LncRNA PCBP1-AS1 suppresses cell growth in oral squamous cell carcinoma by targeting miR-34c-5p/ZFP36 axis.

Oral squamous cell carcinoma (OSCC) is the most frequently diagnosed oral malignancy and poses a great threat to public health. According to bioinformatics analysis, long noncoding RNA PCBP1-AS1 is downregulated in OSCC. In this work, the functions and mechanism of PCBP1-AS1 in OSCC were further investigated. PCBP1-AS1 expression in OSCC cells was measured by quantitative polymerase chain reaction. Cell viability and proliferation were detected using CCK-8 assays and colony-forming assays. TUNEL assays as well as flow cytometry analyses were carried out to detect OSCC cell apoptosis. Binding relationship between PCBP1-AS1 and miR-34c-5p or that between miR-34c-5p and ZFP36 in OSCC cells was identified using RNA immunoprecipitation assays, RNA pulldown assays, and luciferase reporter assays. Experimental results revealed that PCBP1-AS1 was downregulated in OSCC cells. PCBP1-AS1 overexpression hampered cell proliferation and enhanced cell apoptosis in OSCC. PCBP1-AS1 interacted with miR-34c-5p in OSCC and negatively regulated miR-34c-5p. ZFP36 3'untranslated region was targeted by miR-34c-5p. PCBP1-AS1 positively regulated ZFP36 expression. ZFP36 silencing abrogated the suppressive impact of PCBP1-AS1 on OSCC cell growth. In summary, PCBP1-AS1 suppresses cell growth in OSCC by upregulating ZFP36 through interaction with miR-34c-5p.

Benefit-Cost Analysis for Earthquake-Resilient Building Design and Retrofit: State of the Art and Future Research Needs.

This paper reviews the state of the art in using benefit-cost analysis (BCA) to inform earthquake risk reduction decisions by building owners and policymakers. The goal is to provide a roadmap for the application and future development of BCA methods and tools for earthquake risk reduction. Our review covers three earthquake risk reduction measures: adopting up-to-date building codes for new construction, designing new buildings to exceed code requirements, and retrofitting deficient existing buildings. We highlight the factors that influence the cost-effectiveness of building design and retrofit, as well as tactics for increasing the cost-effectiveness of risk reduction strategies. We also present BCA results, methods, and data sources used in the literature to help researchers and practitioners design and conduct a reliable and robust BCA study. In the process, we develop a set of opportunities and challenges for applying BCA to new areas of research, as well as key gaps and limitations in current BCA approaches, including further investigation of above-code design, incorporation of code implementation and enforcement into BCA, quantification of environmental benefits of seismic retrofits, and optimization of seismic retrofits with energy upgrades. Overall, our review provides practical guidance and useful insights into BCA with the goal of increasing the earthquake resilience and economic efficiency of buildings in the United States.

WWOX-related epileptic encephalopathy caused by a novel mutation in the WWOX gene: a case report.

Background: WWOX-related epileptic encephalopathy is an autosomal recessive disorder caused by mutations in the WW-containing oxidoreductase gene, characterized by the onset of refractory seizures in infants. Early-onset epilepsy, electroencephalography abnormalities, and developmental delay or degeneration are the main clinical manifestations. Early death can occur in severe cases. In the present study, a novel variant in WWOX was detected in a patient with epilepsy and his healthy parents. Case presentation: A 5-month-old boy presented with epilepsy. The main manifestations were intractable seizures, mental and motor retardation and hearing impairment. Subsequent genetic testing revealed the presence of an epilepsy-associated novel mutation: c.991C>A (amino acid change: p.Ser304Tyr) in the WWOX gene. Variants were inherited from parents with healthy phenotypes. Finally, a patient died at 6 months of age. Conclusion: The discovery of novel variants has enriched the existing database of WWOX gene variants and may expand the range of clinical options for treating WWOX-related disorders.

[Professor YANG Jun's experience in treatment of neuropathic tinnitus with acupuncture and moxibustion based on disease elements].

Based on Chinese medicine classics, combined with clinical experience and modern research findings, Professor YANG Jun deepens the analysis on the etiology and pathogenesis of neuropathic tinnitus, and has summarized the TCM elements of this disease, including "qi and blood stagnation" and "shen (spirit) hidden and orifices closed". The multiple therapies are used in combination, such as acupuncture, electroacupuncture, warm needling, borneol-moxibustion and herbal medication. The different acupoints are combined according to individuals, especially the application of Tinggong (SI 19) and Yamen (GV 15). The comprehensive treatment overlaps the dose effects, co-acts on activating blood circulation in meridians, calming-down the spirit and opening the orifices so that the therapeutic effect of acupuncture and moxibustion can be improved on this disease.

The characteristics and associations between trait and state time perspective in adolescents with depression: a questionnaire and sandplay study.

Background: Time perspective is strongly associated with depression. However, the characteristics and associations between trait and state time perspective in adolescents with depression remain unknown. Methods: A total of 211 adolescents with depression (mean age: 14.60 ± 1.69 years) and 215 healthy controls (mean age: 14.66 ± 1.73 years) were selected and assessed using the Chinese version of the Zimbardo Time Perspective Inventory to quantify their trait time perspective. Thirty adolescents were randomly selected from each group to create nine-grid sandplay productions to assess their state time perspective. Results: (1) Regarding the trait time perspective, depressed adolescents scored significantly higher on past negative, present fatalistic, present impulsive, and deviation-balanced time perspective (p < 0.001) and significantly lower on past positive and future (p < 0.05) compared to the control group. (2) In terms of state time perspective, depressed adolescents showed a significantly higher number of squares related to past negative, present negative, and future negative in their nine-grid sandplay productions compared to the control group (p < 0.01).Conversely, they had significantly fewer squares associated with past positive, present positive, future positive than the control group (p < 0.05). (3) Past negative, present fatalistic, and deviation from balanced time perspective traits were negatively correlated with positive state time perspective and positively correlated with negative state time perspective. Past positive and future traits were positively correlated with positive state time perspective and negatively correlated with negative state time perspective. Conclusion: Adolescents with depression are characterized by dwelling on the past, having a severely negative attitude toward the past, being pessimistic about the future, and having a tendency to blame fate or external forces for their problems. In the future, standardized methods for measuring state time perspective should be further explored, as well as the effectiveness of the nine-grid sandplay, for improving time perspective in patients with depression.

The impact of indirect structure on functional connectivity in schizophrenia using a multiplex brain network.

It is known that abnormal functional connectivity (FC) in schizophrenia (SZ) is closely related to structural connectivity (SC). We speculate that indirect SC also have an impact on FC in SZ patients. Conventional single-layer network has limitations for studying the relationship between indirect SC and FC. Thus, this study constructed a multiplex network based on structural connectivity and functional connectivity (SC-FC). The SC-FC bandwidth and SC-FC cost are used to analyze the impact of indirect SC on FC. Moreover, this paper proposed mediation ability, mediation cost, mediated strength and mediated cost to quantify the effects of mediator nodes and mediated nodes on indirect SC. The results show that SZ patients exhibit lower SC-FC bandwidth and SC-FC cost compared to healthy controls (HC), which could be caused by the limbic and subcortical network (LSN), default mode network (DMN) and visual network (VN). The mediator and mediated nodes in indirect SC of SZ patients also showed diminished effects. These findings suggest that functional communication ability and cost in SZ patients are influenced by indirect SC. This study provides new perspectives for understanding the relationship between indirect SC and FC, and provides strong evidence for interpreting the physiological mechanisms of SZ patients.

Abnormal Dynamic Reconfiguration of Multilayer Temporal Networks in Patients with Bipolar Disorder.

BACKGROUND: Multilayer networks have been used to identify abnormal dynamic reconfiguration in bipolar disorder (BD). However, these studies ignore the differences in information interactions between adjacent layers when constructing multilayer networks, and the analysis of dynamic reconfiguration is not comprehensive enough; Methods: Resting-state functional magnetic resonance imaging data were collected from 46 BD patients and 54 normal controls. A multilayer temporal network was constructed for each subject, and inter-layer coupling of different nodes was considered using network similarity. The promiscuity, recruitment, and integration coefficients were calculated to quantify the different dynamic reconfigurations between the two groups; Results: The global inter-layer coupling, recruitment, and integration coefficients were significantly lower in BD patients. These results were further observed in the attention network and the limbic/paralimbic and subcortical network, reflecting reduced temporal stability, intra- and inter-subnetwork communication abilities in BD patients. The whole-brain promiscuity was increased in BD patients. The same results were observed in the somatosensory/motor and auditory network, reflecting more functional interactions; Conclusions: This study discovered abnormal dynamic interactions of BD from the perspective of dynamic reconfiguration, which can help to understand the pathological mechanisms of BD.

MAT1-1 and MAT1-2 Ophiocordyceps xuefengensis and Comparison of Their Chemical Composition.

Many Cordyceps sensu lato species are used as traditional Chinese medicines. However, Cordyceps are entomopathogenic fungi in the family Clavicipitaceae of Ascomycota, and excessive harvesting severely disrupts natural habitat ecosystems. Artificial cultivation of Cordyceps fruiting bodies offers a viable strategy to protect the ecological environment and mitigate the depletion of wild resource. In this study, mononucleate hyphae were selected using DAPI fluorescence staining, the MAT1-1 and MAT1-2 strains of O. xuefengensis were successfully distinguished using loop-mediated isothermal amplification (LAMP). The chemical composition and bioactive components of fruiting bodies produced by these strains were compared. Results showed that the levels of adenosine, thymidine, adenine, guanosine, uridine, total amino acids, and total essential amino acids in the fruiting bodies of MAT1-1 strains were 1.31 mg/g, 0.15 mg/g, 0.26 mg/g, 2.40 mg/g, 2.34 mg/g, 270.3 mg/g, and 102.5 mg/g, respectively, which were significantly higher than those in the MAT1-2 sample. Contrastingly, the fruiting bodies of MAT1-2 strains contained higher levels of mannose and polysaccharides, at 11.7% and 12.2%, respectively. The levels of toxic elements such as Al, Pb, As, and Hg in the MAT1-1 fruiting bodies were 1.862 mg/kg, 0.0848 mg/kg, 0.534 mg/kg, and 0.0054 mg/kg, respectively, which were markedly lower than those in the MAT1-2 fruiting bodies.

Host Factor Rab4b Promotes Japanese Encephalitis Virus Replication.

Although the Japanese encephalitis virus (JEV) infects various cell types, its receptor molecules are still not clearly understood. In our laboratory's prior research, Rab4b was identified as a potential host factor that facilitates JEV infection in PK15 cells, utilizing a genome-wide CRISPR/Cas9 knockout library (PK-15-GeCKO). To further explore the effect of Rab4b on JEV replication, we used the Rab4b knockout PK15 cell line using the CRISPR/Cas9 technology and overexpressing the Rab4b PK15 cell line, with IFA, RT-qPCR, and Western blot to study the effect of Rab4b on viral replication in the whole life cycle of the JEV. The results show that the knockout of Rab4b inhibited the replication of the JEV in PK15 cells, and the overexpression of Rab4b promoted the replication of the JEV in PK15 cell lines. Furthermore, we demonstrated for the first time that host factor Rab4b facilitates the adsorption, internalization, assembly, and release of the JEV, thereby promoting JEV replication. This study enriches the regulatory network between the JEV and host factors and lays the experimental foundation for further understanding of the function of the Rab4b protein.

An Engineering Porous Spherical Carbon Cathode for High-Energy Sodium-Ion Capacitor.

Sodium-ion hybrid capacitors (SICs) are emerging as promising devices that can balance energy and power output. However, the lack of a high-capacity cathode that can match the anode has limited its further application. In this work, we develop an efficient method to prepare spherical porous carbons (SPCs) with great specific surface area and narrow pore size distribution from coal-based humic acid via spray drying and a subsequent chemical activation process. Thanks to this unique porous structure, the SPC cathode has a superb capacity of 223 F g-1 at 0.05 A g-1, as well as splendid rate performance and cycling stability. SICs constructed by an SPC cathode and hard carbon anode can exhibit a high energy density of 179.8 Wh kg-1 at 155 W kg-1 and achieved 89.4% capacity retention after 10 000 cycles at 0.5 A g-1. This outcome presents a viable approach to attaining high-capacity cathodes for constructing outstanding performance hybrid capacitors.

Regulatory Network of the Late-Recruited Primary Decarboxylase C4NADP-ME in Sugarcane.

In agronomically important C4 grasses, efficient CO2 delivery to Rubisco is facilitated by NADP-malic enzyme (C4NADP-ME), which decarboxylates malate in bundle sheath cells. However, understanding the molecular regulation of the C4NADP-ME gene in sugarcane (Saccharum spp.) is hindered by its complex genetic background. Enzymatic activity assays demonstrated that decarboxylation in sugarcane Saccharum spontaneum predominantly relies on the NADP-ME pathway, similar to sorghum (Sorghum bicolor) and maize (Zea mays). Comparative genomics analysis revealed the recruitment of eight core C4 shuttle genes, including C4NADP-ME (SsC4NADP-ME2), in the C4 pathway of sugarcane. Contrasting to sorghum and maize, the expression of SsC4NADP-ME2 in sugarcane is regulated by different transcription factors (TFs). We propose a gene regulatory network for SsC4NADP-ME2, involving candidate TFs identified through gene co-expression analysis and yeast one-hybrid experiment. Among these, ABA INSENSITIVE5 (ABI5) was validated as the predominant regulator of SsC4NADP-ME2 expression, binding to a G-box within its promoter region. Interestingly, the core element ACGT within the regulatory G-box was conserved in sugarcane, sorghum, maize, and rice (Oryza sativa), suggesting an ancient regulatory code utilized in C4 photosynthesis. This study offers insights into SsC4NADP-ME2 regulation, crucial for optimizing sugarcane as a bioenergy crop.

Diabetes distress profiles and health outcomes of individuals with type 2 diabetes and overweight/obesity: A cluster analysis.

AIMS: To determine the prevalence and patterns of diabetes distress, and evaluate the differences in health outcomes between profiles. METHODS: This cross-sectional study included 330 adults with T2DM and overweight/obesity. The participants completed questionnaires on diabetes distress, sleep quality, self-efficacy, depression, anxiety and positive and negative affect. A cluster analysis was performed to identify different patterns of diabetes distress and one-way ANOVA was used to investigate the differences in physical and psychological outcomes between profiles. RESULTS: 30.6% of patients were identified as moderately to highly distressed, with the regimen-related distress found to be the most prominent. The Cluster analysis revealed four distinct clusters: (1) "comprehensively exhausted profile"; (2) "strained profile"; (3) "high internal anguish profile"; (4) "unperturbed profile". The measures of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, sleep quality, depression, anxiety, positive and negative affect and self-efficacy differ between clusters. CONCLUSIONS: This study identified important differences that existed in patterns of diabetes distress among people with T2DM and overweight/obesity, and this variation can be utilized to tailor intervention strategies to the particular needs of different subgroups within individuals with T2DM.

Evolution of land system reforms in China: Dynamics of stakeholders and policy transitions toward sustainable farmland use (2004-2019).

China's central government has prioritized land system reforms in rural parts of the country in the past two decades. The transformation of property rights in lands was a significant step for China to pursue the sustainability of farms and permanent food security. The evolution of land system reforms in China involved constant interplay between stakeholders and policy content in terms of policy objectives and instruments, which exhibited various dynamics in different periods. This study adopted a content analysis method to systematically identify the active, passive, and supportive roles of all kinds of stakeholders as well as policy objectives and instruments in the transitional processes of land system reforms in China. We in sum collected 111 policy texts as samples and modeled the relationships of policy keywords. We found Peasants' Households and New Agricultural Business Entities were the most active stakeholders in different periods. Policy objectives are inclined to the stability of legal rights among stakeholders and the scale production of lands, while policy instruments intensively focused on legal regulations with little attention on financial instruments and human resources. We generated two further policy implications, the protection for the exploitation of lands and the involvement of actual operators, based on our findings.

Impact of a Potent Strain of Plant Growth-Promoting Bacteria (PGPB), Bacillus subtilis S1 on Bacterial Community Composition, Enzymatic Activity, and Nitrogen Content in Cucumber Rhizosphere Soils.

Antagonistic bacterial strains from Bacillus spp. have been widely studied and utilized in the biocontrol of phytopathogens and the promotion of plant growth, but their impacts on the rhizosphere microecology when applied to crop plants are unclear. Herein, the effects of applying the antagonistic bacterium Bacillus subtilis S1 as a biofertilizer on the rhizosphere microecology of cucumbers were investigated. In a pot experiment on cucumber seedlings inoculated with S1, 3124 bacterial operational taxonomic units (OTUs) were obtained from the rhizosphere soils using high-throughput sequencing of 16S rRNA gene amplicons, and the most abundant phylum was Proteobacteria that accounted for 49.48% in the bacterial community. S1 treatment significantly reduced the abundances of soil bacterial taxa during a period of approximately 30 days but did not affect bacterial diversity in the rhizosphere soils of cucumbers. The enzymatic activities of soil nitrite reductase (S-Nir) and dehydrogenase (S-DHA) were significantly increased after S1 fertilization. However, the activities of soil urease (S-UE), cellulase (S-CL), and sucrase (S-SC) were significantly reduced compared to the control group. Additionally, the ammonium- and nitrate-nitrogen contents of S1-treated soil samples were significantly lower than those of the control group. S1 fertilization reshaped the rhizosphere soil bacterial community of cucumber plants. The S-CL activity and nitrate-nitrogen content in rhizosphere soil affected by S1 inoculation play important roles in altering the abundance of rhizosphere soil microbiota.

Artificial Intelligence-Based Facial Palsy Evaluation: A Survey.

Facial palsy evaluation (FPE) aims to assess facial palsy severity of patients, which plays a vital role in facial functional treatment and rehabilitation. The traditional manners of FPE are based on subjective judgment by clinicians, which may ultimately depend on individual experience. Compared with subjective and manual evaluation, objective and automated evaluation using artificial intelligence (AI) has shown great promise in improving traditional manners and recently received significant attention. The motivation of this survey paper is mainly to provide a systemic review that would guide researchers in conducting their future research work and thus make automatic FPE applicable in real-life situations. In this survey, we comprehensively review the state-of-the-art development of AI-based FPE. First, we summarize the general pipeline of FPE systems with the related background introduction. Following this pipeline, we introduce the existing public databases and give the widely used objective evaluation metrics of FPE. In addition, the preprocessing methods in FPE are described. Then, we provide an overview of selected key publications from 2008 and summarize the state-of-the-art methods of FPE that are designed based on AI techniques. Finally, we extensively discuss the current research challenges faced by FPE and provide insights about potential future directions for advancing state-of-the-art research in this field.

Type II photoinitiators with collagen-based cyanine for cell encapsulation under green-red LED.

3D bioprinting with cell-laden materials is an emerging technique for fabricating functional tissue constructs. However, current cell-laden bioinks often lack sufficient cytocompatibility with commonly used UV-light sources. In this study, green to red photoinduced hydrogel crosslinking was obtained by introducing synthesized biosafety photoinitiators and used in light-based direct ink writing (DIW) 3D printing for enabling cell encapsulation successfully. The novel type II photointiators contain iodonium (ONI) and synthesized cyanine dyes CZBIN, TDPABIN, Col-SH-CZ, and Col-SH-TD with strong absorption in the range of 400-600 nm. Collagen-based macromolecule dyes Col-SH-CZ and Col-SH-TD showed excellent cytocompatibility. The photochemistry of these photoinitiators revealed an efficient photoinduced electron transfer (PET) process from the singlet excited states of the dyes to iodonium (ONI), facilitating the crosslinking of the biogels. L929 cells were encapsulated in Gel-MA hydrogels containing various photoinitiating systems and exposed to near-ultraviolet, green, or red LED irradiation. DIW-type 3D printing of Gel-MA bioink with L929 cells was also evaluated. The cell viability achieved with green light encapsulation reached 90 %. This novel approach offers promising prospects for bioprinting functional tissues with enhanced cytocompatibility under visible light conditions.

CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Salivary-secreted vitellogenin suppresses H2O2 burst of plants facilitating Recilia dorsalis leafhopper feeding.

BACKGROUND: Vitellogenin (Vg), known as the yolk protein precursor for oocyte development in female insects, can be secreted to plant host from salivary glands of hemipterans, including rice leafhopper Recilia dorsalis. The aim of this study was to investigate the function of salivary-secreted Vg of R. dorsalis (RdVg) in rice host. We propose that RdVg possibly regulates the rice defense against insects, benefiting R. dorsalis feeding. RESULTS: RdVg was released into rice phloem along with saliva during R. dorsalis feeding. Knocking down RdVg increased the level of H2O2 and improved H2O2 metabolism in rice plants, making it difficult for R. dorsalis to feed. The transient expression or overexpression of the lipoprotein N-terminal domain of RdVg (RdVg2) significantly reduced hydrogen peroxide (H2O2) metabolism in plants. This suggests that salivary-secreted RdVg acts as an effector suppressing the H2O2 burst in rice plants, and RdVg2 is the key domain. RdVg2 could interact with rice sulfite oxidase (OsSO), which catalyzes the oxidation of SO3 2- and produces H2O2. Exposure of rice plants to R. dorsalis, overexpression of RdVg2 or knocking out OsSO reduced OsSO accumulation and SO3 2- oxidation, benefiting R. dorsalis feeding. However overexpression of OsSO increased SO3 2- oxidation and H2O2 metabolism, inhibiting R. dorsalis feeding. CONCLUSION: RdVg inhibits H2O2 generation via suppressing OsSO accumulation, ultimately benefiting R. dorsalis feeding. These findings identify RdVg as an effector that suppresses plant defense to insects, and provide insights into the function of salivary-secreted Vg in other Hemiptera insects. © 2024 Society of Chemical Industry.

Altruistic seagull optimization algorithm enables selection of radiomic features for predicting benign and malignant pulmonary nodules.

Accurately differentiating indeterminate pulmonary nodules remains a significant challenge in clinical practice. This challenge becomes increasingly formidable when dealing with the vast radiomic features obtained from low-dose computed tomography, a lung cancer screening technique being rolling out in many areas of the world. Consequently, this study proposed the Altruistic Seagull Optimization Algorithm (AltSOA) for the selection of radiomic features in predicting the malignancy risk of pulmonary nodules. This innovative approach incorporated altruism into the traditional seagull optimization algorithm to seek a global optimal solution. A multi-objective fitness function was designed for training the pulmonary nodule prediction model, aiming to use fewer radiomic features while ensuring prediction performance. Among global radiomic features, the AltSOA identified 11 interested features, including the gray level co-occurrence matrix. This automatically selected panel of radiomic features enabled precise prediction (area under the curve = 0.8383 (95 % confidence interval 0.7862-0.8863)) of the malignancy risk of pulmonary nodules, surpassing the proficiency of radiologists. Furthermore, the interpretability, clinical utility, and generalizability of the pulmonary nodule prediction model were thoroughly discussed. All results consistently underscore the superiority of the AltSOA in predicting the malignancy risk of pulmonary nodules. And the proposed malignant risk prediction model for pulmonary nodules holds promise for enhancing existing lung cancer screening methods. The supporting source codes of this work can be found at: https://github.com/zzl2022/PBMPN.

An Endocellulase-Triggered NO Targeted-Release Enzyme-Prodrug Therapy System and Its Application in Ischemia Injury.

Nitric oxide (NO) is a crucial gaseous signaling molecules in regulating cardiovascular, immune, and nervous systems. Controlled and targeted NO delivery is imperative for treating cancer, inflammation, and cardiovascular diseases. Despite various enzyme-prodrug therapy (EPT) systems facilitating controlled NO release, their clinical utility is hindered by nonspecific NO release and undesired metabolic consequence. In this study, a novel EPT system is presented utilizing a cellobioside-diazeniumdiolate (Cel2-NO) prodrug, activated by an endocellulase (Cel5A-h38) derived from the rumen uncultured bacterium of Hu sheep. This system demonstrates nearly complete orthogonality, wherein Cel2-NO prodrug maintains excellent stability under endogenous enzymes. Importantly, Cel5A-h38 efficiently processes the prodrug without recognizing endogenous glycosides. The targeted drug release capability of the system is vividly illustrated through an in vivo near-infrared imaging assay. The precise NO release by this EPT system exhibits significant therapeutic potential in a mouse hindlimb ischemia model, showcasing reductions in ischemic damage, ambulatory impairment, and modulation of inflammatory responses. Concurrently, the system enhances tissue repair and promotes function recovery efficacy. The novel EPT system holds broad applicability for the controlled and targeted delivery of essential drug molecules, providing a potent tool for treating cardiovascular diseases, tumors, and inflammation-related disorders.