Risk factors for methotrexate resistance in low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4).

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

[Pseudo-targeted metabolomics study of immune stress-mediated idiosyncratic liver injury induced by synergistic effects of bavachin and epimedin B].

Chinese patent medicine preparations containing Epimedii Folium and Psoraleae Fructus have been associated with the occurrence of idiosyncratic drug-induced liver injury(IDILI). However, the specific toxic biomarkers and mechanisms underlying these effects remain unclear. This study aimed to comprehensively assess the impact of bavachin and epimedin B, two principal consti-tuents found in Psoraleae Fructus and Epimedii Folium, on an IDILI model induced by tumor necrosis factor-α(TNF-α) treatment, both in vitro and in vivo. To evaluate the extent of liver injury, various parameters were assessed. Lactate dehydrogenase(LDH) release in the cell culture supernatant, as well as the levels of alanine aminotransferase(ALT) and aspartate transaminase(AST) in mouse plasma were measured. Additionally, histological analysis employing hematoxylin-eosin staining was performed to observe liver tissue changes indicative of the severity of liver injury. Furthermore, a pseudo-targeted metabolomics approach was employed, followed by multivariate analysis, to identify differential metabolites. These identified metabolites were subsequently subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The results showed that at the cellular level, after 2 hours of TNF-α stimulation, bavachin significantly increased the release of LDH in HepG2 cells compared to the normal group and the group treated alone; after the combination of bavachin and epimedin B, the release of LDH further significantly increased on the original basis. Similarly, although the individual or combination treatments of bavachin and epimedin B did not induce liver injury in normal mice, the combination of both drugs induced marked liver injury in TNF-α treated mice, leading to a significant elevation in plasma AST and ALT levels and substantial infiltration of inflammatory immune cells in the liver tissue. Pseudo-targeted metabolomics analysis identified seven common differential metabolites. Among these, D-glucosamine-6-phosphate, N1-methyl-2-pyridone-5-carboxamide, 17beta-nitro-5a-androstane, irisolidone-7-O-glucuronide, and N-(1-deoxy-1-fructosyl) valine emerged as potential biomarkers, with an area under the curve(AUC) exceeding 0.9. Furthermore, our results suggest that the metabolism of nicotinic acid and nicotinamide, as well as the linoleic acid metabolic pathway, may play pivotal roles in bavachin and epimedin B-induced IDILI. In conclusion, within an immune-stressed environment mediated by TNF-α, bavachin and epimedin B appear to induce IDILI through disruptions in metabolic processes.

Exploring the adaptive leisure activities of classified nursing model in elderly colon cancer patients: a perspective on interactive care.

OBJECTIVE: The aims of the study were first to explore the adaptive leisure activities of classified nursing model from the perspective of nurse-patient interactive care, and to explore its impact on the physical and mental health of patients with colon cancer. METHODS: From September 2017 to March 2022 as the observation time node, 82 patients with colon cancer who met the established inclusion and exclusion criteria were regarded as the research objects through the random number table as the grouping tool. The two groups of patients were named as the research group and the control group, with 41 patients in each group. The control group implemented routine nursing measures, and the research group implemented classified nursing mode and adaptive leisure activity mode. The two groups of patients received 4 weeks of nursing intervention. With the help of self-rating anxiety scale, self-rating depression scale, self-care ability evaluation scale and health status survey brief form, the two groups of patients were compared before intervention and at the end of the 4th week after intervention. RESULTS: After the intervention, the anxiety score (t = 6.656, p < 0.001) and depression score (t = 4.851, p < 0.001) of the research group were lower than those of the control group, and the difference was statistically significant. After the intervention, the self-concept (t = 4.845, p < 0.001), self-responsibility (t = 6.071, p < 0.001), self-care skills (t = 3.341, p < 0.001), health knowledge (t = 3.698, p < 0.001) and total score (t = 9.246, p < 0.001) of the research group were higher than those of the control group, and the difference was statistically significant. After the intervention, physical functioning (t = 8.141, p < 0.001), bodily pain (t = 6.083, p < 0.001), general health (t = 9.424, p < 0.001), role-physical (t = 8.057, p < 0.001), role-emotional (t = 13.252, p < 0.001), mental health (t = 12.565, p < 0.001), social functioning (t = 10.813, p < 0.001) and vitality score (t = 12.890, p < 0.001) of the research group were higher than those of the control group, with significant differences. CONCLUSION: Interactive care through adaptive leisure nursing improves mental well-being, self-management, and psychosocial functioning in elderly colon cancer patients, promoting overall health.

Bavachin combined with epimedin B induce idiosyncratic liver injury under immunological stress conditions.

Reports on Chinese patent medicines preparations containing Epimedii Folium (EF) and Psoraleae Fructus (PF) resulting in idiosyncratic drug-induced liver injury (IDILI) have received widespread attention. Previous studies have shown that bavachin and epimedin B-two active ingredients derived from both EF and PF-are potential components associated with IDILI, but the underlying mechanism remains unclear. We evaluated bavachin and epimedin B-induced IDILI under TNF-α-mediated immunological stress conditions and generated liver lipid metabolism profiles using lipidomics and multivariate statistical analysis. We next applied transcriptomics to identify the differential gene expression on the transcription level. Our results showed that co-exposure to bavachin, epimedin B under immunological stress conditions resulted in obvious liver injury. The differential metabolites screened in our study were closely related to the immune homeostasis of the liver. Sixteen differentially expressed genes were found, Zc3h6 and R3hdml were upregulated, while Sumo2, Cd74, Banp, Oas3, Oas2, Gbp8, Slfn8, Gbp2b, Serpina3g, Zbtb40, H2-Ab1, Osgin1, Tgtp1 and Hspa1b were all downregulated. These differentially expressed genes were associated with biological processes concerning metabolic process and immune system process. Further integrative analysis indicated that bavachin combined with epimedin B affected genes that were not only related to immune system processes, but also to lipid metabolism. Ultimately, this led to an imbalance in the immune microenvironment in the liver and may have contributed to the observed liver injury.

Crystal structure of mRNA cap (guanine-N7) methyltransferase E12 subunit from monkeypox virus and discovery of its inhibitors.

In July 2022, the World Health Organization announced monkeypox as a public health emergency of international concern (PHEIC), and over 85,000 global cases have been reported currently. However, preventive and therapeutic treatments for the monkeypox virus (MPXV) remain limited. MPXV mRNA cap N7 methyltransferase (MTase) is composed of two subunits (E1 C-terminal domain (E1CTD) and E12) which are essential for the replication of MPXV. Here, we solved a 2.16 Å crystal structure of E12. We also docked the D1CTD of the vaccinia virus (VACV) corresponding to the E1CTD in MPXV with E12 and found critical residues at their interface. These residues were further used for drug screening. After virtual screening, the top 347 compounds were screened out and a list of top 20 potential MPXV E12 inhibitors were discovered, including Rutin, Quercitrin, Epigallocatechin, Rosuvastatin, 5-hydroxy-L-Tryptophan, and Deferasirox, etc., which were potential E12 inhibitors. Taking the advantage of the previously unrecognized special structure of MPXV MTase composing of E1CTD and E12 heterodimer, we screened for inhibitors targeting MTase for the first time based on the interface between the heterodimer of MPXV MTase. Our study may provide insights into the development of anti-MPXV drugs.

Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir.

Nirmatrelvir is a specific antiviral drug that targets the main protease (Mpro) of SARS-CoV-2 and has been approved to treat COVID-191,2. As an RNA virus characterized by high mutation rates, whether SARS-CoV-2 will develop resistance to nirmatrelvir is a question of concern. Our previous studies have shown that several mutational pathways confer resistance to nirmatrelvir, but some result in a loss of viral replicative fitness, which is then compensated for by additional alterations3. The molecular mechanisms for this observed resistance are unknown. Here we combined biochemical and structural methods to demonstrate that alterations at the substrate-binding pocket of Mpro can allow SARS-CoV-2 to develop resistance to nirmatrelvir in two distinct ways. Comprehensive studies of the structures of 14 Mpro mutants in complex with drugs or substrate revealed that alterations at the S1 and S4 subsites substantially decreased the level of inhibitor binding, whereas alterations at the S2 and S4' subsites unexpectedly increased protease activity. Both mechanisms contributed to nirmatrelvir resistance, with the latter compensating for the loss in enzymatic activity of the former, which in turn accounted for the restoration of viral replicative fitness, as observed previously3. Such a profile was also observed for ensitrelvir, another clinically relevant Mpro inhibitor. These results shed light on the mechanisms by which SARS-CoV-2 evolves to develop resistance to the current generation of protease inhibitors and provide the basis for the design of next-generation Mpro inhibitors.

Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants.

SARS-CoV-2 poses an unprecedented threat to the world as the causative agent of the COVID-19 pandemic. Among a handful of therapeutics developed for the prevention and treatment of SARS-CoV-2 infection, ensitrelvir is the first noncovalent and nonpeptide oral inhibitor targeting the main protease (Mpro) of SARS-CoV-2, which recently received emergency regulatory approval in Japan. Here we determined a 1.8-Å structure of Mpro in complex with ensitrelvir, which revealed that ensitrelvir targets the substrate-binding pocket of Mpro, specifically recognizing its S1, S2, and S1' subsites. Further, our comprehensive biochemical and structural data have demonstrated that even though ensitrelvir and nirmatrelvir (an FDA-approved drug) belong to different types of Mpro inhibitors, both of them remain to be effective against Mpros from all five SARS-CoV-2 variants of concern, suggesting Mpro is a bona fide broad-spectrum target. The molecular mechanisms uncovered in this study provide basis for future inhibitor design.

Improving Chuanxiong Rhizoma quality standards using an effect-constituent index based bioassay.

Chuanxiong Rhizoma is a traditional Chinese medicine (TCM) that is used to promote blood circulation. We set out to improve Chuanxiong Rhizoma quality standards using a bioassay-based Effect-constituent Index (ECI). We performed high performance liquid chromatography (HPLC) analysis to determine the chemical constituents of 10 Chuanxiong Rhizoma samples from different locations. We then constructed a direct bioassay method to investigate each sample's antiplatelet aggregation effects. To screen for active ingredients that promote antiplatelet aggregation, we carried out Pearson correlation analyses between biopotency and compounds identified in the HPLC data. We developed an ECI of platelet aggregation inhibition using a multi-indicator synthetic evaluation method based on the integration of biopotency and active constituents. To further assess the biopotency-based Chuanxiong Rhizoma quality evaluation result accuracy, we compared the ECI with the chemical indicator' method. Eight common chemical fingerprints peaks indicated notable content variation among samples. Biological evaluation showed that all 10 samples could inhibit platelet aggregation, although they had significantly different biological potencies. Using spectrum-effect relationships, we determined that Ligustilide was the significant active constituent responsible for antiplatelet aggregation. Using correlation analysis, we found that ECI correlated with the Chuanxiong Rhizoma extract's platelet aggregation inhibitory effect. Additionally, ECI proved to be a good indicator of Chuanxiong Rhizoma quality, whereas chemical indicators failed to distinguish and predict the biopotency-based quality grade. This work indicates that ECI is a useful tool for associating sample quality with chemical markers linked to TCM clinical effects. ECI also provides a paradigm for improving the quality control of other TCMs that invigorate blood circulation.

Eggshell waste separation process assisted with pressure-vacuum: Process conditions and optimization.

Eggshells and eggshell membranes have high-value recycling applications and have been widely used in pharmaceutical, chemical, and food research. The separation of eggshells and eggshell membranes is a prerequisite to efficiently using both. Therefore, the pressure-vacuum experiment equipment was designed. In this study, research on the separation of eggshells and eggshell membranes from waste eggshells using the pressure-vacuum experiment equipment was carried out. The flash evaporation experiment process controlled the experimental factors to obtain a sufficient moisture content between the eggshell and eggshell membrane with vigorous flash evaporation. The effects of experimental factors such as superheat (5-10°C), temperature (50-70°C), initial pressure (0.6-0.8 MPa), pressurization time (0-40 min), and particle size (6-8 mm) on the separation rate were investigated in the pressure-vacuum experiment process. Through single-factor and orthogonal experiments, it was found that the separation rate was most affected by changes in temperature, initial pressure, and particle size, followed by the interaction of temperature and particle size. The experimental results suggested that the optimum separation of eggshell membranes from eggshells was achieved at higher superheat, higher temperature, higher initial pressure, medium pressurization time, and smaller particle size. Through optimization by response surface methodology, the optimal conditions for the separation of eggshells and eggshell membranes using the flash evaporation method were determined as 15°C of superheat, 70°C of temperature, 0.8 MPa of initial pressure, and 6 mm of particle size. Flash evaporation method is an effective and environmentally friendly method, which provides a new solution for the recycling of waste eggshells. PRACTICAL APPLICATION: In this study, pressure-vacuum experiment equipment was utilized to reuse of waste eggshells, and an innovative and environmentally friendly method of eggshell membrane and eggshell separation was established. The pressure-vacuum experiment equipment has a simple structure and low energy consumption. The results of flash evaporation experiments are instructive for further in-depth studies on the separation of eggshells and eggshell membranes. Furthermore, the separation of eggshells and egg membranes by flash evaporation is of great research value. Most importantly, the separated eggshells and eggshell membrane are available for high-value applications in food, chemical, and biological fields.

Pharmacokinetics, bioavailability, and plasma protein binding study of glytrexate, a novel multitarget antifolate.

Glytrexate, developed by our team, as a novel multitarget folate antagonist, has inhibitory effects on a variety of cancer cell types, especially KB tumor cells (IC50 0.078 nM), and thus has antitumor drug development prospects. However, its pharmacokinetics and plasma protein binding properties remain unknown. In this study a selective and sensitive liquid chromatography-tandem mass spectrometry (LC‒MS/MS) method was developed and verified to facilitate biological analysis. The bioanalysis method was applied to evaluate the stability, plasma protein binding, and pharmacokinetics of glytrexate. Glytrexate is more stable in human plasma than in rat plasma and in human liver microsomes. The binding of glytrexate to human plasma proteins was higher than that to rat plasma proteins, both of which were less than 30%, suggesting that glytrexate may be at a higher concentration at the pharmacologic target receptor(s) in tissues. Pharmacokinetic characteristics were determined by noncompartmental analysis after administration of single oral (12.5, 25 and 50 mg/kg) and intravenous (2 mg/kg) doses in rats. According to the rat oral pharmacokinetic characteristics, glytrexate had linear dynamics in a dose range of 12.5-50 mg/kg and a poor oral bioavailability of 0.57-1.15%. The investigation revealed that the intravenous half-life, AUC, and Cmax of glytrexate were higher than those of pemetrexed. Pemetrexed is generally produced as an injection preparation. This provides ideas for the development of glytrexate formulations. Therefore, glytrexate injection has clinical application prospects compared to oral administration. This study provides a basis for further investigations into the pharmacological effects and clinical uses of glytrexate.

Cdc42 promotes thyroid cancer cell proliferation and migration and tumor-associated macrophage polarization through the PTEN/AKT pathway.

The purpose of this study was to investigate the potential mechanism and function of Cdc42 in thyroid cancer. We found that knockdown of Cdc42 inhibited the migration and proliferation of WRO cells. This role of Cdc42 is achieved by interacting with PTEN and interfering with its PTEN nuclear translocation. The overexpression of Cdc42 enhances the production of lactic acid and promotes the polarization of M2 macrophages, and therefore M2 macrophages inhibit the function of T cells. Overall, Cdc42 can promote cell proliferation and migration through the PTEN/AKT pathway and promote tumor-related M2 macrophage polarization and inhibit T cell activity by enhancing aerobic glycolysis, animal experiments confirmed that tumor volume increased after Cdc42 overexpressed in TBP-3743 murine thyroid cancer cells. Increased infiltration of Treg and macrophages was also observed. taken together, our results indicate that Cdc42 can be used as a diagnostic and thyroid cancer Prognostic biomarkers and potential therapeutic targets.

Sphingolipid Metabolism and Signaling in Lung Cancer: A Potential Therapeutic Target.

Sphingolipids are important bioactive lipids that not only play an important role in maintaining the barrier function and fluidity of cell membranes but also regulate multiple processes in cancer development by controlling multiple signaling pathways in the signal transduction network. Dysregulation of sphingolipid metabolism is thought to be one of the most important dysregulated pathways in lung cancer, the most prevalent type of cancer in terms of incidence and mortality worldwide. This article focuses on lung cancer, reviewing the important lipids in sphingolipid metabolism and the related enzymes in relation to lung cancer progression and their effects on the tumor microenvironment and discussing their roles in the diagnosis and treatment of lung cancer.

Analysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy.

The discovery of immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4, has played an important role in the development of cancer immunotherapy. However, immune-related adverse events often occur because of the enhanced immune response enabled by these agents. Antibiotics are widely applied in clinical treatment, and they are inevitably used in combination with immune checkpoint inhibitors. Clinical practice has revealed that antibiotics can weaken the therapeutic response to immune checkpoint inhibitors. Studies have shown that the gut microbiota is essential for the interaction between immune checkpoint inhibitors and antibiotics, although the exact mechanisms remain unclear. This review focuses on the interactions between immune checkpoint inhibitors and antibiotics, with an in-depth discussion about the mechanisms and therapeutic potential of modulating gut microbiota, as well as other new combination strategies.

Xihuang Pill enhances anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway.

Lung cancer poses a serious threat to human health. Although targeted therapies have led to breakthroughs in the treatment of lung cancer, drug resistance and side effects limit their clinical applications. Xihuang pill (XHW), a classical anti-cancer traditional Chinese medicine formula, has been clinically proven to be an effective complementary therapy in the treatment of various of cancers. However, the underlying mechanism for its use in combination with anti-cancer drugs remains unclear. Here, we explored the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung cancer (LLC). We used gut microbiota and transcriptomics to elucidate the regulatory properties of XHW in improving anti-lung cancer effect of anlotinib. The results showed that combination treatment of XHW with Anlotinib significantly inhibited tumor growth in LLC-bearing mice. We found that XHW played a key role in the regulation of gut microbiota using 16 s rRNA sequencing analysis. Specifically, XHW increased the proportion of the beneficial bacteria Bacteroides and g_norank_f_Muribaculaceae. Based on transcriptomic analysis of tumor tissues, differentially expressed genes in the combination therapy group were related to biological processes concerning angiogenesis, such as regulation of blood vessel diameter, regulation of tube diameter, and regulation of tube size. Our data suggest that XWH enhances the anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway. Combination therapy with anlotinib and XHW may be a novel therapeutic strategy for lung cancer patients.

Novel Angiogenic Regulators and Anti-Angiogenesis Drugs Targeting Angiogenesis Signaling Pathways: Perspectives for Targeting Angiogenesis in Lung Cancer.

Lung cancer growth is dependent on angiogenesis. In recent years, angiogenesis inhibitors have attracted more and more attention as potential lung cancer treatments. Current anti-angiogenic drugs targeting VEGF or receptor tyrosine kinases mainly inhibit tumor growth by reducing angiogenesis and blocking the energy supply of lung cancer cells. However, these drugs have limited efficiency, raising concerns about limited scope of action and mechanisms of patient resistance to existing drugs. Therefore, current basic research on angiogenic regulators has focused more on screening carcinogenic/anticancer genes, miRNAs, lncRNAs, proteins and other biomolecules capable of regulating the expression of specific targets in angiogenesis signaling pathways. In addition, new uses for existing drugs and new drug delivery systems have received increasing attention. In our article, we analyze the application status and research hotspots of angiogenesis inhibitors in lung cancer treatment as a reference for subsequent mechanistic research and drug development.

Promoter Methylation-Mediated NPTX2 Silencing Promotes Tumor Growth in Human Prostate Cancer.

Neuronal pentraxin 2 (NPTX2), a secretory protein of neuronal pentraxins, was first identified in the nervous system. Several studies have shown that expression levels of NPTX2 are associated with the development of various cancers. However, whether NPTX2 is involved in prostate cancer progression is unclear. Herein, we found that NPTX2 is significantly reduced in prostate cancer tissues and cancer cell lines compared to control prostate tissues and control prostatic epithelial cell lines. Furthermore, the NPTX2 promoter is highly methylated in prostate cancer cells. Consistently, NPTX2 could be restored by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (decitabine, 5-AZA-dC). Overexpression of NPTX2 inhibited prostate cancer cell proliferation both in vitro and in vivo. In conclusion, our study demonstrated that NPTX2 acts as a tumor suppressor gene in prostate cancer.

Structural Basis of Zika Virus Helicase in RNA Unwinding and ATP Hydrolysis.

The flavivirus nonstructural protein 3 helicase (NS3hel) is a multifunctional domain protein that is associated with DNA/RNA helicase, nucleoside triphosphatase (NTPase), and RNA 5'-triphosphatase (RTPase) activities. As an NTPase-dependent superfamily 2 (SF2) member, NS3hel employs an NTP-driven motor force to unwind double-stranded RNA while translocating along single-stranded RNA and is extensively involved in the viral replication process. Although the structures of SF2 helicases are widely investigated as promising drug targets, the mechanism of energy transduction between NTP hydrolysis and the RNA binding sites in ZIKV NS3hel remains elusive. Here, we report the crystal structure of ZIKV NS3hel in complex with its natural substrates ATP-Mn2+ and ssRNA. Distinct from other members of the Flavivirus genus, ssRNA binding to ZIKV NS3hel induces relocation of the active water molecules and ATP-associated metal ions in the NTP hydrolysis active site, which promotes the hydrolysis of ATP and the production of AMP. Our findings highlight the importance of the allosteric role of ssRNA on the modulation of ATP hydrolysis and energy utilization.

Improving crude protein and methionine production, selective lignin degradation and digestibility of wheat straw by Inonotus obliquus using response surface methodology.

BACKGROUND: To date, fungus-assisted pretreatment of agricultural residue has not become the preferred method to produce protein-enriched and ruminally digestible animal feed because of low time efficiency of fungal delignification and protein production, i.e. the long solid-state fermentation period, and because of laccase as a potential inhibitor of cellulose activity. In this study, response surface methodology was employed to optimize the parameters in the process of producing nutritious animal feed from wheat straw with Inonotus obliquus pretreatment. RESULTS: The mineral salt solution containing (w/v) (NH4 )2 SO4 1%, MgSO4 ·7H2 O 0.03%, KH2 PO4 0.011%, Tween-80 0.4%, and corn starch 10% with pH of 7.4 was optimized. Inonotus obliquus rapidly and completely colonized on wheat straw with an ergosterol content of 280 µg g-1 dry matter, consuming 45% of lignin after 15 days of fermentation, producing maximums of lignin peroxidase (1729 IU g-1 ), manganese peroxidase (610 IU g-1 ) and laccase (98 IU g-1 ) on days 5, 15, and 25, respectively. The crude protein (102.4 g kg-1 ) of 15-day fermented wheat straw increased by ~132%. After hydrolysis, the essential protein-bound amino acids (15.3 g kg-1 ) increased by ~47%, within which Met and Lys measured ~1070% and ~60% higher. The treatment with I. obliquus also improved the in vitro gas production after 72 h (IVGP72 ) of wheat straw to 178.8 mL g-1 organic matter (~43% increase). CONCLUSION: For the first time, we found that I. obliquus is an effective white rot fungus turning wheat straw into ruminally digestible animal feed without laccase inhibitor.

Cross-Attention Fusion Based Spatial-Temporal Multi-Graph Convolutional Network for Traffic Flow Prediction.

Accurate traffic flow prediction is essential to building a smart transportation city. Existing research mainly uses a given single-graph structure as a model, only considers local and static spatial dependencies, and ignores the impact of dynamic spatio-temporal data diversity. To fully capture the characteristics of spatio-temporal data diversity, this paper proposes a cross-Attention Fusion Based Spatial-Temporal Multi-Graph Convolutional Network (CAFMGCN) model for traffic flow prediction. First, introduce GCN to model the historical traffic data's three-time attributes (current, daily, and weekly) to extract time features. Second, consider the relationship between distance and traffic flow, constructing adjacency, connectivity, and regional similarity graphs to capture dynamic spatial topology information. To make full use of global information, a cross-attention mechanism is introduced to fuse temporal and spatial features separately to reduce prediction errors. Finally, the CAFMGCN model is evaluated, and the experimental results show that the prediction of this model is more accurate and effective than the baseline of other models.