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Nonalcoholic fatty liver disease (NAFLD) is an escalating global health issue, leading to liver fat accumulation, inflammation, fibrosis, and potential liver failure. In our preliminary network pharmacological study, it was hypothesized that Pedalitin (PED), a flavonoid found in black sesame plants, might exhibit protective effects against NAFLD. However, the effects and mechanisms of PED underlying its action on NAFLD are not yet fully understood. This study aimed to explore the potential effects and mechanisms of PED on NAFLD using a combination of network pharmacology, molecular docking, and the LO2 cell model. Potential targets for PED and NAFLD were predicted through public databases. Protein-protein interaction (PPI) networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Molecular docking was used to predict the target genes that could bind to PED. In vitro experiments using the LO2 cell model indicated that PED significantly reduced TG level (p ​

Abstract Early detection of cancer significantly improves patient outcomes, with biomarkers offering a promising avenue for earlier and more precise diagnoses. Microfluidic biosensors have emerged as a powerful tool for detecting these biomarkers in body fluids, providing enhanced sensitivity, specificity, and rapid analysis. This review focuses on recent advances in microfluidic biosensors from 2018 to 2024, detailing their operational principles, fabrication techniques, and integration with nanotechnology for cancer biomarker detection. Additionally, we have reviewed recent innovations in several aspects of microfluidic biosensors, such as novel detection technologies, nanomaterials and novel microfluidic chip structures, which significantly enhance detection capabilities. We highlight key biomarkers pertinent to early cancer detection and explore how these innovations in biosensor technology contribute to the evolving landscape of personalized medicine. We further explore how these technologies could be incorporated into clinical cancer diagnostic workflows to improve early detection and treatment outcomes. These innovations could help enable more precise and personalized cancer diagnostics. In addition, this review addresses several important issues such as enhancing the scalability and sensitivity of these biosensors in clinical settings and points out future possibilities of combining artificial intelligence diagnostics with microfluidic biosensors to optimize their practical applications. This overview aims to guide future research and clinical applications by addressing current challenges and identifying opportunities for further development in the field of biomarker research.

Background: Kidney disease has become a growing public health problem worldwide, and there is an urgent need to develop reliable models for investigating novel and effective treatment strategies. In recent years, kidney organoids, as novel models different from traditional two-dimensional cells and model animals, have attracted more and more attention. Current advances have allowed the generation of kidney organoids from the directed differentiation of induced pluripotent stem cells (iPSCs), which possess similar characteristics to embryonic stem cells (ESCs), but bypass ethical constraints and have a wide range of sources. Summary: Herein, the methods of generating renal organoids from iPSCs, the applications of iPSC-derived renal organoids in disease modeling, drug effectiveness detection, and regenerative medicine as well as the challenges were reviewed. Key messages: iPSC-derived renal organoids can be used to model kidney diseases, and are great models for studying kidney injury and toxicity. Many efforts are needed to finally apply organoids into clinical application.

The advantage of low-temperature forming through direct ink writing (DIW) 3D printing is becoming a strategy for the construction of innovative drug delivery systems (DDSs). Optimization of the complex formulation, including factors such as the printing ink, presence of solvents, and potential low mechanical strength, are challenges during process development. This study presents an application of DIW to fabricate water-soluble, high-dose, and sustained-release DDSs. Utilizing poorly compressible metformin hydrochloride as a model drug, a core-shell delivery system was developed, featuring a core composed of 96 % drug powder and 4 % binder, with a shell structure serving as a drug-release barrier. This design aligns with the sustained-release profile of traditional processes, achieving a 25.8 % reduction in volume and enhanced mechanical strength. The strategy facilitates sustained release of high-dose water-soluble formulations for over 12 h, potentially improving patient compliance by reducing formulation size. Process optimization and multi-batch flexibility were also explored in this study. Our findings provide a valuable reference for the development of innovative DDSs and 3D-printed drugs.

Introduction: Clodronate-Liposomes (Clod-Lipo) injection after hematopoietic stem cell transplantation (HSCT) has been shown to be detrimental to hematopoietic reconstitution after transplantation, and our previous study showed that Clod-Lipo injection after HSCT increased adipocytes in the bone marrow cavity of mice after HSCT, but the reason for the large increase in adipocytes has not been clearly explained. The aim of this study was to investigate the source and mechanism of bone marrow cavity adipocytes after HSCT injection of Clod-Lipo. Methods: BALB/c mice received 7.5 Gy of total body irradiation followed by infusion of 5x106 bone marrow mononuclear cells from C57BL/6 via the tail vein. Clod-Lipo were injected through the tail vein on the first day after HSCT and every 5 days for the rest of the day. BALB/c mice were then divided into three groups: BMT, BMT + Clodronate-Liposomes (BMT + Clod-Lipo), and BMT + PBS-Liposomes (BMT + PBS-Lipo). Bone marrow pathological changes were detected by H&E staining, Western blot was used to detect the expression of NLRP3 and Caspase-1 in mouse bone marrow cells, and RT-qPCR was used to detect the expression levels of the key transcription factors peroxisome proliferator-activated receptor γ (PPAR-γ) and CCAAT/enhancer binding protein (C/EBPα) mRNA in bone marrow cells. Mouse mesenchymal stem cells (MSC) cultured in vitro were identified by flow cytometry, and adipocyte induction assays were performed using Clod-Lipo action for 24 h, Oil red staining was used to identify adipogenesis. Western blot was performed to detect NLRP3 and caspase-1 expression in MSC after Clod-Lipo action. Caspase-1 was blocked with Ac-YVAD-cmk (Ac-YV), followed by adipogenesis assay after 24 h of Clod-Lipo action to observe the change in the amount of adipogenesis. Results: Compared with the other two groups, a significant increase in adipocytes was found in the Clod-Lipo group by HE staining, and increased expression of NLRP3 and Caspase-1 in mouse bone marrow cells was found by western Blot. By culturing MSC in vitro and performing adipogenesis assay after 24 h of Clod-Lipo action, it was found that adipogenesis was increased in the Clod-Lipo group, while the expression of NLRP3 and Caspase-1 was increased in MSCs, and adipogenesis assay was performed after 2 h of action using Caspase-1 inhibitor, and it was found that adipocytes was reduced. Conclusions: The results of this study suggest that MSC are biased towards adipocyte generation in response to Clod-Lipo, a process that may be associated with activation of the NLRP3/caspase-1 pathway.

Abstract Inspired by biological materials, the self-shaping wood composites induced by relative humidity (RH) have been investigated over the last decade. In this study, a wood bilayer was fabricated by assembling two layers with perpendicular fiber orientation in a series of thickness ratios and initial moisture contents (iMC). The self-shaping response of the wood bilayer was explored as a function of its configuration, and the discrepancies between moisture adsorption and desorption processes were clarified. Higher iMC limited the evolution of curvature. During both the adsorption and desorption processes, a reversed bending response was observed, and there was a hysteretic bending behavior between them. Repeatable bending was achieved during the cyclic ad/desorption process, and a larger hysteresis loop was observed at a lower thickness ratio. Finite-element analysis showed that the maximum stress occurred at the interface between the active and passive layers, and larger thickness ratios had lower maximum stress. In addition, the bilayer composed of a 200 μm passive layer and a 400 μm active layer with 0.6% iMC was found to be the most sensitive to RH change. The results of this study elucidate the moisture-dependent bending response of wood bilayers and provide the possibility of precisely controlling the curvature of self-shaping wood composites in industrial applications.

This study aimed to investigate the inhibitory effects of three major flavonoids from the Hippophae rhamnoides subsp. yunnanensis berries on four pathogenic microorganisms. The antimicrobial activity of total flavonoids from Hippophae rhamnoides subsp. yunnanensis berries on Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Candida albicans was firstly measured by filter paper method. Then, the total flavonoids compositions were identified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and the main components were quantified by high performance liquid chromatography (HPLC). Finally, the Bradford method and the double dilution method were used to assess the antimicrobial effect of the three flavonoids. The results showed that the major flavonoid components of the Hippophae rhamnoides subsp. yunnanensis berries were isorhamnetin-3-O-glucoside-7-O-rhamnoside (Is-3-G-7-Rh), quercetin-3-O-rutinoside (Qu-3-R) and isorhamnetin-3-O-glucoside (Is-3-G), which with the contents of 38.43±0.85, 29.44±0.42 and 21.11±0.55 mg/g, respectively. The extract and its three main flavonoids had inhibitory effect on the four microorganisms. The inhibitory effects of Is-3-G-7-Rh and Is-3-G on the microorganisms were better than Qu-3-R and extract, and the results of protein detection showed that flavonoids induced antimicrobial death through intracellular protein efflux. This study can provide a scientific basis for the application of flavonoids in the berries of Hippophae rhamnoides for antimicrobial purposes.

Coenzyme Q10 nanoemulsion (CoQ10-NE) was improved and made utilizing Pinus koraiensis nuts oil as the oil phase, soybean lecithin as the surfactant, and ethanol as the cosurfactant in this study. The effects of different factors on the mean particle size and polydispersity index (PDI) of CoQ10-NE were studied, and the quality was evaluated by DLS, TEM, FT-IR, stability, in vitro release behavior and in vivo pharmacokinetic experiments in rats.The results showed that when the mass ratio of CoQ10 to mixed surfactant was 3:40, the mass ratio of CoQ10 to Pinus koraiensis nuts oil was 1:4, the homogenizing pressure was 800 bar, and the number of cycles was 6 times, the CoQ10-NE of mean particle size of 150.30±1.43 nm and PDI of 0.234±0.012 was obtained. The morphology and microstructure showed that the CoQ10-NE was round and non-adhesive at the size of 500 nm and 1 µm. FT-IR results showed that CoQ10 was completely encapsulated in nanoemulsion. The stability experiment showed that there was no significant difference in the mean particle size and PDI (P>0.05). CoQ10-NE had good stability. In vitro release experiments showed that the cumulative dissolution rate of CoQ10-NE was 4.7-fold that of the CoQ10 suspension at 120 min. The dissolution rate was significantly improved. According to the results of pharmacokinetic investigations in rats, the maximum plasma concentration Cmax of CoQ10-NE was 2.80-fold that of CoQ10 suspension, the drug concentration of CoQ10-NE in rats was greatly enhanced. The area \begin{document}${\rm{AUC}}_{0{\text -}\infty} $\end{document} was 3.25-fold that of the CoQ10 suspension, demonstrating that CoQ10-NE bioavailability and absorption were greatly increased. The CoQ10-NE developed in this study provides a theoretical foundation for investigating the creation of new CoQ10 formulations and their potential application as a functional ingredient in food.

Ginseng holds high medicinal and cosmetic value, with stem and leaf extracts garnering attention for their abundant bioactive ingredients. Meanwhile, fermentation can enhance the effectiveness of cosmetics. The aim of this study was to optimize ginseng fermentation to produce functional cosmetics. Ginseng stem and leaf extracts were fermented with five different strains of lactic acid bacteria. Using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical (·OH), and superoxide anion (O2·−) scavenging activities as indicators, the fermentation process was optimized via response surface methodology. Finally, validation of the antioxidant activity of the optimized fermentation broth was performed using human skin cells (HaCaT and BJ cells). Based on the antioxidant potency composite comprehensive index, Lactiplantibacillus plantarum 1.140 was selected, and the optimized parameters were a fermentation time of 35.50 h, an inoculum size of 2.45%, and a temperature of 28.20 °C. Optimized fermentation boosted antioxidant activity: DPPH scavenging activity increased by 25.00%, ·OH by 94.00%, and O2·− by 73.00%. Only the rare ginsenoside Rg5 showed a substantial rise in content among the 11 ginsenosides examined after fermentation. Furthermore, the flavonoid content and ·OH scavenging activity were significantly negatively correlated (r = −1.00, p < 0.05), while the Rh1 content and O2·− scavenging activity were significantly positively correlated (r = 0.998, p < 0.05). Both the 0.06% (v/v) and 0.25% (v/v) concentrations of the optimized broth significantly promoted cell proliferation, and notable protective effects against oxidative damage were observed in HaCaT cells when the broth was at 0.06%. Collectively, we demonstrated that ginseng fermentation extract effectively eliminates free radicals, preventing and repairing cellular oxidative damage. This study has identified new options for the use of fermented ginseng in functional cosmetics.

The electrocatalytic conversion of biomass into high-value-added chemicals is one of the effective methods of green chemistry. Conventional metal catalysts have disadvantages, such as low atomic utilization and small surface areas. Catalyst materials derived from metal–organic frameworks (MOFs) have received much attention due to their unique physicochemical properties. Here, an MOF-derived non-precious metal CoxNiyS electrocatalyst was applied to the oxidation of biomass-derivative 5-hydroxymethylfurfural (HMF). The HMF oxidation reaction activities were modulated by regulating the content of Co and Ni bimetals, showing a volcano curve with an increasing proportion of Co. When the Co:Ni ratio was 2:1, the HMF conversion rate reached 84.5%, and the yield of the main product, 2,5-furandicarboxylic acid (FDCA), was 54%. The XPS results showed that the presence of high-valent nickel species after electrolysis, which further proved the existence and reactivity of NiOOH, as well as the synergistic effect of Co and Ni promoted the conversion of HMF. Increasing the content of Ni could increase the activity of HMF electrochemical oxidation, and increasing the content of Co could reduce the increase in the anodic current. This study has important significance for designing better HMF electrochemical catalysts in the future.

Objective To understand the contamination pattern of mycotoxin in paddy rice in the main rice-growing regions of Guangdong Province, and analyze the distribution difference of mycotoxin in different areas, so as to provide basis for the implementation of precise prevention and control measures. Methods A total of 120 paddy rice samples were collected from eight cities in the Pearl River Delta, northern, eastern and western Guangdong during 2018 and 2019, and were analyzed for 16 mycotoxins by multiple reaction monitoring mode of ultra performance liquid chromatography-tandem mass spectrometer. Results Among the 120 paddy rice samples, 19.17% (23/120) were positive for mycotoxins, and the main polluants were aflatoxins and fumonisins. FB1 were detected in 9.17% (11/120) of the samples, followed by 8.33% (10/120) for AFB1. Two samples had the AFB1 concentrations above the tolerance limit of 10 μg/kg. The detection values were 73.90 and 18.80 μg/kg, respectively. Among 6 trichothecene mycotoxins, only deoxynivalenol (1.67%, 2/120) and its acetyl derivatives[0.83% (1/120) for 3-Ac-DON and 0.83% (1/120) for 15-Ac-DON] were found. ZEN was found in 3.33% (4/120) of the samples. Additionally, 1.67% (2/120) of the paddy rice samples were positive for sterigmatocystin. The ochratoxin A, nivalenol, T-2 and HT-2 mycotoxins were not found in the paddy rice samples. The co-occurrence of two or more mycotoxins was confirmed in 8.33% (10/120) of the paddy rice samples, mainly combination was AFB1 and other mycotoxins. The contamination patterns were different in the eight cities. The paddy rice samples from Zhanjiang was mainly contaminated by FB1, FB2, DON and 3-Ac-DON. Samples from Heyuan were mainly contaminated by AFB1, AFB2, sterigmatocystin, FB1 and FB2. The concentration levels of ZEN, DON and 3-Ac-DON were relatively higher in samples from Shaoguan. Conclusion The paddy rice samples from Guangdong Province were contaminated by multiple mycotoxins, and the pollution patterns were different in different areas. In terms of the co-occurence of mycotoxins, some measures should be conducted to assess the exposure risk, reduce the damage, and protect the consumers food safety.

The classification of hidden dangers in urban gas pipelines plays a vital role in the smooth operation of urban gas pipelines and in solving the problem of hidden safety dangers in urban gas pipelines. In recent years, the number and proportion of polyethylene (PE) pipelines in urban gas pipelines are increasing day by day, but the current classification of hidden dangers in urban gas pipelines is still based on steel pipelines, and the classification method is highly subjective. Therefore, this paper proposes an improved PLC method that integrates the use of a risk matrix and compensation coefficient to solve the problem of grading the hidden dangers of PE pipelines of urban gas. The improved PLC method is based on the failure database of urban gas PE pipelines to obtain the vulnerability and severity of consequences when determining the initial level of hidden dangers, and the compensation coefficient is modified according to regional vulnerability, ease of rectification, condition around the pipeline, positioning technology, leak detection technology, and emergency ability, which can effectively reduce the subjectivity of hidden danger classification. Using the improved PLC method to classify urban gas pipelines for hidden dangers can provide pipeline operating companies with a basis for decision making in the process of hidden danger disposal and effectively reduce pipeline safety risks.

Maternal regulatory factors endow the oocyte with developmental competence in vivo, which might be absent in current in vitro maturation (IVM) systems, thereby compromising oocyte quality. In the present study, by employing RNA sequencing data analysis, we expect to identify potential contributing factors to support porcine oocyte maturation through binding to their receptors on the oolemma. Here, C-X-C motif chemokine ligand 12 (CXCL12), vascular endothelial growth factor A (VEGFA), and Wingless-type MMTV integration site family member 5A (WNT5A), termed CVW, are selected and confirmed to be important maternal cytokines for porcine oocyte maturation. Combined supplementation of CVW promotes the nuclear maturation percentage from 57.2% in controls to 75.9%. More importantly, these maternal cytokines improve the developmental potential of matured oocytes by parthenogenesis, fertilization, and cloning, as their blastocyst formation efficiencies and total cell numbers are increased. CVW supplementation also enlarges perivitelline space and promotes cumulus expansion, which results in a more complete transzonal projection retraction on the zona pellucida, and a reduced incidence of polyspermy in fertilized oocytes. Meanwhile, inhibiting the CVW receptor-mediated signaling pathways severely impairs oocyte meiotic resumption and cumulus expansion during IVM. We further determine that maturation improvement by CVW is achieved through activating the MAPK pathway in advance and inhibiting the canonical WNT pathway at the end of the IVM period. These findings provide a new combination of three cytokines to promote the porcine IVM process, which also holds potential to be used in human assisted reproduction technologies as well as in other species.

The protein inhibitor of the activated STAT2 (PIAS2) has been implicated in many cellular processes and can also regulate viral replication in mammals. However, the role of PIAS2 in the highly pathogenic avian influenza virus (HPAIV) H5N1 replication in ducks is still unclear. Through liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay, we identified that duck PIAS2 (duPIAS2) was one protein that interacted with the nucleoprotein (NP) from the H5N1 HPAIV strain of DK212. Through confocal microscopy images and Co-IP assay, we confirmed NP could interact with duPIAS2. Overexpression of duPIAS2 in primary duck embryo fibroblast (DEF) cells was shown to promote DK212 replication, and knockdown of duPIAS2 could repress DK212 replication. We further found duPIAS2 could promote NP SUMOylation through duck SUMO1 (duSUMO1), and the potential SUMOylation sites of NP were at lysines 7, 48, and 87. Furthermore, duPIAS2 promoted the replication of DK212, here relying on the activity of its SUMO E3 ligase. Duck SENP1 (duSENP1), a deSUMOylation enzyme, could repress NP SUMOylation and also inhibit DK212 replication. Together, we identified duPIAS2 could interact with NP and that duPIAS2 promoted H5N1 HPAIV replication, which might be related to NP SUMOylation.

Clade 2.3.4.4 H5 avian influenza viruses (AIVs) are widely prevalent and of significant concern to the poultry industry and public health in China. Nowadays, the clade 2.3.4.4 H5N6 virus has become a dominant AIV subtype among domestic ducks in southern China. We found that waterfowl-origin clade 2.3.4.4 H5N6 viruses (A/goose/Guangdong/16568/2016, GS16568 and A/duck/Guangdong/16873/2016, DK16873) isolated from southern China in 2016 could replicate in multiple organs of inoculated ducks. DK16873 virus caused mild infections and killed 2/5 of inoculated ducks, and GS16568 virus did not kill inoculated ducks. In addition, the two viruses could be transmitted via direct contact between ducks. DK16873 and GS16568 viruses killed 2/5 and 1/5 of contact ducks, respectively. Furthermore, ducks inoculated with the two H5N6 viruses exhibited different expressions of immune-related genes in their lungs. The expression of RIG-I, TLR3 and IL6 was significantly upregulated at 12 h post-inoculation (HPI) and most of the tested immune-related genes were significantly upregulated at 3 days post-inoculation (DPI). Notably, the expression of RIG-I and IL-6 in response to DK16873 virus was significantly higher than for GS16568 virus at 12 HPI and 3 DPI. Our research have provided helpful information about the pathogenicity, transmission and immune-related genes expression in ducks infected with new H5N6 AIVs.

H5Nx viruses have continuously emerged in the world, causing poultry industry losses and posing a potential public health risk. Here, we studied the phylogeny, pathogenicity, transmission, and immune response of four H5N6 avian influenza viruses in chickens and mice, which were isolated from waterfowl between 2013 and 2014. Their HA genes belong to Clade 2.3.4.4, circulated in China since 2008. Their NA genes fall into N6-like/Eurasian sublineage. Their internal genes originated from different H5N1 viruses. The results suggested that the four H5N6 viruses were reassortants of the H5N1 and H6N6 viruses. They cause lethal infection with high transmission capability in chickens. They also cause mild to severe pathogenicity in mice and can spread to the brain through the blood−brain barrier. During the infection, the viruses result in the up-regulation of PRRs and cytokine in brains and lungs of chickens and mice. Our results suggested that the high viral loads of several organs may result in disease severity in chickens and mice; there were varying levels of cytokines induced by the H5N6 viruses with different pathogenicity in chickens and mice.

The prevalence and variation of the H9N2 avian influenza virus (AIV) pose a threat to public health. A total of eight viruses isolated from farmed poultry in South China during 2017−2018 were selected as representative strains for further systematic study. Phylogenetic analyses indicated that these prevalent viruses belong to the Y280-like lineage and that the internal genes are highly similar to those of recently circulating human H7N9 viruses. The receptor-binding assay showed that most of the H9N2 isolates preferentially bound to the human-like receptor, increasing the risk of them crossing the species barrier and causing human infection. Our in vitro, multi-step growth curve results indicate these viruses can effectively replicate in mammalian cells. Infection in mice showed that three viruses effectively replicated in the lung of mice. Infection in swine revealed that the viruses readily replicated in the upper respiratory tract of pig and effectively induced viral shedding. Our findings suggested that the H9N2 AIVs circulating in poultry recently acquired an enhanced ability to transmit from avian to mammalians, including humans. Based on our findings, we propose that it is essential to strengthen the efforts to surveil and test the pathogenicity of H9N2 AIVs.