Particulate matter (PM) pollution, which usually carries viruses and bacteria, has drawn considerable attention as a major threat to public health. In this present study, an environment-friendly antibacterial Poly(lactic acid)(PLA)/chitosan composite air filter was fabricated using the one-step electrospinning technique. The composite PLA/chitosan fibres show a highly porous structure, in which chitosan nanoparticles (NPs) were found to be uniformly distributed throughout the entire fibre. The morphologies, through-pore size and distribution, air filtration and anti-microbial properties of these filter media were studied. The results showed that it was not the chitosan content but instead the concentration of the spinning solutions that had the greatest effect on the morphologies of the porous fibres. The relative humidity influenced the nanometre-scale pores on the surface of PLA/chitosan fibres. The PLA/chitosan fibrous membranes with a chitosan to PLA mass ratio of 2.5:8 exhibited a high filtration efficiency of 98.99% and a relatively low pressure drop (147.60 Pa) when the air flow rate was 14 cm/s, while these also had high antibacterial activity of 99.4% and 99.5% against Escherichia coli and Staphylococcus aureus, respectively. It took 33 min for the PM2.5 concentration to decrease to 0 μg/m³ from 999 μg/m³ using the PLA/chitosan fibrous membranes, which demonstrates obviously effective air purification performance.

The preparation of flawless and defect-free mixed matrix membranes (MMMs) comprising metal-organic framework (MOF) and polymer is often difficult owing to the poor MOF/polymer interface compatibility. Herein, we present the synthesis of an important family of pillared-layered MOFs with polymerizable moieties based on the parent structure [Zn2L2P]n [L = vinyl containing benzenedicarboxylic acid linkers; P = 4,4'-bipyridine (bipy)]. The crystalline structures of polymerizable MOFs were analyzed using single-crystal X-ray crystallography. The presence of reactive double bonds in MOFs was verified by the successful thiol-ene click reaction with sulfhydryl compounds. The subsequent copolymerization of polymerizable MOFs with organic monomers produced mixed matrix membranes with enhanced MOF/polymer interfacial adhesion that enabled good separation efficiency of CO2 from flue gas. This strategy provides a stimulating platform to the preparation of highly efficient MMMs that are capable of mitigating energy consumption and environment issues.

Glioma is among the deadliest types of brain cancer, for which there currently is no effective treatment. Chemotherapy is mainstay in the treatment of glioma. However, drug tolerance, non-targeting, and poor blood-brain barrier penetrance severely inhibits the efficacy of chemotherapeutics. An improved treatment method is thus urgently needed. Herein, a multifunctional biomimetic nanoplatform was developed by encapsulating graphene quantum dots (GQDs) and doxorubicin (DOX) inside a homotypic cancer cell membrane (CCM) for targeted chemo-photothermal therapy of glioma. The GQDs with stable fluorescence and a superior light-to-heat conversion property were synthesized as photothermal therapeutic agents and co-encapsulated with DOX in CCM. The as-prepared nanoplatform exhibited a high DOX loading efficiency. The cell membrane coating protected drugs from leakage. Upon an external laser stimuli, the membrane could be destroyed, resulting in rapid DOX release. By taking advantage of the homologous targeting of the cancer cell membrane, the GQDs/DOX@CCM were found to actively target tumor cells, resulting in significantly enhanced cellular uptake. Moreover, a superior suppression efficiency of GQDs/DOX@CCM to cancer cells through chemo-photothermal treatment was also observed. The results suggest that this biomimetic nanoplatform holds potential for efficient targeting of drug delivery and synergistic chemo-photothermal therapy of glioma.

Graphyne sheet exhibits promising potential for nanoscale desalination to achieve both high water permeability and salt rejection rate. Extensive molecular dynamics simulations on pore-size effects suggest that γ-graphyne-4, with 4 acetylene bonds between two adjacent phenyl rings, has the best performance with 100% salt rejection and an unprecedented water permeability, to our knowledge, of ~13 L/cm(2)/day/MPa, 3 orders of magnitude higher than prevailing commercial membranes based on reverse osmosis, and ~10 times higher than the state-of-the-art nanoporous graphene. Strikingly, water permeability across graphyne exhibits unexpected nonlinear dependence on the pore size. This counter-intuitive behavior is attributed to the quantized nature of water flow at the nanoscale, which has wide implications in controlling nanoscale water transport and designing highly effective membranes.

Intracellular transport, regulated by complex cytoarchitectures and active driving forces, is crucial for biomolecule translocations and relates to many cellular functions. Despite extensive knowledge obtained from two-dimensional (2D) experiments, the real three-dimensional (3D) spatiotemporal characteristics of intracellular transport is still unclear. With 3D single-particle tracking, we comprehensively studied the transport dynamics of endocytic cargos. With varying timescale, the intracellular transport changes from thermal-dominated 3D-constrained motion to active-dominated quasi-2D motion. Spatially, the lateral motion is heterogeneous with peripheral regions being faster than perinuclear regions, while the axial motion is homogeneous across the cells. We further confirmed that such anisotropy and heterogeneity of vesicle transport result from actively directed motion on microtubules. Strikingly, inside the vesicles, we observed endocytic nanoparticles make diffusive motions on their inner membranes when microtubules are absent, suggesting endocytic cargos are normally localized at the inner vesicle membranes through a physical connection to the microtubules outside during transport.

Biodegradable materials are a next-generation invention for the treatment of congenital heart diseases. However, the corresponding technology used to develop ideal biomaterials still presents challenges. We previously reported the first biodegradable atrial septal defect (ASD) occluder made of poly-lactic acid (PLLA). Unfortunately, the PLLA occluder had a limited endothelialization effect. In this study, the surface of the occluder membrane was coated with sericin/CD34 antibodies to promote the growth of endothelial cells and the regeneration of defective tissue and enhance the repair of the atrial septal defect. The physicochemical properties of the coat on the surface of the fiber membrane were characterized. The sericin coat successfully covered the fiber surface of the membrane, and the thickness of the membrane increased with the sericin concentration. The swelling rate reached 230%. The microscopic observation of fluorescently labeled CD34 antibodies showed that the antibodies successfully attached to the fiber membrane; the fluorescence intensity of PLLA-SH5 was particularly high. The in vitro experiment showed that the PLLA-SH-CD34 fiber membrane was biocompatible and promoted the adhesion and proliferation of endothelial cells. According to our findings, the PLLA-SH-CD34 membrane provides a theoretical and technical basis for the research and development of novel biodegradable occluders.

Proliferative vitreoretinopathy (PVR) is a disease that causes severe blindness and is characterized by the formation of contractile fibrotic subretinal or epiretinal membranes. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a hallmark of PVR. This work aims to examine the role of a long noncoding RNA (lncRNA) named EMT-related lncRNA in RPE (ERLR, LINC01705-201 (ENST00000438158.1)) in PVR and to explore the underlying mechanisms. In this study, we found that ERLR is upregulated in RPE cells stimulated with transforming growth factor (TGF)-β1 as detected by lncRNA microarray and RT-PCR. Further studies characterized full-length ERLR and confirmed that it is mainly expressed in the cytoplasm. In vitro, silencing ERLR in RPE cells attenuated TGF-β1-induced EMT, whereas overexpressing ERLR directly triggered EMT in RPE cells. In vivo, inhibiting ERLR in RPE cells reduced the ability of cells to induce experimental PVR. Mechanistically, chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor TCF4 directly binds to the promoter region of ERLR and promotes its transcription. ERLR mediates EMT by directly binding to MYH9 protein and increasing its stability. TCF4 and MYH9 also mediate TGF-β1-induced EMT in RPE cells. Furthermore, ERLR is also significantly increased in RPE cells incubated with vitreous PVR samples. In clinical samples of PVR membranes, ERLR was detected through fluorescent in situ hybridization (FISH) and colocalized with the RPE marker pancytokeratin (pan-CK). These results indicated that lncRNA ERLR is involved in TGF-β1-induced EMT of human RPE cells and that it is involved in PVR. This finding provides new insights into the mechanism and treatment of PVR.

Lipopolysaccharide (LPS) is an inhibitory factor that causes hormonal imbalance and subsequently affects ovarian function and fertility in mammals. Previous studies have shown that the exposure of granulosa cells (GC) to LPS leads to steroidogenesis dysfunction. However, the effects of LPS on the viability of GC remain largely unclear. In the present study, we aimed to address this question and unveil the underlying molecular mechanisms using cultured porcine GC. Results showed that GC proliferation and tumor necrosis factor α (TNFα) secretion were significantly increased after exposure to LPS, and these effects were completely reversed by blocking the TNFα sheddase, ADAM17. Moreover, GC proliferation induced by LPS was mimicked by treatment with recombinant TNFα. In addition, SerpinE1 and SerpinB2 expression levels increased in GC after treatment with LPS or recombinant TNFα, whereas blocking the Erk1/2 pathway completely abolished these effects and also inhibited GC proliferation. Further, consistent with the effects of blocking the Erk1/2 pathway, cell proliferation was completely inhibited by knocking down SerpinE1 or SerpinB2 in the presence of LPS or recombinant TNFα. Mitochondrial membrane potential (MMP) polarization in GC was increased by LPS or recombinant TNFα treatment, and these changes were completely negated by Erk1/2 inhibition, but not by SerpinE1 or SerpinB2 knockdown. Taken together, these results suggested that the TNFα-mediated upregulation of SerpinE1 and SerpinB2, through activation of the Erk1/2 pathway plays a crucial role in LPS-stimulated GC proliferation, and the increase in GC MMP may synergistically influence this process.

To elucidate the effects of rice protein on the detoxification and antioxidant defense via the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, adult rats were fed casein and rice protein under cholesterol-free and -enriched dietary conditions. Nrf2 proteins and gene expressions were stimulated by rice proteins with respect to caseins accompanied by up-regulating the expression of gene encoding antioxidant and phase II detoxification in the rice protein groups. In the liver, compared with caseins, rice proteins significantly increased hepatic contents of reduced glutathione (GSH) and mRNA levels of glutamate cysteine ligase catalytic subunit (GCLC), glutamate cysteine ligase modulatory subunit (GCLM), glutathione S-transferase (GST), heme oxygenase 1 (HO-1) and

Iron limitation is a universal strategy of host immunity during bacterial infection. However, the mechanisms by which pathogens antagonize host nutritional immunity have not been fully elucidated. Here, we identified a requirement for the UMPylator YdiU for this process in Salmonella. The expression of YdiU was dramatically induced by the metal starvation signal. The intracellular iron content was much lower in the ΔydiU strain than in wild-type Salmonella, and the ΔydiU strain exhibited severe growth defect under metal deficiency environments. Genome-wide expression analyses revealed significantly decreased expression of iron uptake genes in ΔydiU strain compared with the wild-type strain. Interestingly, YdiU did not affect the expression level of the major iron uptake regulator Fur but directly UMPylated Fur on its H118 residue in vivo and in vitro. UMPylation destroyed the Fur dimer, promoted Fur aggregation, and eliminated the DNA-binding activity of Fur, thus abolishing the ability of Fur to inhibit iron uptake. Restricting Fur to the deUMPylated state dramatically eliminates Salmonella iron uptake in iron deficiency environments. In parallel, YdiU facilitates Salmonella survival within host cells by regulating the iron uptake pathway. IMPORTANCE Salmonella is the major pathogen causing bacterial enteric illness in both humans and animals. Iron availability is strictly controlled upon Salmonella entry into host cells. The mechanisms by which Salmonella balances the acquisition of sufficient iron while preventing a toxic overload has not been fully understood. Here, we reveal a novel regulation process of iron acquisition mediated by the UMPylator YdiU. Fur acts as the central regulator of bacterial iron homeostasis. YdiU UMPylates Fur on H118 and prevents Fur from binding to target DNA, thus activating the expression of iron uptake genes under iron-deficient conditions. We describe the first posttranslational modification-based regulation of Fur and highlight a potential mechanism by which Salmonella can adapt to eliminate host nutritional immunity.

Introducing nitrogen fixation (nif   ) genes into eukaryotic genomes and targeting Nif components to mitochondria or chloroplasts is a promising strategy for engineering nitrogen-fixing plants. A prerequisite for achieving nitrogen fixation in crops is stable and stoichiometric expression of each component in organelles. Previously, we designed a polyprotein-based nitrogenase system depending on Tobacco Etch Virus protease (TEVp) to release functional Nif components from five polyproteins. Although this system satisfies the demand for specific expression ratios of Nif components in Escherichia coli, we encountered issues with TEVp cleavage of polyproteins targeted to yeast mitochondria. To overcome this obstacle, a version of the Nif polyprotein system was constructed by replacing TEVp cleavage sites with minimal peptide sequences, identified by knowledge-based engineering, that are susceptible to cleavage by the endogenous mitochondrial-processing peptidase. This replacement not only further reduces the number of genes required, but also prevents potential precleavage of polyproteins outside the target organelle. This version of the polyprotein-based nitrogenase system achieved levels of nitrogenase activity in E. coli, comparable to those observed with the TEVp-based polyprotein nitrogenase system. When applied to yeast mitochondria, stable and balanced expression of Nif components was realized. This strategy has potential advantages, not only for transferring nitrogen fixation to eukaryotic cells, but also for the engineering of other metabolic pathways that require mitochondrial compartmentalization.

As highly sophisticated intercellular communication vehicles in biological systems, extracellular vesicles (EVs) have been investigated as both promising liquid biopsy-based disease biomarkers and drug delivery carriers. Despite tremendous progress in understanding their biological and physiological functions, mechanical characterization of these nanoscale entities remains challenging due to the limited availability of proper techniques. Especially, whether damage to parental cells can be reflected by the mechanical properties of their EVs remains unknown.

Cervical carcinoma high-expressed long non-coding RNA 1 (CCHE1) has been demonstrated to promote several different types of cancer; however, the involvement of CCHE1 in other types of cancer remains unknown. In the present study, the expression levels of CCHE1 and interleukin (IL)-17A were increased in the plasma of patients with metastatic and non-metastatic colon adenocarcinoma (MC and NMC, respectively) compared with the healthy controls. There was no significant difference in the plasma expression levels of CCHE1 and IL-17A in patients with MC compared with patients with NMC. The plasma expression levels of CCHE1 and IL-17A were positively associated with the primary tumor diameter. A significant correlation as demonstrated between the serum levels of CCHE1 and IL-17A in patients with colon adenocarcinoma, but not in the healthy controls. CCHE1 and IL-17A overexpression promoted colon adenocarcinoma cell proliferation. Transfection of small interfering RNA against IL-17A partially reversed the effects of CCHE1 overexpression on cancer cell proliferation. Upregulation of IL-17A was observed after CCHE1 overexpression, while IL-17A overexpression did not significantly change the expression level of CCHE1. Therefore, CCHE1 may promote growth of colon adenocarcinoma through interactions with IL-17A.

Although mature podocytes lack tight junctions, tight junction integral membrane protein claudin-5 (CLDN5) is predominantly expressed on plasma membranes of podocytes under normal conditions. Using podocyte-specific Cldn5 knockout mice, we identify CLDN5 as a crucial regulator of podocyte function and reveal that Cldn5 deletion exacerbates podocyte injury and proteinuria in a diabetic nephropathy mouse model. Mechanistically, CLDN5 deletion reduces ZO1 expression and induces nuclear translocation of ZONAB, followed by transcriptional downregulation of WNT inhibitory factor-1 (WIF1) expression, which leads to activation of WNT signaling pathway. Podocyte-derived WIF1 also plays paracrine roles in tubular epithelial cells, as evidenced by the finding that animals with podocyte-specific deletion of Cldn5 or Wif1 have worse kidney fibrosis after unilateral ureteral obstruction than littermate controls. Systemic delivery of WIF1 suppresses the progression of diabetic nephropathy and ureteral obstruction-induced renal fibrosis. These findings establish a function for podocyte CLDN5 in restricting WNT signaling in kidney.

Hippocampal mitochondrial dysfunction due to oxidative stress has been considered to play a major role in the pathogenesis of vascular dementia (VD). Previous studies suggested that acupuncture could improve cerebral hypoperfusion-induced cognitive impairments. However, whether hippocampal mitochondria are associated with this cognitive improvement remains unclear. In this study, an animal model of VD was established via bilateral common carotid arteries occlusion (BCCAO) to investigate the alterations of cognitive ability and hippocampal mitochondrial function. BCCAO rats showed impairments in hippocampal mitochondrial function, overproduction of reactive oxygen species (ROS) and learning and memory deficits. After two-week acupuncture treatment, BCCAO-induced spatial learning and memory impairments as shown in Morris water maze were ameliorated. Hippocampal mitochondrial respiratory complex enzymes (complex I, II, IV) activities and cytochrome c oxidase IV expression significantly increased, which might contribute to the reduction of hippocampal ROS generation. In addition, acupuncture significantly improve mitochondrial bioenergy parameters such as mitochondrial respiratory control rate and membrane potential not PDH A1 expression. Placebo-acupuncture did not produce similar therapeutic effects. These findings suggested that acupuncture reversed BCCAO-induced hippocampal mitochondrial dysfunction, which might contribute to its prevention on cognitive deficits.

Hepatic ischemia-reperfusion injury (IRI) remains a common complication during liver transplantation (LT), partial hepatectomy and hemorrhagic shock in patients. As a member of the G protein-coupled receptors adaptors, ARRB2 has been reported to be involved in a variety of physiological and pathological processes. However, whether β-arrestin-2 affects the pathogenesis of hepatic IRI remains unknown. The goal of the present study was to determine whether ARRB2 protects against hepatic IR injury and elucidate the underlying mechanisms. To this end, 70% hepatic IR models were established in ARRB2 knockdown mice and wild-type littermates, with blood and liver samples collected at 1, 6 and 12 h after reperfusion to evaluate liver injury. The effect of ARBB2 on PI3K/Akt signaling during IR injury was evaluated in vivo, and PI3K/Akt pathway regulation by ARRB2 was further assessed in vitro. Our results showed that ARRB2 knockdown aggravates hepatic IR injury by promoting the apoptosis of hepatocytes and inhibiting their proliferation. In addition, ARRB2 deficiency inhibited PI3K/Akt pathway activation, while the administration of the PI3K/Akt inhibitor PX866 resulted in severe IR injury in mice. Furthermore, the liver-protecting effect of ARRB2 was shown to depend on PI3K/Akt pathway activation. In summary, our results suggest that β-Arrestin-2 protects against hepatic IRI by activating PI3K/Akt signaling, which may provide a novel therapeutic strategy for treating liver ischemia-reperfusion injury.

Nucleotide‑binding oligomerization domain, leucine rich repeat, and pyrin domain‑containing protein 3 (NLRP3) inflammasome has been implicated in a series of physiological and pathological processes. However, its correlation in coronary heart disease (CHD) still remains to be elucidated. The present study aimed to determine the expression of NLRP3 inflammasome in peripheral blood monocytes (PBMCs) of stable angina pectoris (SAP) and acute myocardial infarction (AMI) patients. In addition, the effect of rosuvastatin on their activities was analyzed in vitro. A total of 60 participants with SAP (n=20), AMI (n=20) and non‑CHD controls (n=20) were enrolled. Fluorescence‑activated cell sorting, real‑time PCR, western blotting and enzyme‑linked immunosorbent assay were performed to reveal the role of NLRP3 inflammasome. NLRP3 inflammasome was expressed in the PBMCs, and revealed an increased expression along the downstream interleukin (IL)‑1β and IL‑18 in both SAP and AMI groups, compared to the control group. Moreover, there was a more marked increase in the expression of these indicators in AMI patients when compared to SAP patients. Interference with rosuvastatin in vitro revealed that the expression of NLRP3 inflammasome and its downstream cytokines were significantly downregulated in both SAP and AMI groups in a time‑dependent manner. The activation of NLRP3 inflammasome may be involved in the development of CHD, and rosuvastatin could attenuate the inflammatory process of atherosclerosis by downregulating NLRP3 expression and its downstream mediators. These findings indicated a potential role of NLRP3 in the pathogenesis and management of CHD, and also provided new insights into the mechanistic framework of rosuvastatin activity.

Obstructive sleep apnea (OSA) is confirmed to cause lesions in multiple organs, especially in the lung tissue. Tempol is an antioxidant that has been reported to restrain inflammation and oxidative stress, with its role in OSA-induced lung injury being unclear. This study aimed to investigate the beneficial effect of tempol on chronic intermittent hypoxia (IH)-induced lung injury.

Modern lifestyles have altered diet and metabolic homeostasis, with increased sugar intake, glycemic index, and prediabetes. A strong positive correlation between sugar consumption and diabetic incidence is revealed, but the underlying mechanisms remain obscure. Here we show that oral intake of long-term oscillating glucose (LOsG) (4 times/day) for 38 days, which produces physiological glycemic variability in rats, can lead to β-cells gaining metabolic memory in reactive oxygen species (ROS) stress. This stress leads to suppression of forkhead box O1 (FoxO1) signaling and subsequent upregulation of thioredoxin interacting protein, inhibition of insulin and SOD-2 expression, re-expression of Neurog3, and β-cell dedifferentiation and functional failure. LOsG-treated animals develop prediabetes exhibiting hypoinsulinemia and glucose intolerance. Dynamic and timely administration of antioxidant glutathione prevents LOsG/ROS-induced β-cell failure and prediabetes. We propose that ROS stress is the initial step in LOsG-inducing prediabetes. Manipulating glutathione-related pathways may offer novel options for preventing the occurrence and development of diabetes.

Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor.