Circular RNA HIPK3 facilitates ferroptosis in gestational diabetes mellitus by regulating glutathione peroxidase 4 DNA methylation.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequently occurring complication during pregnancy, with a high prevalence rate. Ferroptosis, a type of iron-dependent cell death, is closely associated with GDM nosogenesis. The present study aimed to examine the potential role and mechanism of circHIPK3 in GDM. METHODS: Placental tissues, plasma samples, and HTR-8/SVneo cells were used. A receiver operating characteristic curve was used to analyze the diagnostic value of circHIPK3 in GDM. Actinomycin D and RnaseR were added to identify circHIPK3 characteristics. The expression of circHIPK3, miR-1278, and DNA methyltransferase 1 (DNMT1) was assessed using a quantitative reverse transcriptase-PCR. Cell counting kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling assays and specific kits were employed to assess cell viability, apoptosis, reactive oxygen species (ROS), malondialdehyde, iron, glutathione, and glutathione peroxidase 4 (GPX4) levels. RESULTS: The interaction between miR-1278 and circHIPK3 or DNMT1 was validated via luciferase reporter and RNA pull-down assays. circHIPK3 expression was found to be high in GDM placental tissues, plasma, and cells, with a high diagnostic value. In high glucose (HG)-induced HTR-8/SVneo cells, the inhibition of circHIPK3 provoked cell viability and mitigated cell apoptosis, ROS, and iron levels, but it was rescued through the downregulation of miR-1278. Mechanism experiments showed that circHIPK3 bound with miR-1278 targeting DNMT1 in GDM. The elevation in DNMT1 expression abolished the effects of miR-1278 overexpression on ferroptosis in HG-cultured HTR-8/SVneo cells. CONCLUSIONS: Overall, circHIPK3 might facilitate ferroptosis via miR-1278/DNMT1 to regulate GPX4 DNA methylation in HG-cultured HTR-8/SVneo cells. CircHIPK3 could be a therapeutic agent for GDM treatment.

Studies on the Effect of Lipofectamine and Cell-Penetrating Peptide on the Properties of 10-23 DNAzyme.

Cationic polymeric materials and cell-penetrating peptides (CPPs) were often used as the delivery vectors in the evaluation of nucleic acid therapeutics. 10-23 DNAzyme is a kind of potential antisense therapeutics by catalytic cleavage of the disease-related RNAs. Here, lipofectamine 2000 and Tat peptide were evaluated for their effect on the catalytic activity of 10-23 DNAzyme, with the observed rate constant, thermal stability, CD spectra, and PAGE analysis, with a duplex DNA mimicking DNAzyme-substrate as a control. It was shown that the cationic carriers had a negative effect on the catalytic performance of the 10-23 DNAzyme. Significantly, the destabilizing effect of the cationic carriers on the duplex formation was noteworthy, as a duplex formation is an essential prerequisite in the silencing mechanisms of antisense and RNAi.

Direct Excitation of Aldehyde to Activate the C(sp2 )-H Bond by Cobaloxime Catalysis toward Fluorenones Synthesis with Hydrogen Evolution.

A new way to form fluorenones via the direct excitation of substrates instead of photocatalyst to activate the C(sp2 )-H bond under redox-neutral condition is reported. Our design relies on the photoexcited aromatic aldehyde intermediates that can be intercepted by cobaloxime catalyst through single electron transfer for following ß-H elimination. The generation of acyl radical and successful interception by a metal catalyst cobaloxime avoid the use of a photocatalyst and stoichiometric external oxidants, affording a series of highly substituted fluorenones, including six-membered ketones, such as xanthone and thioxanthone derivatives in good to excellent yields, and with hydrogen as the only byproduct. This catalytic system features a readily available metal catalyst, mild reaction conditions and broad substrate scope, in which sunlight reaction and scale-up experiments by continuous-flow approach make the new methodology sustainable and amenable for potentially operational procedures.

Mechanisms Affecting Physical Aging and Swelling by Blending an Amphiphilic Component.

Polymer blending is a promising method to overcome stability obstacles induced by physical aging and swelling of implant scaffolds prepared from amorphous polymers in biomedical application, since it will not bring potential toxicity compared with chemical modification. However, the mechanism of polymer blending still remains unclearly explained in existing studies that fail to provide theoretical references in material R&D processes for stability improvement of the scaffold during ethylene oxide (EtO) sterilization, long-term storage, and clinical application. In this study, amphiphilic poly(ethylene glycol)-co-poly(lactic acid) (PELA) was blended with amorphous poly(lactic-co-glycolic acid) (PLGA) because of its good miscibility so as to adjust the glass transition temperature (Tg) and hydrophilicity of electrospun PLGA membranes. By characterizing the morphological stability and mechanical performance, the chain movement and the glass transition behavior of the polymer during the physical aging and swelling process were studied. This study revealed the modification mechanism of polymer blending at the molecular chain level, which will contribute to stability improvement and performance adjustment of implant scaffolds in biomedical application.

Value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight infants. / ç”ŸåŽæ—©æœŸåºŠæ—å¿ƒè„è¶ å£°é¢„æµ‹æžä½Žå‡ºç”Ÿä½“é‡å„¿åŠ¨è„‰å¯¼ç®¡æŒç»­å¼€æ”¾çš„ç ”ç©¶.

OBJECTIVES: To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants. METHODS: A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter <2 mm), and PDA closure group (PDA diameter =0 mm). The echocardiographic parameters measured at 72 hours after birth were compared among the three groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of the echocardiographic parameters in predicting persistent patency of the ductus arteriosus (PDA≥2 mm) at the ages of 14 and 28 days. RESULTS: On day 14 after birth, there were 17 infants in the large PDA group, 11 in the small PDA group, and 23 in the PDA closure group. On day 28 after birth, there were 14 infants in the large PDA group, 9 in the small PDA group, and 26 in the PDA closure group. There were significant differences in gestational age, birth weight, rate of pulmonary surfactant use, and incidence rate of hypotension among the three groups (P<0.05). PDA diameter, end-diastolic velocity of the left pulmonary artery, left ventricular output, and left ventricular output/superior vena cava flow ratio measured at 72 hours after birth were associated with persistent patency of the ductus arteriosus at the ages of 14 and 28 days (P<0.05), and the ratio of the left atrium to aorta diameter was associated with persistent patency of the ductus arteriosus at the age of 28 days (P<0.05). The ROC curve analysis showed that the area under the curve that the PDA diameter measured at 72 hours after birth predicting the persistent patency of the ductus arteriosus at the ages of 14 and 28 days was the largest (0.841 and 0.927 respectively), followed by end-diastolic velocity of the left pulmonary artery, with the area under the curve of 0.793 and 0.833 respectively. CONCLUSIONS: The indicators obtained by beside echocardiography at 72 hours after birth, especially PDA diameter and end-diastolic velocity of the left pulmonary artery, can predict persistent patency of the ductus arteriosus at the ages of 14 and 28 days in VLBW infants, which provides a basis for the implementation of early targeted treatment strategy for PDA.

The LINC00477/miR-128 axis promotes the progression of polycystic ovary syndrome by regulating ovarian granulosa cell proliferation and apoptosis.

BACKGROUND: Long noncoding RNAs (lncRNAs) participate in the pathogenesis of various human diseases. This study aims to investigate the roles of lncRNA LINC00477 in polycystic ovary syndrome (PCOS), especially the impacts of LINC00477 on the proliferation and migration of human granulosa cells and the related mechanisms. METHODS: qRT-PCR analysis was performed to examine the expression pattern of LINC00477 in serum samples of PCOS patients as well as PCOS animal models. The effect of LINC00477 on the viability and apoptosis of ovarian granulosa cells was detected by MTT and flow cytometry assays. The correlation between LINC00477 and miR-128 was verified by bioinformatics analysis and dual-luciferase reporter and RNA pull-down assays. Finally, rescue assays were performed to analyze the effects of the LINC00477-miR-128 axis on the biological behaviors of granulosa cells. RESULTS: LINC00477 was significantly upregulated in the serum of PCOS patients as well as PCOS mouse models. LINC00477 overexpression inhibited the proliferation and promoted the apoptosis of granulosa cells, whereas knockdown of LINC00477 yielded the opposite effects. Moreover, miR-128 mimics partially abrogated the effect of LINC00477 on granulosa cells. CONCLUSION: LINC00477 may function as a ceRNA to inhibit proliferation and apoptosis of granulosa cells by modulating miR-128 expression.

Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of prematurity: A post-marketing study to support paediatric labelling in China.

AIMS: The aim of the study was to evaluate the suitability of the current caffeine dosing regimen for the Chinese population using modelling and simulation approach. METHODS: Pharmacokinetic samples were collected from 99 Chinese newborns with premature apnoea. The median (range) of gestational age and postmenstrual age were 28.3 (25.0-33.4) weeks and 31.1 (26.4-38.0) weeks, respectively. Newborns were receiving caffeine citrate at a loading dose of 20 mg/kg/d and a maintenance dose of 5-10 mg/kg/d. Caffeine concentrations and CYP1A2 polymorphisms were investigated. Population pharmacokinetic modelling of caffeine in Chinese preterm newborn on a population-wide scale was conducted using NONMEM. RESULTS: A 1-compartment model with first-order elimination was used to describe population pharmacokinetic. With current weight implemented using 0.75 allometric scaling, clearance (CL) was positively related to current weight and postmenstrual age, but a negative relationship was observed with serum creatinine concentration. Eight genotypes of CYP1A2 were tested and none of them had a significant impact on caffeine pharmacokinetic parameters. Interindividual variability of CL and volume of distribution was 7.70 and 65.9%. The median (range) of 95% confidence intervals of CL were 0.0128 (0.0128-0.0131) L/h/kg. Monte Carlo simulation demonstrated that 80% (loading dose) and 98% (maintenance dose) of premature infants treated with a labelled dosing regimen attained the concentration target range of 5-20 mg/L. CONCLUSION: A population PK model of caffeine was developed in Chinese newborns. Body weight-implemented allometric scaling, postmenstrual age and serum creatinine concentration markedly affected caffeine clearance. The labelled dosing regimen is suitable for Chinese premature infants.

The effect of structural modification of antimicrobial peptides on their antimicrobial activity, hemolytic activity, and plasma stability.

In this article, a series of modifications were made on an antimicrobial peptide F2,5,12 W, including altering the amino acid sequence, introducing cysteine and other typical amino acids, developing peptide dimers via disulfide bonds, and conjugating with mPEG, in order to enhance the antimicrobial activity, plasma stability, and reduce the hemolytic activity of peptides. The results showed that mPEG conjugation could significantly improve the plasma stability and reduce the hemolytic activity of peptides, while the antimicrobial activity decreased meanwhile. However, altering the sequence of the peptide without changing its amino acid composition had little impact on its antimicrobial activity and plasma stability. The introduction of cysteine enhanced the plasma stability of peptides conspicuously, but at the same time, the increased hydrophobicity of peptides increased their hemolysis. The antimicrobial mechanism and cytotoxicity of the peptides with relatively high antimicrobial activity were also studied. In general, this study provided some ideas for the rational design and structure optimization of antimicrobial peptides.

Complexation of an Antimicrobial Peptide by Large-Sized Macrocycles for Decreasing Hemolysis and Improving Stability.

Traditional macrocyclic hosts have finite cavity sizes, generally 5-10 Å, which are commonly adaptive to recognize small guests rather than biological macromolecules. Here two water-soluble large-sized quaterphen[n]arenes (WQPns, n=3, 4) were designed and synthesized. These two hosts present significantly distinct recognition abilities. Specifically, they could strongly complex an antimicrobial peptide, pexiganan (PXG) with the association constants (Ka ) of (4.20±0.23)×104  M-1 for PXG/WQP3 and (2.46±0.44)×105  M-1 for PXG/WQP4. Complexation of PXG by WQP3 and WQP4 served to decrease the hemolysis of PXG in rabbit red blood cells in a statistically significant way. Furthermore, host-guest complexation was shown to substantially enhance metabolic stability of PXG in presence of proteinase K, rat plasma and liver or kidney homogenates.

Recent advances of green pretreatment techniques for quality control of natural products.

A few advancing technologies for natural product analysis have been widely proposed, which focus on decreasing energy consumption and developing an environmentally sustainable manner. These green sample pretreatment and analysis methods following the green Analytical Chemistry (GAC) criteria have the advantage of improving the strategy of chemical analyses, promoting sustainable development to analytical laboratories, and reducing the negative effects of analysis experiments on the environment. A few minimized extraction methodologies have been proposed for replacing the traditional methods in the quality evaluation of natural products, mainly including solid-phase microextraction (SPME) and liquid phase microextraction (LPME). These procedures not only have no need for large numbers of samples and toxic reagent, but also spend a small amount of extraction and analytical time. This overview aims to list out the main green strategies on the application of quality evaluation and control for natural products in the past 3 years.

AK002210 promotes the proliferation, migration and invasion of trophoblast cell through regulating miR-590/NAIP signal axis.

Preeclampsia (PE) is a pregnancy-related syndrome and has become the leading cause of maternal and neonatal morbidity and mortality. LncRNA has been elucidated to play critical roles in the phenotype of trophoblast cells. However, the effect of AK002210 has not been reported. We aim to investigate the effect of AK002210 on the phenotype of trophoblast cells. Quantitative reverse transcription PCR was used to assess the gene expression. CCK-8 assay was used to evaluate the cell proliferation. Transwell assay was performed to detect the migration and invasion of trophoblast cells. Luciferase assay and rescue experiment were carried out to verify the interaction between miR-590-3p and AK002210 as well as NLR family apoptosis inhibitory protein (NAIP). The results revealed that AK002210 promoted the proliferation, migration and invasion of trophoblast cell while AK002210 knockdown inhibited that. Mechanically, we found that AK002210 was targeted by miR-590-3p. Moreover, miR-590-3p also directly targets NAIP which served as a ceRNA of AK002210. Rescue experiment showed that miR-590-3p reversed the effect of AK002210 which further confirmed their interaction. Moreover, AK002210 was proved to participated in the regulation of ERK/MMP-2 signal axis. In conclusion, we found that AK002210 knockdown may play a critical role in the progression of PE via miR-590-3p/NAIP and ERK/MMP signaling. It has potential to be a novel prognostic or therapeutic marker of PE.

Characterization of the molecular mechanism of the autophagy-related Atg8-Atg3 protein interaction in Toxoplasma gondii.

Toxoplasmosis is caused by an obligate intracellular parasite, the protozoan Toxoplasma gondii Discovery of novel drugs against T. gondii infection could circumvent the toxicity of existing drugs and T. gondii resistance to current treatments. The autophagy-related protein 8 (Atg8)-Atg3 interaction in T. gondii is a promising drug target because of its importance for regulating Atg8 lipidation. We reported previously that TgAtg8 and TgAtg3 interact directly. Here we validated that substitutions of conserved residues of TgAtg8 interacting with the Atg8 family-interacting motif (AIM) in Atg3 disrupt the TgAtg8-TgAtg3 interaction and reduce TgAtg8 lipidation and autophagosome formation. These findings were consistent with results reported previously for Plasmodium Atg8, suggesting functional conservation of Atg8 in Toxoplasma and Plasmodium. Moreover, using peptide and AlphaScreen assays, we identified the AIM sequence in TgAtg3 that binds TgAtg8. We determined that the core TgAtg3 AIM contains a Phe239-Ala240-Asp241-Ile242 (239FADI242) signature distinct from the 105WLLP108 signature in the AIM of Plasmodium Atg3. Furthermore, an alanine-scanning assay revealed that the TgAtg8-TgAtg3 interaction in T. gondii also depends strongly on several residues surrounding the core TgAtg3 AIM, such as Asn238, Asp243, and Cys244 These results indicate that distinct AIMs in Atg3 contribute to differences between Toxoplasma and Plasmodium Atg8-Atg3 interactions. By elucidating critical residues involved in the TgAtg8-TgAtg3 interaction, our work paves the way for the discovery of potential anti-toxoplasmosis drugs. The quantitative and straightforward AlphaScreen assay developed here may enable high-throughput screening for small molecules disrupting the TgAtg8-TgAtg3 interaction.

Long non-coding RNA DLX6-AS1 is upregulated in preeclampsia and modulates migration and invasion of trophoblasts through the miR-376c/GADD45A axis.

Long non-coding RNA (lncRNA) are key regulatory molecules that are implicated in diverse biological processes and human diseases, including preeclampsia. However, their expression and functions in the progression of preeclampsia remains largely unclear. In this study, lncRNA DLX6-AS1 was confirmed to be significantly upregulated in the placentas of patients with preeclampsia, compared with normal controls. Overexpression of DLX6-AS1 dramatically decreased proliferation, migration and invasion in trophoblast JEG3 and HTR-8/SVneo cells. Luciferase activity and RNA pull-down assays showed that DLX6-AS1 interacted with miR-376c, and that overexpression of DLX6-AS1 significantly reduced expression of miR-376c in HTR-8/SVneo cells. Also, miR-376c targeted and downregulated GADD45A in HTR-8/SVneo cells. Overexpression of GADD45A effectively attenuated a miR-376c-induced increase in the proliferation, migration and invasion of HTR-8/SVneo cells. Further research showed that DLX6-AS1-induced inhibition of trophoblast proliferation, migration and invasion was effectively neutralized by GADD45A knockdown and miR-376c overexpression. Taken together, these findings suggest that DLX6-AS1 may contribute to preeclampsia by impairing proliferative, migratory and invasive abilities of trophoblasts via the miR-376c/GADD45A axis.

Design, synthesis, and activity evaluation of novel erythropoietin mimetic peptides.

The approval of the erythropoietin (EPO) mimetic peptide drug peginesatide in 2012 was a breakthrough for the treatment of secondary anemia. However, due to severe allergic reactions, peginesatide was recalled a year later. In this study, 12 novel peptides were designed and synthesized by substituting specific amino acids of the monomeric peptide in peginesatide, with the aim of obtaining new EPO mimetic peptides with higher activities and lower side effects than the parent compound. Their cell proliferation activities were evaluated, and the structure-activity relationships were analyzed. Five compounds had equal cell proliferation activity to the control peptide. Among them, one compound showed a higher in vivo activity than the control peptide, with no obvious side effects.

[Clinical features and prognosis of bronchopulmonary dysplasia complicated by pulmonary hypertension in preterm infants].

OBJECTIVE: To study the clinical features and prognosis of bronchopulmonary dysplasia (BPD) complicated by pulmonary hypertension (PH) in preterm infants. METHODS: A retrospective analysis was performed on the clinical data of 191 preterm infants with BPD. RESULTS: In the 191 preterm infants with BPD, 37 (19.4%), all with moderate or severe BPD, developed PH beyond 36 weeks' corrected age. The incidence rates of PH in infants with moderate and severe BPD were 5.7% (5/87) and 47.8% (32/67) respectively. Gestational age and birth weight were lower in infants with PH than in those without PH (P<0.01). Infants with PH had higher incidence rates of small for gestational age (SGA), severe BPD, surgical ligation of patent ductus arteriosus (PDA), neonatal respiratory distress syndrome, hemodynamically significant PDA, and pneumonia than those without PH (P<0.01). Durations of oxygen therapy, intubation, and positive pressure ventilation were longer in infants with PH than in those without PH (P<0.01). Infants with PH had higher incidence rates of retinopathy of prematurity and extrauterine growth retardation, a higher mortality, and a longer length of hospital stay compared with those without PH (P<0.01). In the 37 infants with PH (6 with mild PH, 14 with moderate PH, and 17 with severe PH), those with mild or moderate PH all survived; 15(88%) out of 17 infants with severe PH died. CONCLUSIONS: The incidence of PH is high in preterm infants with moderate or severe BPD. Regular screening of pulmonary artery pressure is recommended for infants with BPD. Infants with low gestational age and birth weight, SGA, and severe BPD are more likely to develop PH. Infants with BPD complicated by PH have relatively high incidence rates of complications, high mortality, and poor prognosis.

Association of gene polymorphisms of FV, FII, MTHFR, SERPINE1, CTLA4, IL10, and TNFalpha with pre-eclampsia in Chinese women.

OBJECTIVES: To investigate the association of polymorphisms in genes involved in coagulation, fibrinolysis, and inflammation with pre-eclampsia (PE) in a Chinese population. METHODS: It is a case-control study of patients with PE (n = 117) and controls (n = 286) from the Maternal and Children's Hospital of Shenzhen City carried out between June 2014 and May 2015. The rs6025, rs6020, rs1801133, rs1799963, rs1799889, rs231775, rs1800896, rs1800629, and rs1799724 polymorphisms were analyzed using Snap Shot. Multifactor dimensionality reduction (MDR) and logistic regression analyses were carried out to assess the interactions among these SNPs. RESULTS: The frequencies of polymorphisms in tumor necrosis factor-α (TNF-α) (rs1800629 and rs1799724) and interleukin 10 (IL-10) (rs1800896) were significantly different between patients with PE and controls (P < 0.05). The best interaction model identified a marginally significant interaction between rs1799724 and rs1800896 (P = 0.05). CONCLUSIONS: This study suggests that polymorphisms in the TNF-α and IL-10 genes could be associated with PE, but additional studies are necessary to explore the mechanisms involving these polymorphisms and the gene-gene interactions involved in the susceptibility to PE.

Design, synthesis, and evaluation of water-soluble morpholino-decorated paclitaxel prodrugs with remarkably decreased toxicity.

Novel water-soluble paclitaxel prodrugs were designed and synthesized by introducing morpholino groups through different linkers. These derivatives showed 400-20,000-times greater water solubility than paclitaxel as well as comparable activity in MCF-7 and HeLa cell lines. The prodrug PM4 was tested in the S-180 tumor mouse model, with paclitaxel as the positive control. The results showed that PM4 had comparable antitumor activity as paclitaxel, with tumor inhibition of 54% versus 56%, and remarkably decreased toxicity. The survival rate of treated mice was 8/8 in the PM4 group, compared to 3/8 in the paclitaxel group.

Triterpene sapogenin-polyarginine conjugates exhibit promising antibacterial activity against Gram-positive strains.

Triterpene sapogenins are a group of biologically active compounds with antibacterial activity. However, the limited solubility and poor bioavailability of triterpene sapogenins restrict their therapeutic application. Polyarginine peptides are small cationic peptides with high affinities for multiple negatively charged cell membranes and possess moderate antibacterial activities. In this study, we designed and synthesized a series of sapogenin-polyarginine conjugates in which the triterpene sapogenin moiety was covalently appended to the positively charged polyarginine via click chemistry. A clear synergistic effect was found, and the conjugates exhibited potent and selective antibacterial activity against Gram-positive strains. Among them, BAc-R3 was the most promising compound, which was also proven to be nontoxic toward mammalian cells as well as stable in plasma. The mechanism of BAc-R3 primarily involves an interaction with the bacterial membrane, similar to that of antimicrobial peptides (AMPs). This scaffold design opens an avenue for the further development of novel antibiotics comprised of the combination of a peptide and a natural product.

Production of xylonic acid by Klebsiella pneumoniae.

The glucose oxidation pathway is important for glucose catabolism in Klebsiella pneumoniae. Gluconic acid and 2-ketogluconic acid are intermediates of this pathway, and the production of these two chemicals has been developed in K. pneumoniae mutants. Catalysis characteristic research in this study has shown that xylose is a suitable substrate of the glucose dehydrogenase of this pathway. Here, using xylose as substrate, xylonic acid was accumulated in the broth of K. pneumoniae culture, and this process was dependent upon acidic conditions. Using a mixture of glucose and xylose as substrates, a mixture of xylonic acid and gluconic acid was produced by the Δgad mutant of K. pneumoniae; gluconic acid was synthesized early, and xylonic acid synthesis began after most glucose was consumed. Using the hydrolysate of bamboo as substrate, mixture of 33 g/L gluconic acid and 14 g/L xylonic acid were produced by K. pneumoniae Δgad. In fed-batch fermentation, 103 g/L xylonic acid was produced after 79 h culture, with a conversion ratio of 1.11 g/g. This is the first report of xylonic acid produced by K. pneumoniae. Production of xylonic acid and gluconic acid using bamboo hydrolysate is a novel approach for biomass utilization.