Dynamic genomic changes in methotrexate-resistant human cancer cell lines beyond DHFR amplification suggest potential new targets for preventing drug resistance.

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.

Role of TFEB-autophagy lysosomal pathway in palmitic acid induced renal tubular epithelial cell injury.

Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagy-lysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Selectively Transport and Removal of Fluoride Ion by Pillar[5]Arene Polymer-Filled Nanochannel Membrane.

Excess fluoride ions in groundwater accumulate through the roots of crops, affecting photosynthesis and inhibiting their growth. Long-term bioaccumulation also threatens human health because it is poorly degradable and toxic. Currently, one of the biggest challenges is developing a unique material that can efficiently remove fluoride ions from the environment. The excellent properties of functionalized pillar[5]arene polymer-filled nanochannel membranes were explored to address this challenge. Constructing a multistage porous nanochannel membrane, consisting of microscale etched nanochannels and nanoscale pillar[5]arene cross-linked polymer voids. A fluoride removal rate of 0.0088 mmol ⋅ L-1 ⋅ min-1 was achieved. Notably, this rate surpassed the rates observed with other control ions by a factor of 6 to 8.8. Our research provides a new direction for developing water fluoride ion removal materials.

Safety and Efficacy of Albumin for Pump Priming in Cardiac Surgery: A Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety of albumin as pump priming fluid in cardiac surgery. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Each study was conducted in a surgical center or intensive care unit. PARTICIPANTS: Adult and pediatric patients undergoing cardiac surgery with cardiopulmonary bypass who received circuit priming fluids. INTERVENTIONS: Extracorporeal circuit priming with either albumin or crystalloid. MEASUREMENTS AND RESULTS: Fourteen eligible randomized controlled trials with 741 patients were included in the present meta-analysis. Albumin prime had lower bleeding (CI -202.20 to -142.88 mL, p < 0.00001) and showed a greater advantage in preserving platelet counts (CI 14.85-21.48 × 103 mm-3, p < 0.00001), maintaining colloid osmotic pressure and sustaining negative fluid balance. No significant differences were found in the remaining study outcomes. CONCLUSIONS: Albumin was shown to be safe and efficacious in extracorporeal circulation perfusion. However, its clinical advantages were not clearly highlighted, as there were no significant differences in the number of deaths, length of hospital stay, or intensive care unit duration. The results should be interpreted cautiously, as most included studies were small in scale, and the total number of participants was limited.

Inertial Measuring System to Evaluate Gait Parameters and Dynamic Alignments for Lower-Limb Amputation Subjects.

The study aims to construct an inertial measuring system for the application of amputee subjects wearing a prosthesis. A new computation scheme to process inertial data by installing seven wireless inertial sensors on the lower limbs was implemented and validated by comparing it with an optical motion capture system. We applied this system to amputees to verify its performance for gait analysis. The gait parameters are evaluated to objectively assess the amputees' prosthesis-wearing status. The Madgwick algorithm was used in the study to correct the angular velocity deviation using acceleration data and convert it to quaternion. Further, the zero-velocity update method was applied to reconstruct patients' walking trajectories. The combination of computed walking trajectory with pelvic and lower limb joint motion enables sketching the details of motion via a stickman that helps visualize and animate the walk and gait of a test subject. Five participants with above-knee (n = 2) and below-knee (n = 3) amputations were recruited for gait analysis. Kinematic parameters were evaluated during a walking test to assess joint alignment and overall gait characteristics. Our findings support the feasibility of employing simple algorithms to achieve accurate and precise joint angle estimation and gait parameters based on wireless inertial sensor data.

Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.

Protein Expression Profiles in Exosomes of Bovine Mammary Epithelial Cell Line MAC-T Infected with Staphylococcus aureus.

Mastitis is a common and widespread infectious disease in dairy farms around the world, resulting in reduced milk production and quality. Staphylococcus aureus is one of the main pathogenic bacteria causing subclinical mastitis in dairy cows. S. aureus can activate inflammatory signaling pathways in bovine mammary epithelial cells. Exosomes produced by cells can directly transfer pathogen-related molecules from cell to cell, thus affecting the process of infection. Protein is the material basis of the immune defense function in the body; therefore, a comprehensive comparison of proteins in exosomes derived from S. aureus-infected (SA group) and normal (control group [C group]) bovine mammary epithelial MAC-T cells was performed using shotgun proteomics by a DIA approach. A total of 7,070 proteins were identified and quantified. Compared with the C group, there were 802 differentially expressed proteins (DEPs) identified in the SA group (absolute log2 fold change [|log2FC|] of ≥0.58; false discovery rate [FDR] of <0.05), among which 325 proteins were upregulated and 477 were downregulated. The upregulated proteins, including complement 3 (C3), integrin alpha-6 (ITGA6), apolipoprotein A1 (APOA1), annexin A2 (ANXA2), tripeptidyl peptidase II (TPP2), keratin 8 (KRT8), and recombinant desmoyokin (AHNAK), are involved mostly in host defense against pathogens, inflammation, and cell structure maintenance. KEGG enrichment analysis indicated that DEPs in S. aureus infection were involved in the complement and coagulation cascade, phagosome, extracellular matrix (ECM)-receptor interaction, and focal adhesion pathways. The results of this study provide novel information about proteins in the exosomes of MAC-T cells infected with S. aureus and could contribute to an understanding of the infectious mechanism of bovine mastitis. IMPORTANCE Mastitis is a widespread infectious disease in dairy farms, resulting in reduced milk production and quality. Staphylococcus aureus is one of the main pathogenic bacteria causing subclinical mastitis. Exosomes contain proteins, lipids, and nucleic acids, which are involved in many physiological and pathological functions. The expression of proteins in exosomes derived from bovine mammary epithelial cells infected by S. aureus is still barely understood. These results provide novel information about MAC-T-derived exosomal proteins, reveal insights into their functions, and lay a foundation for further studying the biological function of exosomes during the inflammatory response.

Recognition of Water-Induced Double-Edged Sword Effects in Photocatalytic Selective Oxidation of Toluene on Titanium Dioxide Clusters with Density Functional Theory Calculations.

Recently, water promotion effects in the selective oxidation of benzyl alcohol to benzaldehyde have been experimentally recognized and identified. However, the effects of water on the photocatalytic selective oxidation of toluene into benzaldehyde remain elusive. In this work, the Ti3O9H6 clusters in different solvents (water and toluene solvent) are used to study the water-induced effects in photocatalytic oxidation reactions in kinetics and thermodynamics using density functional theory (DFT) calculations. In addition, the influences of the OH groups on catalysts (Ti-OH bonds) from photocatalytic water splitting are also considered. The results clearly demonstrate the water-induced double-edged sword effects in the photocatalytic selective oxidation of toluene. We expect that our work can not only shed light on the mechanisms of photocatalytic selective oxidation of toluene into benzaldehyde and other activation reactions of sp3 C-H bonds but also design and modulate highly efficient photocatalysts.

A triphenylamine-based fluorescent probe with phenylboronic acid for highly selective detection of Hg2+ and CH3Hg+ in groundwater.

Mercury is a highly toxic heavy metal and it poses a serious threat to the natural environment and human health. Thus, selective detection of trace mercury (e.g. inorganic mercury and methylmercury) in the environment is critical yet challenging. Herein, we describe the rational design and facile synthesis of a new triphenylamine-based phenylboronic acid fluorescent probe (TPA-PBA) for selective detection of Hg2+ and CH3Hg+. Due to the inherent specificity of the displacement reaction between phenylboronic acid and mercury, this probe exhibits exceptionally high selectivity towards Hg2+/CH3Hg+ against other tested ions with ppb-level sensitivity. More importantly, the probe TPA-PBA is effective and selective in detecting Hg2+/CH3Hg+ in tap water and real-world groundwater, indicating its potential practical applications in in situ and online mercury detection in real-world scenarios. With TPA-PBA based test strips Hg2+ can be distinguished from CH3Hg+ by the naked eye. This study could accelerate the development of low-cost, highly efficient and selective fluorescent probes for rapid trace mercury detection.

A method to protect the endometrium for microwave ablation treating types 1-3 uterine fibroids: a preliminary comparative study.

PURPOSE: To investigate the feasibility of percutaneous intrauterine instillation of chilled saline to protect the endometrium during microwave ablation (MWA) treating types 1-3 uterine fibroids. MATERIALS AND METHODS: Twenty-six patients with types 1-3 uterine fibroids were prospectively enrolled in an intrauterine saline instillation group (study group). The same number of patients with types 1-3 uterine fibroids who previously received MWA without endometrial protection were retrospectively included in a control group. Endometrial impairment was evaluated by hysteroscopy and magnetic resonance imaging (MRI). RESULTS: In the study group, hysteroscopy revealed an intact endometrium in 17 patients, congestion and reddening of the endometrium due to heat in 8 patients, and a burnt necrosis with a size < 1 cm on the functional layer of the endometrium in 1 patient. On MRI, in the study group, there were 17 (65.4%), 6 (23.1%), and 3 (11.5%) patients with grades 0, 1, and 2 endometrial impairment, respectively, but no grade 3 endometrial impairment. In the control group, there were 8 (30.8%), 8 (30.8%), 7 (26.9%), and 3 (11.5%) patients with grades 0, 1, 2, and 3 endometrial impairment, respectively. Endometrial impairment in the study group was significantly better than that in the control group (p = 0.006). One patient had puncture tunnel bleeding and no other complications occurred in the study group. CONCLUSION: Intraoperative percutaneous intrauterine instillation of chilled saline may be effective and safe in reducing the thermal damage to the endometrium caused by MWA for treating types 1-3 uterine fibroids.

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

PINA 3.0: mining cancer interactome.

Protein-protein interactions (PPIs) are crucial to mediate biological functions, and understanding PPIs in cancer type-specific context could help decipher the underlying molecular mechanisms of tumorigenesis and identify potential therapeutic options. Therefore, we update the Protein Interaction Network Analysis (PINA) platform to version 3.0, to integrate the unified human interactome with RNA-seq transcriptomes and mass spectrometry-based proteomes across tens of cancer types. A number of new analytical utilities were developed to help characterize the cancer context for a PPI network, which includes inferring proteins with expression specificity and identifying candidate prognosis biomarkers, putative cancer drivers, and therapeutic targets for a specific cancer type; as well as identifying pairs of co-expressing interacting proteins across cancer types. Furthermore, a brand-new web interface has been designed to integrate these new utilities within an interactive network visualization environment, which allows users to quickly and comprehensively investigate the roles of human interacting proteins in a cancer type-specific context. PINA is freely available at https://omics.bjcancer.org/pina/.

Effects of combined addition of 3-nitrooxypropanol and vitamin B12 on methane and propionate production in dairy cows by in vitro-simulated fermentation.

The compound 3-nitrooxypropanol (3-NOP) is a promising methane inhibitor, which performs well in inhibiting methane emission and does not affect animal feed intake and digestibility. However, it causes a significant increase in hydrogen production while suppressing methane emission, resulting in a waste of feed energy. Vitamin B12 is a key factor in the propionate production pathway and thus plays an important role in regulating the hydrogen utilization pathway. In this study, the effects of 3-NOP combined with vitamin B12 supplementation on rumen fermentation and microbial compositional structure in dairy cattle were investigated by simulating rumen fermentation in vitro. Experiments were performed using a 2 × 2-factorial design: two 3-NOP levels (0 or 2 mg/g dry matter) and 2 vitamin B12 levels (0 or 2 mg/g dry matter). Three experiments were performed, each consisting of 4 treatments, 4 replicates, and 4 blanks containing only inoculum. The combined supplementation of 3-NOP and vitamin B12 reduced methane emission by 12% without affecting dry matter digestibility. The combined addition of 3-NOP and vitamin B12 significantly increased the concentration of propionate and reduced the concentration of acetate and the acetate to propionate ratio. At the bacterial level, 3-NOP increased the relative abundances of Christensenellaceae_R-7_group and Lachnospiraceae_NK3A20_group. Vitamin B12 increased the relative abundances of unclassified_f__Prevotellaceae and Prevotellaceae_UCG-003 and decreased the relative abundance of Lachnospiraceae_NK3A20_group. At the archaeal level, the combination of 3-NOP and vitamin B12 increased the relative abundances of Methanobrevibacter_ sp._ Abm4, OTU1125, and OTU95 and decreased the relative abundances of uncultured_methanogenic_archaeon_g__Methanobrevibacter, OTU1147, OTU1056, and OTU55. The results indicated that 3-NOP combined with vitamin B12 could alleviate rumen hydrogen emission and enhance the inhibition of methane emission compared with 3-NOP alone.

Quantitative assessment of selective degradation behavior of etoxazole in different classes of organisms by compound-specific isotope analysis.

In this paper, the stereoselective degradation and quantitative identification of chiral pesticide etoxazole in organisms with different classes of organisms (soil, chlorella algal fluid and mice) were carried out by compound-specific isotope analysis (CSIA). The degradation behavior and stable isotope fractionation effect of etoxazole in soil, chlorella and mice were investigated. The R-etoxazole degraded faster than S-etoxazole in different classes of organisms. The metabolites M1, M2 and M3 were detected in all three substrates. Biodegradation is the main factor for the change of stable isotope ratio of chiral pesticide etoxazole. Furthermore, the relationship between fractionation value of carbon isotope and residual concentration of etoxazole is established by Rayleigh equation, and the biodegradation rate of etoxazole could be calculated by using CSIA without measuring the concentration of etoxazole. Therefore, the use of CSIA can accurately assess the degradation behavior of pesticide pollution in the environment and provide a certain scientific evidence and technical support in the process of environmental remediation.

Risk aggregation considering probabilistic and consequential interactions: A general formulation with computational cost handling.

Complicated interaction between risk events is the critical obstacle preventing accurate risk aggregation, which is an important issue in risk management. Recent research integrates interaction into risk aggregation with different perspectives and lacks a comprehensive discussion of this issue, making the risk aggregation process not universal for diverse cases, especially in subjective risk assessment contexts. Therefore, this article proposes a theoretically convincing risk aggregation method embedding different types of interaction to support decision analysis more effectively. The main contributions of this article are as follows: (a) more in-depth and stricter definitions, measures, and graphical descriptions of different types of interaction are developed to ensure the accuracy of risk aggregation; (b) a formal risk aggregation approach that could apply in both objective and subjective risk assessment contexts while elegantly embedding risk interactions is proposed; (c) the additivity of risks and risk sets in the risk aggregation process is discussed in detail and the conditions for additivity are clarified; (d) the quasi-two/three-additive measures, which approximately obtain the aggregate risk value within sufficient reliability, are proposed to greatly reduce the computational cost. To examine the applicability of the proposed general risk aggregation method, a case study is finally presented to show the complete risk aggregation process and its application in the decision-making stage.

MS/MS molecular networking-guided in-depth profiling of triterpenoid saponins from the fruit of Eleutherococcus senticosus and their neuroprotectivity evaluation.

INTRODUCTION: Eleutherococcus senticosus fruit (ESF) is a natural health supplement resource that has been extensively applied as a tonic for the nervous system. The structures and neural bioactivities of triterpenoid saponins (TS), which are the major constituents of ESF, have not been comprehensively analyzed thus far. OBJECTIVE: We conducted a complete in-depth MS/MS molecular networking (MN)-based targeted analysis of TS from the crude extract of ESF and investigated its neuroprotective value. METHODS: An MS/MS MN-guided strategy was used to rapidly present a series of precursor ions (PIs) of TS in a compound cluster as TS-targeted information used in the discovery and characterization of TS. In addition, a prepared TS-rich fraction of ESF was assayed for its restraining effects on ß-amyloid-induced inhibition of neurite outgrowth. RESULTS: A total of 87 TS were discovered using a PI tracking strategy, 28 of which were characterized as potentially undescribed structures according to their high-resolution MS values. Furthermore, the TS-rich fraction can significantly reduce ß-amyloid-induced damage to neural networks by promoting the outgrowth of neurites and axons. CONCLUSION: Our findings reveal the richness of TS in ESF and will accelerate their application in the treatment of neurodegenerative diseases.

Heterogeneous Diffusion of Government Microblogs and Public Agenda Networks during Public Policy Communication in China.

During public policy information diffusion, policy interpretation on government microblogs and public attention interact, but there are certain differences. We construct a research framework for the heterogeneous diffusion of public policy information on government microblogs. An empirical study is conducted based on the Network Agenda Setting (NAS) model. First, a combination of topic mining and content analysis is used to identify the issues discussed by government microblogs and citizens. Then, we use the importance of nodes in Degree Structure (DS) and Flow Structure (FS) entropy to measure their attention to different issues. Finally, the Quadratic Assignment Procedure (QAP) correlation and regression analysis explore the degree of heterogeneity and causal relationship between government microblog agenda networks (GMANs) and public agenda networks (PANs). We find that GMANs influence PANs and the degree of heterogeneity between them is relatively low at the beginning of policy implementation. However, as government microblogs reveal positive effects of policy implementation, they fail to influence PANs effectively, and there is a greater degree of heterogeneity between them. Moreover, PANs do not significantly affect GMANs. The dynamic leading relationship between GMANs and PANs in public policy diffusion is clarified, helping to shape the image of digital government in public opinion.

[Varieties systematization and standards status analysis of fermented Chinese medicine].

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.