Visualizing research trends and identifying hotspots of herbal components for treating cardiovascular diseases: A bibliometric analysis from 2000 to 2023.

OBJECTIVE: The objective of this study was to investigate the global research trends in herbal medicine for the treatment of cardiovascular disease (CVD) from 2000 to 2023. A bibliometric approach was employed to analyze international collaborations, knowledge structures, emerging trends, and research frontiers. METHOD: The Web of Science (WOS) core collection was utilized as the database, employing the search formula (((TS = (traditional Chinese medicine)) OR TS = (Chinese herbal medicinal ingredient)) OR TS = (Chinese herbal medicinal constituent)) AND TS = (cardiovascular disease) to conduct the search. The search period spanned from January 1, 2000, to February 14, 2023, and the literature type included articles and reviews. RESULTS: A total of 1478 papers were included in the analysis after searching the WOS database and excluding conference proceedings, news articles, retractions, editorials, and letters. China demonstrated the highest number of publications, followed by the United States and Taiwan (China). The institution with the highest publications was the Chinese Academy of Medical Sciences. China, the United States, and India were the main countries involved in research in this field, and there was significant collaboration among them. The hotspots related to herbal components for treating cardiovascular diseases from 2000 to 2023 included systematic reviews, ischemic reperfusion injury, global burden, type 2 diabetes, and protection. CONCLUSION: This paper provides a reference for the future development of herbal research in cardiovascular aspects by revealing the current status, hotspots, and trends of global herbal research in cardiovascular factors over more than 20 years. Identification of potential collaborators and institutions can assist researchers in exploring new directions for future research and discovering new perspectives for potential collaborations in this field.

Circadian misalignment impairs oligodendrocyte myelination via Bmal1 overexpression leading to anxiety and depression-like behaviors.

Circadian misalignment (CM) caused by shift work can increase the risk of mood impairment. However, the pathological mechanisms underlying these deficits remain unclear. In the present study, we used long-term variable photoperiod (L-VP) in wild-type mice to better simulate real-life shift patterns and study its effects on the prefrontal cortex (PFC) and hippocampus, which are closely related to mood function. The results showed that exposure to L-VP altered the activity/rest rhythms of mice, by eliciting phase delay and decreased amplitude of the rhythms. Mice with CM developed anxiety and depression-like manifestations and the number of mature oligodendrocytes (OL) was reduced in the medial prefrontal cortex and hippocampal CA1 regions. Mood impairment and OL reduction worsened with increased exposure time to L-VP, while normal photoperiod restoration had no effect. Mechanistically, we identified upregulation of Bmal1 in the PFC and hippocampal regions of CM mice at night, when genes related to mature OL and myelination should be highly expressed. CM mice exhibited significant inhibition of the protein kinase B (AKT)/mTOR signaling pathway, which is directly associated to OL differentiation and maturation. Furthermore, we demonstrated in the OL precursor cell line Oli-Neu that overexpression of Bmal1 inhibits AKT/mTOR pathway and reduces the expression of genes OL differentiation. In conclusion, BMAL1 might play a critical role in CM, providing strong research evidence for BMAL1 as a potential target for CM therapy.

FKN secreted by kidney epithelial cells regulates macrophage activation in lupus nephritis via the Hippo signaling pathway.

BACKGROUND: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), and its pathogenesis is not fully understood. Previously, we showed that fractalkine (FKN) expression was positively correlated with the severity of LN. Here, we aimed to study the role of the Hippo signaling pathway (HSP) and its interaction with FKN in LN in an attempt to provide novel strategies for LN treatment. METHODS: In this study, lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-stimulated THP-1 cells were co-cultured with FKN up-regulated or down-regulated kidney epithelial cells Hkb20. FKN-knockout (KO-FKN) mice were used to construct LN model. Flow cytometric analysis, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), pathological staining, Western blot, and immunofluorescence (IF) staining were employed to investigate the role of FKN and its interaction with the Hippo signaling pathway (HSP) in LN. RESULTS: Up-regulation of FKN in kidney epithelial cells was associated with increased macrophage activation. FKN overexpression in kidney epithelial cells suppressed apoptosis, inflammation levels, and M1 polarization of THP-1 cells and inhibited the HSP. Oppositely, FKN knockdown in kidney epithelial cells increased apoptosis, inflammation, and M1 polarization and activated the HSP. HSP inhibitor reversed the effect of FKN knockdown on THP-1 cells. In LN mice, FKN knockout and YAP inhibitor decreased the levels of renal function markers, alleviated kidney injury induced by LN, and inhibited macrophage activation in LN mice. CONCLUSIONS: FKN down-regulation reduced the activation of macrophages in renal tissue and alleviated kidney damage by activating HSP. The regulatory effect of FKN on HSP should be confirmed in patients with LN, and the mechanism of FKN in LN should be further explored.

Identification of key genes as potential diagnostic and therapeutic targets for comorbidity of myasthenia gravis and COVID-19.

Introduction: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Coronavirus disease 2019 (COVID-19) has a significant impact on the health and quality of life of MG patients and may even trigger the onset of MG in some cases. With the worldwide development of the COVID-19 vaccination, several new-onset MG cases and exacerbations following the COVID-19 vaccines have been acknowledged. The potential link between myasthenia gravis (MG) and COVID-19 has prompted the need for further investigation into the underlying molecular mechanism. Methods and results: The differential expression analysis identified six differentially expressed genes (DEGs) shared by myasthenia gravis (MG) and COVID-19, namely SAMD9, PLEK, GZMB, JUNB, NR4A1, and NR1D1. The relationship between the six common genes and immune cells was investigated in the COVID-19 dataset. The predictive value of the shared genes was assessed and a nomogram was constructed using machine learning algorithms. The regulatory miRNAs, transcription factors and small molecular drugs were predicted, and the molecular docking was carried out by AutoDock. Discussion: We have identified six common DEGs of MG and COVID-19 and explored their immunological effects and regulatory mechanisms. The result may provide new insights for further mechanism research.

Harm of circadian misalignment to the hearts of the adolescent wistar rats.

PURPOSE: The purpose of this study was to observe the harm of circadian misalignment (CM), caused by an inverted photoperiod (IP), on the hearts of the adolescent Wistar rats, and to explore the mechanisms leading to harm. METHODS: An IP was used to create a CM model. A total of 174 Wistar rats were randomly divided into circadian alignment (CA) and CM groups (87 rats per group). The different activity rhythms of the two groups of rats were adjusted through different light/dark cycles for 90 days. We recorded the rhythmic activity trajectory and sleep time of the rats. After 90 days of modeling, we performed various analyses (i.e., blood pressure, weight, cardiac ultrasound tests, serological tests, cardiac tissue immunofluorescence, immunohistochemistry, transmission electron microscopy on myocardial mitochondria, western blotting, and quantitative polymerase chain reactions). RESULTS: (1) The IP protocol caused CM in rats. (2) CM rats showed significantly higher blood pressure during the day (resting phase). They also showed significantly higher serum levels of angiotensin II and epinephrine during the day compared to the CA rats. (3) CM caused up-regulation of gene expression of adrenergic receptors α1 (α1-AR) and ß1 (ß1-AR) and down-regulation of the glucocorticoid receptor (Gr) gene expression in rat hearts. It also caused downregulation of Bmal1 expression. In addition, the changes in Bmal1 and Per2 correlated with the changes in ß1-AR and α1-AR. (4) CM had adverse effects on multiple molecular proteins of the heart. (5) CM increased the collagen fibers in the rat heart and increased the destruction of mitochondria. (6) Eventually, CM caused a decrease in the pumping function of the heart and decreased the coronary blood flow rate. CONCLUSIONS: (1) CM significantly affected the cardiac structure and function in the adolescent rats through a variety of mechanisms. (2) CM can regulate the expression of myocardial clock genes, and it is likely to have an impact on the heart through this pathway.

DHA Ameliorates Cognitive Ability, Reduces Amyloid Deposition, and Nerve Fiber Production in Alzheimer's Disease.

Background: The etiology of Alzheimer's disease (AD) is very complex. Docosahexaenoic acid (DHA) is important in cognitive ability and nervous system development. A limited number of studies have evaluated the efficacy of DHA in the treatment of AD. Introduction: We detected neurofibrillary tangles (NFT) in the hippocampus and cortex of transgenic mice brain through silver glycine staining. We determined the activity of neurons by staining Nissl bodies, used liquid NMR to detect metabolites in the brain, and functional magnetic resonance imaging results to observe the connection signal value between brain regions. Materials and Methods: We fed 3-month-old APP/PS1 double transgenic mice with DHA mixed feeds for 4 months to assess the effects of DHA on cognitive ability in AD mice through the Morris water maze and open field tests. To evaluate its effects with AD pathology, continuous feeding was done until the mice reached 9 months of age. Results: Compared to AD mice, escape latency significantly decreased on the fifth day while swimming speed, target quadrant stay time, and the crossing number of platforms increased by varying degrees after DHA treatment. Brain tissue section staining revealed that DHA significantly reduced Aß and nerve fibers in the brain of AD mice. Conclusion: DHA significantly reduced the deposition of Aß in the brain and inhibited the production of nerve fibers, thereby increasing cognitive abilities in AD mice. In addition, DHA suppressed blood lipid levels, and restored uric acid and urea levels, implying that DHA is a potential therapeutic option for early AD.

Lateral Malleolus Reconstruction After Tumor Resection in Children: A Case Report and Literature Review.

BACKGROUND: Pediatric reconstruction of lateral malleolus was necessary and challengeable. Up to now, vascularized fibular was the optimal graft to reconstruct epiphyseal defection. However, the sophisticated microvascular operation has limited the wide application of this technique. CASE PRESENTATION: We present the case of a 9-year-old boy with Ewing sarcoma in left distal fibula. In order to restore the growth capacity, we used reverse-flow vascularized fibular epiphyseal graft with tibialis anterior artery to reconstruct the bone defect after tumor resection with no microvascular anastomosis. More than 4 years after the operation and adjuvant chemotherapy, the patient was free of pain and recurrence, and the function and stability of ankle joint was perfect. Radiology examination revealed satisfied bony union of fibula and normal growth of the fibular head transplant. CONCLUSIONS: The advantage of reverse-flow vascularized fibular epiphyseal graft is requiring no microvascular anastomosis which could not only shorten operating time, but also reduce factitious damage of vessels. This report presented that this technique might be an available option for reconstruction of lateral malleolus in children.

Long-term variable photoperiod exposure impairs the mPFC and induces anxiety and depression-like behavior in male wistar rats.

Long-term shift work can cause circadian misalignment, which has been linked to anxiety and depression. However, the associated pathophysiologic changes have not been described in detail, and the mechanism underlying this association is not fully understood. To address these points, we used a rat model of CM induced by long-term variable photoperiod exposure [L-VP] (ie, for 90 days). We compared the numbers of neurons, astrocytes, and dendritic spines; dendrite morphology; long-term potentiation (LTP), long-term depression (LTD) and paired-pulse ratio (PPR); expression of glutamate receptor [N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)] subunits and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC); and the anxiety and depression behaviors between rats in the circadian misalignment (CM) and circadian alignment (CA, with normal circadian rhythm) groups. The results showed that L-VP reduced the number of neurons and astrocytes in the mPFC and decreased the number of dendritic spines, dendrite complexity, LTP, LTD, PPR, and expression of glutamate receptors (GluR1, GluR2, GluR3, NMDAR2A, and NMDAR2B) and BDNF in the mPFC. L-VP also induced anxiety and depression-like behaviors, as measured by the open field test, elevated plus-maze, sucrose preference test, and forced swim test. These results suggest that CM induces a loss of neurons and astrocytes and synaptic damage in surviving pyramidal cells in the mPFC might be involved in the pathophysiology of anxiety and depression.

Circular RNA-0007059 protects cell viability and reduces inflammation in a nephritis cell model by inhibiting microRNA-1278/SHP-1/STAT3 signaling.

BACKGROUND: Increasing evidence has indicated that circular RNAs (circRNAs) play a role in various diseases. However, the influence of circRNAs in nephritis remains unknown. METHODS: Microarray analysis and RT-qPCR were used to detect the expression of circRNA. Type I IFN were administrated to RMC and HEK293 cells to establish a nephritis cell model. CCK-8, MTT assay, and flow cytometry were used to assess cell proliferation, viability, and apoptosis of cells. Bioinformatics analysis and dual luciferase reporter assay detect the interaction of circ_0007059, miRNA-1278, and SHP-1. Glomerulonephritis was performed in a mouse model by administration of IFNα-expressing adenovirus. IHC staining showed the pathogenic changes. RESULTS: In the present study, the expression of circ_0007059 in type I interferon (IFN)-treated renal mesangial cells (RMCs), lupus nephritis (LN) specimens, and HEK293 cells was downregulated compared with that in normal healthy samples and untreated cells. Circ_0007059 overexpression resulted in increased cell proliferation, cell viability, apoptosis, and inflammation-associated factors (CXCL10, IFIT1, ISG15, and MX1) in RMCs and HEK293 cells. In addition, circ_0007059 overexpression significantly restored cell proliferation and viability and inhibited IFN-induced apoptosis. Further, the increased expression resulted in reduced inflammation and the downregulation of CXCL10, IFIT1, ISG15, and MX1 in RMCs and HEK293 cells. Circ_0007059 serves as a sponge for miR-1278 so that the latter can target the 3'-untranslated region of SHP-1. Overexpressed circ_0007059 inhibited miR-1278 expression and elevated SHP-1 expression, subsequently reducing STAT3 phosphorylation. Meanwhile, miR-1278 was upregulated and SHP-1 was downregulated in LN samples and IFN-treated cells. The restoration of miR-1278 counteracted the effect of circ_0007059 on viability, apoptosis, and inflammation as well as on SHP-1/STAT3 signaling in RMCs and HEK293 cells. We also investigated the role of SHP-1 overexpression in IFN-treated RMCs and HEK293 cells; SHP-1 overexpression resulted in a similar phenotype as that observed with circ_0007059 expression. CONCLUSIONS: The study indicates that circ_0007059 protects RMCs against apoptosis and inflammation during nephritis by attenuating miR-1278/SHP-1/STAT3 signaling.

Effective treatment of anlotinib in giant delayed pulmonary metastasis of osteosarcoma: a case report and literature review.

Tumor relapse and pulmonary metastasis, especially unresectable lesions, are the major cause of poor prognosis of patients with osteosarcoma. Anlotinib, a novel small-molecule tyrosine kinase inhibitor (TKI), has been proved to have desirable anti-tumor effects via blocking VEGFR2 and PDGFRß phosphorylation in several tumors, including non-small cell lung cancer and soft tissue sarcoma. In this study, we presented a case of giant delayed pulmonary metastasis of osteosarcoma which was effectively treated by anlotinib. CT scan of this patient showed a giant neoplasm with the size of 1,366 cm3 in the left lung, clinically diagnosed as pulmonary metastasis of osteosarcoma. Due to refusing to chemotherapy and not eligible for surgery of the giant neoplasm, anlotinib was recommended. As a result, the tumor volume decreased more than 82% during 24-week anlotinib administration, from 1,366 to 247 cm3. Unfortunately, disease progression was observed at 27-week. Although argon-helium cryoablation (AHC) was performed followed by apatinib administration, the patient was dead in 16 weeks after disease progression. The progression-free survival (PFS) and overall survival since anlotinib administration of this patient was 27 weeks and 43 weeks, respectively. The toxicity included hypertension, fatigue and hand-foot skin syndrome in grade 1-2, which were controllable and well tolerated. Meanwhile, immunohistochemical staining showed that the expression of VEGFR2 and PDGFRß was decreased significantly and the whole exon sequencing revealed that c-MYC was duplicated, which was potentially associated with anlotinib resistance. Anlotinib had promising anti-tumor efficiency in the treatment of delayed pulmonary metastatic osteosarcoma. However, the potential mechanism of anlotinib resistance and the subsequent therapy after resistance were still challengeable and needed further investigation.

High-Dose Aluminum Exposure Further Alerts Immune Phenotype in Aplastic Anemia Patients.

This study explored the relationship between immunological status and clinical characteristics of aplastic anemia (AA) patients to plasma aluminum levels, which were increased after constant exposure to high levels of this metal. Sixty-two AA patients (33 cases with high and 29 cases with low or no exposure to aluminum) and 30 healthy controls were selected for this study. Aluminum in human albumin solution was measured by inductivity coupled plasma mass spectrometry. IL-10, IL-12, IL-17, and INF-γ levels were measured by enzyme-linked immunosorbent assay. The distribution of lymphocyte subsets were determined by flow cytometry. The expression levels of immunoglobulins and complement C3 and C4 were also measured. Exposure to high aluminum raised the levels of serum aluminum in AA patients (P < 0.01). The levels of hemoglobin and complement C4 were lower in AA patients with high aluminum exposure (P < 0.05 and < 0.01, respectively). The percentage of CD4+ T cells and the ratio of CD4+/ CD8+T cells in peripheral blood in AA patients with high aluminum exposure were higher compared with control AA patients (P < 0.05 in both cases), while the percentage of CD8+ T cells was significantly lower than that in non-aluminum-exposed AA patients (P < 0.05). Compared with non-aluminum-exposed AA patients, the level of IL-10 in the high aluminum-exposed AA group was significantly higher (P < 0.05 in both cases). The immunological and clinical characteristics of AA patients from regions of high aluminum exposure are different to those in from non-aluminum areas. These results suggest that high aluminum exposure alters the immune system in patients suffering from AA.

Carbon black nanoparticles induce HDAC6-mediated inflammatory responses in 16HBE cells.

Long-term inhalation of carbon black nanoparticles (CBNPs) leads to pulmonary inflammatory diseases. Histone deacetylase 6 (HDAC6) has been identified as an important regulator in the development of inflammatory disorders. However, the direct involvement of HDAC6 in CBNPs-induced pulmonary inflammatory responses remains unclear. To explore whether HDAC6 participates in CBNPs-induced pulmonary inflammation, human bronchial epithelial cell line (16HBE cells) was transfected with HDAC6 small interference RNA (siRNA) and then exposed to CBNPs at concentrations of 0, 25, and 50 µg/ml for 24 h. Intracellular HDAC6 and intraflagellar transport protein 88 (IFT88) mRNA and protein were determined by real-time polymerase chain reaction and Western blot, respectively. The secretions of inflammatory cytokines including interleukin (IL)-8, tumor necrosis factor (TNF)-α, IL-6, and IL-1ß were measured by enzyme-linked immunosorbent assay. CBNPs induced a significant increase in the expressions of IL-8 and IL-6, accompanied by a high level of intracellular HDAC6 mRNA when compared with a blank control group (p < 0.05). However, there were no significant changes in the levels of TNF-α secretion, intracellular HDAC6 and IFT88 protein induced by CBNPs (p > 0.05). The HDAC6 mRNA expression was significantly suppressed in HDAC6 siRNA-transfected cells (p < 0.05). The secretions of IL-8, TNF-α, and IL-6 were significantly less in HDAC6 siRNA-transfected cells than that in normal 16HBE cells with exposure to 25 or 50 µg/ml of CBNPs, but intracellular IFT88 mRNA expression was markedly increased in HDAC6 siRNA-transfected cells when compared with normal 16HBE cells exposed to 50 µg/ml of CBNPs (all p < 0.05). Downregulation of the HDAC6 gene inhibits CBNPs-induced inflammatory responses in bronchial epithelial cells, partially through regulating IFT88 expression. It is suggested that CBNPs may trigger inflammatory responses in bronchial epithelial cells by an HDAC6/IFT88-dependent pathway.

Association between ambient particulate matter exposure and semen quality in Wuhan, China.

BACKGROUND: Health effects of exposure to particulate matter (PM) on male reproductive health remain unclear. Only a limited number of studies have investigated the effects of PM2.5 or PM10 exposure on semen quality, and the results were largely inconsistent. OBJECTIVES: To quantitatively assess the exposure-response association between PM exposure and semen quality in Chinese men who were exposed to a wide concentration range of PM. METHODS: We investigated 1759 men from Wuhan, China, who were partners of women undergoing assisted reproductive technology procedures, and had semen examined at least once between 2013 and 2015. Individual PM2.5 and PM10 exposures during 0-90, 0-9, 10-14 and 70-90days before each semen examination (corresponding to the entire and three key periods of sperm development, respectively) were retrospectively estimated by inverse distance weighting interpolation. Linear mixed models were used to assess exposure-response relations of PM exposure with sperm concentration, count and motility. RESULTS: PM2.5 exposure during 0-90 lag days ranged from 27.3 to 172.4µg/m3. It was linearly and inversely associated with sperm concentration (ß: -0.20; 95% CI: -0.34, -0.07) and count (-0.22; -0.35, -0.08). For the three key exposure periods, only PM2.5 exposure during the 70-90 lag days was significantly associated with sperm concentration (-0.12; -0.22, -0.03) and count (-0.12; -0.21, -0.02). Sensitivity analyses for a subgroup (n=1146) excluding subjects with abnormal sperm concentration, count or motility yielded similar results. Compared with PM2.5, we found generally similar associations for PM10 exposure in relation to sperm concentration and count, except that the associations appeared to be nonlinear with inverted J-shaped relationships. Neither PM2.5 nor PM10 exposure was significantly associated with sperm motility (all p>0.05). CONCLUSIONS: Our results suggest that ambient PM exposure during sperm development adversely affects semen quality, in particular sperm concentration and count.

Global inorganic nitrogen dry deposition inferred from ground- and space-based measurements.

Atmospheric nitrogen (N) dry deposition is an important component in total N deposition. However, uncertainty exists in the assessment of global dry deposition. Here, we develop empirical models for estimating ground N concentrations using NO2 satellite measurements from the Ozone Monitoring Instrument (OMI) and ground measurements from 555 monitoring sites. Global patterns and trends in the fluxes of NO2, HNO3, NH4(+), and NO3(-) were assessed for 2005-2014. Moreover, we estimated global NH3 dry deposition directly using data from 267 monitoring sites. Our results showed that East Asia, the United States, and Europe were important regions of N deposition, and the total annual amount of global inorganic N deposition was 34.26 Tg N. The dry deposition fluxes were low in Africa and South America, but because of their large area, the total amounts in these regions were comparable to those in Europe and North America. In the past decade, the western United States and Eurasia, particularly eastern China, experienced the largest increases in dry deposition, whereas the eastern United States, Western Europe, and Japan experienced clear decreases through control of NOx and NH3 emissions. These findings provide a scientific background for policy-makers and future research into global changes.

Changes in Temperature Sensitivity and Activation Energy of Soil Organic Matter Decomposition in Different Qinghai-Tibet Plateau Grasslands.

Qinghai-Tibet Plateau grasslands are unique geographical regions and store substantial soil organic matter (SOM) in the soil surface, which make them very sensitive to global climate change. Here, we focused on three main grassland types (alpine meadow, steppe, and desert) and conducted a soil incubation experiment at five different temperatures (5, 10, 15, 20, and 25°C) to investigate SOM decomposition rates (R), temperature sensitivity (Q10), and activation energy (Ea). The results showed that grassland type and incubation temperature had significant impact on R (P < 0.001), and the values of R were exponential correlated with incubation temperature in three alpine grasslands. At the same temperature, R was in the following order: alpine meadow > alpinesteppe > alpine desert. The Q10 values differed significantly among different grasslands, and the overall trends were as follows: alpine meadow (1.56 ± 0.09) < alpine steppe (1.88 ± 0.23) < alpine desert (2.39 ± 0.32). Moreover, the Ea values differed significantly across different grassland types (P < 0.001) and increased with increasing incubation time. The exponential negative correlations between Ea and R at 20°C across all grassland types (all Ps < 0.001) indicated that the substrate-quality temperature hypothesis is applicable to the alpine grasslands. Our findings provide new insights for understanding the responses of SOM decomposition and storage to warming scenarios in this Plateau.

Spatial and decadal variations in inorganic nitrogen wet deposition in China induced by human activity.

Atmospheric nitrogen (N) deposition, an important component in the global N cycle, has increased sharply in recent decades in China. Here, we constructed national-scale inorganic N wet deposition (Ndep) patterns in China based on data from 280 observational sites and analysed the effects of anthropogenic sources and precipitation on Ndep. Our results showed that the mean Ndep over China increased approximately 25%, from 11.11 kg ha(-1) a(-1) in the 1990s to 13.87 in the 2000s. Ndep was highest over southern China and exhibited a decreasing gradient from southern to western and northern China. The decadal difference in Ndep between the 1990s and 2000s was primarily caused by increases in energy consumption and N fertiliser use. Our findings conformed that anthropogenic activities were the main reason for the Ndep increase and provide a scientific background for studies on ecological effects of N deposition in China.