Study on the physicochemical properties and gut microbiota regulation of Poria cocos pachyman treated by ball milling.

The effect of ball milling on the physicochemical properties and gut microbiota regulation of Poria cocos pachyman (PAC) was investigated. Ball milling reduced the particle size of PAC from 102 µm to 25.19 µm after 12 h, resulting in increasing particle uniformity. Scanning electron microscopy (SEM) revealed surface roughening and fragmentation of PAC after ball milling. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) indicated reduced crystallinity and increased hydroxyl group exposure in ball-milled PAC (BMP). Thermogravimetric analysis (TGA) showed decreased thermal stability in BMP. The optimal ball milled time was 7 h. Moisture contents in PAC and BMP-7 h were 10.30 ± 0.47 % and 10.72 ± 0.12 %, and carbohydrate contents were 81.02 ± 2.27 % and 74.54 ± 1.46 %. In vivo studies on mice demonstrated that both PAC and BMP-7 h increased diversity and reshaped the composition of gut microbiota, with BMP-7 h showing a more pronounced effect. BMP-7 h reduced the Firmicutes/Bacteroidetes ratio, and raised the abundance of Bacteroides, suggesting enhanced prebiotic potential. These findings highlight the role of ball milling in improving the physicochemical properties and prebiotic potential of water-insoluble polysaccharides and provide a theoretical basis for its broader application in the food and biopharmaceutical industries.

Intrinsic Peroxidase-like Activity of Polystyrene Nanoplastics Mediates Oxidative Stress.

Nanoplastics represent a global environmental concern due to their ubiquitous presence and potential adverse impacts on public and environmental health. There is a growing need to advance the mechanistic understanding of their reactivity as they interact with biological and environmental systems. Herein, for the first time, we report that polystyrene nanoplastics (PSNPs) have intrinsic peroxidase-like activity and are able to mediate oxidative stress. The peroxidase-like activity is dependent on temperature and pH, with a maximum at pH 4.5 and 40 °C. The catalytic activity exhibits saturation kinetics, as described by the Michaelis-Menten model. The peroxidase-like activity of PSNPs is attributed to their ability to mediate electron transfer from peroxidase substrates to H2O2. Ozone-induced PSNP aging can introduce oxygen-containing groups and disrupt aromatic structures on the nanoplastic surface. While ozonation initially enhances peroxidase-like activity by increasing oxygen-containing groups without degrading many aromatic structures, extended ozonation destroys aromatic structures, significantly reducing this activity. The peroxidase-like activity of PSNPs can mediate oxidative stress, which is generally positively correlated with their aromatic structures, as suggested by the ascorbic acid assay. These results help explain the reported oxidative stress exerted by nanoplastics and provide novel insights into their environmental and public health implications.

Mining the Biosynthetic Landscape of Lactic Acid Bacteria Unearths a New Family of RiPPs Assembled by a Novel Type of ThiF-like Adenylyltransferases.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are chemically diverse natural products of ribosomal origin. These peptides, which frequently act as signals or antimicrobials, are biosynthesized by conserved enzymatic machinery, making genome mining a powerful strategy for unearthing previously uncharacterized members of their class. Herein, we investigate the untapped biosynthetic potential of Lactobacillales (i.e., lactic acid bacteria), an order of Gram-positive bacteria closely associated with human life, including pathogenic species and industrially relevant fermenters of dairy products. Through genome mining methods, we systematically explored the distribution and diversity of ThiF-like adenylyltransferase-utilizing RiPP systems in lactic acid bacteria and identified a number of unprecedented biosynthetic gene clusters. In one of these clusters, we found a previously undescribed group of macrocyclic imide biosynthetic pathways containing multiple transporters that may be involved in a potential quorum sensing (QS) system. Through in vitro assays, we determined that one such adenylyltransferase specifically catalyzes the intracyclization of its precursor peptide through macrocyclic imide formation. Incubating the enzyme with various primary amines revealed that it could effectively amidate the C-terminus of the precursor peptide. This new transformation adds to the growing list of Nature's peptide macrocyclization strategies and expands the impressive catalytic repertoire of the adenylyltransferase family. The diverse RiPP systems identified herein represent a vast, unexploited landscape for the discovery of a novel class of natural products and QS systems.

The chemokine CCL14 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma.

BACKGROUND: Chemokine ligand 14, which has a C-C motif (CCL14), mediates the immunological milieu around tumors. However, its role in the progression of lung adenocarcinoma (LUAD) is still unknown. Our objectives were to study the association between CCL14 and tumor-infiltrating immune cells (TIICs) as well as the predictive significance of CCL14 in LUAD. METHODS: The expression of CCL14 in LUAD was examined by using the Oncomine, The Cancer Genome Atlas (TCGA), The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), and Human Protein Atlas databases. To determine the prognostic significance of CCL14 in LUAD, researchers used the Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA, version 2). We utilized TIMER and GEPIA2 to investigate the connection between CCL14 and TIICs. Gene set enrichment analysis (GSEA) was used to test for functional enrichment of genes. We used RT‒qPCR to measure CCL14 expression and Cell Counting Kit-8, Transwell, and wound healing assays to investigate the biological role of CCL14. RESULTS: The prognosis of patients with LUAD was worse when CCL14 expression was low. Statistical analysis revealed that CCL14 mRNA expression was significantly greater in lung epithelial cells than in LUAD cell lines in vitro. Enhancing CCL14 expression reduced cell migration, invasion, and proliferation. The results of the immune infiltration research showed that CCL14 and TIICs were positively correlated. Different immune infiltration patterns associated with CCL14 were also shown by TIIC markers. According to GSEA, histone deacetylases, G2/M checkpoints, and Notch signaling pathways were associated with low CCL14 expression. CONCLUSIONS: CCL14 is anticipated to emerge as a prognostic marker and therapeutic target for LUAD due to its role in regulating TIICs, suggesting that it may be an antioncogene.

A TCN-Linear Hybrid Model for Chaotic Time Series Forecasting.

The applications of deep learning and artificial intelligence have permeated daily life, with time series prediction emerging as a focal area of research due to its significance in data analysis. The evolution of deep learning methods for time series prediction has progressed from the Convolutional Neural Network (CNN) and the Recurrent Neural Network (RNN) to the recently popularized Transformer network. However, each of these methods has encountered specific issues. Recent studies have questioned the effectiveness of the self-attention mechanism in Transformers for time series prediction, prompting a reevaluation of approaches to LTSF (Long Time Series Forecasting) problems. To circumvent the limitations present in current models, this paper introduces a novel hybrid network, Temporal Convolutional Network-Linear (TCN-Linear), which leverages the temporal prediction capabilities of the Temporal Convolutional Network (TCN) to enhance the capacity of LSTF-Linear. Time series from three classical chaotic systems (Lorenz, Mackey-Glass, and Rossler) and real-world stock data serve as experimental datasets. Numerical simulation results indicate that, compared to classical networks and novel hybrid models, our model achieves the lowest RMSE, MAE, and MSE with the fewest training parameters, and its R2 value is the closest to 1.

Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.

Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.

Circulating Tumor Cell Phenotype Detection and Epithelial-Mesenchymal Transition Tracking Based on Dual Biomarker Co-Recognition in an Integrated PDMS Chip.

Circulating tumor cells (CTCs) are widely considered as a reliable and promising class of markers in the field of liquid biopsy. As CTCs undergo epithelial-mesenchymal transition (EMT), phenotype detection of heterogeneous CTCs based on EMT markers is of great significance. In this report, an integrated analytical strategy that can simultaneously capture and differentially detect epithelial- and mesenchymal-expressed CTCs in bloods of non-small cell lung cancer (NSCLS) patients is proposed. First, a commercial biomimetic polycarbonate (PCTE) microfiltration membrane is employed as the capture interface for heterogenous CTCs. Meanwhile, differential detection of the captured CTCs is realized by preparing two distinct CdTe quantum dots (QDs) with red and green emissions, attached with EpCAM and Vimentin aptamers, respectively. For combined analysis, a polydimethylsiloxane (PDMS) chip with simple structure is designed, which integrates the membrane capture and QDs-based phenotype detection of CTCs. This chip not only implements the analysis of the number of CTCs down to 2 cells mL-1, but enables EMT process tracking according to the specific signals of the two QDs. Finally, this method is successfully applied to inspect the correlations of numbers or proportions of heterogenous CTCs in 94 NSCLS patients with disease stage and whether there is distant metastasis.

miR-181a/b-5p negatively regulates keratinocytes proliferation by targeting MELK.

Accumulating evidence indicates that microRNAs (miRNAs) have a vital effect on the pathogenesis of psoriasis. This study is conducted to investigate the potential involvement of miR-181a-5p and miR-181b-5p in the proliferation of HaCaT keratinocytes. Cell viability and proliferation were evaluated respectively in this study using the CCK-8 and the 5-ethynyl-2'-deoxyuridine (EdU) assays. The expression of Maternal Embryonic Leucine Zipper Kinase (MELK) and Keratin 16 (KRT16) mRNA and protein in tissues and cells was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The Luciferase reporter system analyzes the connection between miR-181a-5p/miR-181b-5p and MELK. The results showed that miR-181a/b-5p expression was downregulated in the psoriasis lesions and negatively regulated the proliferation of keratinocytes. MELK was directly targeted by miR-181a-5p/miR-181b-5p. In addition, HaCaT keratinocytes proliferation was inhibited by knockdown of MELK while promoted dramatically by MELK overexpression. Notably, miR-181a/b-5p mimics could attenuate the effects of MELK in keratinocytes. In conclusion, our research findings suggested miR-181a-5p and miR-181b-5p negatively regulate keratinocyte proliferation by targeting MELK, providing potential diagnostic biomarkers and therapeutic targets for psoriasis.

LncRNA MIR181A2HG negatively regulates human keratinocytes proliferation by binding SRSF1.

Psoriasis is a common chronic inflammatory skin disease. Abnormal proliferation of keratinocytes plays an important role in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) are involved in the regulation of a variety of cell biological processes. The purpose of this study was to investigate the potential role of lncRNA MIR181A2HG in the proliferation of human keratinocytes. qRT-PCR and Western blotting were performed to measure the expression levels of MIR181A2HG, SRSF1, KRT6, and KRT16 in tissue specimens and HaCaT keratinocytes. The effects of MIR181A2HG on HaCaT keratinocytes proliferation were evaluated using Cell Counting Kit-8 (CCK-8) assays, 5-Ethynyl-2'-deoxyuridine (EdU) incorporation, and cell-cycle assays. RNA pulldown-mass spectrometry (MS) was applied to identify the proteins interacting with MIR181A2HG. RNA pull-down-Western blotting and RNA immunoprecipitation coupled with real-time quantitative reverse transcription-PCR (RIP-qRT-PCR) assays were used to determine the interactions between MIR181A2HG and its RNA-binding proteins (RBPs). MIR181A2HG was down-regulated in psoriasis tissues. MIR181A2HG overexpression induced G0/G1 and G2/M phase cell cycle arrest and decreased the protein levels of KRT6, KRT16, Cyclin D1, CDK4, and Cyclin A2 in HaCaT keratinocytes. MIR181A2HG knockdown showed the opposite effect. By using RNA pulldown-MS, 356 proteins were identified to interact with MIR181A2HG potentially. Bioinformatics analysis showed that NOP56 and SRSF1 may be RNA binding proteins (RBPs) that may be interact with MIR181A2HG. Furthermore, by using RNA pull-down-Western blotting and RIP-qRT-PCR, SRSF1 was determined to interact with MIR181A2HG. Moreover, silencing of SRSF1 inhibited keratinocytes proliferation, which could be reversed with the knockdown of MIR181A2HG. Our findings indicated that MIR181A2HG can negatively regulate HaCaT keratinocytes proliferation by binding SRSF1, suggesting that MIR181A2HG and SRSF1 may serve as potential targets for the treatment of psoriasis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-024-00621-6.

Global producer responsibility for plastic pollution.

Brand names can be used to hold plastic companies accountable for their items found polluting the environment. We used data from a 5-year (2018-2022) worldwide (84 countries) program to identify brands found on plastic items in the environment through 1576 audit events. We found that 50% of items were unbranded, calling for mandated producer reporting. The top five brands globally were The Coca-Cola Company (11%), PepsiCo (5%), Nestlé (3%), Danone (3%), and Altria (2%), accounting for 24% of the total branded count, and 56 companies accounted for more than 50%. There was a clear and strong log-log linear relationship production (%) = pollution (%) between companies' annual production of plastic and their branded plastic pollution, with food and beverage companies being disproportionately large polluters. Phasing out single-use and short-lived plastic products by the largest polluters would greatly reduce global plastic pollution.

Multiscale Deep Learning for Detection and Recognition: A Comprehensive Survey.

Recently, the multiscale problem in computer vision has gradually attracted people's attention. This article focuses on multiscale representation for object detection and recognition, comprehensively introduces the development of multiscale deep learning, and constructs an easy-to-understand, but powerful knowledge structure. First, we give the definition of scale, explain the multiscale mechanism of human vision, and then lead to the multiscale problem discussed in computer vision. Second, advanced multiscale representation methods are introduced, including pyramid representation, scale-space representation, and multiscale geometric representation. Third, the theory of multiscale deep learning is presented, which mainly discusses the multiscale modeling in convolutional neural networks (CNNs) and Vision Transformers (ViTs). Fourth, we compare the performance of multiple multiscale methods on different tasks, illustrating the effectiveness of different multiscale structural designs. Finally, based on the in-depth understanding of the existing methods, we point out several open issues and future directions for multiscale deep learning.

Combinational delivery of TLR4 and TLR7/8 agonist enhanced the therapeutic efficacy of immune checkpoint inhibitors to colon tumor.

Immunotherapy is regarded as a potent cancer treatment, with DC vaccines playing a crucial role. Although clinical trials have demonstrated the safety and efficacy of DC vaccines, loading antigens in vitro is challenging, and their therapeutic effects remain unpredictable. Moreover, the diverse subtypes and maturity states of DCs in the body could induce both immune responses and immune tolerance, potentially affecting the vaccine's efficacy. Hence, the optimization of DC vaccines remains imperative. Our study discovered a new therapeutic strategy by using CT26 and MC38 mouse colon cancer models, as well as LLC mouse lung cancer models. The strategy involved the synergistic activation of DCs through intertumoral administration of TLR4 agonist high-mobility group nucleosome binding protein 1 (HMGN1) and TLR7/8 agonist (R848/resiquimod), combined with intraperitoneal administration of TNFR2 immunosuppressant antibody. The experimental results indicated that the combined use of HMGN1, R848, and α-TNFR2 had no effect on LLC cold tumors. However, it was effective in eradicating CT26 and MC38 colon cancer and inducing long-term immune memory. The combination of these three drugs altered the TME and promoted an increase in anti-tumor immune components. This may provide a promising new treatment strategy for colon cancer.

Two-Dimensional Layered Heterojunctions for Photoelectrocatalysis.

Two-dimensional (2D) layered nanomaterial heterostructures, arising from the combination of 2D materials with other low-dimensional species, feature a large surface area to volume ratio, which provides a high density of active sites for catalytic applications and for (photo)electrocatalysis (PEC). Meanwhile, their electronic band structure and high electrical conductivity enable efficient charge transfer (CT) between the active material and the substrate, which is essential for catalytic activity. In recent years, researchers have demonstrated the potential of a range of 2D material interfaces, such as graphene, graphitic carbon nitride (g-C3N4), metal chalcogenides (MCs), and MXenes, for (photo)electrocatalytic applications. For instance, MCs such as MoS2 and WS2 have shown excellent catalytic activity for hydrogen evolution, while graphene and MXenes have been used for the reduction of carbon dioxide to higher value chemicals. However, despite their great potential, there are still major challenges that need to be addressed to fully realize the potential of 2D materials for PEC. For example, their stability under harsh reaction conditions, as well as their scalability for large-scale production are important factors to be considered. Generating heterojunctions (HJs) by combining 2D layered structures with other nanomaterials is a promising method to improve the photoelectrocatalytic properties of the former. In this review, we inspect thoroughly the recent literature, to demonstrate the significant potential that arises from utilizing 2D layered heterostructures in PEC processes across a broad spectrum of applications, from energy conversion and storage to environmental remediation. With the ongoing research and development, it is likely that the potential of these materials will be fully expressed in the near future.

Effects of plant growth-promoting rhizobacteria on blueberry growth and rhizosphere soil microenvironment.

Background: Plant growth-promoting rhizobacteria (PGPR) have a specific symbiotic relationship with plants and rhizosphere soil. The purpose of this study was to evaluate the effects of PGPR on blueberry plant growth, rhizospheric soil nutrients and the microbial community. Methods: In this study, nine PGPR strains, belonging to the genera Pseudomonas and Buttiauxella, were selected and added into the soil in which the blueberry cuttings were planted. All the physiological indexes of the cuttings and all rhizospheric soil element contents were determined on day 6 after the quartic root irrigation experiments were completed. The microbial diversity in the soil was determined using high-throughput amplicon sequencing technology. The correlations between phosphorus solubilization, the auxin production of PGPR strains, and the physiological indexes of blueberry plants, and the correlation between rhizospheric microbial diversity and soil element contents were determined using the Pearson's correlation, Kendall's tau correlation and Spearman's rank correlation analysis methods. Results: The branch number, leaf number, chlorophyllcontentand plant height of the treated blueberry group were significantly higher than those of the control group. The rhizospheric soil element contents also increased after PGPR root irrigation. The rhizospheric microbial community structure changed significantly under the PGPR of root irrigation. The dominant phyla, except Actinomycetota, in the soil samples had the greatest correlation with phosphorus solubilization and the auxin production of PGPR strains. The branch number, leaf number, and chlorophyllcontent had a positive correlation with the phosphorus solubilization and auxin production of PGPR strains and soil element contents. In conclusion, plant growth could be promoted by the root irrigation of PGPR to improve rhizospheric soil nutrients and the microenvironment, with modification of the rhizospheric soil microbial community. Discussion: Plant growth could be promoted by the root irrigation of PGPR to improve rhizospheric soil nutrients and the microenvironment, with the modification of the rhizospheric soil microbial community. These data may help us to better understand the positive effects of PGPR on blueberry growth and the rhizosphere soil microenvironment, as well as provide a research basis for the subsequent development of a rhizosphere-promoting microbial fertilizer.

Efficient production of 1,2,4-butanetriol from corn cob hydrolysate by metabolically engineered Escherichia coli.

Corn cob is a major waste mass-produced in corn agriculture. Corn cob hydrolysate containing xylose, arabinose, and glucose is the hydrolysis product of corn cob. Herein, a recombinant Escherichia coli strain BT-10 was constructed to transform corn cob hydrolysate into 1,2,4-butanetriol, a platform substance with diversified applications. To eliminate catabolite repression and enhance NADPH supply for alcohol dehydrogenase YqhD catalyzed 1,2,4-butanetriol generation, ptsG encoding glucose transporter EIICBGlc and pgi encoding phosphoglucose isomerase were deleted. With four heterologous enzymes including xylose dehydrogenase, xylonolactonase, xylonate dehydratase, α-ketoacid decarboxylase and endogenous YqhD, E. coli BT-10 can produce 36.63 g/L 1,2,4-butanetriol with a productivity of 1.14 g/[L·h] using xylose as substrate. When corn cob hydrolysate was used as the substrate, 43.4 g/L 1,2,4-butanetriol was generated with a productivity of 1.09 g/[L·h] and a yield of 0.9 mol/mol. With its desirable characteristics, E. coli BT-10 is a promising strain for commercial 1,2,4-butanetriol production.

Maternal autonomy support and intrusive control in the United States and China: Moment-to-moment associations with preschoolers' agency and defeat.

This study examines the moment-to-moment within-person associations between maternal and child behaviors during a challenging puzzle task and compares these associations between mother-child dyads from the United States (n = 99, 52 boys, Mchild age = 56.05 months, SD = 6.44) and China (n = 101, 46 boys, Mchild age = 57.41 months, SD = 6.58). Maternal autonomy support and intrusive control and child agency and defeat were rated in 15-s intervals by native and bicultural coders. Country was examined as a moderator of the moment-to-moment within-person associations between maternal and child behaviors. The results showed that for both U.S. and Chinese dyads, increases in maternal intrusive control predicted subsequent decreases in child agency, and increases in child defeat predicted subsequent increases in maternal autonomy support. Furthermore, increases in maternal autonomy support predicted subsequent increases in child defeat, but for the Chinese dyads only. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Characterization of Rhizosphere Microbial Diversity and Selection of Plant-Growth-Promoting Bacteria at the Flowering and Fruiting Stages of Rapeseed.

Plant rhizosphere microorganisms play an important role in modulating plant growth and productivity. This study aimed to elucidate the diversity of rhizosphere microorganisms at the flowering and fruiting stages of rapeseed (Brassica napus). Microbial communities in rhizosphere soils were analyzed via high-throughput sequencing of 16S rRNA for bacteria and internal transcribed spacer (ITS) DNA regions for fungi. A total of 401 species of bacteria and 49 species of fungi in the rhizosphere soil samples were found in three different samples. The composition and diversity of rhizosphere microbial communities were significantly different at different stages of rapeseed growth. Plant-growth-promoting rhizobacteria (PGPRs) have been widely applied to improve plant growth, health, and production. Thirty-four and thirty-one PGPR strains were isolated from the rhizosphere soil samples collected at the flowering and fruiting stages of rapeseed, respectively. Different inorganic phosphorus- and silicate-solubilizing and auxin-producing capabilities were found in different strains, in addition to different heavy-metal resistances. This study deepens the understanding of the microbial diversity in the rapeseed rhizosphere and provides a microbial perspective of sustainable rapeseed cultivation.

Moment-to-moment within-person associations between maternal autonomy support and child defeat predicting child behavioral adjustment.

This study examines mother-child mutual regulation processes during a challenging puzzle task as predictors of preschoolers' behavioral adjustment 6 months later in a Chinese sample (N = 101, 46 boys, Mage = 57.41 months, SD = 6.58). Mother-child mutual regulation was measured by the moment-to-moment bidirectional within-person associations between maternal autonomy support and child defeat (i.e., expression of frustration, incapacity to complete the task, or giving up). Children whose mother provided more autonomy support after increases of child defeat showed lower levels of externalizing problems 6 months later, and children who showed less defeat after increases of maternal autonomy support showed higher levels of prosocial behaviors 6 months later. These predictive effects were significant after controlling for child behavioral adjustment at the initial time point, and mean levels of mother's autonomy support and child's defeat throughout the task. The mutual regulation processes did not significantly predict child internalizing problems. The findings suggest that the coordinated mother-child mutual regulation patterns in real time may have positive implications for preschoolers' behavioral adjustment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Lactate dehydrogenase A promotes nasopharyngeal carcinoma progression through the TAK1/NF-κB Axis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor that originates in the nasopharyngeal mucosa and is common in China and Southeast Asian countries. Cancer cells reprogram glycolytic metabolism to promote their growth, survival and metastasis. Glycolysis plays an important role in NPC development, but the underlying mechanisms remain incompletely elucidated. Lactate dehydrogenase A (LDHA) is a crucial glycolytic enzyme, catalyzing the last step of glycolysis. This study aims to investigate the exact role of LDHA, which catalyzes the conversion of pyruvate into lactate, in NPC development. METHODS AND RESULTS: The western blot and immunohistochemical (IHC) results indicated that LDHA was significantly upregulated in NPC cells and clinical samples. LDHA knockdown by shRNA significantly inhibited NPC cell proliferation and invasion. Further knockdown of LDHA dramatically weakened the tumorigenicity of NPC cells in vivo. Mechanistic studies showed that LDHA activated TGF-ß-activated kinase 1 (TAK1) and subsequent nuclear factor κB (NF-κB) signaling to promote NPC cell proliferation and invasion. Exogenous lactate supplementation restored NPC cell proliferation and invasion inhibited by LDHA knockdown, and this restorative effect was reversed by NF-κB inhibitor (BAY 11-7082) or TAK1 inhibitor (5Z-7-oxozeaenol) treatment. Moreover, clinical sample analyses showed that LDHA expression was positively correlated with TAK1 Thr187 phosphorylation and poor prognosis. CONCLUSIONS: Our results suggest that LDHA and its major metabolite lactate drive NPC progression by regulating TAK1 and its downstream NF-κB signaling, which could become a therapeutic target in NPC.