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Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients’ survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

A high concentration of oxalate is associated with an increased risk of kidney calcium oxalate (CaOx) stones, and the degradation of exogenous oxalate mainly depends on oxalate-degrading enzymes from the intestinal microbiome. We found that Zinc Gluconate supplement to patients with CaOx kidney stones could significantly improve the abundance of oxalate metabolizing bacteria in human body through clinical experiments on the premise of simultaneous antibiotic treatment and the imbalance ofLactobacillusand OxDC was involved in CaOx kidney stones through clinical sample analysis. Then, we identified that Zn2+could be used as an external factor to improve the activity of OxDC and protectLactobacillus, achieved the preventive effect on rats with stones aggravated by antibiotics. Finally, by analyzing the three-dimensional structure of OxDC and somein vitroexperiments, we propose a hypothesis Zn2+increases the metabolism of oxalate in humans through its positive effects onLactobacillusand OxDC to reduce CaOx kidney stone symptoms in rats.IMPORTANCEUrinary stone disease is one of the most common urological disorders, and 70%-80% of urinary stones are calcium oxalate (CaOx) stones. We found the structural basis and metabolic mechanism by which oxalate decarboxylase metabolizes oxalate were elucidated, and Zn2+was illustrated to have therapeutic effects on CaOx stones by improving the tolerance of Lactobacillus to antibiotics. According to that, proper Zn2+levels in the diet, the consumption of more probiotic food and avoidance of the antibiotic overuse might be desirable measures for the prevention and treatment of kidney stones.Graphical Abstract

UDP-glucuronosyltransferase 2B15 (UGT2B15) is a crucial phase II drug-metabolizing enzyme, which glucuronidates various compounds, including clinical drugs and hormones. Mutants might affect glucuronidation, leading to a disruption of drug metabolism in vivo and decrease of therapeutic effect. Here, we mainly analyzed two representative mutants, H401P and L446S, on UGT2B15 activity using glucuronidation assays, molecular dynamic (MD) simulation and X-ray diffraction methods. The enzyme activity of L446S (rs1291910239) obviously increased six-fold than the wild type, although the enzyme activities of P191L, T374A, and H401P were lost apparently. Furthermore, we used MD simulations to calculate the energy change in the catalytic process of H401P and L446S, and the results indicated the free binding energies of H401P mutant to oxazepam and UDPGA were -30.98 ± 1.00 kcal/mol and -36.42 ± 1.04 kcal/mol, respectively, increased obviously compared to wild type, suggesting the mutation on position 401 had a crucial effect on the catalysis. Moreover, the three-dimensional structure of UGT2B15 C-terminal domain L446S was determined through protein crystallography and X-ray diffraction technology and the results suggested that one more hydrogen bonding between S446 and K410 was formed in the S446 crystal structure, compared to the wild type. Isothermal titration calorimetry assay further revealed the K

Xylan and cellulose are the two major constituents of numerous types of lignocellulose. The bifunctional enzyme that exhibits xylanase/cellulase activity has attracted a great deal of attention in biofuel production. Previously, a thermostable GH10 family enzyme (XynA) from Bacillus sp. KW1 was found to degrade both xylan and cellulose. To improve bifunctional activity on the basis of structure, we first determined the crystal structure of XynA at 2.3 A. Via molecular docking and activity assays, we revealed that Gln250 and His252 were indispensable to bifunctionality, because they could interact with two conserved catalytic residues, Glu182 and Glu280, while bringing the substrate close to the activity pocket. Then we used a structure-based engineering strategy to improve xylanase/cellulase activity. Although no mutants with increased bifunctional activity were obtained after much screening, we found the answer in the N-terminal 36-amino acid truncation of XynA. The activities of XynA_ΔN36 toward beechwood xylan, wheat arabinoxylan, filter paper, and barley β-glucan were significantly increased by 0.47-, 0.53-, 2.46-, and 1.04-fold, respectively. Furthermore, upon application, this truncation released more reducing sugars than the wild type in the degradation of pretreated corn stover and sugar cane bagasse. These results showed the detailed molecular mechanism of the GH10 family bifunctional endoxylanase/cellulase. The basis of these catalytic performances and the screened XynA_ΔN36 provide clues for the further use of XynA in industrial applications.

Overexpression of AKR1C3, an aldo-keto reductase, was recently discovered in liver cancers. In this study, an inverse correlation between AKR1C3 expression and survival of patients with liver cancer was observed. AKR1C3 inhibitors, however, failed to suppress liver cancer cell growth. The prodrug TH3424, which releases a DNA alkylating reagent upon reduction by AKR1C3, was developed to target tumors with overexpression of AKR1C3. TH3424 showed specific killing of liver cancer cells with AKR1C3 overexpression both in vitro and in vivo. In patient-derived mouse xenograft models, TH3424 at doses as low as 1.5 mg/kg eliminated liver tumors with no apparent toxicity. Therefore, TH3424 is a promising drug candidate for liver cancer and other types of cancers overexpressing AKR1C3.

In recent years, the efficiency of combinatorial methods has been utilized to accelerate the finding or screening of inorganic materials. In this work, based on the double substitution strategy of the cation ions Me2+/Si4+, a series of MeyY3−yAl5−ySiyO12:Eux garnet phosphors (MeYASG:Eu, Me = Mg, Ca, Sr, Ba) were rapidly prepared and screened by a combinatorial method in microreactor arrays. Through parallel experiments of solid-state synthesis, the reliability of the combinatorial screening was verified and an optimal composition of CaY2Al4SiO12:Eu0.03 (CYASG:Eu) with advanced luminous intensity was obtained. Annealing experiments under air and reductive atmospheres were performed and demonstrated the controllability and reversibility of the Eu3+ ↔ Eu2+ valence transition process, thus realizing the tuning of the dominant emission from divalent Eu2+ or trivalent Eu3+. The optimal CYASG:Eu sample showed excellent thermal quenching resistance after annealing at 800 °C for 1 h in a reducing atmosphere. The abnormal intensity of PL increased by 10% in the 50–100 °C region, and retained 63% of the initial value at 250 °C. With the assistance of thermoluminescence characterization, the complementary effect of the release of captured electrons or charge carriers in trap levels on the abnormal increase of PL intensity during the high-temperature luminescence process was revealed. By combination of the double substitution strategy of cations and annealing, a new approach is proposed to creating the coexistence of activator Eu ions with a mixed-valence state. Also, the prepared CYASG:Eu phosphors have promising applications in fields such as plant light supplements in greenhouses and plant factories and as luminescent materials for energy-saving light sources.

Cognitive impairment can seriously affect the quality of life of Parkinson's disease (PD) patients. Although numerous studies showed that N200, P300 latency and amplitude are correlated with cognitive functions, there is a sufficient amount of controversial results. Therefore, it is necessary to conduct a meta-analysis of N200, P300 latency and amplitude data of event-related potential (ERP) in PD.We systematically searched on PubMed and Web of Science for PD-related ERP studies published before December 2021. Standard mean difference (SMD) and 95% confidence interval (CI) estimates of N200 and P300 components were compared among PD patients, PD dementia (PDD) patients, PD non-dementia (PDND) patient, and healthy control (HC).Our meta-analysis showed prolonged N200 latency at the Fz, Cz electrode sites, prolonged P300 latency at the Fz sites in PD patients, compared to HC; prolonged N200 latency at the Cz, Pz electrode sites in PDND patients, compared to HC; prolonged P300 latency at the Cz site in PDD patients, compared to PDND patients; and reduced P300 amplitude at the Fz electrode site in PDND patients, compared to HC.N200 and P300 component may be potential electrophysiological biomarkers of early cognitive impairment in PD patients. Future studies are needed to confirm this conclusion. Estimates of N200 and P300 component can be a valuable support for clinicians in diagnosis of early cognitive impairment in PD patients due to the simplicity and non-invasiveness of the procedure.

Cardiocerebral vascular disease (CCVD) is a common disease with high morbidity, disability, and mortality. Oxidative stress (OS) is closely related to the progression of CCVD. Abnormal redox regulation leads to OS and overproduction of reactive oxygen species (ROS), which can cause biomolecular and cellular damage. The Nrf2/antioxidant response element (ARE) signaling pathway is one of the most important defense systems against exogenous and endogenous OS injury, and Nrf2 is regarded as a vital pharmacological target. The complexity of the CCVD pathological process and the current difficulties in conducting clinical trials have hindered the development of therapeutic drugs. Furthermore, little is known about the role of the Nrf2/ARE signaling pathway in CCVD. Clarifying the role of the Nrf2/ARE signaling pathway in CCVD can provide new ideas for drug design. This review details the recent advancements in the regulation of the Nrf2/ARE system and its role and activators in common CCVD development.

A novel relaxor solid solution of (1-x)Pb(Mg1/3Nb2/3)O3-xPb(Cd1/3Nb2/3)O3 [(1-x)PMN-xPCN] is synthesized by the solid-state reaction method. The crystal structure, electric properties and r...

Fish assemblages inhabiting the Taizi River basin have been severely degraded by anthropogenic disturbances, which weaken the basin’s ecological function and limited revitalization of the northeast industrial base. Long-term ecological rehabilitation has been conducted to restore the fish fauna and improve habitat conditions. To explore fish distribution patterns and key factors after this ecological rehabilitation, a comprehensive and detailed survey of fish fauna was conducted twice in 2021 at 33 sampling sites in the Taizi River. A total of 50 fish species from 13 families were collected, and the dominant species were P. lagowskii, Z. platypus, C. auratus and P. parva. Compared to results reported over the last decade, the increasing trend in fish richness and the change in the longitudinal fish organization were detected. The abundance variation for P. lagowskii, Z. platypus, C. auratus, P. parva, R. ocellatus and H. leucisculus along the upstream to downstream axis contributed most to the fish distribution pattern. Species replacement and addition might have jointly caused the longitudinal changes in the fish fauna, but species replacement was the main underlying mechanism. The canonical correspondence analysis (CCA) results show that the fish structure pattern was mainly shaped by cultivated land coverage and urban land coverage. Our study provides reference sites for future fish-based bioassessment and implications for region-specific management in the Taizi River.

Abstract: Heat shock protein (Hsp) 90 is an ATP-dependent chaperone and plays a vital role in the folding, maturation, and stability of a protein. Hsp90 and its client proteins have become targets of various diseases through the regulation of disease-related proteins. Inhibition of Hsp90 production and activity prevents ATP hydrolysis, resulting in the ubiquitination and proteasome degradation of client proteins. However, the Hsp90 inhibitor has obvious toxic side effects and the inevitable heat shock response. Cell division cycle 37 (Cdc37) is a crucial Hsp90 kinase-specific co-chaperone, which forms a complex with Hsp90 to regulate kinase and non-kinase client’s activities, cell commu-nication, and signal transduction. The Hsp90-Cdc37 complex maintains cell survival by stabilizing abnormal client proteins and regulating cell growth signals. The abnormal activation of Hsp90-Cdc37 protein-protein interaction (PPI) often leads to the aggravation of diseases, such as cancer and neuro-degenerative diseases. Compared with ATP competitive Hsp90 inhibitors, blocking Hsp90-Cdc37 PPI has higher selectivity, fewer toxic side effects, and better application prospects. This review detailed the biological characteristics of Hsp90-Cdc37 PPI and its role in several human diseases. Besides, the latest research progress in inhibitors is summarized and discussed to guide further research and clini-cal application.

Accumulating observations suggest that peripheral somatosensory ganglia may regulate pain transmission, yet direct evidence is sparse. Here we show that the peripheral afferent nociceptive information undergoes dynamic filtering within dorsal root ganglia (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using simultaneous in vivo electrophysiological recordings from the peripheral (spinal nerve) and central (dorsal root) aspects of rodent spinal nerves, ganglionic transplantation of GABAergic progenitor cells, and optogenetics we demonstrate tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically-induced GABA release within DRG enhanced filtering and reduced both acute and chronic inflammatory and neuropathic pain in vivo. These findings support the potential gating of pain information within the somatosensory system, and suggests new therapeutic approaches for pain relief. Significance Statement We show that the ascending somatosensory information undergoes dynamic filtering within the dorsal root ganglia (DRGs). Filtering (i.e. failure of action potentials to propagate through the axonal bifurcation or ‘t-junction’) is predominant in nociceptive nerve fibers and can be scaled up or down by the activity of GABAergic inhibitory system within the ganglia. Thus, spinal ganglion represents an intrinsic filtering device within the peripheral branch of somatosensory system. These findings may identify new strategies for pain relief.

Ceramides, the core of the sphingolipid metabolism, draw wide attention as tumor suppressor, and act directly on mitochondria to trigger apoptotic cell death. Ceramide-based therapies are being developed by using promote ceramide generating agents. The ceramide metabolism balance is regulated by multifaceted factors in cancer development. Ceramide metabolic enzymes can increase the elimination of ceramide and counteract the anti-tumor effects of ceramide. However, recent research showed that these metabolic enzymes were highly expressed in several cancers. Especially ceramide glycosyltransferases, they catalyze ceramide glycosylation and synthesis the skeleton of glycosphingolipids (GSLs), play an important role in regulating tumor progression and have a significant correlation with the poor prognosis of cancer patients. To further understand the biological characteristics of ceramide metabolism in tumor, this review focuses on the role of ceramide glycosylation and related enzymes in cancer signaling and therapy. Besides, the research on multidrug resistance and potential inhibitors of ceramide glycosyltransferases are also discussed. Advance study on the structure of ceramide glycosyltransferases and ceramide glycosylation signaling pathway will open the path to new therapies and treatments.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKK

AlkBH1 is a member of the AlkB superfamily which are kinds of Fe (II) and α-ketoglutarate (α-KG)-dependent dioxygenases. At present, only demethyltransferases FTO and AlkBH5 have relatively clear substrate studies among these members, the types and mechanisms of substrates catalysis of other members are not clear, especially the demethyltransferase AlkBH1. AlkBH1, as a demethylase, has important functions of reversing DNA methylation and repairing DNA damage. And it has become a promising target for the treatment of many cancers, the regulation of neurological and genetic related diseases. Many scholars have made important discoveries in the diversity of AlkBH1 substrates, but there is no comprehensive summary, which affects the design inhibitor target of AlkBH1. Herein, We are absorbed in the latest progress in the study of AlkBH1 substrate diversity and its relationship with human diseases. Besides, we also discuss future research directions and suggest other studies to reveal the specific catalytic effect of AlkBH1 on cancer substrates.

Structural design shows great impact on enhancing the thermoelectric performance of the GeTe-PbTe based materials. The Sm and Se elements are introduced to co-dope the GeTe-PbTe based alloys using a conventional solid-solution method followed by spark plasma sintering technique and thermal annealing. The Se doping can increase the solubility of Pb in the GeTe-based matrix, leading to the suppression of the segregated PbTe-based phases. The Sm–Se co-doping introduced secondary phases and twinning microstructures along with the traditional atomic-scale point defects and grain boundaries contribute to the wide-wavelength phonon scattering, leading to the reduction of lattice thermal conductivity. The co-doping strategy also shows impact on the tuning of carrier concentration and band structures for the optimization of power factor. The minimum lattice thermal conductivity reach to 0.41 Wm−1 K−1 for the sample Ge0.75Pb0.2Sm0.03Te0.7Se0.3 at 573 K, which approaches to the amorphous limit of GeTe. The maximum figure of merit ZT value can be increased to 1.03 for the sample Ge0.75Pb0.2Sm0.03Te0.5Se0.5 at 673 K, making the co-doping strategy quite attractive for further enhancing the thermoelectric performance of GeTe-PbTe based materials. Keywords: Thermoelectric, GeTe, Co-doping, Phase separation, Bandgap

Domain structure plays a critical role in the functionality of ferroelectrics. In this work, the domain structure and local domain switching behaviors of a (001) C -oriented 0.38Bi(Zn 2/3 Nb 1/3 )O 3 -0.62PbTiO 3 single crystal with high Curie temperature (~ 430 °C) and high tetragonality ( c / a > 1.04, where c and a represent the lattice parameters of the tetragonal crystal), were studied by polarized light microscopy (PLM) and piezoresponse force microscopy (PFM). Local polar domains with typical sizes from several nanometers to micrometers were observed by PFM in the crystal. The local domain switching was realized by applying a voltage, indicating the ferroelectricity of the crystal. This work provides a better understanding of the micro-/nanodomain structure and related phenomena in ferroelectrics of complex perovskite structure.

In recent years, the efficiency of combinatorial methods has been utilized to accelerate the finding or screening of inorganic materials. In this work, based on the double substitution strategy of the cation ions Me

UGT1A1 is the only enzyme that can metabolize bilirubin, and its encoding gene is frequently mutated. UGT1A1*6 (G71R) is a common mutant in Asia which leads to the decrease of UGT1A1 activity and abnormal bilirubin metabolism. However, it is not clear whether low UGT1A1 activity-induced bilirubin metabolism disorder increases hepatocyte fragility. ugt1a+/- mice were used to simulate the UGT1A1*6 (G71R) population. Under the same CCl4 induction condition, ugt1a+/- mice showed severer liver damage and fibrosis, indicating that ugt1a1 dysfunction increased liver burden and aggravated hepatocyte damage. In the animal experiment with a continuous intraperitoneal injection of bilirubin, the ugt1a+/- mice livers had more serious unconjugated bilirubin accumulation. The accumulated bilirubin leads to hyperphosphorylation of IκB-α, Ikk-β, and p65 and a significant increase of inflammatory factor. The α-SMA and Collagen I proteins markedly up-regulated in the ugt1a+/- mice livers. Immunofluorescence and confocal microscopy showed that hepatic stellate cells and Kupffer cells were activated in ugt1a+/- mice. Comprehensive results show that there was a crosstalk relationship between low UGT1A1 activity-bilirubin-liver damage. Furthermore, cell experiments confirmed that unconjugated bilirubin activated the NF-κB pathway and induced DNA damage in hepatocytes, leading to the significant increase of inflammatory factors. UGT1A1 knockdown in hepatocytes aggravated the toxicity of unconjugated bilirubin. Conversely, overexpression of UGT1A1 had a protective effect on hepatocytes. Finally, Schisandrin B, an active ingredient with hepatoprotective effects, extracted from a traditional Chinese medicinal herb, which could protect the liver from bilirubin metabolism disorders caused by ugt1a1 deficiency by downregulating p65 phosphorylation, inhibiting Kupffer cells, reducing inflammation levels. Our data clarified the mechanism of liver vulnerability caused by cross-talk between low UGT1A1 activity bilirubin, and provided a reference for individualized prevention of liver fragility in Gilbert's syndrome.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF

Xylan and cellulose are the two major constituents in numerous types of lignocellulose. Thus, bifunctional enzyme incorporated xylanase/cellulase activity has attracted considerable attention since it has great cost savings potential. Recently, a novel GH10 family enzyme XynA identified from Bacillus sp. was found to degrade both cellulose and xylan. To understand its molecular catalytic mechanism, here we first solve the crystal structure of XynA at 2.3 Å. XynA is characterized with a classic (α/β)8 TIM-barrel fold (GH10 domain) flanked by the flexible N-terminal domain and C-terminal domain. XynA has a longer N-terminal and C-terminal than most other GH10 family enzymes. The important thing is that the activity of our N-terminal truncated XynA_ΔN37 is significantly improved. And we found that the C-terminus is crucial to protein expression in solution. Protein thermal shift and enzyme activity assays reveal that conserved residues Glu182 and Glu280 are both important for catalytic activities of XynA, which is verified by the crystal structure of XynA with double mutant E182A/E280A. Molecular docking studies of XynA with xylohexaose and cellohexaose, together with site-directed mutagenesis and enzyme activity assay, demonstrate that Gln250 and His252 are indispensable to bifunctional activity. These results elucidate the structural and biochemical features of XynA, providing clues for further modification of XynA for industrial application.

Additional file of Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis

Background Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and chemoresistance. This study aimed to explore the role and molecular mechanism of circ_0006168 in Taxol resistance of ESCC. Methods The expression levels of circ_0006168, microRNA-194-5p (miR-194-5p) and jumonji domain containing 1C (JMJD1C) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The half-inhibition concentration (IC50) value of Taxol was evaluated by Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Cell migration and invasion were detected by transwell assay. Cell apoptosis was determined by flow cytometry. The interaction between miR-194-5p and circ_0006168 or JMJD1C was predicted by bioinformatics analysis (Circinteractome and TargetScan) and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. The mice xenograft model was established to investigate the roles of circ_0006168 in vivo. Results Circ_0006168 and JMJD1C were upregulated and miR-194-5p was downregulated in ESCC tissues, ESCC cells, and Taxol-resistant cells. Functionally, knockdown of circ_0006168 or JMJD1C increased Taxol sensitivity of ESCC in vitro via inhibiting cell proliferation, migration and invasion, and promoting apoptosis. Moreover, circ_0006168 could directly bind to miR-194-5p and JMJD1C was verified as a direct target of miR-194-5p. Mechanically, circ_0006168 was a sponge of miR-194-5p to regulate JMJD1C expression in ESCC cells. Furthermore, JMJD1C overexpression reversed the promotive effect of circ_0006168 knockdown on Taxol sensitivity. Besides, circ_0006168 silence suppressed tumor growth in vivo. Conclusion Circ_0006168 facilitated Taxol resistance in ESCC by regulating miR-194-5p/JMJD1C axis, providing a promising therapeutic target for ESCC chemotherapy.

Xylan and cellulose are the two major constituents in numerous types of lignocellulosic biomass, representing a promising resource for biofuels and other biobased industries. The efficient degradation of lignocellulose requires the synergistic actions of cellulase and xylanase. Thus, bifunctional enzyme incorporated xylanase/cellulase activity has attracted considerable attention since it has great cost savings potential. Recently, a novel GH10 family enzyme XynA identified fromBacillussp. is found to degrade both cellulose and xylan. To understand its molecular catalytic mechanism, here we first solve the crystal structure of XynA at 2.3 Å. XynA is characterized with a classic (α/β)8 TIM-barrel fold (GH10 domain) flanked by the flexible N-terminal domain and C-terminal domain. Circular dichroism, protein thermal shift and enzyme activity assays reveal that conserved residues Glu182 and Glu280 are both important for catalytic activities of XynA, which is verified by the crystal structure of XynA with E182A/E280A double mutant. Molecular docking studies of XynA with xylohexaose and cellohexaose as well as site-directed mutagenesis and enzyme activity assay demonstrat that Gln250 and His252 are indispensible to cellulase and bifunctional activity, separately. These results elucidate the structural and biochemical features of XynA, providing clues for further modification of XynA for industrial application.