Carvedilol induces pyroptosis through NLRP3-caspase1-ASC inflammasome by nuclear migration of NF-κB in prostate cancer models.

BACKGROUND: Pyroptosis is an inflammatory type of programmed cell death, and could overcome the drug-resistance induced by anti-apoptotic effect of cancers. Carvedilol (CVL), a ß-adrenergic receptors antagonist, has shown anti-inflammatory response and anti-cancer effect. The aim of this study is to investigate whether pyroptosis can be activated by CVL in prostate cancer (PCa). METHODS AND RESULTS: Datasets were used to analyze the expressions of pyroptosis-related proteins. Intracellular morphological change, cell viability, LDH and Il-1ß release by cells,, and Hoechst/PI staining were used to detect the occurrence of pyroptosis. Realtime-PCR, western blot, immunofluorescence, and immunohistochemistry (IHC) were used to investigate the expressions of pyroptosis-related proteins. Datasets analyze showed the expressions of NLRP3, Caspase 1, ASC and GSDMD were all decreased in PCa comparing with normal tissues, but without prognostic significance. CVL treatment weakened the viabilities of PCa cells. Cell morphology changing, cytoplasmic vacuole formation, membrane integrity loss, LDH and IL-1ß release and PI positive cells increasing were observed. NLRP3, Caspase 1, ASC, GSDMD and N-GSDMD expressions were elevated after CVL treatment, accompanied by a tendency of NF-κB transferring into nucleus. In vivo, CVL inhibited the growth of subcutaneous transplanted tumor. IHC showed CVL increased the expressions of NLRP3, ASC, and GSDMD, and decreased the expression of Ki-67 in transplanted tumor tissues. CONCLUSION: This study demonstrated that CVL could induce pyroptosis in PCa cells through NLRP3-caspase1-ASC inflammasome by promoting nuclear translocation of NF-κB, which would lay a foundation for the application of adrenergic receptor antagonist in PCa.

Biodegradation of various grades of polyethylene microplastics by Tenebrio molitor and Tenebrio obscurus larvae: Effects on their physiology.

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 µm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae-1⋅day-1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics.

Edaravone Dexborneol Alleviates Neuroinflammation by Reducing Neuroglial Cell Proliferation and Suppresses Neuronal Apoptosis/Autophagy in Vascular Dementia Rats.

More and more evidence shows that the pathological mechanism of vascular dementia (VD) is closely related to oxidative stress injury, cell apoptosis, autophagy, inflammatory response, excitatory amino acid toxicity, synaptic plasticity change, calcium overload, and other processes. Edaravone dexborneol (EDB) is a new type of neuroprotective agent that can improve the neurological damage caused by an ischemic stroke. Previous studies showed that EDB has effects on synergistic antioxidants and induces anti-apoptotic responses. However, it remains unclear whether EDB can affect apoptosis and autophagy by activating the PI3K/Akt/mTOR signaling pathway and its impact on the neuroglial cells. In this study, we established the VD model of rats by bilateral carotid artery occlusion to explore the neuroprotective effect of EDB and its mechanism. Morris Water Maze test was applied to assess the cognitive function of rats. H&E and TUNEL staining were applied to observe the cellular structure of the hippocampus. Immunofluorescence labeling was used to observe the proliferation of astrocytes and microglia. ELISA was applied to examine the levels of TNF-α, IL-1ß and IL-6, and RT-PCR was applied to examine their mRNA expression levels. Western blotting was applied to examine apoptosis-related proteins (Bax, Bcl-2, Caspase-3), autophagy-related proteins (Beclin-1, P62, LC3B), PI3K/Akt/mTOR signaling pathway proteins and their phosphorylation levels. The results indicated that EDB ameliorates learning and memory in rats subjected to the VD model, alleviates neuroinflammatory response by reducing the proliferation of the neuroglial cell and inhibits apoptosis and autophagy, which may be mediated by the PI3K/Akt/mTOR signaling pathway.

ABCB1-mediated docetaxel resistance reversed by erastin in prostate cancer.

Docetaxel (Doc) currently serves as the primary first-line treatment for patients with castrate-resistant prostate cancer (CRPC). Erastin, a small molecule compound, can trigger inhibition of the cystine-glutamate reverse transport system and other pathways, leading to iron-dependent cell death (ferroptosis). Beyond its role in inducing cancer cell death, erastin demonstrates potential when combined with chemotherapy drugs to heighten cancer cell drug susceptibility. However, the augmentation by erastin of the effects of Doc treatment on prostate cancer, and the underlying mechanisms involved, remain unclear. In the present study, we determined the role and the underlying molecular mechanism of erastin against CRPC. The results showed that CRPC cell lines were resistant to Doc, and the expression of ferroptosis-related factors in drug-resistant cell lines was downregulated. Erastin, in synergy with Doc, exerts a pro-apoptotic effect. Erastin significantly inhibited the activity of ATP-binding cassette subfamily B member 1 (ABCB1) but did not change its protein expression and localization. Finally, in mice, erastin treatment dramatically reduced tumor growth in vivo. Taken together, our findings demonstrate that erastin enhances Doc-induced apoptosis to a certain extent and reverses Doc resistance in prostate cancer by inhibiting the activity of multidrug-resistant protein ABCB1.

Inhibition of ß2-adrenergic receptor regulates necroptosis in prostate cancer cell.

As the malignant tumor with the highest incidence in male, prostate cancer poses a significant threat to the reproductive health of elderly men. Our previous studies have shown that promoting necroptosis of cancer cells can effectively inhibit cancer cell proliferation. This study includes lentivirus-mediated knockdown of ß2AR which resulted in stable transfectants that exhibited an increased ability to form clones compared to that of the negative control group. In the protein and mRNA levels, necroptosis associated RIP and mixed lineage kinase domain-like (MLKL) were significantly higher in the treatment group than they were in the control group. Furthermore, cells treated with propranolol exhibited necrotic morphology as observed by transmission electron microscopy. The combination of ß2AR suppression and necroptosis inhibitors resulted in a more potent suppression of cell proliferation compared to that observed in the control and negative control groups. Additionally, it elevated in the necrosis rate as determined by flow cytometry. Immunofluorescence staining revealed enhanced RIP and MLKL expression in the sh-ß2AR group compared to levels in the negative control group. Co-immunoprecipitation experiments detected an interaction between ß2AR and RIP. MLKL and RIPK3 levels were significantly higher in xenograft tumor sections from the sh-ß2AR group compared to levels in the sh-NC group. To conclude, our research indicates the proliferation of PC-3 and DU-145 cprostate cancer cells can be suppressed by inhibiting ß2AR, and this occurs through the RIP/MLKL-mediated pathway of necroptosis.

Construction of Fe(III) Active Sites on Phenanthroline-Grafted g-C3N4: Reduced Work Function and Enhanced Intramolecular Charge Transfer for Efficient N2 Photofixation.

Photocatalytic nitrogen fixation is one of the important pathways for green and sustainable ammonia synthesis, but the extremely high bonding energy of the N≡N triple bond makes it difficult for conventional nitrogen fixation photocatalysts to directly activate and hydrogenate. Given this, we covalently grafted the phenanthroline unit onto graphitic carbon nitride nanosheets (CN) by the simple thermal oxidation method and complexed it with transition metal Fe3+ ions to obtain stable dispersed Fe active sites, which can significantly improve the photocatalytic activity. The Fe(III)-4-P-CN photocatalyst morphology consists of porous lamellar structures internally connected by nanowires. The special morphology of the catalysts gives them excellent nitrogen fixation performance, with an average NH3 yield of 492.9 µmol g-1 h-1, which is 6.5 times higher than that of the pristine CN, as well as better photocatalytic cycling stability. Comprehensive experiments and density-functional theory results show that Fe(III)-4-P-CN is more favorable than pristine CN for *N2 activation, effectively lowering the reaction energy barrier. Moreover, other byproducts (such as nitrate and H2O2) are also produced during the photocatalytic nitrogen fixation process, which also provides a new way for nitrogen-fixing photocatalysts to achieve multifunctional applications.

Baicalein ameliorates cognitive impairment of vascular dementia rats via suppressing neuroinflammation and regulating intestinal microbiota.

Neuroinflammation induced by chronic cerebral hypoperfusion (CCH) plays a crucial role in the pathophysiologic mechanisms of vascular dementia (VD). A growing body of research has found that intestinal microbiota is associated with a variety of central nervous system disorders and that there is a relationship between intestinal microbiota dysbiosis and cognitive dysfunction and inflammatory responses. Baicalein belongs to the class of flavonoids and has a variety of biological functions, including anti-inflammatory, antioxidant and anti-apoptotic. Baicalein has a significant improvement in memory and learning, and can be used as a potential drug for the protection and treatment of central nervous system disorders. Whether baicalein has an ameliorative effect on cognitive impairment in VD, and whether its mechanism is related to the inhibition of inflammatory response and regulation of intestinal microbiota has not been reported. We used bilateral common carotid artery occlusion (BCCAO) to establish a VD rat model. Morris water maze (MWM) test showed that baicalein improved cognitive dysfunction in VD rats. We applied HE staining, immunofluorescence and ELISA to observe that baicalein treatment significantly improved CCH-induced neuronal damage in the CA1 region of the hippocampus, and reduced glial cell activation and release of pro-inflammatory factors. Western blot showed that baicalein inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway in VD rats. We applied 16 S rDNA sequencing to analyze the composition of the intestinal microbiota. The results showed that baicalein modulated the diversity and composition of the intestinal microbiota, and suppressed the relative abundance of inflammation-associated microbiota in VD rats. In conclusion, this study found that baicalein ameliorated cognitive impairment, attenuated hippocampal inflammatory responses, inhibited the TLR4/MyD88/NF-κB signaling pathway, and modulated intestinal microbiota in VD rats.

Blockchain technology and application: an overview.

In recent years, with the rise of digital currency, its underlying technology, blockchain, has become increasingly well-known. This technology has several key characteristics, including decentralization, time-stamped data, consensus mechanism, traceability, programmability, security, and credibility, and block data is essentially tamper-proof. Due to these characteristics, blockchain can address the shortcomings of traditional financial institutions. As a result, this emerging technology has garnered significant attention from financial intermediaries, technology-based companies, and government agencies. This article offers an overview of the fundamentals of blockchain technology and its various applications. The introduction defines blockchain and explains its fundamental working principles, emphasizing features such as decentralization, immutability, and transparency. The article then traces the evolution of blockchain, from its inception in cryptocurrency to its development as a versatile tool with diverse potential applications. The main body of the article explores fundamentals of block chain systems, its limitations, various applications, applicability etc. Finally, the study concludes by discussing the present state of blockchain technology and its future potential, as well as the challenges that must be surmounted to unlock its full potential.

A hybrid and scalable nanofabrication approach for bio-inspired bactericidal silicon nanospike surfaces.

Insects and plants exhibit bactericidal properties through surface nanostructures, such as nanospikes, which physically kill bacteria without antibiotics or chemicals. This is a promising new avenue for achieving antibacterial surfaces. However, the existing methods for fabricating nanospikes are incapable of producing uniform nanostructures on a large scale and in a cost-effective manner. In this paper, a scalable nanofabrication method involving the application of nanosphere lithography and reactive ion etching for constructing nanospike surfaces is demonstrated. Low-cost silicon nanospikes with uniform spacing that were sized similarly to biological nanospikes on cicada wings with a 4-inch wafer scale were fabricated. The spacing, tip radius, and base diameter of the silicon nanospikes were controlled precisely by adjusting the nanosphere diameters, etching conditions, and diameter reduction. The bactericidal properties of the silicon nanospikes with 300 nm spacing were measured quantitatively using the standard viability plate count method; they killed E. coli cells with 59 % efficiency within 30 h. The antibacterial ability of the nanospike surface was further indicated by the morphological differences between bacteria observed in the scanning electron microscopic images as well as the live/dead stains of fluorescence signals. The fabrication process combined the advantages of both top-down and bottom-up methods and was a significant step toward affordable bio-inspired antibacterial surfaces.

Baicalin facilitates remyelination and suppresses neuroinflammation in rats with chronic cerebral hypoperfusion by activating Wnt/ß-catenin and inhibiting NF-κB signaling.

One main factor contributing to the cognitive loss in vascular dementia (VD) is white matter lesions (WMLs) carried on by chronic cerebral hypoperfusion (CCH). A secondary neuroinflammatory response to CCH accelerates the loss and limits the regeneration of oligodendrocytes, leading to progressive demyelination and insufficient remyelination in the white matter. Thus, promoting remyelination and inhibiting neuroinflammation may be an ideal therapeutic strategy. Baicalin (BAI) is known to exhibit protective effects against various inflammatory and demyelinating diseases. However, whether BAI has neuroprotective effects against CCH has not been investigated. To determine whether BAI inhibits CCH-induced demyelination and neuroinflammation, we established a model of CCH in rats by occluding the two common carotid arteries bilaterally. Our results revealed that BAI could remarkably ameliorate cognitive impairment and mitigate CA1 pyramidal neuron damage and myelin loss. BAI exhibited enhancement of remyelination by increasing the expression of myelin basic protein (MBP) and oligodendrocyte transcription factor 2 (Olig2), inhibiting the loss of oligodendrocytes and promoting oligodendrocyte regeneration in the corpus callosum of CCH rats. Furthermore, BAI modified microglia polarization to the anti-inflammatory phenotype and inhibited the release of pro-inflammatory cytokines. Mechanistically, BAI treatment significantly induced phosphorylation of glycogen synthase kinase 3ß (GSK3ß), enhanced the expression of ß-catenin and its nuclear translocation. Simultaneously, BAI reduced the expression of nuclear NF-κB. Collectively, our results suggest that BAI ameliorates cognitive impairment in CCH-induced VD rats through its pro-remyelination and anti-inflammatory capacities, possibly by activating the Wnt/ß-catenin and suppressing the NF-κB signaling.

Liquid metal integrated PU/CNT fibrous membrane for human health monitoring.

Wearable flexible sensors are widely used in several applications such as physiological monitoring, electronic skin, and telemedicine. Typically, flexible sensors that are made of elastomeric thin-films lack sufficient permeability, which leads to skin inflammation, and more importantly, affects signal detection and consequently, reduces the sensitivity of the sensor. In this study, we designed a flexible nanofibrous membrane with a high air permeability (6.10 mm/s), which could be effectively used to monitor human motion signals and physiological signals. More specifically, a flexible membrane with a point (liquid metal nanoparticles)-line (carbon nanotubes)-plane (liquid metal thin-film) multiscale conductive structure was fabricated by combining liquid metal (LM) and carbon nanotubes (CNTs) with a polyurethane (PU) nanofibrous membrane. Interestingly, the excellent conductivity and fluidity of the liquid metal enhanced the sensitivity and stability of the membrane. More precisely, the gauge factor (GF) values of the membrane is 3.0 at 50% strain and 14.0 at 400% strain, which corresponds to a high strain sensitivity within the whole range of deformation. Additionally, the proposed membrane has good mechanical properties with an elongation at a break of 490% and a tensile strength of 12 MPa. Furthermore, the flexible membrane exhibits good biocompatibility and can efficiently monitor human health signals, thereby indicating potential for application in the field of wearable electronic devices.

Small-diameter PCL/PU vascular graft modified with heparin-aspirin compound for preventing the occurrence of acute thrombosis.

The occurrence of acute thrombosis, directly related to platelet aggregation and coagulant system, is a considerable reason for the failure of small-diameter vascular grafts. Heparin is commonly used as a functional molecule for graft modification due to the strong anticoagulant effect. Unfortunately, heparin cannot directly resist the adhesion and aggregation of platelets. Therefore, we have prepared a heparin-aspirin compound by coupling heparin with aspirin, an antiplatelet drug, and covalently grafted it onto the surface of polycaprolactone/polyurethane composite tube. In this way, the graft not only showed a dual function of both anticoagulation and antiplatelet, but also effectively avoided the rapid drug release and excessive toxicity to other organs caused by simple blending the medicine with material matrix. The compound retained the original function of heparin, showing good hydrophilicity and biocompatibility, which could promote the adhesion and proliferation of endothelial cells (ECs) and facilitate the process of tissue regeneration. What's more, the compound showed more effective than heparin in reducing platelet activation and preventing thrombosis. The graft modified by this compound maintained completely unobstructed for one month of implantation, while severe obstruction or stenosis occurred in PCL/PU and PCL/PU-Hep lumen at the first week, verifying the effect of the compound on preventing acute thrombosis. In general, this study proposed a designing method for small-diameter vascular graft which could prevent acute thrombosis and promote intimal construction.

Wearable and battery-free wound dressing system for wireless and early sepsis diagnosis.

Sepsis is a severe organ dysfunction typically caused by wound infection which leads to septic shock, organ failure or even death if no early diagnosis and property medical treatment were taken. Herein, we report a soft, wearable and battery-free wound dressing system (WDS) for wireless and real-time monitoring of wound condition and sepsis-related biomarker (procalcitonin [PCT]) in wound exudate for early sepsis detection. The battery-free WDS powered by near-field communication enables wireless data transmission, signal processing and power supply, which allows portable intelligent wound caring. The exudate collection associates with soft silicone based microfluidic technologies (exudate collection time within 15 s), that can filtrate contamination at the cell level and enable a superior filtration rate up to 95% with adopting microsphere structures. The battery-free WDS also includes state-of-the-art biosensors, which can accurate detect the pH value, wound temperature, and PCT level and thus for sepsis diagnosis. In vivo studies of SD rats prove the capability of the WDS for continuously monitoring wound condition and PCT concentration in the exudate. As a result, the reported fully integrated WDS provides a potential solution for further developing wearable, multifunctional and on-site disease diagnosis.

Intelligent Soft Sweat Sensors for the Simultaneous Healthcare Monitoring and Safety Warning.

Intelligent monitoring human physiological information in real time raises the demand for skin-integrated electronics, as which is a flexible format and can be mounted onto the curved human skin for noninvasive healthcare monitoring. The biofluid such as sweat from skin contains abundant biomarkers reflecting body health conditions. Here, a skin-integrated sweat monitor with six biosensors embedded for the detection of NH4 + , Na+ , glucose, pH, skin impedance, and surface temperature is described, which could decode the information in the fresh sweat generated during exercising. Furthermore, the system also includes an innovative safety warning mechanism, which is based on a miniaturized actuator to provide mechanical stimuli, and coupled with six changeable colors light emitting diodes corresponding to the six biosensors for providing simultaneous safety alarming to users. The self-developed microfluidics system with a hydrophilic surface allows to enhance the sweat collection rate. Meanwhile, microfluidic filters can reduce the interruption of skin debris during biosignal monitoring. These state-of-art biosensors can real-time monitor health related signals with excellent linearity and specificity. The skin-integrated sweat monitor system exhibits a great potential in human healthcare monitoring and medical treatment.

Dl-3-n-Butylphthalide Improves Neuroinflammation in Mice with Repeated Cerebral Ischemia-Reperfusion Injury through the Nrf2-Mediated Antioxidant Response and TLR4/MyD88/NF-κB Signaling Pathway.

Increasing evidence shows that oxidative stress and neuroinflammation play a crucial role in the pathology of vascular dementia (VD). Previously, we have found that Dl-3-n-butylphthalide (NBP) has antioxidant and anti-inflammatory activities in VD, whereas little is known about its mechanism. Therefore, the objective of our study was to explore the contribution of nuclear factor erythroid-2 related factor 2 (Nrf2) to NBP and its effects on anti-inflammatory activity in a mouse model of VD. Our studies revealed that NBP could effectively mitigate cognitive deficits, neuron cell loss, and apoptosis in mice subjected to repeated cerebral ischemia-reperfusion (RCIR). Additionally, NBP promoted both the expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in hippocampus tissue. NBP exhibited antioxidant activity by enhancing Nrf2 nuclear accumulation, increasing HO-1 and NQO1 expression, enhancing SOD activity, and inhibiting RCIR-induced MDA and 8-iso PGF2α generation in the hippocampus. NBP also significantly inhibited TLR4/MyD88/NF-κB signaling and suppressed microglial proliferation and the production of proinflammatory mediators in RCIR mice. Importantly, the antioxidant, antineuroinflammatory, and neuroprotective effects of NBP above were abolished by Nrf2 knockout. Collectively, these results indicated the effects of NBP on neuroinflammation were strongly associated with the Nrf2 pathway. Modulation of TLR4/MyD88/NF-κB pathway by Nrf2 is involved in the neuroprotective effect of NBP against VD induced by RCIR injury. With antioxidant and anti-neuroinflammatory properties, NBP could be a promising drug candidate for the prevention and/or treatment of VD and other neuroinflammatory disorders.

Impacts of physical-chemical property of polyethylene on depolymerization and biodegradation in yellow and dark mealworms with high purity microplastics.

Yellow and dark mealworms (Tenebrio molitor and Tenebrio obscurus) biodegrade commercial polyethylene (PE) materials at a high rate. We examined the impact of physical and chemical properties on biodegradation using high purity microplastics (MPs). These included high-density polyethylene (HDPE), low-density polyethylene (LDPE), and linear low-density polyethylene (LLDPE), all with different weight average molecular weights (Mw) and different crystallinity degrees in T. molitor and T. obscurus larvae. The biodegradation extent in the two mealworms was similar but strongly depended on the polymer type in sequence, since LDPE > LLDPE> HDPE (with respective Mw of 222.5, 110.5 and 182 kDa). When LDPE MPs with Mw of 0.84, 6.4 and 106.8 kDa and HDPE with Mw of 52, 105 and 132.7 kDa were tested, the PE MPs with lower Mw showed a greater extent of depolymerization. The results of dominance analysis indicated that less branching structure and higher crystallinity degree negatively impacted depolymerization and biodegradation. Py-GC/MS analysis confirmed the breaking of the macromolecule backbone as well as the formation of oxidized functional groups after all the tested PE materials passed through the mealworm intestine. The results demonstrated that molecular weight, PE type, branching, and crystallinity degree significantly affect the biodegradation capability of PE by the mealworms, and possibly by other biological systems as well.

Neuroprotection of Intermedin Against Cerebral Ischemia/Reperfusion Injury Through Cerebral Microcirculation Improvement and Apoptosis Inhibition.

Ischemic stroke is the primary cause of disability and mortality worldwide. Ischemia/reperfusion (I/R)-induced microcirculatory dysfunction and organ injury generally occur after ischemic stroke. Several studies have shown that intermedin (IMD) has a regulating function on cerebral microcirculation and blood-brain barrier via relaxing cerebral vessels and improving the local blood supply after cerebral ischemia. However, a unified conclusion has not been reached, and the underlying mechanism remains unclear. To observe and analyze the changes of cerebral microcirculation perfusion of cerebral IRI by IMD post-treatment in the rats and further explore the mechanism underlying the beneficial effect of IMD on cerebral IRI. Thirty-nine rats were divided into three groups: sham, I/R, and I/R + IMD groups. After IMD ischemia post-treatment, the rat cerebral infarction rate and the degree of neurological deficit were evaluated by TTC staining and neurological function score; the changes in the amount of cerebral microcirculation implantation on the injured side of the rats were observed by laser Doppler; the pathological changes and cell ultrastructure of rat cortex and hippocampus were observed by HE staining and transmission electron microscopy; the neuron apoptosis in the rat cortex and hippocampus was detected by TUNEL staining and immunohistochemical staining. Impaired neurological function, abnormal cortical/hippocampal neuron morphology, and the proportion of cerebral infarction were significantly improved in the IMD group compared with the I/R group, which suggested a possible neuroprotective role of IMD. IMD treatment also increased the average perfusion of cerebral surface microcirculation in rats by astonished 42.7 times. Finally, IMD administration decreased the caspase-3- and Bax-positive cell numbers and apoptotic cell ratio. IMD has a significant protective effect on neuronal damage caused by cerebral I/R in rats by improving cerebral microcirculation and inhibiting apoptosis.

DL-3-n-butylphthalide suppressed autophagy and promoted angiogenesis in rats with vascular dementia by activating the Shh/Ptch1 signaling pathway.

DL-3-n-butylphthalide (NBP) has neuroprotective effect on chronic cerebral hypoperfusion animals. Here, we explored the role and underlying mechanism of NBP on autophagy and angiogenesis in rats with vascular dementia (VD). Adult male Sprague-Dawley (SD) rats were subjected to permanent bilateral occlusion of the common carotid arteries (2VO) to establish VD model. These rats were randomly divided into five groups: sham, model, NBP120 (120 mg/kg), Shh siRNA (50 nM), and NBP120 + Shh siRNA groups. Our results showed that NBP treatment attenuated memory damage in rats with VD, as demonstrated by Morris water maze tests. Immunofluorescence (IF) assay revealed that NBP induced neuronal process length and neuronal activity in hippocampus, which were reversed by Shh silencing. Furthermore, NBP treatment also reduced the expression of autophagy marker proteins B-cell lymphoma-2 interacting protein 1 (Beclin 1) and microtubule-associated protein 1 light chain 3 (LC3), which were further enhanced by Shh silencing. Meanwhile, NBP promoted the angiogenesis, which was accompanied by upregulated vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-1, and Angiopoietin (Ang) expression in the hippocampus. And Shh siRNA co-treatment blocked the angiogenesis induced by NBP. Altogether, our results established that NBP treatment suppressed autophagy and improved angiogenesis and neurobehavioral recovery in VD rats partly by activating the Shh/Ptch1 signaling pathway.

Superior antibacterial activity of gallium based liquid metals due to Ga3+ induced intracellular ROS generation.

Gallium-based liquid metals have increasing applications in a wide variety of emerging areas and they are involved more in frontier studies, the energy industry and additive manufacturing production, and even in daily life. When exposed to open air, large amounts of microorganisms may interact with liquid metals. However, the research of the relationship between pure gallium-based liquid metals and bacterial cells is still limited. In this study, the antibacterial properties of eutectic gallium-indium (EGaIn) alloys were tested against the typical Gram-negative bacteria-Escherichia coli and the Gram-positive bacteria-Staphylococcus aureus and the experimental results displayed that the antibacterial rates reached 100%. We also explored the mechanism of the anti-bacterial properties of EGaIn alloys by measuring the surface composition of the EGaIn film and the concentration of dissolved metal ions. The morphology of the bacterial cells showed that the cell growth and division were influenced by exposure to EGaIn. We also found that the synergistic antibacterial effect came along with the production of reactive oxygen species (ROS). Moreover, the EGaIn film showed enhanced antibacterial activity compared to gallium nitrate at the same initial ion concentration in the solution. This study shows the enormous potential of the anti-bacterial effect of liquid metals.

Novel coagulation waste-based Fe-containing carbonaceous catalyst as peroxymonosulfate activator for pollutants degradation: Role of ROS and electron transfer pathway.

A facile one-step pyrolysis method was employed to prepare an iron containing carbonaceous catalyst using coagulation waste (CW) from paper mill. The catalyst (noted as PMCW) was used to activate peroxymonosulfate (PMS) for decomposition of Reactive Red 2 (RR2). The degradation mechanism was analyzed by reactive oxygen species (ROS) scavenging experiments, electron spin resonance spectroscopy, electrochemical measurements, selective deactivation of the functional groups on the catalyst surface, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. Results showed that, besides ROS (•OH, SO4•- and 1O2), electron transfer pathways induced by -OH functional groups and the π-π* system are involved in the degradation mechanism of RR2. Concerning different decomposition pathways, seven intermediates were identified, and three important steps, including attack on the azo group, cleaving the N9-C10 bond, and opening the naphthalene ring, were deduced via application and analysis of quadrupole time-of-flight liquid chromatography/mass spectrometry (QTOF LC/MS) and density functional theory (DFT) calculations based on Fukui indices and electrostatic potential (ESP) distributions. This work not only provides a novel facile recycling strategy of industrial waste from paper manufacturing to good carbonaceous catalysts but also deepens the understanding of the mechanisms of PMS activation with carbonaceous materials.