Oral Saccharomyces cerevisiae-Guided Enzyme Prodrug Therapy Combined with Immunotherapy for the Treatment of Orthotopic Colorectal Cancer.

Colorectal cancer (CRC) is a major global health concern, and the development of effective treatment strategies is crucial. Enzyme prodrug therapy (EPT) shows promise in combating tumors but faces challenges in achieving sustained expression of therapeutic enzymes and optimal biological distribution. To address these issues, a fungi-triggered in situ chemotherapeutics generator (named as SC@CS@5-FC) was constructed via oral delivery of a prodrug (5-fluorocytosine, 5-FC) for the treatment of orthotopic colorectal tumor. When SC@CS@5-FC targets the tumor through tropism by Saccharomyces cerevisiae (SC), the chemotherapeutic generator could be degraded under abundant hyaluronidase (HAase) in the tumor microenvironment by an enzyme-responsive gate to release prodrug (5-FC). And nontoxic 5-FC was catalyzed to toxic chemotherapy drug 5-fluorouracil (5-FU) by cytosine deaminase (CD) of SC. Meanwhile, SC and zinc-coordinated chitosan nanoparticles could be used as immune adjuvants to activate antigen-presenting cells and further enhance the therapeutic effect. Our results demonstrated that SC@CS@5-FC could effectively inhibit tumor growth and prolong mouse survival in an orthotopic colorectal cancer model. This work utilizes living SC as a dynamotor and positioning system for the chemotherapeutic generator SC@CS@5-FC, providing a strategy for oral enzyme prodrug therapy for the treatment of orthotopic colorectal.

Role of hsa_circ_0007482 in pterygium development: insights into proliferation, apoptosis, and clinical correlations.

AIM: To investigate the impact of hsa_circ_0007482 on the proliferation and apoptosis of human pterygium fibroblasts (HPFs) and its correlation with the severity grades of pterygium. METHODS: Pterygium and normal conjunctival tissues were collected from the superior area of the same patient's eye (n=33). The correlation between pterygium severity and hsa_circ_0007482 expression using quantitative reverse-transcription polymerase chain reaction (RT-qPCR) were analyzed. Three distinct siRNA sequences targeting hsa_circ_0007482, along with a negative control sequence, were transfected into HPFs. Cell proliferation was assessed using the cell counting kit-8. Expression levels of Ki67, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bax, B-cell lymphoma-2 (Bcl-2), and Caspase-3 were measured via RT-qPCR. Immunofluorescence staining was employed to detect Ki67 and vimentin expressions. Apoptosis was evaluated using flow cytometry. RESULTS: Hsa_circ_0007482 expression was significantly higher in pterygium tissues compared to normal conjunctival tissues (P<0.001). Positive correlations were observed between hsa_circ_0007482 expression and pterygium severity, thickness, and vascular density. Knockdown of hsa_circ_0007482 inhibited cell proliferation, reducing the mRNA expression of Ki67, PCNA, and Cyclin D1 in HPFs. Hsa_circ_0007482 knockdown induced apoptosis, increasing mRNA expression levels of Bax and Caspase-3, while decreasing Bcl-2 expression in HPFs. Additionally, hsa_circ_0007482 knockdown attenuated vimentin expression in HPFs. CONCLUSION: The downregulation of hsa_circ_0007482 effectively hampers cell proliferation and triggers apoptosis in HPFs. There are discernible positive correlations detected between the expression of hsa_circ_0007482 and the severity of pterygium.

Design and synthesis of 7-azaindole derivatives as potent CDK8 inhibitors for the treatment of acute myeloid leukemia.

It is of great significance to design and synthesize novel structural inhibitors with good antitumor activity. In this study, based on rational design, a total of 42 7-azaindole derivatives as novel CDK8 inhibitors were designed and synthesized. All compounds were screened with antitumor activity and compound 6 (1-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)phenyl)-3-(m-tolyl)urea) exhibited the best activity, especially in acute myeloid leukemia (GI50 MV4-11 = 1.97 ± 1.24 µM). This compound also exhibited excellent inhibitory activity against CDK8 (IC50 = 51.3 ± 4.6 nM). Further mechanism studies shown that it could inhibit STAT5 phosphorylation and induce cell cycle arrest in the G1 phase, leading to apoptosis in acute myeloid leukemia cells. In addition, acute toxicity at a dose of 1000 mg kg-1 indicated the low toxicity of this compound.

Small Molecules Blocking the Assembly of TCAB1 and Telomerase Complexes: Lead Discovery and Biological Activity.

The vast majority of tumor cells maintain the length of the telomeres through a telomerase-dependent maintenance mechanism, allowing for unlimited proliferation. TCAB1 is indispensable for the correct assembly of telomerase complexes and the delivery of telomerase to the telomere. Therefore, this study aimed to explore small molecules capable of interfering with the assembly of TCAB1 and the telomerase complex as novel efficient telomerase inhibitors. Through virtual screening, biological evaluation, and the confirmation of target engagement, the potential ligands of TCAB1 effectively inhibiting telomerase activity were discovered. Among them, compound 9 exhibited telomerase inhibitory activity at a two-digit nanomolar level (IC50 = 0.03 µM), which was dramatically enhanced in comparison with the previously reported telomerase inhibitors. This research, based on the blockage of telomerase assembly through disturbing TCAB1, provides a novel strategy and a potential target for telomerase inhibitor discovery.

Nanoengineered Nonenzymatic Paper-Based Fluorescent Platform for Pre-Dilution-Free and Visual Real-Time Home Monitoring of Urea for Early Warning of Abnormal Nitrogen-Based Unhealthy Issues.

Distorted urea levels indicate several liver, kidney, or metabolic diseases; however, traditional clinical urea detection relies on urease-based methods enslaved to well-known limitations of high-price, unstable properties, complicated sample pretreatment and analysis procedures, and difficult visual real-time monitoring. Herein, nonenzymatic paper-based fluorescent materials (UFP-BP) are strategically integrated with an on-demand fluorescent-sensor (UFP) self-aggregated nanoparticle on commercial filter paper for pre-dilution-free and visual real-time urea monitoring. The UFP is synthesized and self-aggregated into the fluorescent nanoparticles for selective urea recognition. Then, the nanoparticles are interstitially loaded on filter paper to nanoengineer the UFP-BP, achieving selective quantitative urea detection in the normal concentration range (10-1000 mm). UFP and UFP-BP can successfully monitor urea levels in real rat urine, artificial simulants, and milk. The proposed sensing platform, integrated with smartphones, offers accurate, quantitative, nonenzymatic, noninvasive, pre-dilution-free, on-site, rapid, low-cost, easy-to-operate, real-time visual urea detection in food samples and human body fluids. The designed sensing system can provide early warnings of abnormal nitrogen-based health issues.

Advances in small-molecule fluorescent probes for the study of apoptosis.

Apoptosis, as type I cell death, is an active death process strictly controlled by multiple genes, and plays a significant role in regulating various activities. Mounting research indicates that the unique modality of cell apoptosis is directly or indirectly related to different diseases including cancer, autoimmune diseases, viral diseases, neurodegenerative diseases, etc. However, the underlying mechanisms of cell apoptosis are complicated and not fully clarified yet, possibly due to the lack of effective chemical tools for the nondestructive and real-time visualization of apoptosis in complex biological systems. In the past 15 years, various small-molecule fluorescent probes (SMFPs) for imaging apoptosis in vitro and in vivo have attracted broad interest in related disease diagnostics and therapeutics. In this review, we aim to highlight the recent developments of SMFPs based on enzyme activity, plasma membranes, reactive oxygen species, reactive sulfur species, microenvironments and others during cell apoptosis. In particular, we generalize the mechanisms commonly used to design SMFPs for studying apoptosis. In addition, we discuss the limitations of reported probes, and emphasize the potential challenges and prospects in the future. We believe that this review will provide a comprehensive summary and challenging direction for the development of SMFPs in apoptosis related fields.

Advances in the synthesis and applications of macrocyclic polyamines.

Macrocyclic polyamines constitute a significant class of macrocyclic compounds that play a pivotal role in the realm of supramolecular chemistry. They find extensive applications across diverse domains including industrial and agricultural production, clinical diagnostics, environmental protection and other multidisciplinary fields. Macrocyclic polyamines possess a distinctive cavity structure with varying sizes, depths, electron-richness degrees and flexibilities. This unique feature enables them to form specific supramolecular structures through complexation with diverse objects, thereby attracting considerable attention from chemists, biologists and materials scientists alike. However, there is currently a lack of comprehensive summaries on the synthesis methods for macrocyclic polyamines. In this review article, we provide an in-depth introduction to the synthesis of macrocyclic polyamines while analysing their respective advantages and disadvantages. Furthermore, we also present an overview of the recent 5-year advancements in using macrocyclic polyamines as non-viral gene vectors, fluorescent probes, diagnostic and therapeutic reagents as well as catalysts. Looking ahead to future research directions on the synthesis and application of macrocyclic polyamines across various fields will hopefully inspire new ideas for their synthesis and use.

Histone deacetylase 8 promotes innate antiviral immunity through deacetylation of RIG-I.

Histone deacetylates family proteins have been studied for their function in regulating viral replication by deacetylating non-histone proteins. RIG-I (Retinoic acid-inducible gene I) is a critical protein in RNA virus-induced innate antiviral signaling pathways. Our previous research showed that HDAC8 (histone deacetylase 8) involved in innate antiviral immune response, but the underlying mechanism during virus infection is still unclear. In this study, we showed that HDAC8 was involved in the regulation of vesicular stomatitis virus (VSV) replication. Over-expression of HDAC8 inhibited while knockdown promoted VSV replication. Further exploration demonstrated that HDAC8 interacted with and deacetylated RIG-I, which eventually lead to enhance innate antiviral immune response. Collectively, our data clearly demonstrated that HDAC8 inhibited VSV replication by promoting RIG-I mediated interferon production and downstream signaling pathway.

Deuterium Editing of Small Molecules: A Case Study on Antitumor Activity of 1,4-Benzodiazepine-2,5-dione Derivatives.

Substituting hydrogen with deuterium in drug molecules is an appealing bioisosteric strategy for the generation of novel chemical entities in drug development. Optimizing lead compounds through deuteration has proven to be challenging and unpredictable, particularly for compounds with multiple metabolic sites. This study presents the pioneering achievement of substituting up to 19 hydrogen atoms with deuterium on 1,4-benzodiazepine-2,5-dione derivatives, shedding light on the structure-metabolism relationship and the impact of multiple deuterations on drug-like properties. Notably, the deuterated compound 3f exhibited remarkable antitumor activity in vivo and demonstrated favorable drug-like properties as a drug candidate.

Construction of Iron-Scavenging Hydrogel via Thiol-Ene Click Chemistry for Antibiotic-Free Treatment of Bacterial Wound Infection.

Bacteria, especially drug-resistant strains, can quickly cause wound infections, leading to delayed healing and fatal risk in clinics. With the growing need for alternative antibacterial approaches that rely less on antibiotics or eliminate their use altogether, a novel antibacterial hydrogel named Ovtgel is developed. Ovtgel is formulated by chemically crosslinking thiol-modified ovotransferrin (Ovt), a member of the transferrin family found in egg white, with olefin-modified agarose through thiol-ene click chemistry. Ovt is designed to sequester ferric ions essential for bacterial survival and protect wound tissues from damages caused by the reactive oxygen species (ROS) generated in Fenton reactions. Experimental data have shown that Ovtgel significantly enhances wound healing by inhibiting bacterial growth and shielding tissues from ROS-induced harms. Unlike traditional antibiotics, Ovtgel targets essential trace elements required for bacterial survival in the host environment, preventing the development of drug resistance in pathogenic bacteria. Ovtgel exhibits excellent biocompatibility due to the homology of Ovt to mammalian transferrin. This hydrogel has the potential to serve as an effective antibiotic-free solution for combating bacterial infections.

One-step approach to fabricating amphoteric polymer fatliquors for chrome-free tanned leather eco-manufacturing.

The leather manufacturing industry is increasingly embracing chrome-free tanning methods to promote environmental sustainability. However, the transition to chrome-free tanning systems presents a notable obstacle: the incompatibility of traditional anionic wet finishing materials with chrome-free tanned leather due to differences in surface electrical behavior. Herein, an amphoteric polymer, referred to P(AA-co-DMAEMA-co-DA), was synthesized through a simple one-step free radical copolymerization using acrylic acid (AA), dimethylaminoethyl methacrylate (DMAEMA), and dodecyl acrylate (DA). Notably, the isoelectric point of P(AA-co-DMAEMA-co-DA) is 7.7, which contributes to improving the leather's positive electric property and enhancing the binding between the amphoteric polymer fatliquors (APF) and collagen fiber. The APF achieves a remarkable absorption rate of 96.2% and a dyeing uptake rate of 94.3% for anionic dyes, resulting in a uniformly bright surface color of the dyed leather and further significantly reducing the dye usage. Overall, the comprehensive properties of APF align with the electrical origins of organic chrome-free tanning leather, exhibiting a pronounced fatliquoring effect while reducing the dye content in the waste liquor. This contribution holds promise for advancing chrome-free tanning technology toward greener environmental practices.

FAK inhibitors in cancer, a patent review - an update on progress.

INTRODUCTION: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation. AREAS COVERED: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research. EXPERT OPINION: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.

Integrative transcriptomic profiling of ncRNAs and mRNAs in developing mouse lens.

In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.

Discarded enoki mushroom root-derived multifunctional chrome-free chitosan-based tanning agent for eco-leathers manufacturing: Tanning-dyeing, non-acid soaking, and non-basifying.

The aim of this study was to develop new discarded enoki mushroom root-derived multifunctional chrome-free chitosan-based tanning agents that can be used for eco-leather manufacturing. In this study, oligochitosan (OCS) was prepared from chitosan extracted from the enoki mushrooms and chemically modified using reactive dye R19 and epichlorohydrin (ECH) to prepare chromium-free tanning agent (OCS-R19-ECH) with both tanning and dyeing functions. FT-IR, XRD, and NMR (1H) confirmed the successful synthesis of the product. The molecular weight of OCS-R19-ECH is 6355 g/mol, with an average particle size of 1249.37 nm and an epoxy value of 0.276 mol/100 g. OCS-R19-ECH was used for tanning experiments on bated sheepskin, and the results showed that the leather tanned with OCS-R19-ECH not only exhibited excellent wet-heat stability (shrinkage temperature = 81 °C), but also superior dyeing uniformity, resistance to dry and wet abrasion, mechanical strength (tensile strength = 12.4 MPa, tear strength = 57.3 N/mm), and outstanding antimicrobial properties. Most importantly, compared with traditional tanning agents, OCS-R19-ECH has a higher pH (9.0), tanning-dyeing integration, non-acid soaking, and non-basifying can be achieved in leather making, which can greatly simplify the tanning processes. This new multifunctional chrome-free chitosan-based tanning agent facilitates high-value utilization of waste resources.

Neratinib impairs function of m6A recognition on AML1-ETO pre-mRNA and induces differentiation of t (8;21) AML cells by targeting HNRNPA3.

Acute myeloid leukemia (AML) is frequently linked to genetic abnormalities, with the t (8; 21) translocation, resulting in the production of a fusion oncoprotein AML1-ETO (AE), being a prevalent occurrence. This protein plays a pivotal role in t (8; 21) AML's onset, advancement, and recurrence, making it a therapeutic target. However, the development of drug molecules targeting AML1-ETO are markedly insufficient, especially used in clinical treatment. In this study, it was uncovered that Neratinib could significantly downregulate AML1-ETO protein level, subsequently promoting differentiation of t (8; 21) AML cells. Based on "differentiated active" probes, Neratinib was identified as a functional inhibitor against HNRNPA3 through covalent binding. The further studies demonstrated that HNRNPA3 function as a putative m6A reader responsible for recognizing and regulating the alternative splicing of AML-ETO pre-mRNA. These findings not only contribute to a novel insight to the mechanism governing post-transcriptional modification of AML1-ETO transcript, but also suggest that Neratinib would be promising therapeutic potential for t (8; 21) AML treatment.

Local Application of Tanshinone IIA protects mesenchymal stem cells from apoptosis and promotes fracture healing in ovariectomized mice.

BACKGROUND: Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing. METHODS: MSCs were pretreated with or without different concentrations of Tanshinone IIA followed by H2O2 treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel. RESULTS: Tanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited H2O2-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed H2O2-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation. CONCLUSIONS: Taken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from H2O2-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.

All-weather-available down carbon fiber hydrogel with enhanced mechanical properties for simultaneous efficient clean water generation and dye adsorption from dye wastewater.

Solar-driven photothermal conversion can produce clean water from dye wastewater while leaving the dye in the evaporation medium. Herein, a biomass-based composite hydrogel via down-fiber carbon (DFC) aerogel modified with chitosan-polyvinyl alcohol (CS-PVA) hydrogel was designed to address the aforementioned problem. The CS-PVA@DFC hydrogel integrated the capacity of simultaneous clean water production/dye adsorption during the day and continuous dye adsorption during the night. Furthermore, the modification of the CS-PVA hydrogel endowed the composite hydrogel with enhanced compression stress of 190.07 kPa (76.03 times that of DFC aerogel of 2.50 kPa) and impressive resilient recovery. Moreover, the CS-PVA@DFC hydrogel possessed solar light absorption of 99.56 % and strengthened water replenishment capacity due to the high porosity and CS-PVA hydrophilic network structure. The CS-PVA@DFC hydrogel demonstrated a stable, high evaporation rate of 2.34 kg·m-2·h-1 and simultaneous dye adsorption capacity of 70.39 % for treating methyl orange dye solution within 5 h. Additionally, the 24-h outdoor test showed that the CS-PVA@DFC hydrogel possessed excellent clean water production capacity during the daytime (reaching 4.17 kg·m-2·h-1 at 1:00p.m.) and continuous satisfactory dye adsorption capacity all day (89.68 %). These findings will inspire researchers seeking opportunities to improve the mechanical properties of aerogel and its application for treating wastewater, especially wastewater with harmful dyes.

Material Engineering Strategies for Efficient Hydrogen Evolution Reaction Catalysts.

Water electrolysis, a key enabler of hydrogen energy production, presents significant potential as a strategy for achieving net-zero emissions. However, the widespread deployment of water electrolysis is currently limited by the high-cost and scarce noble metal electrocatalysts in hydrogen evolution reaction (HER). Given this challenge, design and synthesis of cost-effective and high-performance alternative catalysts have become a research focus, which necessitates insightful understandings of HER fundamentals and material engineering strategies. Distinct from typical reviews that concentrate only on the summary of recent catalyst materials, this review article shifts focus to material engineering strategies for developing efficient HER catalysts. In-depth analysis of key material design approaches for HER catalysts, such as doping, vacancy defect creation, phase engineering, and metal-support engineering, are illustrated along with typical research cases. A special emphasis is placed on designing noble metal-free catalysts with a brief discussion on recent advancements in electrocatalytic water-splitting technology. The article also delves into important descriptors, reliable evaluation parameters and characterization techniques, aiming to link the fundamental mechanisms of HER with its catalytic performance. In conclusion, it explores future trends in HER catalysts by integrating theoretical, experimental and industrial perspectives, while acknowledging the challenges that remain.

Successful diagnosis of Mycobacterium marinum infection by mNGS in a patient with Human Immunodeficiency Virus: a case report.

INTRODUCTION: Mycobacterium marinum infection rarely occurs and has atypical symptoms. It is challenging to distinguish disseminated M. marinum infection from multifocal dermatosis caused by other factors clinically. CASE PRESENTATION: Herein, we reported a 68-year-old male patient with Human Immunodeficiency Virus (HIV) who presented redness and swelling in his left hand after being stabbed by marine fish for over 2 months. Mycobacterium tuberculosis infection was considered according to biochemical and pathological examinations, while empirical anti-infection treatment was ineffective. RESULTS: The metagenomic next-generation sequencing (mNGS) detected a large amount of M. marinum sequences, and the patient was finally diagnosed with M. marinum infection. After one month of combination therapy with ethambutol, rifabutin, moxifloxacin, and linezolid, the swelling disappeared significantly. In this case, the successful application of mNGS in diagnosing and treating M. marinum infection has improved the understanding of the microbe both in the laboratory and clinically, especially in patients with HIV. CONCLUSIONS: For diseases with atypical symptoms or difficulty in determining the pathogens, mNGS is suggested in clinical procedures for rapid and accurate diagnosis and treatment.

Effect of cellulase on dough structure and quality characteristics of tough biscuits enriched with potato whole flour.

Potato whole flour is a promising way to improve the nutrition of tough biscuits, while its gluten-free characteristic was difficult to form acceptable texture properties. In this study, cellulase was used to degrade the cellulose in dough enriched with potato whole flour, so as to mitigate the interference of cellulose with the gluten network, resulting in forming the potato whole flour biscuit with great characteristics. Results indicated that cellulase within 0.2% led to the gradually reduced G' and G'' values of dough from 5.50×104 to 4.00×104 and 2.66×104 to 1.35×104, respectively. Cellulase at 0.2% resulted in the significantly increased tensile properties of the dough compared to the control. The incorporation of cellulase within 0.2% also led to the tightly ordered and intact network structure base on the results of SEM, disulfide bonds determination and FTIR. Those results indicated that cellulase was beneficial to improve the baking quality of dough, which was conductive to form tough biscuit with great characteristics. The hardness, crunchiness, crispness and specific volume analysis results confirmed that 0.2% cellulase resulted in the significantly decreased hardness by 45.25% and the significantly increased specific volume, crunchiness and crispness by 24.74%, 121.20% and 156.47%, respectively. Overall, cellulase ultimately improved the quality of the biscuits by improving the properties and structure of the dough. It was of great significance for the utilization of potato whole flour resources and the industrial production of its tough biscuits. PRACTICAL APPLICATION: The results showed that inclusion of cellulase led to the reduced hardness and increased crunchiness, crispness, and specific volume of potato whole flour tough biscuits. Cellulase could be used as a potential improver of tough biscuits. This study will provide guidance for practical uses of cellulase in improving potato whole flour dough and tough biscuit quality.