[Role and mechanism of ginsenoside Rg1 in ameliorating sepsis-induced acute lung injury based on PERK/eIF2α/ATF4/CHOP-induced alveolar epithelial cell apoptosis].

The study investigates the therapeutic effects and mechanisms of ginsenoside Rg_1(GRg_1) on sepsis-induced acute lung injury(SALI). A murine model of SALI was created using cecal ligation and puncture(CLP) surgery, and mice were randomly assigned to groups for GRg_1 intervention. Survival and body weight changes were recorded, lung function was assessed with a non-invasive lung function test system, and lung tissue damage was evaluated through HE staining. The content and expression of inflammatory factors were measured by ELISA and qRT-PCR. Apoptosis was examined using flow cytometry and TUNEL staining. The activation and expression of apoptosis-related molecules cysteinyl aspartate specific proteinase 3(caspase-3), B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), and endoplasmic reticulum stress-related molecules protein kinase R-like endoplasmic reticulum kinase(PERK), eukaryotic initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) were studied using Western blot and qRT-PCR. In addition, an in vitro model of lipopolysaccharide(LPS)-induced lung alveolar epithelial cell injury was used, with the application of the endoplasmic reticulum stress inducer tunicamycin to validate the action mechanism of GRg_1. RESULTS:: indicated that, when compared to the model group, GRg_1 intervention significantly enhanced the survival time of CLP mice, mitigated body weight loss, and improved impaired lung function indices. The GRg_1-treated mice also displayed reduced lung tissue pathological scores, a reduced lung tissue wet-to-dry weight ratio, and lower protein content in the bronchoalveolar lavage fluid. Serum levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α), as well as the mRNA expressions of these cytokines in lung tissues, were decreased. There was a notable decrease in the proportion of apopto-tic alveolar epithelial cells, and down-regulated expressions of caspase-3, Bax, PERK, eIF2α, ATF4, and CHOP and up-regulated expression of Bcl-2 were observed. In vitro findings showed that the apoptosis-lowering and apoptosis-related protein down-regulating effects of GRg_1 were significantly inhibited with the co-application of tunicamycin. Altogether, GRg_1 reduces apoptosis of alveolar epithelial cells, inhibits inflammation in the lungs, alleviates lung injury, and enhances lung function, possibly through the PERK/eIF2α/ATF4/CHOP pathway.

Absorption enhancement of peach kernel oil on hydroxysafflor yellow A in safflower extracts and its mechanisms.

Carthamus tinctorius L. (Safflower) is extensively used as a functional food and herbal medicine, with its application closely associated with hydroxysafflor yellow A (HSYA). However, the low oral bioavailability of HSYA in safflower extract (SFE) limits its health benefits and application. Our study found that co-administration of 250, 330, and 400 mg/kg peach kernel oil (PKO) increased the oral bioavailability of HSYA in SFE by 1.99-, 2.11-, and 2.49-fold, respectively. The enhanced bioavailability is attributed to improved lipid solubility and intestinal permeability of HSYA in SFE due to PKO. PKO is believed to modify membrane fluidity and tight junctions, increase paracellular penetration, and inhibit the expression and function of P-glycoprotein, enhancing the transcellular transport of substrates. These mechanisms suggest that PKO is an effective absorption enhancer. Our findings provide valuable insights for developing functional foods with improved bioavailability.

Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibitors and their mechanisms in cancer therapy. The review includes original articles utilizing in vitro and in vivo experimental methods, literature reviews, and clinical trials. Key terms used were "Autophagy", "Inhibitors", "Molecular mechanism", "Cancer therapy", and "Clinical trials". Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches.

A Hydrogel-coated Wood Membrane with Intelligent Oil Pollution Detection for Emulsion Separation.

Considering the potential threats posed by oily wastewater to the ecosystem, it is urgently in demand to develop efficient, eco-friendly, and intelligent oil/water separation materials to enhance the safety of the water environment. Herein, an intelligent hydrogel-coated wood (PPT/PPy@DW) membrane with self-healing, self-cleaning, and oil pollution detection performances is fabricated for the controllable separation of oil-in-water (O/W) emulsions and water-in-oil (W/O) emulsions. The PPT/PPy@DW is prepared by loading polypyrrole (PPy) particles on the delignified wood (DW) membranes, further modifying the hydrogel layer as an oil-repellent barrier. The layered porous structure and selective wettability endow PPT/PPy@DW with great separation performance for various O/W emulsions (≥98.69% for separation efficiency and ≈1000 L m-2 h-1 bar-1 for permeance). Notably, the oil pollution degree of PPT/PPy@DW can be monitored in real-time based on the changed voltage generated during O/W emulsion separation, and the oil-polluted PPT/PPy@DW can be self-cleaned by soaking in water to recover its separation performance. The high affinity of PPT/PPy@DW for water makes it effective in trapping water from the mixed surfactant-stabilized W/O emulsions. The prepared eco-friendly and low-cost multifunctional hydrogel wood membrane shows promising potential in on-demand oil/water separation and provides new ideas for the functional improvement of new biomass oil/water separation membrane materials.

5-Aza-2'-Deoxycytidine Ameliorates Choroidal Neovascularization by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

Purpose: Choroidal neovascularization (CNV) can constitute the final pathology of many ocular diseases and result in severe vision loss. Studies have demonstrated that DNA methylation is critical in retinal development, aging, and disorders. The current work investigated the effects and underlying mechanism of 5-Aza-2'-deoxycytidine (5-aza-dC), a suppressor of DNA methylation, in the pathological progression of CNV. Methods: The DNA methylation profiles of retinal pigment epithelial (RPE)/choroidal complexes in normal and laser-induced CNV mice were assessed by Arraystar Mouse RefSeq Promoter Arrays. The CNV area and blood flow density and intensity were observed by optical coherence tomography angiography, and fluorescence leakage was examined by fundus fluorescein angiography in CNV mice with systemic administration of 5-aza-dC. The effects of 5-aza-dC on the biological functions of bEnd.3 cells were estimated by related assays. Notum gene promoter methylation was measured using bisulfite sequencing PCR. Methyltransferases and Wnt signaling-related genes were detected in animal and cell culture experiments by real-time PCR and immunoblot. Results: Methyltransferases were upregulated, but Notum (a secretion inhibitor of Wnt signaling) was downregulated in the RPE/choroidal complexes of mice with experimental CNV. Intraperitoneal injection of 5-aza-dC inactivated the Wnt pathway and ameliorated the lesion area and the intensity and density of blood flow, as well as the degree of leakage in CNV. In vitro, vascular endothelial growth factor A (VEGFA) stimulation promoted methyltransferases expression and suppressed Notum expression, consequently activating Wnt signaling, whereas exogenous 5-aza-dC reversed VEGFA-induced hyperpermeability, proliferation, migration, and tube formation in bEnd.3 cells via demethylation of Notum promoter. Conclusions: We observed that 5-aza-dC attenuates the growth of CNV by inhibiting the Wnt signaling pathway via promoter demethylation of the Wnt antagonist Notum. These findings provide a theoretical basis for methylation-based treatment with the Notum gene as a potential target for CNV treatment.

Dissecting the pleiotropic roles of reactive oxygen species (ROS) in lung cancer: From carcinogenesis toward therapy.

Lung cancer is a major cause of morbidity and mortality. The specific pulmonary structure to directly connect with ambient air makes it more susceptible to damage from airborne toxins. External oxidative stimuli and endogenous reactive oxygen species (ROS) play a crucial role in promoting lung carcinogenesis and development. The biological properties of higher ROS levels in tumor cells than in normal cells make them more sensitive and vulnerable to ROS injury. Therefore, the strategy of targeting ROS has been proposed for cancer therapy for decades. However, it is embarrassing that countless attempts at ROS-based therapies have had very limited success, and no FDA approval in the anticancer list was mechanistically based on ROS manipulation. Even compared with the untargetable proteins, such as transcription factors, ROS are more difficult to be targeted due to their chemical properties. Thus, the pleiotropic roles of ROS provide therapeutic potential for anticancer drug discovery, while a better dissection of the mechanistic action and signaling pathways is a prerequisite for future breakthroughs. This review discusses the critical roles of ROS in cancer carcinogenesis, ROS-inspired signaling pathways, and ROS-based treatment, exemplified by lung cancer. In particular, an eight considerations rule is proposed for ROS-targeting strategies and drug design and development.

Sodium Alginate Aerogel as a Carrier of Organogelators for Effective Oil Spill Solidification and Recovery.

Marine oil spills pose a serious threat to the marine ecological environment. Phase-selective organogelators (PSOGs) are ideal candidates for oil spill gelation when used in combination with a mechanical recovery method. However, the toxicity of an organic solvent carrier has become a key problem when it is applied in the remediation of marine oil pollution. In this study, through an inexpensive and nontoxic ionic cross-linking and freeze-drying method, we successfully developed composite oil gelling agents that used a biomass sodium alginate aerogel as the carrier of 12-hydroxystearic acid (12-HSA). Simultaneously, carboxylated cellulose nanofibers (CNF-C) with large specific surface area and graphene oxide (GO) with excellent mechanical properties as reinforcing fillers were combined with an alginate matrix. 12-HSA, as a green and inexpensive organic gelator, was uniformly loaded on the aerogels by vacuum impregnation. The sodium alginate aerogel was capable of absorbing and storing oil due to its three-dimensional network skeleton and high porosity. Rheological studies have demonstrated that the organic gelator 12-HSA can be released from the aerogel substrate and self-assemble to form an oleogel with the absorbed oil quickly. The synergistic effect between absorption and congelation endows the composite oil gelling agent with efficient oil spill recovery capability. Based on eco-friendly, biodegradable, and simple synthesis methods, this composite oil gelling agent shows great potential for application in marine oil spill recovery.

Joule Heating-Assisted Crude Oil Purification by a Poly(pyrrole)-Modified Microfibril Cellulose Membrane.

Using membrane materials to purify viscous watery oil from industrial production processes and accidental oil spills is of great importance but still challenging. Based on the excellent electrical conductivity and electric-thermal conversion of poly(pyrrole) (PPy), a hydrophobic PPy-modified micro-fibrillated cellulose membrane (P-CP) was successfully prepared. The size of the P-CP membrane can be customized to meet specific requirements. In this research, the membrane diameter is capable of reaching 24 cm. By applying a voltage ranging from 0 to 12 V, the surface temperature of the P-CP membrane can be elevated to roughly 120 °C. After 10 cycles of heating and cooling under 12 V voltage, the electric-thermal curves, surface hydrophobicity, and pore structure of P-CP membrane can remain stable, which suggests remarkable electric-thermal stability and reliability despite prolonged operation. The P-CP membrane shows good linearity between voltage and current (R2 = 0.997) and easy temperature control from room temperature to ∼120 °C at low supply voltage (0-12 V). Under the condition of 12 V power supply and self-gravity, the separation flux of the P-CP membrane for water-in-oil (W/O) emulsions (kerosene, diesel) is 2-3 times higher than that at room temperature, and the separation efficiency is also improved. Importantly, the P-CP membrane shows excellent separation performance for high viscosity water-in-crude oil emulsions, with a separation flux of 40 L m-2 h-1 by gravity. Compared to the situation without electricity, the separation flux of water-in-crude oil emulsion has increased four-fold. The joule heating of the P-CP membrane expands its service time and application scenarios, demonstrating its great application prospects in actual viscous oil-water emulsion separation.

Study on the Mechanism of Rapid Oil-Water Separation by a Fe3 O4 @PMMA@PDMS Intelligent Superhydrophobic Micro/Nanorobot.

We prepared an environmentally friendly intelligent Fe3 O4 @PMMA@PDMS superhydrophobic oil-absorbing material with simple process and excellent performance, and investigated the effects of different particle sizes of Fe3 O4 , different concentrations of PDMS, and different heating times on the superhydrophobicity of the coating. The best performance of the coating was achieved at a particle size combination of 20/500 nm for Fe3 O4 , a PDMS to Fe3 O4 @PMMA mass ratio of 6 : 1, and a heating time of 2 min at 400 °C. H2-SPSS coating not only has excellent superhydrophobicity, abrasion resistance, self-cleaning property, and chemical corrosion, but also has good flux and efficiency for separating oil-water mixture, with fluxes of 40,540, 32,432, and 37,027 Lm-2 h-1 for trichloromethane, dichloromethane and bromoethane, respectively, and separation efficiencies of 99.78 %, 99.74 % and 99.73 %, respectively. In addition, we also prepared a superhydrophobic magnetic polyurethane (SPPU) sponge using Fe3 O4 @PMMA@PDMS, which not only has a good oil absorption capacity of 18-44 g/g for different oil substances, it can also move directionally by magnet attraction and absorb oil along a fixed path. Under the control of the magnet, SPPU completes the whole oil absorption process in only 4 s, showing excellent oil absorption and intelligence.

Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing.

Unprogrammed macrophage polarization, especially prolonged activation of proinflammatory macrophages, is associated with delayed wound healing in diabetic objectives. Macrophage-derived exosomes cargo a variety of microRNAs (miRNAs), participating in different stages in wound healing. Here, exosomes were isolated from naive bone marrow-derived macrophages (BMDMs) (M0-Exos), interferon-γ plus lipopolysaccharide-polarized BMDMs (M1-Exos), and interleukin-4-polarized BMDMs (M2-Exos). M1-Exos impaired migration and tube formation in human umbilical vein endothelial cells (HUVECs) compared to M0-Exos, whereas M2-Exos exhibited the opposite effects. High-throughput sequencing was performed to decipher the miRNA expression profiles in M0-Exos, M1-Exos, and M2-Exos. A total of 63 miRNAs were identified to be differentially expressed in exosomes derived from polarized BMDMs. Among them, miRNA-155-5p is highly expressed in M1-Exos, which interrupted angiogenesis in HUVECs. Furthermore, miRNA-155-5p directly binds to the 3' UTR of growth differentiation factor 6 (GDF6) mRNA to suppress its protein expression. Lastly, local administration of a temperature-sensitive hydrogel Pluronic F-127 loading miRNA-155-5p antagomiR promoted angiogenesis and accelerated wound healing in diabetic db/db mice via enhancing GDF6. In summary, this study deciphered the miRNA expression profiles in exosomes from polarized macrophages. M2-like macrophage-derived exosomes and miRNA-155-5p inhibitors could be promising therapeutics against diabetic foot ulcers.

Higher waist circumference is associated with increased likelihood of female infertility: NHANES 2017-2020 results.

Background: Waist circumference can be used as an anthropometric measure to assess central obesity and is easier and more convenient than the waist-to-hip ratio in identifying the risk of obesity and medical problems. Most studies showing an association between obesity and infertility in women have used BMI to measure obesity. Our goal was to examine any potential association between waist circumference and infertility. Methods: This cross-sectional study, which formed part of the National Health and Nutrition Examination Survey (NHANES), comprised women ages 18 to 45 between 2017 and 2020. Participants without waist circumference data or information on infertility were removed from the study. The independent relationship between waist circumference and infertility was investigated using weighted binary logistic regression and subgroup analysis. Results: We investigated 1509 participants and discovered that the prevalence of infertility rose as the WC trisection rose. (tertile 1, 7.55%; tertile 2, 10.56%; tertile 3, 15.28%; trend < 0.001). Multivariate logistic regression showed that after total adjustment, higher WC levels were associated with an increased likelihood of infertility in women (OR1.02; 95% CI 1.01-1.03), and There was a 2% rise in the incidence of infertility for every unit (cm) increased WC. Subgroup analysis and interaction tests showed no significant dependence of the effects of marital status, diabetes, hypertension, and high cholesterol on the association between WC and infertility (p for all interaction tests > 0.05). The inflection point of the positive non-linear relationship between WC and infertility was 116.6 cm. Conclusion: Excessive waist circumference assessment may increase the probability of infertility, and more attention should be paid to the management of waist circumference should be given more attention.

Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10.

Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.

Strategies targeting endoplasmic reticulum stress to improve Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder with motor symptoms, which is caused by the progressive death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Accumulating evidence shows that endoplasmic reticulum (ER) stress occurring in the SNpc DA neurons is an early event in the development of PD. ER stress triggers the activation of unfolded protein response (UPR) to reduce stress and restore ER function. However, excessive and continuous ER stress and UPR exacerbate the risk of DA neuron death through crosstalk with other PD events. Thus, ER stress is considered a promising therapeutic target for the treatment of PD. Various strategies targeting ER stress through the modulation of UPR signaling, the increase of ER's protein folding ability, and the enhancement of protein degradation are developed to alleviate neuronal death in PD models. In this review, we summarize the pathological role of ER stress in PD and update the strategies targeting ER stress to improve ER protein homeostasis and PD-related events.

Comprehensive metabolome and transcriptome analyses demonstrate divergent anthocyanin and carotenoid accumulation in fruits of wild and cultivated loquats.

Eriobotrya is an evergreen fruit tree native to South-West China and adjacent countries. There are more than 26 loquat species known in this genus, while E. japonica is the only species yet domesticated to produce fresh fruits from late spring to early summer. Fruits of cultivated loquat are usually orange colored, in contrast to the red color of fruits of wild E. henryi (EH). However, the mechanisms of fruit pigment formation during loquat evolution are yet to be elucidated. To understand these, targeted carotenoid and anthocyanin metabolomics as well as transcriptomics analyses were carried out in this study. The results showed that ß-carotene, violaxanthin palmitate and rubixanthin laurate, totally accounted for over 60% of the colored carotenoids, were the major carotenoids in peel of the orange colored 'Jiefangzhong' (JFZ) fruits. Total carotenoids content in JFZ is about 10 times to that of EH, and the expression levels of PSY, ZDS and ZEP in JFZ were 10.69 to 23.26 folds to that in EH at ripen stage. Cyanidin-3-O-galactoside and pelargonidin-3-O-galactoside were the predominant anthocyanins enriched in EH peel. On the contrary, both of them were almost undetectable in JFZ, and the transcript levels of F3H, F3'H, ANS, CHS and CHI in EH were 4.39 to 73.12 folds higher than that in JFZ during fruit pigmentation. In summary, abundant carotenoid deposition in JFZ peel is well correlated with the strong expression of PSY, ZDS and ZEP, while the accumulation of anthocyanin metabolites in EH peel is tightly associated with the notably upregulated expressions of F3H, F3'H, ANS, CHS and CHI. This study was the first to demonstrate the metabolic background of how fruit pigmentations evolved from wild to cultivated loquat species, and provided gene targets for further breeding of more colorful loquat fruits via manipulation of carotenoids and anthocyanin biosynthesis.

Enriched environment alleviates neurological deficits via downregulation of Cx43 after experimental stroke.

While it has been demonstrated that enriched environment (EE) can protect against cerebral ischemia/reperfusion (I/R) injury, the underlying mechanism remains largely unknown. Connexin 43 (Cx43) is a key component of gap junctions, which may mediate cell-to-cell communication in neural cells. This study aimed to investigate the neuroprotective effects of EE against cerebral I/R injury in rats by modulating Cx43. A rat model of cerebral I/R injury was established by middle cerebral artery occlusion (MCAO)/reperfusion. Rats were randomly divided into the sham, MCAO, MCAO + EE, MCAO + Gap19, and MCAO + EE + Gap19 groups. The modified neurological severity score test and Morris water maze assay were used to assess neurological deficits. The infarct volume was measured using triphenyltetrazolium chloride (TTC) staining. Neuronal survival was detected by immunofluorescence. The indices of oxidative stress were determined using ELISA, and the reactive oxygen species levels were determined using a dihydroethidium probe. Cx43 and inflammation-related protein expression levels were also measured using western blotting and immunohistochemistry. EE and Gap19 treatment significantly improved neurological deficits, reduced infarct volumes, attenuated neuronal injury, and suppressed inflammatory cytokine expression and oxidative stress. Furthermore, EE and Gap19 treatment notably downregulated the expression of Cx43 and the inflammation-related pathway TLR4/MyD88/NF-κB in the ischemic penumbra. Gap19, a Cx43 inhibitor, markedly enhanced the neuroprotective effects of EE in rats with cerebral I/R injury. EE treatment protects against cerebral I/R injury in rats via Cx43 downregulation. Our findings may shed light on the mechanism underlying the protective efficacy of EE.

Coupling of static ultramicromagnetic field with elastic micropillar-structured substrate for cell response.

Micropillars have emerged as promising tools for a wide range of biological applications, while the influence of magnetic fields on cell behavior regulation has been increasingly recognized. However, the combined effect of micropillars and magnetic fields on cell behaviors remains poorly understood. In this study, we investigated the responses of H9c2 cells to ultramicromagnetic micropillar arrays using NdFeB as the tuned magnetic particles. We conducted a comparative analysis between PDMS micropillars and NdFeB/PDMS micropillars to assess their impact on cell function. Our results revealed that H9c2 cells exhibited significantly enhanced proliferation and notable cytoskeletal rearrangements on the ultramicromagnetic micropillars, surpassing the effects observed with pure PDMS micropillars. Immunostaining further indicated that cells cultured on ultramicromagnetic micropillars displayed heightened contractility compared to those on PDMS micropillars. Remarkably, the ultramicromagnetic micropillars also demonstrated the ability to decrease reactive oxygen species (ROS) levels, thereby preventing F-actin degeneration. Consequently, this study introduces ultramicromagnetic micropillars as a novel tool for the regulation and detection of cell behaviors, thus paving the way for advanced investigations in tissue engineering, single-cell analysis, and the development of flexible sensors for cellular-level studies.

Natural exosomes-like nanoparticles in mung bean sprouts possesses anti-diabetic effects via activation of PI3K/Akt/GLUT4/GSK-3ß signaling pathway.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia and insulin resistance. Mung bean sprouts are traditionally considered a "folk" hypoglycemic food and their pharmacological effects and underlying mechanisms warrant further investigation. PURPOSE: This study aimed to investigate the anti-diabetic effects of the exosomes-like nanoparticles in mung bean sprouts (MELNs) and explore the related molecular mechanisms. RESULTS: MELNs were isolated using a differential centrifugation-polyethylene glycol (PEG) method, and the identification of MELNs were confirmed by PAGE gel electrophoresis, agarose gel electrophoresis, thin-layer chromatography (TLC), and transmission electron microscopy (TEM). In the high-fat diet/streptozotocin (HFD/STZ) mouse model, MELNs ameliorated the progression of T2DM by increasing oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results, decreasing the fasting blood glucose level, and reducing the serum triglycerides (TG) and total cholesterol (TC). Histopathological examinations indicated MELNs diminished inflammatory infiltration of hepatocytes and amplified the area of islet B cells. In addition, MELNs decreased the oxidative stress levels in liver tissue and had good biocompatibility. In vitro experiments verified that MELNs improved the viability of glucosamine (GlcN) induced insulin-resistant hepatocytes. Furthermore, this study also revealed that MELNs upregulated GLUT4 & Nrf2 and down-regulated GSK-3ß via activating the PI3K/Akt signaling pathway, promoting the production of antioxidant enzymes, such as HO-1 and SOD, to reduce oxidative stress. CONCLUSION: MELNs mitigated the progression of type 2 diabetes in HFD/STZ mouse model. The underlying molecular mechanism is related to PI3K/Akt/GLUT4/GSK-3ß signaling pathway.

Nifuroxazide boosts the anticancer efficacy of palbociclib-induced senescence by dual inhibition of STAT3 and CDK2 in triple-negative breast cancer.

Though palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor has been approved for treating breast cancer, two major clinical challenges remain: (i) Triple-negative breast cancer (TNBC) appears to be more resistant to palbociclib, and (ii) Palbociclib-induced senescence-associated secretory phenotype (SASP) has a pro-tumorigenic function. Here we report that combining palbociclib with the STAT3 inhibitor nifuroxazide uncouples SASP production from senescence-associated cell cycle exit. Moreover, we identified nifuroxazide as a CDK2 inhibitor that synergistically promotes palbociclib-induced growth arrest and senescence in TNBC cells. In vitro, the combination of nifuroxazide with palbociclib further inhibited the TNBC cell proliferation and enhanced palbociclib-induced cell cycle arrest and senescence. The modulation of palbociclib-induced SASP by nifuroxazide was associated with the reduction of phosphorylated-STAT3. Nifuroxazide also blocks SASP-dependent cancer cell migration. Furthermore, thermal shift assay and molecular docking of nifuroxazide with STAT3 and CDK2 revealed that it binds to their active sites and acts as a potent dual inhibitor. In vivo, the combination of nifuroxazide with palbociclib suppressed 4T1 tumor growth and lung metastasis. Our data suggest that nifuroxazide enhances the anticancer effects of palbociclib in TNBC by uncoupling SASP production from senescence-associated cell cycle exit and inhibiting CDK2 to promote tumor senescence.

Rapid and visual detection of dichloroacetonitrile in water.

Dichloroacetonitrile (DCAN) is a common biotoxic disinfection by-product (DBP) of chlorine. The current methods used for detecting DCAN are tedious and heavily instrument-dependent, and are not suitable for on-site detection. In the present study, we developed a colorimetric assay for rapid detection of DCAN. DCAN in water acted as a complexing agent that formed a complex with cuprous species. The cuprous species was then extracted by chloroform and visualized using dithizone. The visual detection limit for DCAN was 20 ng mL-1, while fluorescence quantification could detect DCAN at a concentration as low as 8.75 ng mL-1. Moreover, haloacetonitriles (HANs) derived from chlorine disinfection and structurally similar to DCAN, including TCAN, BCAN, and DBAN, could also be detected using this method. Other DBPs at concentrations as high as 200 ng mL-1 did not affect the detection process. The low cost and instrument-independence characteristic of the present method enables its routine determination of the concentration of DCAN in water.

Advances in the Research of Photo, Electrical, and Magnetic Responsive Smart Superhydrophobic Materials: Synthesis and Potential Applications.

With the rapid advancement of technology, the wettability of conventional superhydrophobic materials no longer suffice to meet the demands of practical applications. Intelligent responsive superhydrophobic materials have emerged as a highly sought-after material in various fields. The exceptional superhydrophobicity, reversible wetting, and intelligently controllable characteristics of these materials have led to extensive applications across industries, including industry, agriculture, defense, and medicine. Therefore, the development of intelligent superhydrophobic materials with superior performance, economic practicality, enhanced sensitivity, and controllability assumes utmost importance in advancing technology worldwide. This article provides a summary of the wettability principles of superhydrophobic surfaces and the mechanisms behind intelligent responsive superhydrophobicity. Furthermore, it reviews and analyzes the recent research progress on light, electric, and magnetic responsive superhydrophobic materials, encompassing aspects such as material synthesis, modification, performance, and responses under diverse external stimuli. The article also explores the challenges associated with different types of responsive superhydrophobic materials and the unique application prospects of light, electric, and magnetic responsive superhydrophobic materials. Additionally, it outlines the future directions for the development of intelligent responsive superhydrophobic materials.