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Background and Objectives: The Hot AXIOS system, which features a cautery-enhanced lumen-apposing metal stent, facilitates EUS-guided transmural drainage of pancreatic fluid collection (PFC). We aimed to evaluate the safety and efficacy of stents in a multicenter Chinese cohort. Patients and Methods: Thirty patients from nine centers with a single pancreatic pseudocyst (PP) or walled-off necrosis (WON) who underwent EUS-guided transgastric or transduodenal drainage with the novel stent were prospectively enrolled. Results: We included 15 (50%) patients with PPs and 15 (50%) with WONs. The mean diameter of the PFCs was 11.06 ± 3.56 cm. Stent placement was technically successful in all patients (100%), whereas clinical success was achieved in 93.3% of patients (28/30). Clinical success was defined as the alleviation of clinical symptoms combined with at least a 50% reduction in PFC diameter within 60 days after surgery. 73.3% (22/30) of AXIOS stents were removed after reaching clinical success in the 1st month of follow-up. A total of 14 (46.7%) PFC-associated infections occurred (4 pre- and 10 postoperation), which recovered within 1 week after treatment. Other complications included three (10%) partially or fully blocked stents and two (6.7%) stent migrations. Regarding the fully opened stent without blocking, complete remission of PFCs within 1 month was independently predicted by a previous pancreatitis attack > 6 months prior (adjusted odds ratio: 11.143; 95% confidence interval: 1.108-112.012; P = 0.041). Conclusion: EUS-guided drainage of PFCs using the Hot AXIOS system is safe and efficient. Regarding completely patent stents, a previous pancreatitis attack > 6 months prior predicts a greater chance of achieving 100% remission of PFCs within 1 month of AXIOS treatment.
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AIM: Long noncoding RNAs (lncRNAs) are key mediators with a wide range of pathophysiological functions, but their role in human hepatocellular carcinoma (HCC) is still unclear. METHODS: An unbiased microarray study evaluated a novel lncRNA, HClnc1, that is linked to the development of HCC. In vitro cell proliferation assays and an in vivo xenotransplanted HCC tumor model were performed to determine its functions, followed by antisense oligo-coupled mass spectrometry to identify HClnc1-interacting proteins. To study relevant signaling pathways, in vitro experiments were performed, including chromatin isolation by RNA purification, RNA immunoprecipitation, luciferase, and RNA pull-down assay. RESULTS: HClnc1 levels were considerably greater in patients with advanced tumor-node-metastatic stages, and it was found to be inversely connected to survival rates. Moreover, the proliferative and invasive potential of the HCC cells was attenuated by HClnc1 RNA knockdown in vitro, while HCC tumor growth and metastasis were found to be reduced in vivo. HClnc1 interacted with pyruvate kinase M2 (PKM2) to prevent its degradation and thus facilitated aerobic glycolysis and PKM2-STAT3 signaling. CONCLUSIONS: HClnc1 is involved in a novel epigenetic mechanism of HCC tumorigenesis and PKM2 regulation. HClnc1 is not only a more accurate prognostic indicator of HCC but also a potential therapeutic target for HCC treatment.
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Microplastics have been widely studied for their ability to adsorb heavy metals. In the natural environment, arsenic exists in different forms and its toxicity depends mainly on its form and concentration. However, different forms of arsenic combined with microplastics have yet to be explored for their biological hazards. This study was conducted to reveal the adsorption mechanism of different forms of arsenic onto PSMP and to study the effects of PSMP on the tissue accumulation and developmental toxicity of different forms of arsenic in zebrafish larvae. As a result, the absorbing ability of PSMP for As(III) was 35 times higher than that of DMAs, in which hydrogen bonding plays an important role in the adsorption process. In addition, the adsorption kinetics of As(III) and DMAs on PSMP were in good agreement with the pseudo-second-order kinetic model. Furthermore, PSMP reduced the accumulation of As(III) early in zebrafish larvae development, thereby increasing hatching rates compared with the As(III)-treated group, whereas PSMP had no significant effect on DMAs accumulation in zebrafish larvae, but decreased hatching rates compared with the DMAs-treated group. In addition, except for the microplastic exposure group, the other treatment groups could lead to a decrease in the heart rate of zebrafish larvae. Both PSMP+As(III) and PSMP+DMAs exhibited aggravated oxidative stress compared with PSMP-treated group, but PSMP+As(III) caused more severe oxidative stress at later stages of zebrafish larvae development. Moreover, specific metabolic differences (e.g., AMP, IMP, and guanosine) were produced in the PSMP+As(III) exposure group, which would mainly affect purine metabolism and promoted specific metabolic disturbances. However, PSMP+DMAs exposure shared metabolic pathways altered by PSMP and DMAs, indicating an independent effect of these two chemicals. Taken together, our findings emphasized that the combined toxicity of PSMP and different forms of arsenic posed a health risk that cannot be ignored.
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BACKGROUND: The geographic origin of Radix bupleuri is an important factor affecting its efficacy, which needs to be effectively identified. OBJECTIVE: The goal is to enrich and develop the intelligent recognition technology applicable to the identification of the origin of traditional Chinese medicine. METHODS: This paper establishes an identification method of Radix bupleuri geographic origin based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and support vector machine (SVM) algorithm. The Euclidean distance method is used to measure the similarity between Radix bupleuri samples, and the quality control chart method is applied to quantitatively describe their quality fluctuation. RESULTS: It is found that the samples from the same origin are relatively similar and mainly fluctuate within the control limit, but the fluctuation range is large, and it is impossible to distinguish the samples from different origins. The SVM algorithm can effectively eliminate the impact of intensity fluctuations and huge data dimensions by combining the normalization of MALDI-TOF MS data and the dimensionality reduction of principal components, and finally achieve efficient identification of the origin of Radix bupleuri, with an average recognition rate of 98.5%. CONCLUSION: This newly established approach for identification of the geographic origin of Radix bupleuri has been realized, and has the advantages of objectivity and intelligence, which can be used as a reference for other medical and food-related research. HIGHLIGHTS: A new intelligent recognition method of medicinal material origin based on MALDI-TOF MS and SVM has been established.
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In this Letter, we show stable suspension and directional manipulation of microdroplets on a liquid surface employing simple-mode fiber with a Gaussian beam at 1480-nm wavelength using the photothermal effect. The intensity of the light field generated by the single-mode fiber is used to generate droplets of different numbers and sizes. In addition, the effect of the heat generated at different heights from the liquid surface is discussed through numerical simulation. In this work, the optical fiber is not only free to move at any angle, solving the difficulty that a certain working distance is needed to generate microdroplets on free space, it can also allow the continuous generation and directional manipulation of multiple microdroplets, which is of tremendous scientific relevance and application value in promoting the development and cross-fertilization of life sciences and other interdisciplinary fields.
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Different habitats harbor different microbial communities with elusive assembly mechanisms. This study comprehensively investigated the global assembly mechanisms of microbial communities and effects of community-internal influencing factors using the Earth Microbiome Project (EMP) data set. We found that deterministic and stochastic processes contribute approximately equally to global microbial community assembly, and, specifically, deterministic processes generally play a major role in free-living and plant-associated (but not plant corpus) environments, while stochastic processes are the major contributor in animal-associated environments. In contrast with the assembly of microorganisms, the assembly of functional genes, predicted from PICRUSt, is mainly attributed to deterministic processes in all microbial communities. The sink and source microbial communities are normally assembled using similar mechanisms, and the core microorganisms are specific to different environment types. On a global scale, deterministic processes are positively related to the community alpha diversity, microbial interaction degree and bacterial predatory-specific gene abundance. Our analysis provides a panoramic picture and regularities of global and environment-typical microbial community assemblies.
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BACKGROUND: Plantaginis Herba (Plantago asiatica L.) has the effects of clearing heat and diuresis, oozing wet and drenching. As the main active components of Plantaginis Herba (Plantago asiatica L.), plantamajoside have a wide range of antitumor activities but very low bioavailability. The process of interacting between plantamajoside and gut microbiota remains unclear. PURPOSE: To illustrate the process of interacting between plantamajoside and gut microbiota based on high-resolution mass spectrometry and targeted metabolomics methods. STUDY DESIGN AND METHODS: This experiment was divided into two parts. First, metabolites produced from plantamajoside by gut microbiota were identified and quantified based on high-resolution mass spectrometry and LC-MS/MS. Additionally, stimulation of plantamajoside on gut microbiota-derived metabolites was determined by targeted metabolomics and gas chromatography. RESULTS: We first found that plantamajoside was rapidly metabolized by gut microbiota. Then, we identified metabolites of plantamajoside by high-resolution mass spectrometry and speculated that plantamajoside was metabolized into five metabolites including calceolarioside A, dopaol glucoside, hydroxytyrosol, 3-(3-hydroxyphenyl) propionic acid (3-HPP) and caffeic acid. Among them, we quantitatively analyzed four possible metabolites based on LCâMS/MS and found that hydroxytyrosol and 3-HPP were final products by the gut microbiota. In addition, we studied whether plantamajoside could affect the short-chain fatty acid (SCFA) and amino acid metabolites. We found that plantamajoside could inhibit the acetic acid, kynurenic acid (KYNA) and kynurenine (KN) produced by intestinal bacteria and promote the indole propionic acid (IPA) and indole formaldehyde (IALD) produced by intestinal bacteria. CONCLUSION: An interaction between plantamajoside and gut microbiota was revealed in this study. Unlike the traditional metabolic system, the special metabolic characteristics of plantamajoside in gut microbiota was found. Plantamajoside was metabolized into the following active metabolites: calceolarioside A, dopaol glucoside, hydroxytyrosol, caffeic acid and 3-HPP. Besides, plantamajoside could affect SCFA and tryptophan metabolism by gut microbiota. Especially, the exogenous metabolites hydroxytyrosol, caffeic acid and endogenous metabolites IPA may have potential association with the antitumor activity of plantamajoside.
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BACKGROUND: Stress hyperglycemia ratio (SHR), a novel biomarker of stress hyperglycemia, was proved to be a reliable predictor of short-term adverse outcomes in patients with acute coronary syndromes (ACS). However, its impact on long-term prognosis remained controversial. METHODS: A total of 7662 patients with ACS from a large nationwide prospective cohort between January 2015 and May 2019 were included. SHR was calculated by the following formula: SHR = admission glucose (mmol/L)/(1.59 × HbA1c [%]-2.59). The primary end point was a major adverse cardiovascular event (MACE) during follow-up, a composite of all-cause death, myocardial infarction, and unplanned revascularization. The second end point was the separate components of the primary end points. RESULTS: During a median follow-up of 2.1 years, 779 MACE events occurred. After multivariable adjustment, ACS patients with the highest SHR tertile were significantly associated with increased long-term risks of MACE (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.24-1.88), all-cause death (HR 1.80, 95% CI 1.29-2.51) and unplanned revascularization (HR 1.44, 95% CI 1.09-1.91). Although significant associations between the highest SHR tertile and risks of MACE and all-cause death were assessed in both diabetic and nondiabetic patients, the patterns of risk were different in these two groups. CONCLUSION: Elevated SHR was independently associated with a higher risk of long-term outcomes irrespective of diabetic status, suggesting that SHR was a potential biomarker for risk stratification after ACS.
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While CO can already be produced at industrially relevant current densities via CO2 electrolysis, the selective formation of C2+ products seems challenging. CO electrolysis, in principle, can overcome this barrier, hence forming valuable chemicals from CO2 in two steps. Here we demonstrate that a mass-produced, commercially available polymeric pore sealer can be used as a catalyst binder, ensuring high rate and selective CO reduction. We achieved above 70% faradaic efficiency for C2+ products formation at j = 500 mA cm-2 current density. As no specific interaction between the polymer and the CO reactant was found, we attribute the stable and selective operation of the electrolyzer cell to the controlled wetting of the catalyst layer due to the homogeneous polymer coating on the catalyst particles' surface. These results indicate that sophistically designed surface modifiers are not necessarily required for CO electrolysis, but a simpler alternative can in some cases lead to the same reaction rate, selectivity and energy efficiency; hence the capital costs can be significantly decreased.
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Recent translational efforts in brain-machine interfaces (BMI) are demonstrating the potential to help people with neurological disorders. The current trend in BMI technology is to increase the number of recording channels to the thousands, resulting in the generation of vast amounts of raw data. This in turn places high bandwidth requirements for data transmission, which increases power consumption and thermal dissipation of implanted systems. On-implant compression and/or feature extraction are therefore becoming essential to limiting this increase in bandwidth, but add further power constraints - the power required for data reduction must remain less than the power saved through bandwidth reduction. Spike detection is a common feature extraction technique used for intracortical BMIs. In this paper, we develop a novel firing-rate-based spike detection algorithm that requires no external training and is hardware efficient and therefore ideally suited for real-time applications. Key performance and implementation metrics such as detection accuracy, adaptability in chronic deployment, power consumption, area utilization, and channel scalability are benchmarked against existing methods using various datasets. The algorithm is first validated using a reconfigurable hardware (FPGA) platform and then ported to a digital ASIC implementation in both 65 nm and 0.18MU m CMOS technologies. The 128-channel ASIC design implemented in a 65 nm CMOS technology occupies 0.096 mm2 silicon area and consumes 4.86MU W from a 1.2 V power supply. The adaptive algorithm achieves a 96% spike detection accuracy on a commonly used synthetic dataset, without the need for any prior training.
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The dynamic tumor microenvironment, especially the immune microenvironment, during the natural progression and/or chemotherapy treatment is a critical frontier in understanding the effects of chemotherapy on pancreatic cancer. Non-stratified pancreatic cancer patients always receive chemotherapeutic strategies, including neoadjuvant chemotherapy and adjuvant chemotherapy, predominantly according to their physical conditions and different disease stages. An increasing number of studies demonstrate that the pancreatic cancer tumor microenvironment could be reshaped by chemotherapy, an outcome caused by immunogenic cell death, selection and/or education of preponderant tumor clones, adaptive gene mutations, and induction of cytokines/chemokines. These outcomes could in turn impact the efficacy of chemotherapy, making it range from synergetic to resistant and even tumor-promoting. Under chemotherapeutic impact, the metastatic micro-structures in the primary tumor may be built to leak tumor cells into the lymph or blood vasculature, and micro-metastatic/recurrent niches rich in immunosuppressive cells may be recruited by cytokines and chemokines, which provide housing conditions for these circling tumor cells. An in-depth understanding of how chemotherapy reshapes the tumor microenvironment may lead to new therapeutic strategies to block its adverse tumor-promoting effects and prolong survival. In this review, reshaped pancreatic cancer tumor microenvironments due to chemotherapy were reflected mainly in immune cells, pancreatic cancer cells, and cancer-associated fibroblast cells, quantitatively, functionally, and spatially. Additionally, small molecule kinases and immune checkpoints participating in this remodeling process caused by chemotherapy are suggested to be blocked reasonably to synergize with chemotherapy.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have seriously attacked the antibody barrier established by natural infection and/or vaccination, especially the recently emerged BQ.1.1 and XBB.1. However, crucial mechanisms underlying the virus escape and the broad neutralization remain elusive. Here, we present a panoramic analysis of broadly neutralizing activity and binding epitopes of 75 monoclonal antibodies isolated from prototype inactivated vaccinees. Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1. We report a broad nAb, VacBB-551, that effectively neutralizes all tested subvariants including BA.2.75, BQ.1.1, and XBB.1. We determine the cryoelectron microscopy (cryo-EM) structure of VacBB-551 complexed with the BA.2 spike and perform detailed functional verification to reveal the molecular basis of N460K and F486V/S mutations mediating the partial escape of BA.2.75, BQ.1.1, and XBB.1 from the neutralization of VacBB-551. Overall, BQ.1.1 and XBB.1 raised the alarm over SARS-CoV-2 evolution with unprecedented antibody evasion from broad nAbs elicited by prototype vaccination.
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Sea cucumbers Apostichopus japonicus will vomit their intestines during certain stimulations, and the collagen of the body wall will then be degraded. To define the effect of the sea cucumber intestine extracts on the body wall, the intestinal extracts and crude collagen fibers (CCF) of sea cucumber A. japonicus were prepared. According to the gelatin zymography, the type of endogenous enzymes in intestinal extracts were mainly serine endopeptidases with optimal activities at pH 9.0 and 40 °C. According to the rheology results, the viscosity of 3% CCF decreased from 32.7 Pa·s to 5.3 Pa·s by adding intestine extracts. The serine protease inhibitor phenylmethanesulfonyl fluoride inhibited the activity of intestinal extracts and increased the viscosity of collagen fibers to 25.7 Pa·s. The results proved that serine protease in the intestinal extracts participated in the process of body wall softening in sea cucumbers.
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Green chromatography techniques using low-toxic mobile phase are getting increasingly attention in recent years. The core is developing stationary phases that possess adequate retention and separation under the mobile phase of high content water. Using thiol-ene click chemistry, an undecylenic acid-bonded silica stationary phase (UAS) was prepared in a facile manner. Elemental analysis (EA), solid-state 13C NMR spectroscopy and Fourier transform infrared spectrometry (FT-IR) confirmed the successful preparation of UAS. The synthesized UAS was employed for per aqueous liquid chromatography (PALC), which uses little organic solvent during separation. Due to the hydrophilic carboxy, thioether group and hydrophobic alkyl chains of the UAS, various categories of compounds (including nucleobases, nucleosides, organic acids and basic compounds) with different properties can achieve enhanced separation under the mobile phase of high content water compared with commercial C18 and silica stationary phases. Overall, our present UAS stationary phase shows excellent separation ability toward highly polar compounds and meets the requirements of green chromatography.
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BACKGROUND: Autogenous osteochondral mosaicplasty (AOM) is a widely used optimal surgical technique for cartilage repair in young patients with focal articular cartilage defects. However, the alterations in balance control in these patients after AOM have not been sufficiently investigated. This study aimed to compare different balance control performances between the patients with knee cartilage defects and healthy controls before and after AOM, as well as evaluate the influence of AOM on balance control in these patients. METHODS: Static posturographic tests were performed in twenty-four patients who were scheduled for AOM two weeks pre-, three months, and one year postoperatively, along with thirty matched controls, respectively. All participants underwent posturography under four standing conditions: eyes open and closed, without and with foam support to assess the balance control ability. Subsequently, patient-reported outcome measures (PROMs) were synchronously obtained and analyzed. RESULTS: Compared to the control subjects, less efficient balance control was observed in study patients at three testing phases (p < 0.05), whereas no alterations in postural control were visible in these patients within a year following AOM (p > 0.05). Significant improvements were found in all PROMs such as the International Knee Documentation Committee, the Lysholm Knee Score, and the visual analogue scale in the study patients postoperatively (p < 0.01). CONCLUSION: The results indicated that patients with knee cartilage defects have a prominent balance control deficit compared to healthy individuals. Furthermore, AOM does not improve balance control in these patients for at least one year postoperatively, and more effective approaches for postural regulation are required for the management of cartilage defect patients.
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Doenças das Cartilagens , Cartilagem Articular , Humanos , Projetos Piloto , Resultado do Tratamento , Doenças das Cartilagens/cirurgia , Cartilagem Articular/cirurgia , Articulação do Joelho/cirurgia , Transplante AutólogoRESUMO
Gut microbiota has been reported to participate in bone metabolism. However, no article has quantitatively and qualitatively analyzed this crossing field. The present study aims to analyze the current international research trends and demonstrate possible hotspots in the recent decade through bibliometrics. We screened out 938 articles meeting the standards from 2001 to 2021 in the Web of Science Core Collection database. Bibliometric analyses were performed and visualized using Excel, Citespace, and VOSviewer. Generally, the annual number of published literatures in this field shows an escalating trend. The United States has the largest number of publications, accounting for 30.4% of the total. Michigan State University and Sichuan University have the largest number of publications, while Michigan State University has the highest average number of citations at 60.00. Nutrients published 49 articles, ranking first, while the Journal of Bone and Mineral Research had the highest average number of citations at 13.36. Narayanan Parameswaran from Michigan State University, Roberto Pacifici from Emory University, and Christopher Hernandez from Cornell University were the three professors who made the largest contribution to this field. Frequency analysis showed that inflammation (148), obesity (86), and probiotics (81) are keywords with the highest focus. Moreover, keywords cluster analysis and keywords burst analysis showed that "inflammation", "obesity", and "probiotics" were the most researched topics in the field of gut microbiota and bone metabolism. Scientific publications related to gut microbiota and bone metabolism have continuously risen from 2001 to 2021. The underlying mechanism has been widely studied in the past few years, and factors affecting the alterations of the gut microbiota, as well as probiotic treatment, are emerging as new research trends.
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The incidence of acute myocardial infarction (AMI) in hemodialysis (HD) patients is high and the prognosis is extremely poor. However, the potential connection between HD and AMI, and its regulatory mechanisms remain unclear. In this study, the gene expression profiles of HD (GSE15072) and AMI (GSE66360) were downloaded from the Gene Expression Omnibus database, common differentially expressed genes (DEGs) were obtained using the limma R package, the biological functions were analyzed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, machine learning was conducted to identify hub genes. Receiver operating characteristic curves and gene set enrichment analyses were used to explore the characters and biological function of hub genes, networks were used for candidate identification of transcription factor (TF), microRNA (miRNA), and drug. After a total of 255 common DEGs were selected, GO and KEGG analyses indicated that neutrophil extracellular trap (NET) may be a potential connection between HD and AMI, LILRB2, S100A12, CYBB, ITGAM, and PPIF were finally identified as hub genes. The area under curve of LILRB2, S100A12, and PPIF was higher than 0.8 in both datasets. Networks show the relationship between hub genes, TF, and miRNA, also the relationship between potential drugs and protein. In conclusion, NETs may be the potential connection between AMI and HD. The potential hub gene, signaling pathways, and drugs provided by this study may contribute to future AMI prevention and intervention in HD patients.
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An integrated treatment coupling peracetic acid delignification, dimethyl sulfoxide extraction, and ethanol precipitation were performed to isolate hemicellulose from de-starched corn fiber. Based on chemical composition, molecular weight distribution, methylation, and nuclear magnetic resonance spectroscopy, it is proposed that hemicelluloses in corn fiber were composed of two polysaccharides, glucuronoarabinoxylan (about 80 %) and xyloglucan (about 20 %). Xylose (about 46 %) and arabinose (about 32 %) were the main components in glucuronoarabinoxylan. More than half of the xylose units in the glucuronoarabinoxylan backbone chain were substituted at O-2 and/or O-3 by various monomers or oligomeric side chains. Based on structure analysis, five hemicellulases were selected and added to Penicillium oxalicum MCAX enzymes for enzymatic hydrolysis of corn fiber. The results showed that the addition of hemicellulases increased the sugar yield of corn fiber. These results demonstrate the effectiveness of enzyme consortium constructed by elucidating the chemical structure of hemicellulose in corn fiber for the degradation of corn fiber and also provide a general solution for the rational construction of targeted and efficient enzyme systems for the degradation of lignocellulosic biomass.
