In vivo identification of bioactive components of Poria cocos for adjusting mitochondria against metabolic dysfunction-associated fatty liver disease.

Currently, no specific treatment exists to alleviate metabolic dysfunction-associated fatty liver (MAFLD). Previously, Poria cocos (PC) effectively relieved MAFLD, but its bioactive components are still unknown. The bioactive substances in PC that regulate mitochondria function to alleviate MAFLD were thus determined. The L02 hepatocyte model induced by fat emulsion and the MAFLD rat model induced by a high-fat diet (HFD) were developed to explore the efficacy of PC against MAFLD. The activity of PC-derived components in the liver mitochondria of HFD-fed rats was evaluated using the L02 hepatocyte model. Additionally, the PC-derived components from the liver mitochondria were identified by ultra-high performance liquid chromatography/mass spectrometry. Finally, the anti-steatosis ability of PC-derived monomers and monomers groups was evaluated using the adipocyte model. PC maintained the mitochondrial ultrastructure, alleviated mitochondrial oxidative stress, and regulated the energy metabolism and the fatty acid ß oxidation to relieve lipid emulsion-induced cellular steatosis and HFD-induced MAFLD. PC-derived components entering the liver mitochondria inhibited oxidative stress injury and improved the energy metabolism to fight cellular steatosis. Additionally, 15 chemicals were identified in the PC-treated rat liver mitochondria. These identified chemical molecules and molecule groups in the mitochondria prevented cellular steatosis by regulating mitochondrial oxidative stress and energy metabolism. PC restores mitochondrial structure and function, alleviating MAFLD, which is related to oxidative stress, energy metabolism, and fatty acid ß oxidation. The identified 15 components may be the main effective PC components regulating mitochondria function to alleviate MAFLD. Thus, PC may be a promising mitochondrial regulator to prevent MAFLD.

Recognition on pharmacodynamic ingredients of natural products.

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

Efficacy and Postoperative Complication Rates of Different Surgical Approaches for Calcaneal Fractures: A Network Meta-analysis.

Context: Calcaneal fractures (CFs) are the most common kind of tarsal fracture. The choice of surgical approach is a key element in the management of CFs, but the best method remains in dispute. Also, no single approach is appropriate for all kinds of CFs. Objective: The study intended to evaluate the relationship between six surgical approaches for clinical treatment of CFs and prevention of postoperative complications, to provide an evidence-based approach for treatment. Design: The research team performed a meta-analysis using the data from a previously published review and updating that data through a new narrative review. The team performed a systematic search in PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Internet (CNKI) from inception until January 2022, with no language restrictions. The search used the following keywords for the search: calcaneus, heel bone, surgical wounds, surgical incisions, prospective trials, prospective trials, and randomized controlled trials. Outcome Measures: The research team compared the complication rates, American Orthopedic Foot and Ankle Society (AOFAS) scores, and Bohler's angles for the six surgical approaches, which were: (1) the extensive lateral approach (ELA), (2) the sinus tarsi approach (STA), (3) the horizontal arc approach (HAA), (4) the longitudinal approach (LA), (5) the oblique lateral incision (OLI), and (6) the modified incision (MI)). The team summarized the results using a random effects model. Results: The research team analyzed the data from 19 RCTs with 1521 participants. They all were randomized controlled trials (RCTs). The complication rates were available for 18 studies, which included 1474 participants. The rates were significantly lower: (1) for HAA compared to ELA, [OR=-2.03; 95% CrI: [-3.63, -0.43)]; (2) for LA compared to ELA (OR=-1.83; 95% CrI: [-2.83, -0.84]); and (3) for STA compared to ELA (OR=- 1.22; 95% CrI: [-1.67, -0.78]). Of the 19 studies, 11 RCTs, with 942 participants, used the AOFAS scale. The probabilities for the surface under the cumulative ranking curve (SUCRA) indicated that OLI (0.694 ) >LA (0.596) >HAA (0.51) >STA (0.477) >ELA (0.224). In addition, ELA had the worst SUCRA (0.224). Of the 19 studies, 15 RCTs, with 1376 participants, used the Bohler angle as an outcome measure. The probability of SUCRA for the surgical approaches indicated that LA (0.723) >ELA (0.667) >STA (0.468) >HAA (0.373) >MI (0.27). Conclusions: The meta-analysis provides an evidence-based approach to the clinical treatment of CFs for six surgical approaches. HAA had the best outcomes, and ELA had the worst.

Characterization of immune microenvironment in patients with HPV-positive and negative head and neck cancer.

Human papillomavirus (HPV) status strongly predicts positive clinical outcomes in patients with head and neck squamous cell cancer (HNSCC); however, the potential reasons have not been fully elucidated. Here, we characterized the immune context in HPV+ and HPV- HNSCC by integrating scRNA-seq and bulk RNA-seq data. In scRNA-seq data, HPV + HNSCC displayed increased B cells, plasma cells, CD4+ effector T cells, and decreased macrophages and mast cells. This finding was validated using bulk-cell data. Plasma cells predicted improved survival, and macrophages were associated with survival disadvantage. 1403 upregulated and 1877 downregulated differential expressed genes (DEGs) were obtained. Gene Ontology and KEGG enrichment analysis showed these DEGs focused on cytokine-related activity. Transcriptional analysis of B and plasma cells revealed associations between B-cell surface marker FCER2 and improved survival. In vitro assays confirmed the ability of FCER2 to suppress cellular proliferation and migration of HPV + tumors. In conclusion, our analysis revealed a heterogeneous tumor immune environment (TME) for HPV+ and HPV- HNSCC. Further, FCER2+ B cells contribute to antitumor immunity.

Formation and characterization of konjac glucomannan/ethyl cellulose films by using ethanol and water as the solvents.

Hydrophilic konjac glucomannan (KGM)/hydrophobic ethyl cellulose (EC) film was prepared in the ethanol/water environment. The film-forming solution and film properties were both characterized to analyze the molecular interaction changes. Although higher ethanol usage enhanced the stability of the film-forming solution, it did not benefit the film property improvement. The SEM images showed some fibrous structure on the air surface of the films, consistent with the XRD results. The changing trend of mechanical properties and the FTIR results suggested that both ethanol content and ethanol evaporation impacted the molecular interaction during the film formation. The surface hydrophobicity results indicated that the ethanol content could cause significant EC aggregation changes on the film surface only with high EC contents. The water vapor permeability results suggested that higher ethanol usage decreased the compactness of the films. Considering all results, the 20 % ethanol content and the weight ratio of KGM: EC = 7:3 were suggested for the film preparation due to the superior properties in most properties. This study contributed to the understanding of polysaccharide interaction in the ethanol/water environment and offered an alternative biodegradable packaging film.

In vivo recognition of bioactive substances of Polygonum multiflorum for protecting mitochondria against metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a severe threat to human health. Polygonum multiflorum (PM) has been proven to remedy mitochondria and relieve MAFLD, but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear. AIM: To research the active ingredients of PM adjusting mitochondria to relieve high-fat diet (HFD)-induced MAFLD in rats. METHODS: Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms. The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats (mitochondrial pharmacology). PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry (mitochondrial pharmacochemistry). The abilities of PM-derived monomer and monomer groups were evaluated by the adipocyte model and MAFLD mouse model, respectively. RESULTS: PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD. PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis. Eight chemicals were found in the liver mitochondria of PM-administrated rats. The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated. CONCLUSION: PM restored mitochondrial structure and function and alleviated MAFLD, which may be associated with the remedy of oxidative stress and energy production. The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD. Thus, PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction. Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases.

A survey of field programmable gate array (FPGA)-based graph convolutional neural network accelerators: challenges and opportunities.

Graph convolutional networks (GCNs) based on convolutional operations have been developed recently to extract high-level representations from graph data. They have shown advantages in many critical applications, such as recommendation system, natural language processing, and prediction of chemical reactivity. The problem for the GCN is that its target applications generally pose stringent constraints on latency and energy efficiency. Several studies have demonstrated that field programmable gate array (FPGA)-based GCNs accelerators, which balance high performance and low power consumption, can continue to achieve orders-of-magnitude improvements in the inference of GCNs models. However, there still are many challenges in customizing FPGA-based accelerators for GCNs. It is necessary to sort out the current solutions to these challenges for further research. For this purpose, we first summarize the four challenges in FPGA-based GCNs accelerators. Then we introduce the process of the typical GNN algorithm and several examples of representative GCNs. Next, we review the FPGA-based GCNs accelerators in recent years and introduce their design details according to different challenges. Moreover, we compare the key metrics of these accelerators, including resource utilization, performance, and power consumption. Finally, we anticipate the future challenges and directions for FPGA-based GCNs accelerators: algorithm and hardware co-design, efficient task scheduling, higher generality, and faster development.

In vivo identification of the pharmacodynamic ingredients of Polygonum cuspidatum for remedying the mitochondria to alleviate metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease that currently lacks approved pharmacological treatment options. The mechanisms and active ingredients of Polygonum cuspidatum (PC) that regulate the mitochondria to relieve MAFLD have not been assessed. Thus, this study was designed to explore the bioactive components of PC extract in regulating mitochondria to alleviate high-fat diet-induced MAFLD using mitochondrial pharmacology and pharmacochemistry. Our results demonstrate that PC protected the mitochondrial ultrastructure and inhibited oxidative stress and energy metabolism disorder in the liver mitochondria. Furthermore, PC-derived components in the liver mitochondria attenuated oxidative stress and restored the energy metabolism of fat emulsion-induced steatosis in L02 cell. Sixteen compounds were identified in the liver-mitochondrial extracts of PC-treated rats. The antisteatotic effects of three identified monomers and anti-MAFLD ability of the monomer group were confirmed. Collectively, our data suggest that the extract of PC can alleviate lipid metabolism disorder in MAFLD by protecting the mitochondrial ultrastructure, reducing oxidative stress injury, and promoting energy metabolism. The sixteen identified compounds were potentially the main effective ingredients of PC in treating MAFLD. Thus, PC shows potential in treating MAFLD and related mitochondrial dysfunction. The proposed strategy to identify the ingredients of herbal medicines based on mitochondrial pharmacology and pharmacochemistry presents a new approach in exploring the pharmacodynamic components of herbal medicines that regulate mitochondria in preventing and treating diseases.

Growth Study of Hierarchical Pore SSZ-13 Molecular Sieves with Improved CO2 Adsorption Performance.

SSZ-13, with a unique pore structure and excellent thermal stability, showed a potential application in the adsorption and catalysis industry. In this work, Al(NO3)3 was used as an Al source to study the performance and morphology of the zeolite. The zeolite was prepared with an unconventional process by adding an Al source before the structure-directing agent and base. When inorganic oxygen-containing anions were introduced into the unconventional synthesis system, the crystals of the zeolite conform to the unconventional growth mode. The zeolites with large crystals were assembled from small unit nanocrystals. Extending the reaction time, aging time and adding fluoride ions introduced a multistage pore structure on the surface of the molecular sieve, which improved the CO2 adsorption performance. When aging for 24 h, reaction for 96 h, and the amount of fluorine added was 0.05 (F/Si), the sample had the best hierarchical pore structure. The SSZ-13 molecular sieve with an added amount of 0.1 (F/Si) has the highest CO2 adsorption performance. The adsorption amount was 4.55 mmol/g at 1 bar, which is 20.4% higher than that of zeolite SSZ-13 prepared by the conventional process.

Optimized Preparation of Nanosized Hollow SSZ-13 Molecular Sieves with Ultrasonic Assistance.

Because of its unique eight-membered ring pore structure and the arrangement of cations in its structure, the SSZ-13 molecular sieve has a higher affinity for CO2 than other gases, meaning it has attracted more attention than other porous materials for CO2 adsorption. However, the expensive template and long preparation time limits the industrial production of SSZ-13. In this work, a hollow structure was successfully introduced into the nanosized SSZ-13 molecular sieve with ultrasonic treatment. The effects of the amount of seed added and the ultrasonic time on the structure were investigated. When the amount of seed added was 0.5 wt.% and the ultrasonic time was 60 min, the sample showed a hollow cubic crystal with a diameter of about 50 nm. The specific surface area reached 791.50 m2/g, and the mesoporous ratio was 66.3%. The samples were tested for CO2 adsorption performance at 298 K. It was found that the hollow sample prepared in this work has higher CO2 adsorption capacity compared with the SSZ-13 zeolite prepared with conventional methods. When the adsorption pressure was 0.27 bar, the adsorption amount reached 2.53 mmol/g. The hollow SSZ-13 molecular sieve reached a CO2 adsorption capacity of 4.24 mmol/g at 1 bar.