Corrigendum: Characterizing the neutrophilic inflammation in chronic rhinosinusitis with nasal polyps.

[This corrects the article DOI: 10.3389/fcell.2021.793073.].

Oleanane-type triterpenoids from Sabia limoniacea and their anti-inflammatory activities.

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Quantum modeling simulates nutrient effect of bioplastic polyhydroxyalkanoate (PHA) production in Pseudomonas putida.

Polyhydroxyalkanoates (PHAs) could be used to make sustainable, biodegradable plastics. However, the precise and accurate mechanistic modeling of PHA biosynthesis, especially medium-chain-length PHA (mcl-PHA), for yield improvement remains a challenge to biology. PHA biosynthesis is typically triggered by nitrogen limitation and tends to peak at an optimal carbon-to-nitrogen (C/N) ratio. Specifically, simulation of the underlying dynamic regulation mechanisms for PHA bioprocess is a bottleneck owing to surfeit model complexity and current modeling philosophies for uncertainty. To address this issue, we proposed a quantum-like decision-making model to encode gene expression and regulation events as hidden layers by the general transformation of a density matrix, which uses the interference of probability amplitudes to provide an empirical-level description for PHA biosynthesis. We implemented our framework modeling the biosynthesis of mcl-PHA in Pseudomonas putida with respect to external C/N ratios, showing its optimization production at maximum PHA production of 13.81% cell dry mass (CDM) at the C/N ratio of 40:1. The results also suggest the degree of P. putida's preference in channeling carbon towards PHA production as part of the bacterium's adaptative behavior to nutrient stress using quantum formalism. Generic parameters (kD, kN and theta θ) obtained based on such quantum formulation, representing P. putida's PHA biosynthesis with respect to external C/N ratios, was discussed. This work offers a new perspective on the use of quantum theory for PHA production, demonstrating its application potential for other bioprocesses.

Porcine deltacoronavirus nucleocapsid protein interacts with the Grb2 through its proline-rich motifs to induce activation of the Raf-MEK-ERK signal pathway and promote virus replication.

Porcine deltacoronavirus (PDCoV), an enteropathogenic coronavirus, causes severe watery diarrhoea, dehydration and high mortality in piglets, which has the potential for cross-species transmission in recent years. Growth factor receptor-bound protein 2 (Grb2) is a bridging protein that can couple cell surface receptors with intracellular signal transduction events. Here, we investigated the reciprocal regulation between Grb2 and PDCoV. It is found that Grb2 regulates PDCoV infection and promotes IFN-ß production through activating Raf/MEK/ERK/STAT3 pathway signalling in PDCoV-infected swine testis cells to suppress viral replication. PDCoV N is capable of interacting with Grb2. The proline-rich motifs in the N- or C-terminal region of PDCoV N were critical for the interaction between PDCoV-N and Grb2. Except for Deltacoronavirus PDCoV N, the Alphacoronavirus PEDV N protein could interact with Grb2 and affect the regulation of PEDV replication, while the N protein of Betacoronavirus PHEV and Gammacoronavirus AIBV could not interact with Grb2. PDCoV N promotes Grb2 degradation by K48- and K63-linked ubiquitin-proteasome pathways. Overexpression of PDCoV N impaired the Grb2-mediated activated effect on the Raf/MEK/ERK/STAT3 signal pathway. Thus, our study reveals a novel mechanism of how host protein Grb2 protein regulates viral replication and how PDCoV N escaped natural immunity by interacting with Grb2.

Oleandrin enhances radiotherapy sensitivity in lung cancer by inhibiting the ATM/ATR-mediated DNA damage response.

Despite active clinical trials on the use of Oleandrin alone or in combination with other drugs for the treatment of solid tumors, the potential synergistic effect of Oleandrin with radiotherapy remains unknown. This study reveals a new mechanism by which Oleandrin targets ATM and ATR kinase-mediated radiosensitization in lung cancer. Various assays, including clonogenic, Comet, immunofluorescence staining, apoptosis and Cell cycle assays, were conducted to evaluate the impact of oleandrin on radiation-induced double-strand break repair and cell cycle distribution. Western blot analysis was utilized to investigate alterations in signal transduction pathways related to double-strand break repair. The efficacy and toxicity of the combined therapy were assessed in a preclinical xenotransplantation model. Functionally, Oleandrin weakens the DNA damage repair ability and enhances the radiation sensitivity of lung cells. Mechanistically, Oleandrin inhibits ATM and ATR kinase activities, blocking the transmission of ATM-CHK2 and ATR-CHK1 cell cycle checkpoint signaling axes. This accelerates the passage of tumor cells through the G2 phase after radiotherapy, substantially facilitating the rapid entry of large numbers of inadequately repaired cells into mitosis and ultimately triggering mitotic catastrophe. The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.

Characterisation of the novel HLA-A*24:630 allele by sequencing-based typing.

HLA-A*24:630 differs from HLA-A*24:20:01:01 by one nucleotide substitution in codon 131 in exon 3.

Bacillus subtilis JATP3 improved the immunity of weaned piglets by improving intestinal flora and producing Citalopram.

The purpose of this study was to evaluate the ability of Bacillus subtilis JATP3 to stimulate immune response and improve intestinal health in piglets during the critical weaning period. Twelve 28-day-old weaned piglets were randomly divided into two groups. One group was fed a basal diet, while the other group was fed a basal diet supplemented with B. subtilis JATP3 (1 × 109 CFU/mL; 10 mL) for 28 days. The results revealed a significant increase in the intestinal villus gland ratio of weaned piglets following the inclusion of B. subtilis JATP3 (P < 0.05). Inclusion of a probiotic supplement improve the intestinal flora of jejunum and ileum of weaned piglets. Metabolomics analysis demonstrated a notable rise in citalopram levels in the jejunum and ileum, along with elevated levels of isobutyric acid and isocitric acid in the ileum. The results of correlation analysis show that indicated a positive correlation between citalopram and microbial changes. Furthermore, the probiotic-treated group exhibited a significant upregulation in the relative expression of Claudin, Zonula Occludens 1 (ZO-1), and Interleukin 10 (IL-10) in the jejunum and ileum, while displaying a noteworthy reduction in the relative expression of Interleukin 1ß (IL-1ß). Overall, these findings suggest that B. subtilis JATP3 can safeguard intestinal health by modulating the structure of the intestinal microbiota and their metabolites, wherein citalopram might be a key component contributing to the therapeutic effects of B. subtilis JATP3.

Non-target lesion progression: Unveiling critical predictors and outcomes in patients with in-stent restenosis.

BACKGROUND: Percutaneous coronary intervention (PCI) has become the primary treatment for coronary artery disease. However, while PCI effectively addresses severe stenosis or occlusive lesions in target vessels, the progression of non-target vessel plaque remains a critical determinant of long-term patient prognosis. AIMS: The purpose of this study was to investigate the impact of non-target vascular plaque progression on prognosis after PCI for ISR. METHODS: This study included 195 patients diagnosed with ISR and multivessel disease who underwent successful PCI with drug-eluting stent (DES) placement, along with intraoperative optical coherence tomography (OCT) assessment of the culprit stent. Subsequent rechecked coronary angiography categorized eligible patients into non-target lesion progression (N-TLP) and no-N-TLP groups. We evaluated the baseline morphological characteristics of N-TLP by OCT and investigated the relationship between N-TLP, non-culprit vessel-related major adverse cardiovascular events (NCV-MACE), and pan-vascular disease-related clinical events (PVD-CE) incidence. RESULTS: Multivariate logistic regression analysis revealed that diabetes mellitus (OR 3.616, 95% CI: 1.735-7.537; P = 0.001), uric acid level (OR 1.005, 95% CI: 1.001-1.009; P = 0.006), in-stent neoatherosclerosis (ISNA) (OR 1.334, 95% CI: 1.114-1.985; P = 0.047) and heterogeneous neointima morphology (OR 2.48, 95% CI: 1.18-5.43; P = 0.019) were independent predictors for N-TLP. Furthermore, N-TLP was associated with a high incidence of NCV-MACE (19.4% vs 6.9%, P = 0.009) and PVD-CE (83.9% [95% CI: 79.7%-88.3%] vs 93.1% [95% CI: 88.4%-98.0%], P = 0.038) after PCI in ISR patients. CONCLUSION: Diabetes, uric acid levels, ISNA, and heterogeneous neointima are predictive factors for subsequent rapid plaque progression, with N-TLP exacerbating the incidence of NCV-MACE and PVD-CE after PCI.

Gypenoside inhibits gastric cancer proliferation by suppressing glycolysis via the Hippo pathway.

Gastric cancer (GC) remains a global disease with a high mortality rate, the lack of effective treatments and the high toxicity of side effects are primary causes for its poor prognosis. Hence, urgent efforts are needed to find safe and effective therapeutic strategies. Gypenoside (Gyp) is a widely used natural product that regulates blood glucose to improve disease progression with few toxic side effects. Given the crucial role of abnormal glycometabolism in driving tumor malignancy, it is important to explore the association between Gyp and glycometabolism in GC and understand the mechanism of action by which Gyp influences glycometabolism. In this study, we demonstrated that Gyp suppresses GC proliferation and migration both in vitro and in vivo. We identified that Gyp suppresses the malignant progression of GC by inhibiting glycolysis using network pharmacology and metabolomics. Transcriptome analysis revealed that the Hippo pathway is a key regulator of glycolysis by Gyp in GC. Furthermore, Gyp induced upregulation of LATS1/2 proteins, leading to increased YAP phosphorylation and decreased TAZ protein expression. The YAP agonist XMU-MP-1 rescued the inhibitory effect of Gyp on GC proliferation by reversing glycolysis. These findings confirmed that Gyp inhibits GC proliferation by targeting glycolysis through the Hippo pathway. Our study examined the role of Gyp in the malignant progression of GC, explored its therapeutic prospects, elucidated a mechanism by which Gyp suppresses GC proliferation through interference with the glycolytic process, thus providing a potential novel therapeutic strategy for GC patients.

Decoding human somatosensory sensitivity through resting EEG and behavioral analysis: a multimodal fusion approach.

In precision medicine and clinical pain management, the creation of quantitative, objective indicators to assess somatosensory sensitivity was essential. This study proposed a fusion approach for decoding human somatosensory sensitivity, which combined multimodal (quantitative sensory test and neurophysiology) features to classify the dataset on individual somatosensory sensitivity and reveal distinct types of brain activation patterns. Sixty healthy participants took part in the experiment on somatosensory sensitivity that implemented cold, heat, mechanical punctate, and pressure stimuli, and the resting-state electroencephalography (EEG) was collected using BrainVision. The quantitative sensory testing (QST) scores of the participants were clustered using the unsupervised k-means algorithm into four subgroups: generally hypersensitive (HS), generally non-sensitive (NS), predominantly thermally sensitive (TS), and predominantly mechanically sensitive (MS). Furthermore, two types of power spectral density (PSD), band-based PSD (BB-PSD) and frequency-based PSD (FB-PSD), and two types of inter-electrode connectivity (IEC), band-based connectivity (BBC) and frequency-based connectivity (FBC), derived from resting-state EEG were subjected to feature selection with a proposed prior-compared minimum-redundancy maximum-relevance (PCMRMR) protocol. Their effectiveness was then tested by the supervised classification tasks using support vector machine (SVM), k-nearest neighbor (kNN), random forest (RF), and Gaussian classifier (GC). Brain networks of four somatosensory types were revealed by decoding fused multimodal data, namely type-averaged connectivity. The data from sixty healthy individuals were divided into training (n = 59) and validation (n = 1) datasets according to leave-one-subject-out (LOSO) criteria. The FBC was identified, which can serve as better brain signatures than BB-PSD, FB-PSD, and BBC to classify subjects as HS, NS, TS, or MS groups. Using the SVM, kNN, RF, and GC models, the best accuracy of 87% was obtained when classifying participants into HS, NS, TS, or MS groups. Moreover, the brain networks were decoded from HS, NS, TS, and MS groups by decoding the type-averaged connectivity fused from somatosensory phenotypes and selected FBC. It indicated that quantified multi-parameter somatosensory sensitivity could be achieved with acceptable accuracy, leading to considerable possibilities for using objective pain perception evaluation in clinical practice.

Cyclophilin A promotes porcine deltacoronavirus replication by regulating autophagy via the Ras/AKT/NF-κB pathway.

Porcine deltacoronavirus (PDCoV) is an important enteric coronavirus that has caused major worldwide economic losses in the pig industry. Previous studies have shown that cyclophilin A (CypA), a key player in aetiological agent infection, is involved in regulating viral infection. However, the role of CypA during PDCoV replication remains unknown. Therefore, in this study, the role of CypA in PDCoV replication was determined. The results demonstrated that PDCoV infection increased CypA expression in LLC-PK1 cells. CypA overexpression substantially promoted PDCoV replication. Proteomic analysis was subsequently used to assess changes in total protein expression levels after CypA overexpression. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to further determine the mechanisms by which CypA affects viral replication. Proteomic analysis revealed that CypA protein overexpression significantly upregulated 75 differentially expressed proteins and significantly downregulated 172 differentially expressed proteins. The differentially expressed proteins were involved mainly in autophagy and activation of the host innate immune pathway. Subsequent experimental results revealed that the CypA protein promoted viral replication by reducing the levels of natural immune cytokines and mitigated the inhibitory effect of chloroquine (CQ) on viral replication. Further investigation revealed that CypA could activate the Ras/AKT/NF-κB pathway, mediate autophagy signalling and promote PDCoV replication. In summary, the findings of this study may help elucidate the role of CypA in PDCoV replication.

Association between hypertensive disorders of pregnancy and gestational diabetes and risk of atopic dermatitis in childhood: A systematic review and meta-analysis.

The purpose of this review was to examine if maternal hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) result in an increased risk of atopic dermatitis or eczema (AD-E) in childhood. We searched the databases of PubMed, Embase, CENTRAL, Web of Science, and Scopus for cohort or case-control studies up to 25th June 2023. Random-effects meta-analysis was done to generate the odds ratio (OR) of the association between HDP/GDM and AD-E. Eight studies were included. Meta-analysis of five studies showed that GDM in the mother was associated with an increased risk of AD-E in the offspring (OR: 1.35 95% CI: 1.13, 1.61 I2 = 61%). Pooled analysis of four studies demonstrated no association between HDP and risk of AD-E in the offspring (OR: 1.03 95% CI: 0.99, 1.08 I2 = 0%). The results did not change on sensitivity analysis and subgroup analysis based on study type, method of AD-E diagnosis, and sample size. This meta-analysis suggests that GDM may significantly increase the risk of AD-E in childhood, however, HDP does not seem to impact the risk of AD-E. Evidence is limited by the small number of studies and high interstudy heterogeneity. Further studies are needed to improve the quality of evidence.

Clinical features and genetic analysis of developmental and epileptic encephalopathy caused by biallelic variants of CACNA1B.

Objective: To analyze the clinical features and genetic etiology of a patient with developmental and epileptic encephalopathy. Methods: The clinical information and peripheral blood of the patient and their family members were collected before the whole exome sequencing analysis was performed and Sanger sequencing was employed to verify the potential variant. Results: The patient presented with epilepsy and cerebral palsy with his parents, brother, and sister being all healthy. Whole exome sequencing analysis revealed that the child carried the paternal c.823del (p. R275Gfs*31) heterozygous variant and the maternal c.2456del (p.V819Gfs*190) heterozygous variant of the CACNA1B gene. Pedigree verification found that the elder brother and amniotic fluid of fetus in womb carried the paternal c.823del heterozygous variant, and the elder sister carried the maternal c.2456del heterozygous variant, which conformed to the law of autosomal recessive inheritance. Neither of these two variants has been reported in the literature and has not been included in the Genomic Mutation Frequency Database (gnomAD); according to the American Academy of Medical Genetics and Genomics Variation Grading Guidelines (ACMG), both variants are classified as pathogenic variants (PVS1+PM2-Supporting + PM3). Conclusion: This study reported the first case of a child with neurodevelopmental disorder and epilepsy caused by a new compound heterozygous variant of the CACNA1B gene in China, clarified its genetic etiology, enriched the mutation spectrum and disease spectrum of CACNA1B gene, and provided a basis for prenatal diagnosis of the family.

[Mechanism of Mailuo Shutong Pills on posterior limb muscle swelling caused by femoral fracture in rats based on network pharmacology and experimental verification].

This study aims to investigate the mechanism of Mailuo Shutong Pills(MLST) on posterior limb muscle swelling caused by femoral fracture(SCFF) through network pharmacology and animal experiments. The plasma components of MLST were analyzed by LC-MS, and the target and signal pathway of SCFF were predicted by network pharmacology and verified by molecular docking. SCFF model rats were established through animal experiments, and different doses of MLST were administered to detect the degree of limb swelling. Hematoxylin-eosin(HE) staining was used to observe pathological changes in muscle tissue, and interleukin-6(IL-6), interleukin-1ß(interleukin-1ß), and tumor necrosis factor-α(TNF-α) in peripheral blood were determined by enzyme-linked immunosorbent assay(ELISA). The expression of relevant signaling pathways was measured by Western blot. Network pharmacological results showed that MLST and SCFF had a total of 153 disease targets, and the key targets were IL-6, TNF, etc., involving mitogen-activated protein kinase(MAPK) signaling pathway, phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, etc. The binding energies of the main components and key targets were lower than-7.0 kcal·mol~(-1), indicating that the network analysis results were reliable. The results of animal experiments showed that MLST could reduce the swelling degree and pathological damage of the posterior limb muscles of SCFF rats compared with the model group. ELISA results showed that MLST could reduce the levels of IL-6, IL-1ß, and TNF-α in the serum of SCFF rats. Western blot results showed that MLST can reduce the expression of p-AKT, p-PI3K, p-NF-κB, p-p38 MAPK, and p-ERK in SCFF rats. MLST may reduce the content of inflammatory factors in serum by regulating the expression of PI3K/AKT and MAPK-related signaling pathway protein and improving posterior limb muscle SCFF in rats.

[Characteristics of Pollution and Microbial Community Structure in the Antimony Mining Area of Longnan, Gansu Province].

Antimony （Sb） is a major pollutant that poses a serious threat to the environment in the mining and processing of nonferrous metals, coexisting with sulfide and oxide of arsenic （As）. Microorganisms play an important role in the migration, transformation, and repair of metals in soil. The ecological effects of bioavailable Sb and As on the microbial community in antimony mining areas（mining and smelting areas）are still poorly understood. The Wenzel method and high-throughput 16S rDNA amplicon were used to characterize soil pollution characteristics in different functional areas, and the relationship between the bacterial community and bioavailable concentrations have been investigated comprehensively. The results showed that： Chemical speciation of Sb and As were amorphous, and poorly crystalline hydrous oxides of Fe and Al （F3） > well-crystallized hydrous oxides of Fe and Al （F4） > residual phases （F5） > specifically adsorbed （F2） > non-specifically adsorbed （F1）. According to the estimation of the potential ecological risk index （RI） and geo-accumulation index （Igeo）, the Sb pollution degree was： smelting area > mining area > contrast area, in which the smelting area showed serious pollution, and the mining area showed moderate to severe pollution. The As pollution degree was： mining area > smelting area > contrast area, in which the mining area and smelting area showed moderate to severe pollution. High-throughput 16S rDNA amplicon showed that Proteobacteria was the most abundant phylum in mining and smelting areas； Kaistobacter, Pseudomonas, Sphingomonas, and Lysobacter were the most abundant microbial genera； Geobacter and Luteolibacter had a high LDA score in mining areas； and Thiobacillus had a high LDA score in antimony-contaminated areas. Spearman correlation analysis, variation partitioning analysis （VPA）, and random forest （RF） analysis showed that Sb, As, bioavailable antimony [Sb （Bio）], and bioavailable arsenic [As （Bio）]were the main factors affecting the microbial community structure in different functional areas of antimony ore. Redundancy analysis （RDA） indicated that Sb and its bioavailable concentrations showed uniformly negative associations with the relative abundance of bacteria Nitrospirae and showed a significant positive correlation with Thiobacillus （P<0.05）. The in-depth research on the ecological effects of bioavailable Sb and As on the bacterial community provides references and new perspectives for environmental monitoring and management.

[Knock-down of long noncoding RNA H19 (lncRNA H19) promotes human colorectal cell autophagy and inhibits cell apoptosis induced by lipopolysaccharide].

Objective To investigate the expression levels of lncRNA H19 in ulcerative colitis (UC) patients and its role in UC. Methods Colonic mucosa and serum samples were collected from 25 UC patients and 25 healthy individuals at the General Hospital of Xizang Military Region. The expression levels of lncRNA H19 were detected, and the receiver operating characteristic (ROC) curve analysis was performed using serum samples. An in vitro inflammatory model was established in HT29 colorectal cells under lipopolysaccharide (LPS) stimulation, and the expression levels of lncRNA H19 were observed in HT29 cells through fluorescence quantitative PCR. HT29 cells with downregulated lncRNA H19 was constructed using lentivirus-mediated shRNA. The effect of lncRNA H19 on cell survival was analyzed through MTT assay. Cell apoptosis was detected by flow cytometry, and the protein expression levels of apoptosis and autophagy markers were analyzed through Western blot. After treatment with rapamycin, the survival of HT29 cells was observed by MTT assay. Results lncRNA H19 was highly expressed in the colonic mucosa and serum samples of UC patients with the ROC area being 0.786. Following LPS stimulation, the expression levels of lncRNA H19 was significantly increased in a time-dependent manner. Downregulation of lncRNA H19 can promote cell survival, inhibit cell apoptosis and increase autophagy level in HT29 cells. Treatment with rapamycin significantly increased the cell survival rate. Conclusion Knock-down of lncRNA H19 increases autophagy levels, inhibits LPS-induced apoptosis and promotes the survival of colon cells.

Research progress on insomnia treated by traditional Chinese medicine and acupuncture based on microbial-gut-brain axis theory.

Insomnia, as one of the emotional diseases, has been increasing in recent years, which has a great impact on people's life and work. Therefore, researchers are eager to find a more perfect treatment. The microbiome-gut-brain axis is a new theory that has gradually become popular abroad in recent years and has a profound impact in the field of insomnia. In recent years, traditional Chinese medicine (TCM) has played an increasingly important role in the treatment of insomnia, especially acupuncture and Chinese herbal medicine. It is the main method of TCM in the treatment of insomnia. This paper mainly reviews the combination degree of "microorganism-gut-brain axis" theory with TCM and acupuncture under the system of TCM. To explore the mechanism of TCM and acupuncture in the treatment of insomnia under the guidance of "microorganism-gut-brain axis" theory, in order to provide a new idea for the diagnosis and treatment of insomnia.

Site-specific apparent optimum air temperature for vegetation photosynthesis across the globe.

The apparent optimum air temperature for vegetation photosynthesis (Topt) is a key temperature parameter in terrestrial ecosystem models estimating daily photosynthesis or gross primary production (GPP, g C/m2/day). To date, most models use biome-specific Topt (Topt-biome) parameter values. Given vegetation acclimation and adaptation to local climate, site-specific Topt (Topt-site) is needed to reduce uncertainties in estimating daily GPP across the scales from site to region and the globe. Previous studies have demonstrated using the Enhanced Vegetation Index (EVI) derived from Moderate Resolution Imaging Spectroradiometer (MODIS) images and daytime air temperature data to estimate the Topt-site at the eddy covariance tower sites. This study used MODIS-derived EVI and ERA5 climate data to estimate and generate global Topt-site data products from 2000 to 2019. The Topt-site of individual pixels within a biome has large variation, which clearly cannot be represented accurately by the widely used Topt-biome. Therefore, using this global dataset of Topt-site estimates might significantly affect GPP simulation in current ecosystem models.