Proximal tubular FHL2, a novel downstream target of hypoxia inducible factor 1, is a protector against ischemic acute kidney injury.

Four-and-a-half LIM domains protein 2 (FHL2) is an adaptor protein that may interact with hypoxia inducible factor 1α (HIF-1α) or ß-catenin, two pivotal protective signaling in acute kidney injury (AKI). However, little is known about the regulation and function of FHL2 during AKI. We found that FHL2 was induced in renal tubular cells in patients with acute tubular necrosis and mice model of ischemia-reperfusion injury (IRI). In cultured renal proximal tubular cells (PTCs), hypoxia induced FHL2 expression and promoted the binding of HIF-1 to FHL2 promoter. Compared with control littermates, mice with PTC-specific deletion of FHL2 gene displayed worse renal function, more severe morphologic lesion, more tubular cell death and less cell proliferation, accompanying by downregulation of AQP1 and Na, K-ATPase after IRI. Consistently, loss of FHL2 in PTCs restricted activation of HIF-1 and ß-catenin signaling simultaneously, leading to attenuation of glycolysis, upregulation of apoptosis-related proteins and downregulation of proliferation-related proteins during IRI. In vitro, knockdown of FHL2 suppressed hypoxia-induced activation of HIF-1α and ß-catenin signaling pathways. Overexpression of FHL2 induced physical interactions between FHL2 and HIF-1α, ß-catenin, GSK-3ß or p300, and the combination of these interactions favored the stabilization and nuclear translocation of HIF-1α and ß-catenin, enhancing their mediated gene transcription. Collectively, these findings identify FHL2 as a direct downstream target gene of HIF-1 signaling and demonstrate that FHL2 could play a critical role in protecting against ischemic AKI by promoting the activation of HIF-1 and ß-catenin signaling through the interactions with its multiple protein partners.

Circular single-stranded DNA as a programmable vector for gene regulation in cell-free protein expression systems.

Cell-free protein expression (CFE) systems have emerged as a critical platform for synthetic biology research. The vectors for protein expression in CFE systems mainly rely on double-stranded DNA and single-stranded RNA for transcription and translation processing. Here, we introduce a programmable vector - circular single-stranded DNA (CssDNA), which is shown to be processed by DNA and RNA polymerases for gene expression in a yeast-based CFE system. CssDNA is already widely employed in DNA nanotechnology due to its addressability and programmability. To apply above methods in the context of synthetic biology, CssDNA can not only be engineered for gene regulation via the different pathways of sense CssDNA and antisense CssDNA, but also be constructed into several gene regulatory logic gates in CFE systems. Our findings advance the understanding of how CssDNA can be utilized in gene expression and gene regulation, and thus enrich the synthetic biology toolbox.

MbEOMT1 regulates methyleugenol biosynthesis in Melaleuca bracteata F. Muell.

Methyleugenol, a bioactive compound in the phenylpropene family, undergoes its final and crucial biosynthetic transformation when eugenol O-methyltransferase (EOMT) converts eugenol into methyleugenol. While Melaleuca bracteata F. Muell essential oil is particularly rich in methyleugenol, it contains only trace amounts of its precursor, eugenol. This suggests that the EOMT enzyme in M. bracteata is highly efficient, although it has not yet been characterized. In this study, we isolated and identified an EOMT gene from M. bracteata, termed MbEOMT1, which is primarily expressed in the flowers and leaves and is inducible by methyl jasmonate (MeJA). Subcellular localization of MbEOMT1 in the cytoplasm was detected. Through transient overexpression experiments, we found that MbEOMT1 significantly elevates the concentration of methyleugenol in M. bracteata leaves. Conversely, silencing of MbEOMT1 via virus-induced gene silencing led to a marked reduction in methyleugenol levels. Our in vitro enzymatic assays further confirmed that MbEOMT1 specifically catalyzes the methylation of eugenol. Collectively, these findings establish that the MbEOMT1 gene is critical for methyleugenol biosynthesis in M. bracteata. This study enriches the understanding of phenylpropene biosynthesis and suggests that MbEOMT1 could serve as a valuable catalyst for generating bioactive compounds in the future.

Neuromelanin-sensitive MRI of the substantia nigra distinguishes bipolar from unipolar depression.

Depression in bipolar disorder (BD-II) is frequently misdiagnosed as unipolar depression (UD) leading to inappropriate treatment and downstream complications for many bipolar sufferers. In this study, we evaluated whether neuromelanin-MR signal and volume changes in the substantia nigra (SN) can be used as potential biomarkers to differentiate BD-II from UD. The signal intensities and volumes of the SN regions were measured, and contrast-to-noise ratio (CNR) to the decussation of the superior cerebellar peduncles were calculated and compared between healthy controls (HC), BD-II and UD subjects. Results showed that compare to HC, both BD-II and UD subjects had significantly decreased CNR and increased volume on the right and left sides. Moreover, the volume in BD-II group was significantly increased compared to UD group. The area under the receiver operating characteristic curve (AUC) for discriminating BD from HC was the largest for the Volume-L (AUC, 0.85; 95% confidence interval [CI]: 0.77, 0.93). The AUC for discriminating UD from HC was the largest for the Volume-L (AUC, 0.76; 95% CI: 0.65, 0.86). Furthermore, the AUC for discriminating BD from UD was the largest for the Volume-R (AUC, 0.73; 95% CI: 0.62, 0.84). Our findings suggest that neuromelanin-sensitive magnetic resonance imaging techniques can be used to differentiate BD-II from UD.

Decoding the Different Aroma-Active Compounds in Soy Sauce for Cold Dishes via a Multiple Sensory Evaluation and Instrumental Analysis.

Screening the suitability of soy sauce for specific cooking methods from various products is beneficial for the fine development of the soy sauce industry. Multiple sensory evaluation and gas chromatography-mass spectrometry/olfactometry (GC-MS/O) analysis were combined to decode the suitability of soy sauces for cold dishes and characterize their differential aroma-active compounds. Thirty-two kinds of soy sauce with 42 sensory descriptors were determined via a check-all-that-apply analysis, and werefurther classified into six categories via a cluster analysis. The sensory evaluation results showed that seven soy sauce samples had the highest acceptance in each category. Solid-phase microextraction and solid phase extraction results combined with the GC-MS/O analysis results showed that a total of 38 aroma-active compounds were identified in seven soy sauce samples, among which 2-methoxy-phenol (6-93), ethyl acetate (2-48), 3-methyl-1-butanol (4-30), 3-methyl-butanal (5-24), methional (0-22), dimethyl trisulfide (5-19) and dimethyl disulfide (0-8) showed a higher relative odor activity value (ROAV). A partial least squares regression prediction combined with additional tests further confirmed that 2,5-dimethyl-pyrazine; 2,6-dimethyl-pyrazine; and 2-ethyl-6-methyl-pyrazine significantly contributed to the roasted attributes, methional significantly contributed to the sauce-like notes, ethanol significantly contributed to the alcoholic notes and 2-methoxy-phenol significantly contributed to the smoky notes. 2,5-Dimethyl-pyrazine; methional; 2,6-dimethyl-pyrazine and 2-ethyl-6-methyl-pyrazine significantly contributed to the caramel-like attributes.

Manganese supplementation of orthopedic implants: a new strategy for enhancing integrin-mediated cellular responses.

Integrin-mediated osteoblast adhesion to adsorbed extracellular ligands on orthopedic implants is crucial for the subsequent osteoblast behaviors and ultimate osseointegration. Considerable research efforts have focused on the development of implant surfaces that promote the adsorption of extracellular ligands, but ignored the fact that integrin binding to ligands requires divalent cations (such as Mn2+). Here, three kinds of Mn-doped nanowire-structured TiO2 coatings with 1.9, 3.9, and 8.8 wt% dopant contents (Mn1-, Mn2-, and Mn3-TiO2) were synthesized on Ti implants to enhance integrin-mediated osteoblastic responses. The Mg-doped and undoped TiO2 nanocoatings served as the control. Mn element was not only successfully incorporated into the TiO2 matrix, but also formed an oxygen-deficient Mn oxide on the nanowire surface. Although the adsorbed fibronectin (Fn) amount on Mn-doped nanocoatings and its unfolded status were slightly attenuated with increasing Mn amount, the interaction between the coating extract and Fn demonstrated a Mn2+-induced unfolding of Fn with the exposure of the RGD motif. Compared to the Mn1-, Mn2- and Mg-doped TiO2 nanocoatings, the Mn3-TiO2 nanocoating significantly upregulated the expression of integrin α5ß1 probably through increasing the ligand-binding affinity of the integrin rather than integrin binding sites in Fn. Consistent with the activation trend of integrin α5ß1, the Mn3-TiO2 nanocoating enhanced cell adhesion with the long stretched structure of actin fibers and extensive formation of vinculin focal adhesion spots and upregulated the levels of alkaline phosphatase and osteocalcin activities. Therefore, Mn supplementation of orthopedic implants may be a promising way to improve osteogenesis at the implant surface.

The Role of MbEGS1 and MbEGS2 in Methyleugenol Biosynthesis by Melaleuca bracteata.

Many aromatic plant volatile compounds contain methyleugenol, which is an attractant for insect pollination and has antibacterial, antioxidant, and other properties. The essential oil of Melaleuca bracteata leaves contains 90.46% methyleugenol, which is an ideal material for studying the biosynthetic pathway of methyleugenol. Eugenol synthase (EGS) is one of the key enzymes involved in the synthesis of methyleugenol. We recently reported two eugenol synthase genes (MbEGS1 and MbEGS2) present in M. bracteata, where MbEGS1 and MbEGS2 were mainly expressed in flowers, followed by leaves, and had the lowest expression levels in stems. In this study, the functions of MbEGS1 and MbEGS2 in the biosynthesis of methyleugenol were investigated using transient gene expression technology and virus-induced gene silencing (VIGS) technology in M. bracteata. Here, in the MbEGSs genes overexpression group, the transcription levels of the MbEGS1 gene and MbEGS2 gene were increased 13.46 times and 12.47 times, respectively, while the methyleugenol levels increased 18.68% and 16.48%. We further verified the function of the MbEGSs genes by using VIGS, as the transcript levels of the MbEGS1 and MbEGS2 genes were downregulated by 79.48% and 90.35%, respectively, and the methyleugenol content in M. bracteata decreased by 28.04% and 19.45%, respectively. The results indicated that the MbEGS1 and MbEGS2 genes were involved in the biosynthesis of methyleugenol, and the transcript levels of the MbEGS1 and MbEGS2 genes correlated with the methyleugenol content in M. bracteata.

Preservation of Litchi Fruit with Nanosilver Composite Particles (Ag-NP) and Resistance against Peronophythora litchi.

Litchi (Litchi chinensis Sonn.) is susceptible to infection by Peronophythora litchi post storage, which rapidly decreases the sensory and nutritional quality of the fruit. In this study, the effects of nanosilver (Ag-NP) solution treatment on the shelf life of litchi fruit and the inhibition of P. litchi were examined, and the underlying mechanisms were discussed. For investigations, we used one variety of litchi ('Feizixiao'), dipping it in different concentrations of Ag-NP solution after harvesting. Meanwhile, we treated P. litchi with different concentrations of Ag-NP solution. According to the data analysis, litchi treated with 400 µg/mL Ag-NPs and stored at 4 °C had the highest health rate and the lowest browning index among all the samples. In the same trend, treatment with 400 µg/mL Ag-NPs produced the best results for anthocyanin content, total soluble solids content, and titratable acidity content. Additionally, according to the results of the inhibition test, 800 µg/mL Ag-NP solution had a 94.97% inhibition rate against P. litchi. Within 2-10 h following exposure to 400 µg/mL Ag-NP solution, the contents of superoxide dismutase, peroxidase, and catalase in P. litchi gradually increased and peaked, followed by a gradual decline. At this time, the integrity of the cell membrane of P. litchi could be broken by Ag-NP solution, and the sporangia showed deformed germ tubes and abnormal shapes. Taken together, these results suggested that Ag-NP treatment inhibited respiration and P. litchi activity, which might attenuate litchi pericarp browning and prolong the shelf life of litchi. Accordingly, Ag-NPs could be used as an effective antistaling agent in litchi fruit and as an ecofriendly fungicide for the post-harvest control of litchi downy blight. This study provides new insights into the application of Ag-NP as an antistaling agent for fruit storage and as an ecofriendly fungicide.

Visible-light-responsive reduced graphene oxide/g-C3N4/TiO2 composite nanocoating for photoelectric stimulation of neuronal and osteoblastic differentiation.

Restoration of nerve supply in newly formed bone is critical for bone defect repair. However, nerve regeneration is often overlooked when designing bone repair biomaterials. In this study, employing graphitic carbon nitride (g-C3N4) as a visible-light-driven photocatalyst and reduced graphene oxide (rGO) as a conductive interface, an rGO/g-C3N4/TiO2 (rGO/CN/TO) ternary nanocoating with photoelectric conversion ability was fabricated on a Ti-based orthopedic implant for photoelectric stimulation of both bone and nerve repair. Compared with g-C3N4/TiO2 (CN/TO) and TiO2 nanocoatings, the ternary nanocoating exhibited stronger visible-light absorption as well as higher transient photocurrent density and open circuit potential under blue LED exposure. The improved photo-electrochemical properties of the ternary nanocoating were attributed to the enhanced separation of photogenerated carriers at the heterointerface. For the tested nanocoatings, introducing blue LED light irradiation enhanced MC3T3-E1 osteoblastic differentiation and neurite outgrowth of PC12 cells. Among them, the rGO/CN/TO nanocoating exerted the greatest enhancement. In a coculture system, PC12 cells on the ternary nanocoating released a higher amount of neurotransmitter calcitonin gene-related peptide (CGRP) under light irradiation, which in turn significantly enhanced osteoblastic differentiation. The results may provide a prospective approach for targeting nerve regeneration to stimulate osteogenesis when designing bone repair biomaterials.

Engineering Nanopatterned Structures to Orchestrate Macrophage Phenotype by Cell Shape.

Physical features on the biomaterial surface are known to affect macrophage cell shape and phenotype, providing opportunities for the design of novel "immune-instructive" topographies to modulate foreign body response. The work presented here employed nanopatterned polydimethylsiloxane substrates with well-characterized nanopillars and nanopits to assess RAW264.7 macrophage response to feature size. Macrophages responded to the small nanopillars (SNPLs) substrates (450 nm in diameter with average 300 nm edge-edge spacing), resulting in larger and well-spread cell morphology. Increasing interpillar distance to 800 nm in the large nanopillars (LNPLs) led to macrophages exhibiting morphologies similar to being cultured on the flat control. Macrophages responded to the nanopits (NPTs with 150 nm deep and average 800 nm edge-edge spacing) by a significant increase in cell elongation. Elongation and well-spread cell shape led to expression of anti-inflammatory/pro-healing (M2) phenotypic markers and downregulated expression of inflammatory cytokines. SNPLs and NPTs with high availability of integrin binding region of fibronectin facilitated integrin ß1 expression and thus stored focal adhesion formation. Increased integrin ß1 expression in macrophages on the SNPLs and NTPs was required for activation of the PI3K/Akt pathway, which promoted macrophage cell spreading and negatively regulated NF-κB activation as evidenced by similar globular cell shape and higher level of NF-κB expression after PI3K blockade. These observations suggested that alterations in macrophage cell shape from surface nanotopographies may provide vital cues to orchestrate macrophage phenotype.

Host-Induced Gene Silencing of a Sclerotinia sclerotiorum oxaloacetate acetylhydrolase Using Bean Pod Mottle Virus as a Vehicle Reduces Disease on Soybean.

A lack of complete resistance in the current germplasm complicates the management of Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum in soybean. In this study, we used bean pod mottle virus (BPMV) as a vehicle to down-regulate expression of a key enzyme in the production of an important virulence factor in S. sclerotiorum, oxalic acid (OA). Specifically, we targeted a gene encoding oxaloacetate acetylhydrolase (Ssoah1), because Ssoah1 deletion mutants are OA deficient and non-pathogenic on soybean. We first established that S. sclerotiorum can uptake environmental RNAs by monitoring the translocation of Cy3-labeled double-stranded and small interfering RNA (ds/siRNAs) into fungal hyphae using fluorescent confocal microscopy. This translocation led to a significant decrease in Ssoah1 transcript levels in vitro. Inoculation of soybean plants with BPMV vectors targeting Ssoah1 (pBPMV-OA) also led to decreased expression of Ssoah1. Importantly, pBPMV-OA inoculated plants showed enhanced resistance to S. sclerotiorum compared to empty-vector control plants. Our combined results provide evidence supporting the use of HIGS and exogenous applications of ds/siRNAs targeting virulence factors such as OA as viable strategies for the control of SSR in soybean and as discovery tools that can be used to identify previously unknown virulence factors.

CircSCAP Aggravates Oxidized Low-density Lipoprotein-induced Macrophage Injury by Upregulating PDE3B by miR-221-5p in Atherosclerosis.

ABSTRACT: Atherosclerosis (AS) is a major risk factor for cardiovascular disease, in which circular RNAs play important regulatory roles. This research aimed to explore the biological role of circular RNA Sterol Regulatory Element Binding Transcription Factor Chaperone (circSCAP) (hsa_circ_0001292) in AS development. Real-time PCR or Western blot assay was conducted to analyze RNA or protein expression. Cell proliferation and apoptosis were analyzed by CCK-8 assay and flow cytometry. The levels of lipid accumulation-associated indicators and oxidative stress factors were detected using commercial kits. The levels of inflammatory cytokines were examined using enzyme-linked immunosorbent assay. Intermolecular interaction was verified by dual-luciferase reporter analysis or RNA pull-down analysis. CircSCAP and phosphodiesterase 3B (PDE3B) levels were elevated, whereas the miR-221-5p level was decreased in patients with AS and oxidized low-density lipoprotein (ox-LDL)-induced THP-1 cells. CircSCAP absence suppressed lipid deposition, inflammation, and oxidative stress in ox-LDL-induced THP-1 cells. MiR-221-5p was a target of circSCAP, and anti-miR-221-5p largely reversed si-circSCAP-induced effects in ox-LDL-induced THP-1 cells. PDE3B was a target of miR-221-5p, and PDE3B overexpression largely counteracted miR-221-5p accumulation-mediated effects in ox-LDL-induced THP-1 cells. NF-κB signaling pathway was regulated by circSCAP/miR-221-5p/PDE3B axis in ox-LDL-induced THP-1 cells. In conclusion, circSCAP facilitated lipid accumulation, inflammation, and oxidative stress in ox-LDL-induced THP-1 macrophages by regulating miR-221-5p/PDE3B axis.

Effectors of Plant Necrotrophic Fungi.

Plant diseases caused by necrotrophic fungal pathogens result in large economic losses in field crop production worldwide. Effectors are important players of plant-pathogen interaction and deployed by pathogens to facilitate plant colonization and nutrient acquisition. Compared to biotrophic and hemibiotrophic fungal pathogens, effector biology is poorly understood for necrotrophic fungal pathogens. Recent bioinformatics advances have accelerated the prediction and discovery of effectors from necrotrophic fungi, and their functional context is currently being clarified. In this review we examine effectors utilized by necrotrophic fungi and hemibiotrophic fungi in the latter stages of disease development, including plant cell death manipulation. We define "effectors" as secreted proteins and other molecules that affect plant physiology in ways that contribute to disease establishment and progression. Studying and understanding the mechanisms of necrotrophic effectors is critical for identifying avenues of genetic intervention that could lead to improved resistance to these pathogens in plants.

Zn-doped MnO2 nanocoating with enhanced catalase-mimetic activity and cytocompatibility protects pre-osteoblasts against H2O2-induced oxidative stress.

Therapeutic application in prevention and treatment of bone diseases, particularly osteoporosis, has recently started to emerge for manganese dioxide (MnO2) nanoparticles and nanocoatings whereby their antioxidant catalase-mimetic property can be exploited to control oxidative stress by reducing the amount of H2O2. Doping is an efficient method to enhance the catalase-mimetic activity of MnO2, which can potentially ameliorate osteogenesis under oxidative stress. Herein, Zn2+ doped MnO2 (Zn-MnO2) nanocoating was fabricated on orthopedic titanium implant by a facile UV-photolysis reaction. The Zn-MnO2 nanocoating showed better cytocompatibility than the MnO2 nanocoating, as indicated by enhanced cell proliferation, differentiation and mineralization of MC3T3-E1 pre-osteoblasts. This was probably due to the increased surface hydrophilicity as well as the combination effect of released Zn2+ and Mn2+ from the Zn-MnO2 nanocoating. Importantly, the Zn-MnO2 nanocoating with enhanced catalase-like activity exerted greater effects to suppress the intracellular oxidation products generation and prevent the depletion of dismutase superoxide levels under H2O2-induced oxidative stress, which in turn protected MC3T3-E1 pre-osteoblast functions. Overall, surface modification of titanium implants with the Zn-MnO2 nanocoating could be utilized to ameliorate oxidative stress-inhibited osteogenesis.

A novel three-TMH Na+/H+ antiporter and the functional role of its oligomerization.

Na+/H+antiportersare a category of ubiquitous transmembrane proteins with various important physiological roles in almost all living organisms ranging from bacteria to humans. However, the knowledge of novel Na+/H+antiporters remains to be broadened, and the functional roles ofoligomerization in theseantiportershave not yet been thoroughly understood. Here, we reported functional analysis of an unknown transmembrane protein composed of 103 amino acid residues. This protein was found to function as a Na+(Li+, K+)/H+ antiporter. To the best of our knowledge, this antiporter is the minimal one of known Na+/H+antiporters and thus designated as NhaM to represent the minimal Na+/H+antiporter. NhaM and its homologs have not yet been classified into any protein family. Based on phylogenetic analysis and protein alignment, we propose NhaM and its homologs to constitute a novel transporter family designated as NhaM family. More importantly, we found that NhaM is assembled with parallel protomers into a homo-oligomer and oligomerization is vital for the function of this antiporter. This implies that NhaM may adopt and require an oligomer structure for its normal function to create a similar X-shaped structure to that of the NhaA fold. Taken together, current findings not only present the proposal of a novel transporter family but also positively contribute to the functional roles of oligomerization in Na+/H+antiporters.

Cerium Oxide Nanoparticles Regulate Osteoclast Differentiation Bidirectionally by Modulating the Cellular Production of Reactive Oxygen Species.

BACKGROUND: Cerium oxide nanoparticles (CeO2NPs) are potent scavengers of cellular reactive oxygen species (ROS). Their antioxidant properties make CeO2NPs promising therapeutic agents for bone diseases and bone tissue engineering. However, the effects of CeO2NPs on intracellular ROS production in osteoclasts (OCs) are still unclear. Numerous studies have reported that intracellular ROS are essential for osteoclastogenesis. The aim of this study was to explore the effects of CeO2NPs on osteoclast differentiation and the potential underlying mechanisms. METHODS: The bidirectional modulation of osteoclast differentiation by CeO2NPs was explored by different methods, such as fluorescence microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. The cytotoxic and proapoptotic effects of CeO2NPs were detected by cell counting kit (CCK-8) assay, TdT-mediated dUTP nick-end labeling (TUNEL) assay, and flow cytometry. RESULTS: The results of this study demonstrated that although CeO2NPs were capable of scavenging ROS in acellular environments, they facilitated the production of ROS in the acidic cellular environment during receptor activator of nuclear factor kappa-Β ligand (RANKL)-dependent osteoclast differentiation of bone marrow-derived macrophages (BMMs). CeO2NPs at lower concentrations (4.0 µg/mL to 8.0 µg/mL) promoted osteoclast formation, as shown by increased expression of Nfatc1 and C-Fos, F-actin ring formation and bone resorption. However, at higher concentrations (greater than 16.0 µg/mL), CeO2NPs inhibited osteoclast differentiation and promoted apoptosis of BMMs by reducing Bcl2 expression and increasing the expression of cleaved caspase-3, which may be due to the overproduction of ROS. CONCLUSION: This study demonstrates that CeO2NPs facilitate osteoclast formation at lower concentrations while inhibiting osteoclastogenesis in vitro by inducing the apoptosis of BMMs at higher concentrations by modulating cellular ROS levels.

Precisely Patterned Nanostrand Surface of Cucurbituril[n]-Based Nanofiltration Membranes for Effective Alcohol-Water Condensation.

Low concentration alcohols produced by state-of-the-art biological fermentation restrict subsequent purification processes for chemical, pharmaceutical, biofuel, and other applications. Herein, a rarely reported cucurbituril[n] (n = 6, 8) is employed to pattern the thin-film composite membranes with controllable and quantifiable nanostrand structures through a host-guest strategy. The resulting nanofiltration membrane with such morphology is the first report that exhibits excellent separation performance for isopropyl alcohol (IPA) and water, condensing the initial 0.5 wt % IPA aqueous solution to 9.0 wt %. This not only provides a novel strategy for patterning nanostructural morphology but also makes nanofiltration membranes promising for alcohol condensation in the biological fermentation industry that may reduce energy consumption and postprocessing costs.

Poly(dA:dT) Suppresses HSV-2 Infection of Human Cervical Epithelial Cells Through RIG-I Activation.

Epithelial cells of the female reproductive tract (FRT) participate in the initial innate immunity against viral infections. Poly(dA:dT) is a synthetic analog of B form double-stranded (ds) DNA which can activate the interferon (IFN) signaling pathway-mediated antiviral immunity through DNA-dependent RNA Polymerase III. Here we investigated whether poly(dA:dT) could inhibit herpes simplex virus type 2 (HSV-2) infection of human cervical epithelial cells (End1/E6E7). We demonstrated that poly(dA:dT) treatment of End1/E6E7 cells could significantly inhibit HSV-2 infection. Mechanistically, poly(dA:dT) treatment of the cells induced the expression of the intracellular IFNs and the multiple antiviral IFN-stimulated genes (ISGs), including IFN-stimulated gene 15 (ISG15), IFN-stimulated gene 56 (ISG56), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 2 (OAS2), myxovirus resistance protein A (MxA), myxovirus resistance protein B (MxB), virus inhibitory protein, endoplasmic reticulum-associated, IFN-inducible (Viperin), and guanylate binding protein 5 (GBP5). Further investigation showed that the activation of RIG-I was largely responsible for poly(dA:dT)-mediated HSV-2 inhibition and IFN/ISGs induction in the cervical epithelial cells, as RIG-I knockout abolished the poly(dA:dT) actions. These observations demonstrate the importance for design and development of AT-rich dsDNA-based intervention strategies to control HSV-2 mucosal transmission in FRT.

Effects and Molecular Mechanism of L-Type Calcium Channel on Fluoride-Induced Kidney Injury.

This study aimed to investigate the role and molecular mechanism of L-type calcium channel (LTCC) on fluoride exposure-induced kidney injury. Subchronic and chronic fluoride exposures were included in the experiment. Each part contained 140 ICR male mice. They were randomly divided into 7 groups: control group, high-fluoride group (NaF 30 mg/L), low-fluoride group (NaF 5 mg/L), high/low-fluoride + agonist (FPL64176) group, high/low-fluoride + inhibitor (nifedipine) group. One week before the end of fluoride exposure, each mouse in the fluoride exposure group was injected intraperitoneally with LTCC agonist (FPL64176) or inhibitor (nifedipine) (5 mg/kg day). The apoptosis of kidney cell was observed by TUNEL, and the protein expression levels of Cav1.2 and CaM, CaMKII, Bcl-2, and Bax were detected by Western blot. Compared with the control group, the protein expression levels of Cav1.2, CaM, and Bax significantly increased, and those of CaMKII and Bcl-2 significantly decreased, the ratio of Bax/Bcl-2 also significantly increased, and the number of apoptotic kidney cells significantly increased in the high/low-fluoride group and in the high/low-fluoride + agonist group. The above indicators and fluoride exposure concentrations showed in time- and dose-dependent changes. Compared with the high/low-fluoride + agonist group, the protein expression level of the molecular in the kidney cells above mentioned was significantly opposite and the number of apoptotic kidney cells significantly decreased in the high/low-fluoride + inhibitor group. In conclusion, LTCC mediates the kidney injury induced by fluoride exposure in mice. Fluoride exposure induced abnormal expression of the Cav1.2 protein, Ca2+ signal transduction pathway, and apoptosis-regulated proteins, which is one of the molecular mechanisms. Nifedipine may be a new and effective anti-fluoride drug.

Self-Cleaning Nanofiltration Membranes by Coordinated Regulation of Carbon Quantum Dots and Polydopamine.

Performance declination of nanofiltration (NF) membranes caused by concentration polarization (CP) and membrane fouling has severely restricted their practical application in many fields. This work reports the construction of a novel interlayer between the substrate and the selective layer of conventional composite membranes by coordinating regulation of carbon quantum dots (CQDs) and polydopamine (PDA). Unlike traditional methods that treat CP and fouling separately, the new strategy grants the membrane with dual functions at one time. First, the insertion of the PDA-CQDs layer reformulates the interfacial polymerization process that reduces the solute transport resistance and mitigates the CP issue. Second, the sandwiched photoactive CQDs can degrade organic molecules adsorbed on the membrane surface under visible light, which is promising for low-cost fouling remediation. This study may offer valuable insights into the preparation of durable self-cleaning NF membranes for the effective treatment of complex wastewater in various industries.