Dynamic immobilization of bacterial cells on biofilm in a polyester nonwoven chemostat.

Cell immobilization plays an important role in biocatalysis for high-value products. It is necessary to maintain the viability of immobilized cells for bioconversion using viable cells as biocatalysts. In this study, a novel polyester nonwoven chemostat was designed for cell immobilization to investigate biofilm formation and the dynamic balance between adsorption and desorption of cells on polyester nonwoven. The polyester nonwoven was suitable for cell immobilization, and the cell numbers on the polyester nonwoven can reach 6.5 ± 0.38 log CFU/mL. After adding the polyester nonwoven to the chemostat, the fluctuation phenomenon of free bacterial cells occurred. The reason for this phenomenon was the balance between adsorption and desorption of bacterial cells on the polyester nonwoven. Bacterial cells could adhere to the surface of polyester nonwoven via secreting extracellular polymeric substances (EPS) to form biofilms. As the maturation of biofilms, some dead cells inside the biofilms can cause the detachment of biofilms. This process of continuous adsorption and desorption of cells can ensure that the polyester nonwoven chemostat has lasting biological activity.

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedic condition with an uncertain etiology, possibly involving genetics and biomechanics. Factors like changes in chondrocyte microenvironment, oxidative stress, inflammation, and immune responses affect KOA development. Early-stage treatment options primarily target symptom relief. Mesenchymal stem cells (MSCs) show promise for treatment, despite challenges. Recent research highlights microRNAs (miRNAs) within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression. This suggests exosomes (Exos) as a promising avenue for future treatment. While these findings emphasize the need for effective KOA progression management, further safety and efficacy validation for Exos is essential. AIM: To explore miR-29a's role in KOA, we'll create miR-29a-loaded vesicles, testing for early treatment in rat models. METHODS: Extraction of bone marrow MSC-derived extracellular vesicles, preparation of engineered vesicles loaded with miR-29a using ultrasonication, and identification using quantitative reverse transcription polymerase chain reaction; after establishing a rat model of KOA, rats were randomly divided into three groups: Blank control group injected with saline, normal extracellular vesicle group injected with normal extracellular vesicle suspension, and engineered extracellular vesicle group injected with engineered extracellular vesicle suspension. The three groups were subjected to general behavioral observation analysis, imaging evaluation, gross histological observation evaluation, histological detection, and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis. RESULTS: General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Additionally, the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis. Using the Pelletier gross score evaluation, the engineered extracellular vesicle group had the slowest progression of arthritis. Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group, and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition. Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group. Compared to the normal extracellular vesicle group, the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells. CONCLUSION: Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability, thereby protecting articular cartilage, and slowing the progression of KOA.

Kinetics-based development of two-stage continuous fermentation of 1,3-propanediol from crude glycerol by Clostridium butyricum.

BACKGROUND: Glycerol, as a by-product, mainly derives from the conversion of many crops to biodiesel, ethanol, and fatty ester. Its bioconversion to 1,3-propanediol (1,3-PDO) is an environmentally friendly method. Continuous fermentation has many striking merits over fed-batch and batch fermentation, such as high product concentration with easy feeding operation, long-term high productivity without frequent seed culture, and energy-intensive sterilization. However, it is usually difficult to harvest high product concentrations. RESULTS: In this study, a three-stage continuous fermentation was firstly designed to produce 1,3-PDO from crude glycerol by Clostridium butyricum, in which the first stage fermentation was responsible for providing the excellent cells in a robust growth state, the second stage focused on promoting 1,3-PDO production, and the third stage aimed to further boost the 1,3-PDO concentration and reduce the residual glycerol concentration as much as possible. Through the three-stage continuous fermentation, 80.05 g/L 1,3-PDO as the maximum concentration was produced while maintaining residual glycerol of 5.87 g/L, achieving a yield of 0.48 g/g and a productivity of 3.67 g/(L·h). Based on the 14 sets of experimental data from the first stage, a kinetic model was developed to describe the intricate relationships among the concentrations of 1,3-PDO, substrate, biomass, and butyrate. Subsequently, this kinetic model was used to optimize and predict the highest 1,3-PDO productivity of 11.26 g/(L·h) in the first stage fermentation, while the glycerol feeding concentration and dilution rate were determined to be 92 g/L and 0.341 h-1, separately. Additionally, to achieve a target 1,3-PDO production of 80 g/L without the third stage fermentation, the predicted minimum volume ratio of the second fermenter to the first one was 11.9. The kinetics-based two-stage continuous fermentation was experimentally verified well with the predicted results. CONCLUSION: A novel three-stage continuous fermentation and a kinetic model were reported. Then a simpler two-stage continuous fermentation was developed based on the optimization of the kinetic model. This kinetics-based development of two-stage continuous fermentation could achieve high-level production of 1,3-PDO. Meanwhile, it provides a reference for other bio-chemicals production by applying kinetics to optimize multi-stage continuous fermentation.

Perturbations in gut and respiratory microbiota in COVID-19 and influenza patients: a systematic review and meta-analysis.

Objectives: Coronavirus disease-19 (COVID-19)/influenza poses unprecedented challenges to the global economy and healthcare services. Numerous studies have described alterations in the microbiome of COVID-19/influenza patients, but further investigation is needed to understand the relationship between the microbiome and these diseases. Herein, through systematic comparison between COVID-19 patients, long COVID-19 patients, influenza patients, no COVID-19/influenza controls and no COVID-19/influenza patients, we conducted a comprehensive review to describe the microbial change of respiratory tract/digestive tract in COVID-19/influenza patients. Methods: We systematically reviewed relevant literature by searching the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2023. We conducted a comprehensive review to explore microbial alterations in patients with COVID-19/influenza. In addition, the data on α-diversity were summarized and analyzed by meta-analysis. Results: A total of 134 studies comparing COVID-19 patients with controls and 18 studies comparing influenza patients with controls were included. The Shannon indices of the gut and respiratory tract microbiome were slightly decreased in COVID-19/influenza patients compared to no COVID-19/influenza controls. Meanwhile, COVID-19 patients with more severe symptoms also exhibited a lower Shannon index versus COVID-19 patients with milder symptoms. The intestinal microbiome of COVID-19 patients was characterized by elevated opportunistic pathogens along with reduced short-chain fatty acid (SCFAs)-producing microbiota. Moreover, Enterobacteriaceae (including Escherichia and Enterococcus) and Lactococcus, were enriched in the gut and respiratory tract of COVID-19 patients. Conversely, Haemophilus and Neisseria showed reduced abundance in the respiratory tract of both COVID-19 and influenza patients. Conclusion: In this systematic review, we identified the microbiome in COVID-19/influenza patients in comparison with controls. The microbial changes in influenza and COVID-19 are partly similar.

Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta-analysis.

Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta-analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P < 0.00001] and stroke volume [MD = 6.59, 95% CI (3.22, 9.96), P = 0.0001] and significantly reduced left ventricular end-systolic volume [standard mean difference (SMD) = -0.52, 95% CI (-0.67, -0.37), P < 0.00001], left ventricular end-diastolic volume index [SMD = -1.24, 95% CI (-1.61, -0.86), P < 0.00001], and left ventricular end-systolic volume index [SMD = -1.06, 95% CI (-1.43, -0.70), P < 0.00001]. In terms of biomarkers, levosimendan significantly reduced the level of brain natriuretic peptide [SMD = -1.08, 95% CI (-1.60, -0.56), P < 0.0001], N-terminal pro-brain natriuretic peptide [SMD = -0.99, 95% CI (-1.41, -0.56), P < 0.00001], and interleukin-6 [SMD = -0.61, 95% CI (-0.86, -0.35), P < 0.00001]. Meanwhile, levosimendan may increase the incidence of hypotension [risk ratio (RR) = 1.24, 95% CI (1.12, 1.39), P < 0.0001], hypokalaemia [RR = 1.57, 95% CI (1.08, 2.28), P = 0.02], headache [RR = 1.89, 95% CI (1.50, 2.39), P < 0.00001], atrial fibrillation [RR = 1.31, 95% CI (1.12, 1.52), P = 0.0005], and premature ventricular complexes [RR = 1.86, 95% CI (1.27, 2.72), P = 0.001]. In addition, levosimendan reduced all-cause mortality [RR = 0.83, 95% CI (0.74, 0.94), P = 0.002]. In conclusion, our study found that levosimendan might reverse ventricular remodelling when applied in patients with left ventricular systolic dysfunction, especially in patients undergoing cardiac surgery, decompensated heart failure, and septic shock.

[Regulation Effects of Humus Active Components on Soil Cadmium Availability and Critical Threshold for Rice Safety].

Organic materials containing humic acids (HAs) play important roles in regulating the bioavailability of cadmium (Cd) in soils and thus its accumulation in crops. The effects of the two active components of HAs, humic acid (HA) and fulvic acid (FA), in organic materials and their different ratios (HA/FA) on Cd uptake and accumulation in rice were investigated using a field plot experiment, and their relationships with the Cd fractions and availability in paddy soil as influenced by the use of these organic materials were analyzed in combination with the fractionation method of chemical continuous extraction. The results showed that the effects of HAs on Cd availability in soil and Cd accumulation in rice grains were controlled by the ratios of the active components in the organic materials. The treatments with an HA/FA ratio ≥ 4/6 had a passivating effect on soil Cd, resulting in a significant reduction in Cd availability. Compared with that in the control without the application of HAs (CK), rice grain Cd concentration was reduced by 15.2%-33.3%, whereas those with an HA/FA ratio ≤ 2/8 activated Cd in soil, and the available Cd content was significantly increased. Compared with that in CK, rice grain Cd concentration was increased by 24.2%-42.4%. The ratios of HA/FA in HAs affected the morphological transformation of soil Cd. Compared with the CK treatment, the treatments with ratios of HA/FA ≥ 4/6 promoted the transformation of soil Cd from the exchangeable form (EX-Cd) with high activity to the carbonate bound form (CA-Cd) and Fe and Mn oxide-bound forms (FM-Cd) with low activity, whereas those with ratios of HA/FA ≤ 2/8 showed the opposite effects. The effects of HA and FA on soil pH and available sulfur concentration differed. Soil pH had a significant positive correlation with HA addition but a negative correlation with FA addition, and soil available sulfur content had a significant positive correlation with FA addition at the rice tillering stage. Therefore, to ensure the quality and safety of rice, organic materials with an HA/FA ratio ≥ 4/6 should be selected. The results provided a scientific basis for the directed utilization of organic materials containing HAs.

Defective kernel 58 encodes an Rrp15p domain-containing protein essential to ribosome biogenesis and seed development in maize.

Ribosome biogenesis is a highly dynamic and orchestrated process facilitated by hundreds of ribosomal biogenesis factors and small nucleolar RNAs. While many of the advances are derived from studies in yeast, ribosome biogenesis remains largely unknown in plants despite its importance to plant growth and development. Through characterizing the maize (Zea mays) defective kernel and embryo-lethal mutant dek58, we show that DEK58 encodes an Rrp15p domain-containing protein with 15.3% identity to yeast Rrp15. Over-expression of DEK58 rescues the mutant phenotype. DEK58 is localized in the nucleolus. Ribosome profiling and RNA gel blot analyses show that the absence of DEK58 reduces ribosome assembly and impedes pre-rRNA processing, accompanied by the accumulation of nearly all the pre-rRNA processing intermediates and the production of an aberrant processing product P-25S*. DEK58 interacts with ZmSSF1, a maize homolog of the yeast Ssf1 in the 60S processome. DEK58 and ZmSSF1 interact with ZmCK2α, a putative component of the yeast UTP-C complex involved in the small ribosomal subunit processome. These results demonstrate that DEK58 is essential to seed development in maize. It functions in the early stage of pre-rRNA processing in ribosome biogenesis, possibly through interacting with ZmSSF1 and ZmCK2α in maize.

Dynamic flux balance analysis of 1,3-propanediol production by clostridium butyricum fermentation.

To study the relationship between the yield of 1,3-propanediol (1,3-PDO) and the flux change of the Clostridium butyricum metabolic pathway, an optimized calculation method based on dynamic flux balance analysis was used by combining genome-scale flux balance analysis with a kinetic model. A more comprehensive and extensive metabolic pathway was obtained by optimization calculations. The primary extended branches include: the dihydroxyacetone node, which enters the pentose phosphate pathway; the α-oxoglutarate node, which has synthetic metabolic pathways for glutamic acid and amino acids; and the serine and homocysteine nodes, which produce cystathionine before homocysteine enters the methionine cycle pathway. According to the expanded metabolic network, the flux distribution of key nodes in the metabolic pathway and the relationship between the flux distribution ratio of nodes and the yield of 1,3-PDO were analyzed. At the dihydroxyacetone node, the flux of dihydroxyacetone converted to dihydroxyacetone phosphate was positively correlated with the yield of 1,3-PDO. As an important intermediate product, the flux change in the metabolic pathway of α-oxoglutarate reacting with amino acids to produce glutamic acid is positively correlated with the yield. When pyruvate was used as the central node to convert into lactic acid and α-oxoglutarate, the proportion of branch flux was negatively correlated with the yield of 1,3-PDO. These studies provide a theoretical basis for the optimization and further study of the metabolic pathway of C. butyricum.

Exploring the role of aquaporin proteins in the pre-protective action of Sanwei sandalwood decoction from adriamycin-induced chronic heart failure: A mechanistic study.

This study employed network pharmacology, molecular docking technology, and modern pharmacological research methods to explore the pre-protective effect and underlying mechanism, Sanwei sandalwood decoction, against Adriamycin-induced Chronic Heart Failure, with a particular focus on the involvement of aquaporins. Additionally, the study highlighted aquaporins as a significant factor, affecting processes such as cell proliferation and response to reactive oxygen species. The results of in vivo experiments demonstrated that the administration of Sanwei sandalwood decoction in rats with chronic heart failure led to an enhancement in the ejection fraction and improved heart ejection function. Additionally, the decoction significantly reduced the serum levels of Creatine Kinase, Creatine Kinase-MB, and N-terminal pro-B-type natriuretic peptide. Furthermore, the relative expression of Aquarporin-1, 4, and 7mRNAs and proteins in the hearts of rats with chronic heart failure was down-regulated upon treatment. Overall, Sanwei sandalwood decoction can have an effective cardioprotective effect in preventing Adriamycin-induced Chronic Heart Failure in rats.

First Report of Erysiphe astragali Causing Powdery Mildew on Astragalus mongholicus in China.

Astragalus mongholicus Bge. [A. membranaceus Bge. var. mongholicus (Bge.) Hsiao] is a highly valuable perennial medicinal plant mainly distributed in China, whose dry roots are known as Huangqi in traditional Chinese medicine for reinforcing vital energy, strengthening superficial resistance, and promoting tissue regeneration (Lin et al. 2000). A. mongholicus roots of high quality are produced in Northwest and North China. Since July 2021, powdery mildew outbreaks happened annually on the leaves of A. mongholicus in a plantation (123° 56' 40'' E, 47° 22' 20'' N) in Qiqihar city, Heilongjiang Province, China. Disease incidence reached 100% by October (Fig. 1A-C), causing severe impairment of growth. Powdery mildew spots of circular or irregular shapes emerged on upper surface of leaf, resulting in plentiful lesion specks. Dense white hyphae appeared chaotically intertwined. Hyphae were hyaline and highly flexuous, 5.3 - 10.7 µm in diameter (n = 20). Chasmothecia were globose or slightly ovoid-shaped and turned dark brown when matured. Chasmothecia (diameter: 135.2 - 222.9 µm, n = 20) existed abundantly on the diseased leaves in the fields. Conidiophores were 89.0 - 129.9 µm in length (n = 20) and composed of one cylindrical, straight foot cell, followed by two cells and one to three conidia. Conidia were slim ellipsoid-shaped, occasionally ovoid-shaped, measuring 14.6 - 24.7 µm by 6.4 to10.4 µm, length/width ratio was 1.8 - 3.0 (n = 30). Hyphal appressoria were nipple-shaped and appeared in singular, occasionally in pairs. Unbranched germ tube emerged reaching out of the germinating conidia while forming an acute angle with the long axis. Comprehensively, the pathogen exhibited micro-morphology of the genus Erysiphe. For molecular identification, pathogen was carefully scraped off diseased leaves for DNA extraction. We used the DNA samples of three biological replicates for the sequencing of the ITS rDNA fragment (primers by (White et al. 1990). All the samples resulted in an identical ITS sequence (deposited in GenBank as OQ390098.1). It displayed 99.83% identity with OP806835.1 of an E. astragali voucher collected in Iran (Fig. 1D-M, O). Hence, our pathogen was identified as an E. astragali stain. Additionally, we amplified the Mcm7 sequence (using primers by (Ellingham et al. 2019), deposited as OQ397582.1). We propagated 40-day-old A. mongholicus plants via germinating seeds in pot soil and performed pathogenicity tests. Firstly, we incubated detached healthy leaves of propagated plants with severely symptomatic leaves collected from the fields in petri dishes under saturated moisture content and room temperature. Powdery mildew symptoms emerged on each healthy leaf (n = 5) after two weeks. Further, we infected healthy plants (n = 5) by gently pressing and rubbing symptomatic leaves on each healthy leaf, and kept them in a greenhouse (24 ℃, 80% humidity, 16/8-hour light/dark cycle). After a month, symptoms emerged on a number of leaves of each infected plant. We performed micromorphology observation (Fig. 1N-P) and ITS sequencing to confirm that the results fulfilled Koch's postulates. Powdery mildew caused by E. astragali on A. strictus in Tibet (Wang and Jiang 2023) and on A. scaberrimus in Inner Mongolia (Sun et al. 2023) have been reported. Here we report powdery mildew caused by E. astragali on Astragalus mongholicus for the first time. These Astragalus spp. are all acknowledged to have medicinal values in China but their usages are quite different.

Using Piezosurgery in Anterior Cervical Discectomy and Fusion to Treat Complex Cervical Spondylotic Myelopathy Is Safe and Effective.

Objective: To investigate the safety and efficacy of piezosurgery in anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy (CSM). Methods: 47 patients with complex CSM (cCSM) underwent ACDF surgery from 2014 to 2017. Among these patients, 26 underwent ACDF using piezosurgery (group A) and 21 underwent ACDF by using traditional tools such as high-speed air drill, bone curette, and Kerrison bone punch (group B). Average surgical time, intraoperative blood loss, surgical complications, preoperative and postoperative Japanese Orthopaedic Association (JOA) scores, and improvement rate were measured. Results: Average surgical time and intraoperative blood loss were significantly lower in group A than those in group B (P < 0.01). The incidences of surgical complications were 3.8% and 23.8% in the A and B groups (P < 0.05), respectively. There were no significant differences in JOA scores and improvement rates between data collection periods at preoperative, 3-day postoperative, and 1-year postoperative follow-ups (P > 0.05). Conclusion: For treating cCSM, both the piezosurgery and traditional tools led to significant neurological improvement. However, the piezosurgery was superior to the traditional tools in terms of surgical time, blood loss, and complication rate. Hence, piezosurgery was a safe and effective adjunct for ACDF treating cCSM.

[Research progress in microevolutionary process of excellent traits and quality of Dao-di herbs].

Dao-di herbs are the treasure of Chinese materia medica and one of the characteristic research objects of traditional Chinese medicine(TCM). Probing into the microevolution of Dao-di herbs can help to reveal their biological essence and quality formation mechanisms. The progress in molecular biology and omics provides the possibility to elucidate the phylogenetic and quality forming characteristics of Dao-di herbs at the molecular level. In particular, genomics serves as a powerful tool to decipher the genetic origins of Dao-di herbs, and molecular markers have been widely used in the research on the genetic diversity and population structure of Dao-di herbs. Focusing on the excellent traits and quality of Dao-di herbs, this paper reviews the studies about the microevolution process of quality formation mechanisms of Dao-di herbs with the application of molecular markers and omics, aiming to underpin the protection and utilization of TCM resources.

Sanwei sandalwood decoction improves function of the gut microbiota in heart failure.

Objective: To investigate the effects of Sanwei sandalwood decoction on improving function of the intestinal flora in doxorubicin-induced heart failure in rats. Materials and methods: Thirty Sprague-Dawley rats were screened and randomly assigned into a blank group, a model group, and a Sanwei sandalwood decoction group (treatment group). The rat model of heart failure was prepared and established in the latter two groups. After successful model establishment, the treatment group received Sanwei sandalwood decoction by continuous gavage at 2 g/kg, once daily for 4 weeks. The other groups were given an equivalent volume of saline. After the final dose, fecal samples were collected from each group and analyzed by macrogenomics and nontargeted metabolomics to characterize the intestinal flora and associated metabolites. Results: The composition of gut microbiota was significantly different between the three groups. There were 778,808 common genes between the blank and model groups, while 49,315 genes were lost and 521,008 were gained in the model group relative to the blank group. At the phylum level, all groups of rat fecal samples were dominated by Firmicutes, Bacteroidota, Actinobacteria, and Proteobacteria. At the genus level, the microbial community composition in all experimental groups of rat fecal samples was dominated by Lactobacillus, Bifidobacterium, Limosilactobacillus, Allobaculum, Prevotella, and Ligilactobacillus spp. Interestingly, cluster analysis was performed on the top 30 KEGG ontology (KO) terms displaying significant differences in relative abundance in the rat fecal microbiome among experimental groups. The relative frequency of posttranslational modification, coenzyme transport and metabolism, cell wall, membrane, and envelope biogenesis in the eggNOG and CAZy databases. In the nontargeted metabolomics, the group principal component analysis revealed that the groups were well distinguished from one another. The different metabolites were screened with VIP >1, and the KEGG different metabolite classification and enrichment analysis revealed that there includes 15 metabolites pathway, including loxoprofen, conifery-l-acetate, trichilin A, and others. The arachidonic acid pathway also accounted for a significant portion of the KEGG pathway classification analysis. Conclusion: Sanwei sandalwood decoction positively affects the intestinal microbial environment of rats with heart failure, improving the gut dysbiosis that is caused by the condition. This treatment intervention inhibits the growth of pathogenic bacteria and promotes the growth of beneficial species.

The image quality and diagnostic performance of CT perfusion-derived CT angiography versus that of conventional CT angiography.

Background: The combination of computed tomography angiography (CTA) and computed tomography perfusion (CTP) evaluation of cerebral perfusion status and vascular conditions can improve the diagnostic accuracy of infarction, ischemia, and vascular occlusion in stroke patients, as well as a comprehensive assessment of cerebral edema, collateral circulation, and blood perfusion in the lesion area. However, the consequent radiation safety and contrast agent nephropathy have aroused increasing concern. The purpose of this study was to assess the image quality and diagnostic accuracy of CTA images derived from CTP data, and to explore the feasibility of replacing conventional CTA. Methods: A total of 31 consecutive patients with suspected acute ischemic stroke were retrospectively analyzed. All patients underwent head and neck CTA and brain CTP examinations. All the CTP images were transmitted to the ShuKun artificial intelligence system, which reconstructs CTA derived from CTP (CTA-DF-CTP). The images were divided into 2 groups, including CTA-DF-CTP (Group A) and conventional CTA (Group B). The CT attenuation values, subjective image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), image quality, CT volume dose index (CTDIvol), dose length product (DLP), and effective radiation dose (ED) were compared between the 2 groups. Moreover, the consistency of vascular stenosis and stenosis degree between the 2 groups were measured and evaluated. Results: There were no significant differences in image noise, SNR, or CNR between Groups A and B (P>0.05). The CT attenuation values of the arteries were higher in Group A than in B [internal carotid artery (ICA) =548±112 vs. 454±85 Hounsfield units (HU), middle cerebral artery (MCA) =453±118 vs. 388±70 HU, and basilar artery (BA) =431±99 vs. 360±83 HU] (P<0.01). The image quality of the 2 groups met the requirement of clinical diagnosis (4.97±0.18 vs. 4.94±0.25). No significant difference was found in subjective evaluation (P>0.05). In Group A compared with Group B, the following reductions were observed: CTDIvol (10.7%; 100.8 vs. 112.9 mGy), DLP (23.0%; 1,613±0 vs. 2,093±88 mGy·cm), and ED (23.0%; 5.00±0.00 vs. 6.49±0.27 mSv). Conclusions: CTA-DF-CTP data provide diagnostic accuracy and image quality similar to those of conventional CTA of head and neck CTA.

Liver Metabolomics Analysis Revealing Key Metabolites Associated with Different Stages of Nonalcoholic Fatty Liver Disease in Hamsters.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is not only the top cause of liver diseases but also a hepatic-correlated metabolic syndrome. This study performed untargeted metabolomics analysis of NAFLD hamsters to identify the key metabolites to discriminate different stages of NAFLD. METHODS: Hamsters were fed a high-fat diet (HFD) to establish the NAFLD model with different stages (six weeks named as the NAFLD1 group and twelve weeks as the NAFLD2 group, respectively). Those liver samples were analyzed by untargeted metabolomics (UM) analysis to investigate metabolic changes and metabolites to discriminate different stages of NAFLD. RESULTS: The significant liver weight gain in NAFLD hamsters was observed, accompanied by significantly increased levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Moreover, the levels of TG, LDL-C, ALT, and AST were significantly higher in the NAFLD2 group than in the NAFLD1 group. The UM analysis also revealed the metabolic changes; 27 differently expressed metabolites were detected between the NAFLD2 and NAFLD1 groups. More importantly, the levels of N-methylalanine, allantoin, glucose, and glutamylvaline were found to be significantly different between any two groups (control, NAFLD2 and NAFLD1). Receiver operating characteristic curve (ROC) curve results also showed that these four metabolites are able to distinguish control, NAFLD1 and NAFLD2 groups. CONCLUSION: This study indicated that the process of NAFLD in hamsters is accompanied by different metabolite changes, and these key differently expressed metabolites may be valuable diagnostic biomarkers and responses to therapeutic interventions.

Flexible multilevel nonvolatile biocompatible memristor with high durability.

Current protein or glucose based biomemristors have low resistance-switching performance and require complex structural designs, significantly hindering the development of implantable memristor devices. It is imperative to discover novel candidate materials for biomemristor with high durability and excellent biosafety for implantable health monitoring. Herein, we initially demonstrate the resistance switching characteristics of a nonvolatile memristor in a configuration of Pt/AlOOH/ITO consisting of biocompatible AlOOH nanosheets sandwiched between a Indium Tin Oxides (ITO) electrode and a platinum (Pt) counter-electrode. The hydrothermally synthesized AlOOH nanosheets have excellent biocompatibility as confirmed through the Cell Counting Kit-8 (CCK-8) tests. Four discrete resistance levels are achieved in this assembled device in responsible to different compliance currents (ICC) for the set process, where the emerging multilevel states show high durability over 103 cycles, outperforming the protein-based biomemristors under similar conditions. The excellent performance of the Pt/AlOOH/ITO memristor is attributed to the significant role of hydrogen proton with pipe effect, as confirmed by both experimental results and density functional theory (DFT) analyses. The present results indicate the nonvolatile memristors with great potential as the next generation implantable multilevel resistive memories for long-term human health monitoring.

[Advances in research and application of Trichoderma for inducing resistance against root rot diseases in root and rhizome of Chinese medicinal materials].

Root rot is a microbial disease that is difficult to control and can result in serious losses in the planting of most Chinese medicinal materials. As high as 87.6% of roots or rhizomes of Chinese medicinal materials are susceptible to root rot, which seriously affects the cultivation development of Chinese medicinal materials. Trichoderma fungi, possessing biological control functions, can induce plants to improve their resistance to microbial diseases, promote plant growth, and effectively reduce the losses caused by various microbial diseases on cultivation. At present, Trichoderma is rarely used in the cultivation of Chinese medicinal materials, so it has great application potential for the prevention and control of root rot diseases in farmed Chinese medicinal materials. Based on the above situation, after comparison and discussion, it is believed that compared with chemical control and physical control, biological control of root rot diseases of Chinese medicinal materials is more efficient and meets the development needs of Chinese medicinal materials ecological planting in China. This paper reviewed the progress in the research and application of Trichoderma in the control of root rot diseases in the root and rhizome of farmed Chinese medicinal materials in the past 10 years and found that most of the current research on the biological control of root rot diseases in Chinese medicinal materials was mostly limited to the verification of the inhibitory effect of Trichoderma strains on the growth of the pathogenic microbes. Studies on the induction effect of Trichoderma on Chinese medicinal materials are not in depth. Studies on the responding mechanisms of most Chinese medicinal materials to Trichoderma are highly absent. Moreover, there are few reports on field experiments, which indicates that there is a long way to go before Trichoderma is widely applied in the farming practice of Chinese medicinal materials. To sum up, this paper aimed to link the present and the future and advocated further relevant research and more experiments on the application of Trichoderma in the farming of Chinese medicinal materials.

Single-cell morphological and topological atlas reveals the ecosystem diversity of human breast cancer.

Digital pathology allows computerized analysis of tumor ecosystem using whole slide images (WSIs). Here, we present single-cell morphological and topological profiling (sc-MTOP) to characterize tumor ecosystem by extracting the features of nuclear morphology and intercellular spatial relationship for individual cells. We construct a single-cell atlas comprising 410 million cells from 637 breast cancer WSIs and dissect the phenotypic diversity within tumor, inflammatory and stroma cells respectively. Spatially-resolved analysis identifies recurrent micro-ecological modules representing locoregional multicellular structures and reveals four breast cancer ecotypes correlating with distinct molecular features and patient prognosis. Further analysis with multiomics data uncovers clinically relevant ecosystem features. High abundance of locally-aggregated inflammatory cells indicates immune-activated tumor microenvironment and favorable immunotherapy response in triple-negative breast cancers. Morphological intratumor heterogeneity of tumor nuclei correlates with cell cycle pathway activation and CDK inhibitors responsiveness in hormone receptor-positive cases. sc-MTOP enables using WSIs to characterize tumor ecosystems at the single-cell level.

[Multicenter Prospective Study of Different Induction Regimens of Azacytidine in Treatment of Elderly Patients with Acute Myeloid Leukemia].

OBJECTIVE: To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML). METHODS: A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m2·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety. RESULTS: There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05). CONCLUSIONS: Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.

[Characterization of brain deactivations elicited by transient painful and tactile stimuli using functional MRI].

The aim of the present study was to explore the specific pattern of brain deactivation elicited by painful stimuli, in contrast with that elicited by tactile stimuli. Functional magnetic resonance imaging (fMRI) data were collected from 62 healthy subjects under painful and tactile stimuli with varying intensities. The brain deactivations under different conditions were identified using the general linear model. Two-way analysis of variance (ANOVA) was performed to test whether there was a significant interaction between perceived stimulus intensity (factor 1: high intensity, low intensity) and stimulus modality (factor 2: pain, touch) on the brain deactivations. The results showed that there were significant interactions between stimulus intensity and stimulus modality on the deactivations of left medial superior frontal gyrus, left middle occipital gyrus, left superior frontal gyrus and right middle occipital gyrus (P < 0.05, Cluster-level FWE). The deactivations induced by painful stimuli with low perceived intensity (ß = -3.38 ± 0.52) were significantly stronger than those induced by painful stimuli with high perceived intensity (ß = -1.22 ± 0.54) (P < 0.001), whereas the differences between the deactivations induced by tactile stimuli with different perceived intensities were not statistically significant. In addition, there were no significant differences between the deactivations elicited by painful and tactile stimuli with the same stimulus intensities. These results suggest that there is a specific relationship between the deactivations induced by painful stimuli in multiple brain regions (such as the left medial superior frontal gyrus) and the stimulus intensity, providing evidence for a deeper understanding of the brain mechanisms underlying pain perception.