understood. The objective of our study is to investigate how DRTs modify the evolution of RBD in a longitudinal cohort study of initially PD patients. Four hundred and five drug-naive patients with early-stage PD were included. RBD symptoms were assessed using the 10-item RBD Screening Questionnaire (RBDSQ) at baseline and during the 5-year follow-up. A generalized estimating equation was used to examine predictors of the evolution of RBD symptoms. For patients without baseline pRBD, patients on levodopa treatment showed a greater increase in RBDSQ scores than those not on levodopa treatment, and the increase in RBDSQ scores was significantly correlated with the levodopa-LEDD. Moreover, the changes in RBDSQ scores at a given post-baseline visit were significantly associated with the use of levodopa (OR = 1.875, = 0.008) and the combined use of levodopa and DA (OR = 2.188, = 0.012), as well as the levodopa-LEDD (OR = 1.001, = 0.005) at that visit. The use of DA alone or the DA-LEDD was not a significant predictor of changes in RBDSQ scores. Similarly, a conversion from pRBD negative to pRBD positive was significantly associated with levodopa-LEDD (OR = 1.001, = 0.014) but not DA-LEDD. Together, these finding implicated that the use of levodopa may act as a contributing factor to the increasing prevalence of RBD after the onset of PD, suggesting different mechanisms underlying prodromal RBD and late-onset RBD.
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http://dx.doi.org/10.3389/fneur.2022.880583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226298PMC
June 2022

Acute toxicity of broflanilide on neurosecretory system and locomotory behavior of zebrafish (Danio rerio).

Chemosphere 2022 Jun 22:135426. Epub 2022 Jun 22.

Plant Protection College, Shenyang Agricultural University, Shenyang, China. Electronic address:

Broflanilide, a novel meta-diamide insecticide, possesses moderate acute toxicity to zebrafish, with a 96-h median lethal concentration (96-LC) of 0.76 mg/L. However, its effect on fish behavior and the underlying mechanisms are still unclear. The present study evaluated the effects of broflanilide on the zebrafish brain over a 96-h exposure by comparing the histopathological changes and relative expression of targeted genes with the behavioral metrics. The results of the toxicity test showed that broflanilide could cause deformities, such as deformation of the operculum and spinal curvature, at 0.6, 0.82 and 1.15 mg/L. Results also showed tissue damage and apoptosis in the cerebellum under 0.27 and 0.6 mg/L exposure. Additionally, broflanilide affected the neurotransmitters, metabolites and transcripts of genes associated with dopamine, gamma-aminobutyric acid expression. and the signaling pathways in zebrafish brains at 0.60 mg/L after 1 h and 96 h of exposure, while the levels of glutamate, glutamate decarboxylase, GABA transaminase, nicotinamide adenine dinucleotide (NADH) and adenosine triphosphate (ATP) were also inhibited at 0.27 mg/L after 96 h of exposure. The accumulated swimming distance was significantly longer and the average speed was significantly faster than the control at 0.27 and 0.6 mg/L after 1-h of exposure, while these metrics were lowered at 0.6 mg/L after 96 h of exposure. The study results demonstrates that broflanilide affects the zebrafish brain, neurotransmitters and associated fish behaviors. This study also provides deeper insight into the mechanistic understanding of the effects of broflanilide on the zebrafish brain.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135426DOI Listing
June 2022

Exploring the risk factors of COVID-19 Delta variant in the USA based on Bayesian spatio-temporal analysis.

Transbound Emerg Dis 2022 Jun 25. Epub 2022 Jun 25.

Center for Applied Statistics, School of Statistics, Renmin University of China, Beijing, 100872, China.

The transmission of COVID-19 epidemic is a global emergency which is worsened by the genetic mutations of SARS-CoV-2. However, till date, few statistical studies have researched the COVID-19 spread patterns in terms of the variant cases. Hence, this paper aims to explore the associated risk factors of Delta variant, the most contagious strain of COVID-19. The study collected the state-level COVID-19 Delta variant cases in the United States during a 12-week period and included potential environmental, socioeconomic and public prevention factors as independent variables. Instead of regarding the covariate effects as constant, this paper proposes a flexible Bayesian hierarchical model with spatio-temporally varying coefficients to account for data heterogeneity. The method enables us to cluster the states into distinctive groups based on the temporal trends of the coefficients and simultaneously identify significant risk factors for each cluster. The findings contribute novel insight into the dynamics of covariate effects on the COVID-19 Delta variant over space and time, which could help the government develop targeted prevention measures for vulnerable regions based on the selected risk factors. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/tbed.14623DOI Listing
June 2022

The telomere-to-telomere gap-free genome of four rice parents reveals SV and PAV patterns in hybrid rice breeding.

Plant Biotechnol J 2022 Jun 24. Epub 2022 Jun 24.

School of Advanced Agriculture Sciences and School of Life Sciences, State Key Laboratory of Protein and Plant Gene Research, Peking University, Beijing, 100871, China.

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http://dx.doi.org/10.1111/pbi.13880DOI Listing
June 2022

Distinguishing the respective determining factors for spectral broadening and concentration quenching in multiple resonance type TADF emitter systems.

Mater Horiz 2022 Jun 24. Epub 2022 Jun 24.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Joint International Research Laboratory of Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, P. R. China.

Multiple resonance (MR) type thermally activated delayed fluorescence (TADF) emitters have attracted much recent attention due to their narrow emission spectra and high photoluminescence quantum yields (PLQYs). Spectral broadening and concentration quenching at high doping concentrations are two issues currently limiting the development of MR-TADF emitters. However, the origins of these have not been fully clarified so far. In this work, by investigating emitters with the same MR cores but peripheral groups of different steric types, we distinguished that the spectral broadening and concentration quenching are mainly caused by excimer formation and triplet exciton annihilation, respectively. This understanding on aggregated behaviors of MR emitters provides new insight for the further development of high-performance MR-TADF emitters with low concentration sensitivities.
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http://dx.doi.org/10.1039/d2mh00511eDOI Listing
June 2022

Sodium-Based Cylindrical Plasmonic Waveguides in the Near-Infrared.

Nanomaterials (Basel) 2022 Jun 7;12(12). Epub 2022 Jun 7.

Key Laboratory of Infrared Imaging Materials and Detectors, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083, China.

Subwavelength optical field confinement and low-loss propagation are of great significance for compact photonic integration. However, the field confinement capability of plasmonic devices is always accompanied by the inherent Ohmic loss. Although recent studies have shown that sodium (Na) exhibits lower loss than noble metals in the near-infrared band, the field confinement ability has not been adequately assessed. Meanwhile, the high chemical reactivity of Na should be regulated for practical application. Two dielectric-coated Na nanowires, consisting of cylindrical Na nanowires with one or two dielectric layers as claddings, are proposed and investigated in this paper. Based on finite element calculations, we thoroughly study the modal fields and low-loss propagation properties of dielectric-coated Na nanowires. The results demonstrate that Na exhibits lower loss and stronger field confinement than the typical plasmonic material silver. These findings indicate the performance of plasmonic devices can be considerably improved by employing the metal Na compared with devices using noble metals, which may promote the applications in subwavelength photonic devices.
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http://dx.doi.org/10.3390/nano12121950DOI Listing
June 2022

Reinforcement Analysis of an Old Multi-Beam Box Girder Based on a New Embedded Steel Plate (ESP) Strengthening Method.

Materials (Basel) 2022 Jun 20;15(12). Epub 2022 Jun 20.

College of Civil Engineering and Architecture, Zijingang Campus, Zhejiang University, Anzhong Building B718, Yuhangtang Road 866, Hangzhou 310058, China.

Multi-beam box girder bridges have been applied widely throughout the world for many years. However, the cracking of longitudinal joints between the box girders always leads to reflective cracking of the bridge decks during the service period and thus finally affects the safety and durability of the actual bridges. An embedded steel plate (ESP) strengthening method was presented by introducing carbon-A/-B glue to reinforce the longitudinal joints of old multi-beam box girder bridges for this problem. In order to evaluate the feasibility of the proposed method for actual bridges, an old multi-beam box girder bridge was reinforced, and structural parameters including strain, frequency, and deflection were obtained by adopting field tests before and after strengthening. In addition, the corresponding finite element (FE) model of the background bridge was also set up using ANASYS 18.0 to analyze the strengthening process. Analysis results of the actual bridge and FE model indicate that structural stiffness and load lateral transferring performance between the box girders were enhanced after ESP strengthening. Therefore, this proposed strengthening method can be used to improve the mechanical performance of multi-beam box girder bridges and provide reference for such bridge reinforcement.
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http://dx.doi.org/10.3390/ma15124353DOI Listing
June 2022

Optimization of Laser-MAG Hybrid Welding Parameters of Ship Steel Based on Response Surface Methodology.

Materials (Basel) 2022 Jun 18;15(12). Epub 2022 Jun 18.

Beijing Institute of Petrochemical Technology, Beijing 102617, China.

In this paper, the optimization of laser-MAG hybrid welding parameters of 10CrNi3MoV ship steel was developed. Using the Box-Behnken Design (BBD) model in Response Surface Methodology (RSM) and taking laser power, welding speed and welding current as response factors, the design matrix was completed and verified by experiment. The regression model associated with welding parameters was established by measuring the response indices, such as penetration, tensile strength and impact absorption energy. Through the model check, it was found that the accuracy of penetration and tensile strength of the model was high, and the optimized parameters were as follows: laser power (P) = 3700 W, welding speed (V) = 0.8 m/min, wire feeding speed (Vs) = 7 m/min. On the premise of meeting mechanical performance inspection standards, the maximum penetration was 8 mm.
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http://dx.doi.org/10.3390/ma15124328DOI Listing
June 2022

Tubulin TUBB4B Is Involved in Spermatogonia Proliferation and Cell Cycle Processes.

Genes (Basel) 2022 Jun 17;13(6). Epub 2022 Jun 17.

National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

(tubulin β-4b chain) is essential for cell growth and development as a microtubule network protein. Previous studies have shown that TUBB4B affects mouse pronucleus migration, but the gene function has yet to be elucidated. To study TUBB4B-related functions in mouse reproductive development, we designed a single sgRNA in chromosome 2 and generated a knockout spermatogonia cell line of the β-tubulin isoform by the CRISPR/Cas9 system. -KO spermatogonia recognized abnormal lysosomal membranes and cell morphology defects. Compared to control mouse spermatogonia, the proliferation rate was significantly slower and cycling stagnated in the G1/0 population. Although spermatogonia lacking TUBB4B have abnormal divisions, they are not lethal. We detected the mRNA levels of the cell-regulating cyclins , , , , , and the cell growth factors , , and in the spermatogonia of -KO and found that the expressions of , and cell growth factors were significantly reduced. Further analysis revealed that 675 genes were expressed differently after deletion and were enriched in negative regulation of cell population proliferation (GO:0008285), negative regulation of cell cycle G2/M phase transition (GO:1902750), and positive regulation of cell death (GO: 0010942). We also found that there is a common gene Cdkn1a (P21) in these three GO pathways related to cell proliferation and cell cycle, and both quantitative analysis and transcriptome sequencing results showed that the expression of this gene was up-regulated in knockout cells. This implies that may be involved in the division of spermatogonia with multiple cell cycle regulatory proteins. Overall, these data indicate that has a specific role in regulating spermatogonia proliferation and cell cycle.
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http://dx.doi.org/10.3390/genes13061082DOI Listing
June 2022

The Effect of Non-Invasive Brain Stimulation on the Downregulation of Negative Emotions: A Meta-Analysis.

Brain Sci 2022 Jun 15;12(6). Epub 2022 Jun 15.

The School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei 230032, China.

(1) Background: Emotion regulation (ER) is regarded as a core treatment target for depression and other mental illnesses. In recent years, non-invasive brain stimulation (NIBS) has been extensively used as an intervention for mental illnesses, but there has been no systematic review conducted regarding its effect on emotion regulation. Therefore, we conducted a meta-analysis of the effectiveness of NIBS for emotion regulation; (2) Methods: Systematic searches were conducted in Embase, Web of Science, PubMed, and Cochrane Library. We analyzed the effects of NIBS on tasks assessing emotion regulation using a random-effects model, and further explored the moderating role of the following factors on transcranial direct current stimulation (tDCS) studies by conducting subgroup analyses and meta-regression: target electrode placement, return electrode placement, current intensity, target electrode size, and duration of intervention; (3) Results: A total of 17 studies were included. Our meta-analysis indicated a small but significant effect of NIBS on the downregulation of negative emotions. Separate analyses indicated that repetitive transcranial magnetic stimulation (rTMS) had a medium and significant effect on the downregulation of negative emotions, whereas tDCS had no significant effect. Subgroup analyses showed that the effect of tDCS was moderated by target and return electrode placemen; (4) Conclusions: These results indicate that NIBS had a positive effect on the downregulation of negative emotions. The stimulation protocols should be carefully considered and the underlying mechanisms should be further explored.
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http://dx.doi.org/10.3390/brainsci12060786DOI Listing
June 2022

National emissions inventory and future trends in greenhouse gases and other air pollutants from civil airports in China.

Environ Sci Pollut Res Int 2022 Jun 23. Epub 2022 Jun 23.

Key Laboratory of Beijing On Regional Air Pollution Control, Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, China.

Civil aviation is an important source of air pollutants, but this field has received insufficient attention in China. Based on the standard emissions model of the International Civil Aviation Organization (ICAO) and actual flight information from 241 airports, this study estimated a comprehensive emissions inventory for 2010-2020 by considering the impacts of mixing layer height. The results showed that annual pollutant emissions rapidly trended upward along with population and economic growth; however, the emissions decreased owing to the impacts of the COVID-19 pandemic. In 2020, the emissions of carbon monoxide (CO), nitrogen oxides (NO), particulate matter (PM), methane (CH), nitrous oxide (NO), carbon dioxide (CO), and water vapor (HO) were 34.34, 65.73, 0.10, 0.34, 0.40, 14,706.26, and 5733.11 Gg, respectively. The emissions of total volatile organic compounds (VOCs) from China's civil airports in 2020 were estimated at 17.20 Gg; the major components were formic acid (1.70 Gg), acetic acid (1.62 Gg), 1-butylene (1.03 Gg), acetone (0.96 Gg), and acetaldehyde (0.93 Gg). The distribution of pollutant emissions was consistent with the level of economic development, mainly in Beijing, Guangzhou, and Shanghai. In addition, we estimated future pollution trends for the aviation industry under four scenarios. Under the comprehensive scenario, which considered the impacts of economic growth, passenger turnover, cargo turnover, COVID-19, and technological efficiency, the levels of typical pollutants were expected to increase by nearly 1.51-fold from 2010 to 2035.
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http://dx.doi.org/10.1007/s11356-022-21425-1DOI Listing
June 2022

TSPO knockdown attenuates OGD/R-induced neuroinflammation and neural apoptosis by decreasing NLRP3 inflammasome activity through PPARγ pathway.

Brain Res Bull 2022 Jun 20;187:1-10. Epub 2022 Jun 20.

Department of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, Jiangsu, China. Electronic address:

Ischemic stroke is a cerebrovascular disease which is related to brain function loss induced by cerebral ischemia. Translocator protein (TSPO) is an important regulator in inflammatory diseases, while its role in ischemic stroke remains largely unknown. This research aimed to explore the role and action mechanism of TSPO in oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuron cell damage. The differentially expressed genes in ischemic stroke were predicted using GSE140275 dataset, DisGeNet, and GeneCards databases. Differentiated SH-SY5Y cells and primary neurons were subjected to transfection, and stimulated with OGD/R or MCC950 (NLRP3 inhibitor). Proteins were detected by western blotting and ELISA. Cell apoptosis was evaluated through CCK-8, caspase-3 activity and TUNEL assays. TSPO was upregulated in ischemic stroke and in SH-SY5Y cells and primary neurons after OGD/R treatment. TSPO silencing attenuated OGD/R-induced inflammation and apoptosis by decreasing NLRP3 inflammasome activity. TSPO downregulation increased PPARγ expression and decreased HMGB1 expression in OGD/R-treated cells, which was reversed by silencing PPARγ. PPARγ knockdown abolished the effect of TSPO silence on NLRP3 inflammasome activity, inflammation, and cell apoptosis in OGD/R-treated cells, while PPARγ overexpression alleviated OGD/R-induced injury in SH-SY5Y cells. In conclusion, TSPO knockdown attenuates neuroinflammation and neural apoptosis by decreasing NLRP3 inflammasome activity through PPARγ pathway.
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http://dx.doi.org/10.1016/j.brainresbull.2022.06.009DOI Listing
June 2022

Impact of allograft types on outcomes after pediatric liver transplantation due to biliary atresia.

Pediatr Transplant 2022 Jun 23:e14342. Epub 2022 Jun 23.

Department of Pediatric transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China.

Background: Several surgical strategies, including split donor transplantation and living donor transplantation, have been used to increase the donor liver pool. This report focuses on the effects of whole, split, and LDLT on recipient outcomes.

Methods: We retrospectively analyzed the records of all patients with biliary atresia at Tianjin First Central Hospital between April 2013 and December 2019.

Results: A total of 882 patients were included and divided into three groups by graft type, with 198 in the whole-liver-transplantation group, 78 in the split liver transplantation group, and 606 in the LDLT group. The median follow-up time was 39 months, patient survival rates of three groups were 94.4%, 88.5%, and 95.0%, respectively, and graft survival rates were 90.2%, 83.3%, and 94.7%, respectively. We divided the split liver transplantation group into two subgroups according to the donor's age, and patient survival rates exhibited a significant difference only in the group whose donor age was over 45 years. The postoperative complication rates were significantly higher with respect to hepatic artery thrombosis, portal stenosis, and AR; and lower in hepatic venous stenosis, PTLDs, CMV virus, and EBV infection in the WLT group. Our multivariate model showed that donor age ≥45 years, RBC transfusion, pneumonia, and HAT were the independent predictors of allograft loss.

Conclusions: The survival of split liver transplantation group was slightly lower. The types of complications are different from different graft types. Therefore, postoperative monitoring and treatment need to be adjusted according to the different graft types used.
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http://dx.doi.org/10.1111/petr.14342DOI Listing
June 2022

Genome sequence of Gossypium anomalum facilitates interspecific introgression breeding.

Plant Commun 2022 Jun 22:100350. Epub 2022 Jun 22.

Key Laboratory of Cotton and Rapeseed (Nanjing), Ministry of Agriculture and Rural Affairs, the Institute of Industrial Crops, Jiangsu Academy of Agricultural Sciences, Nanjing, China. Electronic address:

Crop wild relatives are an important reservoir of natural biodiversity. However, incorporating wild genetic diversity into breeding programs is often hampered by reproductive barriers and the lack of accurate genomic information. We assembled a high-quality, centromere accurately-anchored genome of Gossypium anomalum, a stress-tolerant wild cotton species. We provided a strategy to transfer and discover agronomically valuable genes from wild diploid species to tetraploid cotton cultivars. With a bridge parent of (G. hirsutum ×G. anomalum)2 hexaploid, we firstly developed a set of 74 diploid wild cotton species G. anomalum chromosome segment substitution lines (CSSLs) on the G. hirsutum background. This set of CSSLs included 70 homozygous substitutions and four heterozygous substitutions, and collectively contained about 72.22% of the G. anomalum genome. Twenty-four QTLs associated with plant height, yield, and fiber qualities were detected on 15 substitution segments. Integrating the reference genome with agronomic traits evaluation of CSSLs, two G. anomalum genes encoding peroxiredoxin and putative callose synthase 8 respectively conferring drought tolerance and improving fiber strength are readily located and cloned. We have demonstrated the power of a high-quality wild species reference genome in identifying agronomic valuable alleles to facilitate interspecific introgression breeding in crop.
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http://dx.doi.org/10.1016/j.xplc.2022.100350DOI Listing
June 2022

Nitric oxide improves regeneration and prevents calcification in bio-hybrid vascular grafts via regulation of vascular stem/progenitor cells.

Cell Rep 2022 Jun;39(12):110981

State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Key Laboratory of Bioactive Materials (Ministry of Education), Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address:

Vascular bypass surgery continues to use autologous grafts and often suffers from a shortage of donor grafts. Decellularized xenografts derived from porcine veins provide a promising candidate because of their abundant availability and low immunogenicity. Unfortunately, transplantation outcomes are far from satisfactory because of insufficient regeneration and adverse pathologic remodeling. Herein, a nitrate-functionalized prosthesis has been incorporated into a decellularized porcine vein graft to fabricate a bio-hybrid vascular graft with local delivery of nitric oxide (NO). Exogenous NO efficiently promotes vascular regeneration and attenuates intimal hyperplasia and vascular calcification in both rabbit and mouse models. The underlying mechanism was investigated using a Sca1 2A-CreER; Rosa-RFP genetic-lineage-tracing mouse model that reveals that Sca1 stem/progenitor cells (SPCs) are major contributors to vascular regeneration and remodeling, and NO plays a critical role in regulating SPC fate. These results support the translational potential of this off-the-shelf vascular graft.
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http://dx.doi.org/10.1016/j.celrep.2022.110981DOI Listing
June 2022

Worsening hearing was associated with higher β-amyloid and tau burden in age-related hearing loss.

Sci Rep 2022 Jun 21;12(1):10493. Epub 2022 Jun 21.

Department of Otorhinolaryngology Head and Neck Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, 41 Xibei street, Ningbo, 315010, Zhejiang, China.

Age-related hearing loss (ARHL) represents the frequently occurring disability that affects the elderly worldwide. The recent evidence has calculated ARHL to be most potential risk factor to predict dementia. β-amyloid plaques and tau accumulation in brain are hallmarks pathologic feature of Alzheimer's disease (AD), which is a leading cause resulting in dementia. However, the potential mechanistic associations between ARHL and dementia remains unknown. We performed the present cross-sectional cohort study by enrolling 72 patients from research on hearing as well as the pathologic hallmarks of AD in brain. The exposure of hearing was measured by either word recognition score or mean pure-tone of the superior ear. The brain β-amyloid and tau standardized uptake value ratio (SUVR) were measured by positron emission tomography (PET). The covariates included gender, age, cardiovascular disease, education and hearing aid use. To analyze the association between hearing and β-amyloid/tau, linear regression was used and adjusted for potentially confounding covariates. Our data showed that the mean age was 67.1 ± 2.9 years. After adjusted for all the covariates, SUVR of β-amyloid showed an increase of 0.028 [95% confidence interval (CI) 0.004-0.061; P = 0.026], while that of tau exhibited an increase of 0.026 (95% CI 0.003-0.056; P = 0.033) per mean pure-tone increase by 10 dB (worsening). Likewise, per mean word-recognition score increase by 10%, the SUVR of β-amyloid showed an increase of 0.060 (95% CI 0.008-0.113; P = 0.023), while that of tau exhibited an increase of 0.059 (95% CI 0.009-0.111; P = 0.031). Taken together, our data demonstrates that hearing worsening was related to the increased burdens of β-amyloid as well as tau detected by PET, which were the AD pathological markers.
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http://dx.doi.org/10.1038/s41598-022-14466-6DOI Listing
June 2022

Efficacy and safety of befotertinib (D-0316) in patients with EGFR T790M mutated non-small cell lung cancer that had progressed after prior EGFR TKI therapy: A phase 2, multicenter, single-arm, open-label study.

J Thorac Oncol 2022 Jun 17. Epub 2022 Jun 17.

Department of Medical Oncology/Chemotherapy, The First Affiliated Hospital of University of Science and Technology of China, Anhui Provincial Hospital, Hefei, China.

Introduction: Befotertinib (D-0316) is a novel, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy.

Methods: This was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression following prior first- or second- generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156.

Results: A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data-cutoff (August 15, 2021), IRC-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. Investigator-assessed disease control rate was 93.2% (95% CI: 88.4%-96.4%) in cohort A and 94.8% (95% CI: 91.6%-97.1%) in cohort B. Investigator-assessed intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A and 57.1% (95% CI: 34.0%-78.2%) in cohort B. The median investigator-assessed progression-free survival (PFS) was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median investigator-assessed intracranial PFS was 16.5 (95% CI: 8.6-not evaluable [NE]) months in cohort A and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A, and in 29.3% and 10.0% of patients in cohort B, respectively.

Conclusion: Befotertinib of 75-100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second- generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).
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http://dx.doi.org/10.1016/j.jtho.2022.06.002DOI Listing
June 2022

7-Methylxanthine Influences the Behavior of ADORA2A-DRD2 Heterodimers in Human Retinal Pigment Epithelial Cells.

Ophthalmic Res 2022 Jun 20. Epub 2022 Jun 20.

Introduction: The goal of this study was to investigate the presence of ADORA2A-DRD2 heterodimers in human RPE cells; determine if 7-methylxanthine (7-MX), a non-selective adenosine receptor antagonist which was used to control myopia progression can influence the behavior of retinal pigment epithelial (RPE) cells through the ADORA2A-DRD2 receptor pathway, and assess the changes in the expression of signaling molecules during cellular signal transduction.

Methods: Human RPE cells were cultured in vitro in the presence or absence of 7-MX. Cell proliferation was evaluated with the CCK-8 assay. Apoptosis and necrosis rates were determined by annexin V-FITC/propidium iodide (PI) staining and flow cytometry. Immunofluorescence and coimmunoprecipitation were used to examine the protein expression and colocalization of ADORA2A and DRD2 in RPE cells. ADORA2A and DRD2 were knocked down with small interfering RNAs (siRNAs). Changes in the protein expression of ERK1/2 and phospho-ERK1/2 (pERK 1/2), which are signaling molecules downstream of dopamine (DA) receptors, were evaluated by western blot analysis.

Results: Immunofluorescence and coimmunoprecipitation showed that ADORA2A and DRD2 were colocalized in RPE cells. The expression of ADORA2A in RPE cells was inhibited by treatment with 50 µmol/l 7-MX for 48 h, and the expression of DRD2, ERK1/2, and pERK1/2 was increased after treatment with 50 µmol/l 7-MX for 48 h. After siRNA-mediated knockdown of DRD2 in RPE cells and further treatment with 50 µmol/l 7-MX for 48 h, the expression of DRD2 was nearly restored to the level observed in the native control. At the experimental concentrations, 7-MX and siRNAs did not affect the proliferation or apoptosis of human RPE cells.

Conclusions: ADORA2A and DRD2 heterodimers were present in RPE cells. 7-MX may affect the behaviors of RPE cells through the ADORA2A-DRD2 receptor pathway. 7-MX is an inhibitor of ADORA2A receptors that can prevent inhibition of the D2 receptor pathway and increase D2 receptor pathway activity. This phenomenon may explain the mechanism of action through which 7-MX can control myopia progression.
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http://dx.doi.org/10.1159/000525563DOI Listing
June 2022

FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1.

Neuro Oncol 2022 Jun 20. Epub 2022 Jun 20.

Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Background: We previously report that yes-associated protein (YAP), the core downstream effector of Hippo pathway, promotes the malignant progression of glioblastoma (GBM). However, although classical regulatory mechanisms of YAP are well explored, how YAP is modulated by the Hippo-independent manner remains poorly understood. Meanwhile, the non-receptor tyrosine kinase Fyn-related kinase (FRK), which exhibits low expression and possesses tumor suppressor effects in GBM, is reported to be involved in regulation of protein phosphorylation. Here, we examined whether FRK could impede tumor progression by modulating YAP activities.

Methods: Human GBM cells and intracranial GBM model were used to assess the effects of FRK and YAP on the malignant biological behaviors of GBM. Immunoblotting and immunohistochemistry were used to detect the expression of core proteins in GBM tissues. Co-immunoprecipitation, proximity ligation assay, luciferase assay and ubiquitination assay were utilized to determine the protein-protein interactions and related molecular mechanisms.

Results: The expression levels of FRK and YAP were inversely correlated with each other in glioma tissues. In addition, FRK promoted the ubiquitination and degradation of YAP, leading to tumor suppression in vitro and in vivo. Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP. Siah1 is required for YAP destabilization initiated by FRK.

Conclusions: We identify a novel mechanism by which FRK orchestrates tumor-suppression effect through phosphorylating YAP and inducing its ubiquitination by Siah1. FRK-Siah1-YAP signaling axis may serve as a potential therapeutic target for GBM treatment.
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http://dx.doi.org/10.1093/neuonc/noac156DOI Listing
June 2022

Nomograms for Predicting the Incidence of Late-Onset Acute Cellular Rejection in Patients After Pediatric Liver Transplantation.

Front Pediatr 2022 3;10:915795. Epub 2022 Jun 3.

Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China.

Background: Late-onset acute cellular rejection (LACR) is a special type of acute rejection (AR) only rarely studied after pediatric liver transplantation (pLT). Our study aimed to explore the influencing factors of LACR after pLT and establish a nomogram to provide an individualized prediction of LACR after pLT.

Materials And Methods: Data from 640 children who underwent pLT at Tianjin First Central Hospital from January 2016 to December 2019 were collected as part of this retrospective study. The nomogram was then established through the results of the multivariable analysis.

Results: Forty-one patients experienced LACR > 1 ≤ 2 years after pLT. Cold ischemia time, donor-specific antibodies (DSAs), and tacrolimus concentration were independent influencing factors, and a nomogram was established with an AUC value of 0.834 (95% confidence interval, 0.755-0.912). Ten-fold cross-validation showed that the accuracy of the nomogram was about 76%. Sixty-three patients experienced LACR > 2 years after pLT. Child-Pugh grade, cold ischemic time, DSAs, early acute cellular rejection, and tacrolimus concentration were independent influencing factors, and a nomogram was established with an AUC value of 0.827 (95% confidence interval, 0.774-0.881). Ten-fold cross-validation showed that the accuracy of the nomogram was about 80.9%.

Conclusion: We established nomograms to predict the incidence of LACR > 1 ≤ 2 and > 2 years after pLT, respectively. The verification results showed that nomograms had good accuracy and clinical practicability.
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http://dx.doi.org/10.3389/fped.2022.915795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203720PMC
June 2022

PrecisionFDA Truth Challenge V2: Calling variants from short and long reads in difficult-to-map regions.

Cell Genom 2022 May 27;2(5). Epub 2022 Apr 27.

The Canadian Center for Computational Genomics (C3G), Montréal, QC, Canada.

The precisionFDA Truth Challenge V2 aimed to assess the state of the art of variant calling in challenging genomic regions. Starting with FASTQs, 20 challenge participants applied their variant-calling pipelines and submitted 64 variant call sets for one or more sequencing technologies (Illumina, PacBio HiFi, and Oxford Nanopore Technologies). Submissions were evaluated following best practices for benchmarking small variants with updated Genome in a Bottle benchmark sets and genome stratifications. Challenge submissions included numerous innovative methods, with graph-based and machine learning methods scoring best for short-read and long-read datasets, respectively. With machine learning approaches, combining multiple sequencing technologies performed particularly well. Recent developments in sequencing and variant calling have enabled benchmarking variants in challenging genomic regions, paving the way for the identification of previously unknown clinically relevant variants.
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http://dx.doi.org/10.1016/j.xgen.2022.100129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205427PMC
May 2022

The Correlation Between Immune Invasion and SARS-COV-2 Entry Protein ADAM17 in Cancer Patients by Bioinformatic Analysis.

Front Immunol 2022 3;13:923516. Epub 2022 Jun 3.

Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China.

SARS-Cov-2 caused the COVID-19 pandemic worldwide. ADAM17 functions as a disintegrin and transmembrane metalloproteinase domain protein involved in the regulation of SARS-CoV-2 receptor ACE2. However, its impact on cancer patients infected with COVID-19 and its correlation with immune cell infiltration is unclear. This study compared ADAM17 expression between normal and tumor tissues based on GEPIA. The correlations between ADAM17 expression and immune cell infiltration and immunomodulators were investigated. Besides, treated drugs for targeting ADAM17 were searched in the TISDB database. We found that ADAM17 was highly conserved in many species and was mainly expressed in lung, brain, female tissues, bone marrow and lymphoid tissues. It was also highly expressed in respiratory epithelial cells of rhinitis and bronchus. ADAM17 expression in tumors was higher than that in several paired normal tissues and was negatively correlated with the prognosis of patients with malignant tumors. Interestingly, ADAM17 expression significantly correlated with immunomodulators and immune cell infiltration in normal and tumor tissues. Moreover, eight small molecules targeting ADAM17 only demonstrate therapeutic significance. These findings imply important implications for ADAM17 in cancer patients infected with COVID-19 and provide new clues for development strategy of anti-COVID-19.
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http://dx.doi.org/10.3389/fimmu.2022.923516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203860PMC
June 2022

Impact of inactivated COVID-19 vaccines on viral shedding in B.1.617.2 (Delta) variant-infected patients.

Sci China Life Sci 2022 Jun 14. Epub 2022 Jun 14.

School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

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http://dx.doi.org/10.1007/s11427-021-2115-7DOI Listing
June 2022

Adherence to a healthy lifestyle in relation to colorectal cancer incidence and all-cause mortality after endoscopic polypectomy: a prospective study in three U.S. cohorts.

Int J Cancer 2022 Jun 18. Epub 2022 Jun 18.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

It remains unknown whether maintenance of a healthy lifestyle after endoscopic polypectomy could still confer benefit for colorectal cancer (CRC) incidence and mortality. In this study, we defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption, and diet (range, 0-5). We used Cox proportional hazards regression to estimate the hazard ratios (HRs) for the associations of healthy lifestyle score and individual lifestyle factors with CRC incidence and all-cause mortality. During a median of 10 years of follow-up of 24668 participants who underwent endoscopic polypectomy, we documented 161 CRC cases and 4857 all-cause deaths. A higher healthy lifestyle score after endoscopic polypectomy was associated with lower risk of CRC and all-cause mortality. Compared to individuals with 0-1 healthy lifestyle factors, those with 2, 3, and 4-5 healthy lifestyle factors had a HR for CRC risk of 0.86 [95% confidence interval (CI), 0.60-1.24], 0.73 (95% CI, 0.47-1.14), and 0.52 (95% CI, 0.27-1.01), respectively (P =0.03). The corresponding HR (95% CI) for all-cause mortality was 0.83 (95% CI, 0.76-0.90), 0.63 (95% CI, 0.56-0.70), and 0.56 (95% CI, 0.48-0.65), respectively (P <0.0001). In the joint analysis of pre- and post-polypectomy periods, patients with a healthy post-polypectomy lifestyle had a lower incidence of CRC regardless of their pre-polypectomy exposure, whereas those with a healthy lifestyle in both periods had a lower mortality than those with an unhealthy lifestyle in either period. In conclusion, adherence to a healthy lifestyle after polypectomy may confer significant benefit for CRC prevention and reduction in all-cause mortality. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.34176DOI Listing
June 2022

Outcome of Split Liver Transplantation from Pediatric Donors Weighing 25 kg or Less.

Liver Transpl 2022 Jun 17. Epub 2022 Jun 17.

Organ Transplantation Center, Tianjin, Tianjin, China.

The lower limit of body weight for "splitable" liver grafts remains unknown. To examine the outcome of split liver transplantation (SLT) from pediatric donors ≤ 25 kg relative to conventional graft type liver transplantation from deceased donors under corresponding conditions, a total of 158 patients who received primary liver transplantation, including 22 SLTs from donors ≤ 25 kg, 46 SLTs from donors > 25 kg, 76 whole liver transplantations (WLTs) and 14 reduced liver transplantations (RLTs) in donors ≤ 25 kg, between January 2018 and December 2019 were included in the study. There was no significant difference in the complications, patient survival and graft survival between each of the latter three groups and SLT ≤ 25 kg group. Pediatric end-stage liver disease (PELD) score was the independent predictor of graft loss (death or retransplantation). Graft weight was the independent predictor of hepatic artery thrombosis (HAT). SLT using well-selected pediatric donors ≤ 25 kg is an effective strategy to increase organ availability, especially for low body weight recipients, compared with conventional graft type from deceased donors under the condition of corresponding donor weight without increasing morbidity and mortality.
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http://dx.doi.org/10.1002/lt.26530DOI Listing
June 2022

Ejiao ameliorates lipopolysaccharide-induced pulmonary inflammation via inhibition of NFκB regulating NLRP3 inflammasome and mitochondrial ROS.

Biomed Pharmacother 2022 Aug 14;152:113275. Epub 2022 Jun 14.

Institute of Energy Metabolism and Health, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

There is no effective treatment for acute lung injury (ALI) at present. Some studies have reported the anti-inflammatory effect of Ejiao, but no study has addressed the underlying action mechanism. In this study, the CCK8 assay displayed Ejiao had a protective effect against LPS-elicited inflammatory lung epithelial Beas 2B cells (LILEB 2B cells). Beas 2B cells treated with LPS and Ejiao were challenged with NFκB inhibitor Bay11-7082 and ROS scavenger N-acetyl cysteine (NAC) alone and in combination. The results of qRT-PCR, Western blotting and fluorescence labeling experiments using Bay11-7082 and NAC demonstrated Ejiao could significantly decrease the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1β related to pyroptosis of LILEB 2B cells. Moreover, Ejiao reduced the production of mitochondrial ROS and reversed the change of mitochondrial membrane potential of LILEB 2B cells. Then, HE staining demonstrated Ejiao had a protective effect against the LPS-elicited ALI mouse model (LAMM). Ejiao also dramatically decreased the cell amount and the overall protein concentration of bronchoalveolar lavage fluid in LAMM. Immunohistochemical staining showed Ejiao remarkably reduced the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1β. The ELISA of IL-1β revealed Ejiao could dose-dependably decrease the concentration of IL-1β in lung tissues, serum and BALF of LAMM. Finally, fluorescence labeling demonstrated Ejiao significantly reduced the mitochondrial ROS generation in the lung tissue of LAMM. This finding may afford a novel strategy for the precaution and therapy of ALI.
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http://dx.doi.org/10.1016/j.biopha.2022.113275DOI Listing
August 2022

PlMYB308 Regulates Flower Senescence by Modulating Ethylene Biosynthesis in Herbaceous Peony.

Front Plant Sci 2022 31;13:872442. Epub 2022 May 31.

College of Landscape Architecture and Arts, Northwest A&F University, Yangling, China.

Herbaceous peony is an important cut-flower plant cultivated worldwide, but its short vase life substantially restricts its economic value. It is well established that endogenous hormones regulate the senescence process, but their molecular mechanism in flower senescence remains unclear. Here, we isolated a MYB transcription factor gene, , from herbaceous peony flowers, based on transcriptome data. Quantitative real-time PCR analysis showed that is strongly up-regulated in senescing petals, and its expression was induced by abscisic acid or ethylene and reduced by gibberellin in petals. Treatment with abscisic acid or ethylene accelerated herbaceous peony petal senescence, and gibberellin delayed the process. silencing delayed peony flower senescence and dramatically increased gibberellin, but reduced ethylene and abscisic acid levels in petals. ectopic overexpression in tobacco accelerated flower senescence and reduced gibberellin, but increased ethylene and abscisic acid accumulation. Correspondingly, five endogenous hormone biosynthetic genes showed variable expression levels in petals after silencing or overexpression. A dual-luciferase assay and yeast one-hybrid analysis showed that PlMYB308 specifically binds the promoter. Moreover, treatment with ethylene and 1-MCP can accelerate silencing-reduced senescence and delay - overexpression-induced senescence. We also found that silencing delayed senescence in herbaceous peony petals. Taken together, our results suggest that the PlMYB308- regulatory checkpoints positively mediate the production of ethylene, and thus contribute to senescence in herbaceous peony flowers.
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http://dx.doi.org/10.3389/fpls.2022.872442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194951PMC
May 2022

High-Definition Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex Modulates the Electroencephalography Rhythmic Activity of Parietal Occipital Lobe in Patients With Chronic Disorders of Consciousness.

Front Hum Neurosci 2022 27;16:889023. Epub 2022 May 27.

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: Disorders of consciousness (DOC) are a spectrum of pathologies affecting one's ability to interact with the external world. At present, High-Definition Transcranial Direct Current Stimulation (HD-tDCS) is used in many patients with DOC as a non-invasive treatment, but electrophysiological research on the effect of HD-tDCS on patients with DOC is limited.

Objectives: To explore how HD-tDCS affects the cerebral cortex and examine the possible electrophysiological mechanisms underlying the effects of HD-tDCS on the cerebral cortex.

Methods: A total of 19 DOC patients were assigned to HD-tDCS stimulation. Each of them underwent 10 anodal HD-tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC) over 5 consecutive days. Coma Recovery Scale-Revision (CRS-R) scores were recorded to evaluate the consciousness level before and after HD-tDCS, while resting-state electroencephalography (EEG) recordings were obtained immediately before and after single and multiple HD-tDCS stimuli. Depending on whether the CRS-R score increased after stimulation, we classified the subjects into responsive (RE) and non-responsive (N-RE) groups and compared the differences in power spectral density (PSD) between the groups in different frequency bands and brain regions, and also examined the relationship between PSD values and CRS-R scores.

Results: For the RE group, the PSD value of the parieto-occipital region increased significantly in the 6-8 Hz frequency band after multiple stimulations by HD-tDCS. After a single stimulation, an increase in PSD was observed at 10-13 and 13-30 Hz. In addition, for all subjects, a positive correlation was observed between the change in PSD value in the parieto-occipital region at 10-13 and 6-8 Hz frequency band and the change in CRS-R score after a single stimulation.

Conclusion: Repeated anodal HD-tDCS of the left DLPFC can improve clinical outcomes in patients with DOC, and HD-tDCS-related increased levels of consciousness were associated with increased parieto-occipital PSD.
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http://dx.doi.org/10.3389/fnhum.2022.889023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196904PMC
May 2022

Beijing Pinggu Childhood Eye Study: The Baseline Refractive Characteristics in 6- to 12-Year-Old Chinese Primary School Students.

Front Public Health 2022 27;10:890261. Epub 2022 May 27.

Children and Adolescent Health, Beijing Center for Disease Prevention and Control, Beijing, China.

Purpose: To report the design and baseline data of a 3-year cohort study in Beijing Pinggu District primary school students in China after COVID-19.

Methods: Noncycloplegic and cycloplegic spherical equivalent refraction (SER) were measured, ocular biometry, including the axial length (AL), anterior chamber depth (ACD) and corneal power (CP), were collected before cycloplegia. Corneal radius (CR), AL-to-CR ratio, and lens power (LP) were calculated.

Results: Among the 4,806 (89.1%) eligible students (51.5% male), the prevalence of emmetropia, myopia, mild hyperopia, and mild-to-high hyperopia was 12.8, 30.8, 53.0, and 3.3% after cycloplegia, respectively. Myopia increased from 2.5% in 6- to 71.6% in 12-year-old students, with 9- and 10-year-olds showing the most prominent increases. The median of cycloplegic SER was 0.50 (IQR = 1.63), and the noncycloplegic SER was -0.38 D (IQR = 1.50), which is more negative than the cycloplegic refraction. The mean AL increased with age, from 22.46 ± 0.70 mm to 24.26 ± 1.07 mm. The ACD increased from 3.38 ± 0.28 mm to 3.70 ± 0.30 mm, and the AL-to-CR ratio increased from 2.91 ± 0.08 to 3.12 ± 0.13 between 6- and 12-year-old students. AL, CR and LP explained the SER variance with of 86.4% after adjusting the age and gender.

Conclusions And Relevance: The myopia prevalence since emergence of COVID-19 rapidly increased from 6- to 12-year primary school Chinese children, especially after 7 years of age. The non-cycloplegia SER overestimated the prevalence of myopia, and the cycloplegic SER is a more accurate and reliable method to assess the prevalence of refractive status.
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http://dx.doi.org/10.3389/fpubh.2022.890261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196872PMC
June 2022

Regional and seasonal partitioning of water and temperature controls on global land carbon uptake variability.

Nat Commun 2022 Jun 16;13(1):3469. Epub 2022 Jun 16.

Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing, 100871, China.

Global fluctuations in annual land carbon uptake (NEE) depend on water and temperature variability, yet debate remains about local and seasonal controls of the global dependences. Here, we quantify regional and seasonal contributions to the correlations of globally-averaged NEE against terrestrial water storage (TWS) and temperature, and respective uncertainties, using three approaches: atmospheric inversions, process-based vegetation models, and data-driven models. The three approaches agree that the tropics contribute over 63% of the global correlations, but differ on the dominant driver of the global NEE, because they disagree on seasonal temperature effects in the Northern Hemisphere (NH, >25°N). In the NH, inversions and process-based models show inter-seasonal compensation of temperature effects, inducing a global TWS dominance supported by observations. Data-driven models show weaker seasonal compensation, thereby estimating a global temperature dominance. We provide a roadmap to fully understand drivers of global NEE and discuss their implications for future carbon-climate feedbacks.
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http://dx.doi.org/10.1038/s41467-022-31175-wDOI Listing
June 2022
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