Scalable Fabrication of Electrospun True-Nanoscale Fiber Membranes for Effective Selective Separation.

Electrospun fibers have received wide attention in various fields ranging from the environment and healthcare to energy. However, nearly all electrospun fibers suffer from a pseudonanoscale diameter, resulting in fabricated membranes with a large pore size and limited separation performance. Herein, we report a novel strategy based on manipulating the equilibrium of stretch deformation and phase separation of electrospun jets to develop true-nanoscale fibers for effective selective separation. The obtained fibers present true-nanoscale diameters (∼67 nm), 1 order of magnitude less than those of common electrospun fibers, which endows the resultant membranes with remarkable nanostructural characteristics and separation performances in areas of protective textiles (waterproofness of 113 kPa and breathability of 4.1 kg m-2 d-1), air filtration (efficiency of 99.3% and pressure drop of 127.4 Pa), and water purification (flux of 81.5 kg m-2 h-1 and salt rejection of 99.94%). This work may shed light on developing high-performance separation materials for various applications.

Two-Dimensional Nanofibrous Networks by Superspreading-Based Phase Inversion for High-Efficiency Separation.

Two-dimensional (2D) nanomaterials have been widely applied as building blocks of nanoporous materials for high-precision separations. However, most existing 2D nanomaterials suffer from poor continuity and a lack of interior linking, resulting in deteriorated performance when assembled into macroscopic bulk structures. Here, a unique superspreading-based phase inversion technique is proposed to directly construct 2D nanofibrous networks (NFNs) from a polymer solution. By tailoring capillary behavior, polymer solution droplets evolve into ultrathin liquid films through superspreading; manipulating phase instability, subsequently, enables the liquid film to phase invert into continuous nanostructured networks. The assembled single-layered NFNs possess integrated structural superiorities of 1D nanoscale fiber diameter (∼40 nm) and 2D lateral infinity, exhibiting a weblike nanoarchitecture with extremely small through-pores (∼100 nm). Our NFNs show remarkable performances in air filtration (PM0.3 removal) and water purification (microfiltration level). This creation of such attractive 2D fibrous nanomaterials can pave the way for versatile high-performance separation applications.

High-Performance Waterproof, Breathable, and Radiative Cooling Membranes Based on Nanoarchitectured Fiber/Meshworks.

Smart membranes with protection and thermal-wet comfort are highly demanded in various fields. Nevertheless, the existing membranes suffer from a tradeoff dilemma of liquid resistance and moisture permeability, as well as poor thermoregulating ability. Herein, a novel strategy, based on the synchronous occurrence of humidity-induced electrospinning and electromeshing, is developed to synthesize a dual-network structured nanofiber/mesh for personal comfort management. Manipulating the ejection, deformation, and phase separation of spinning jets and charged droplets enables the creation of nanofibrous membranes composed of radiative cooling nanofibers and 2D nanostructured meshworks. With a combination of a true-nanoscale fiber (∼70 nm) in 2D meshworks, a small pore size (0.84 µm), and a superhydrophobic surface (151.9°), the smart membranes present high liquid repellency (95.6 kPa), improved breathability (4.05 kg m-2 d-1), and remarkable cooling performance (7.9 °C cooler than commercial cotton fabrics). This strategy opens up a pathway to the design of advanced smart textiles for personal protection.

Electrospun Nanofibrous Membranes: A Versatile Medium for Waterproof and Breathable Application.

Waterproof and breathable membranes that prevent liquid water penetration, while allowing air and moisture transmission, have attracted significant attention for various applications. Electrospun nanofiber materials with adjustable pore structures, easily tunable wettability, and good pore connectivity, have shown significant potential for constructing waterproof and breathable membranes. Herein, a systematic overview of the recent progress in the design, fabrication, and application of waterproof and breathable nanofibrous membranes is provided. The various strategies for fabricating the membranes mainly including one-step electrospinning and post-treatment of nanofibers are given as a starting point for the discussion. The different design concepts and structural characteristics of each type of waterproof and breathable membrane are comprehensively analyzed. Then, some representative applications of the membranes are highlighted, involving personal protection, desalination, medical dressing, and electronics. Finally, the challenges and future perspectives associated with waterproof and breathable nanofibrous membranes are presented.

Jatrorrhizine ameliorates Schwann cell myelination via inhibiting HDAC3 ability to recruit Atxn2l for regulating the NRG1-ErbB2-PI3K-AKT pathway in diabetic peripheral neuropathy mice.

Diabetic peripheral neuropathy (DPN) is a chronic complication associated with nerve dysfunction and uncontrolled hyperglycemia. Unfortunately, due to its complicated etiology, there has been no successful therapy for DPN. Our research recently revealed that jatrorrhizine (JAT), one of the active constituents of Rhizoma Coptidis, remarkably ameliorated DPN. This work highlighted the potential mechanism through which JAT relieves DPN using db/db mice. The results indicated that JAT treatment significantly decreased the threshold for thermal and mechanical stimuli and increased nerve conduction velocity. Histopathological analysis revealed that JAT significantly increased the number of sciatic nerve fibers and axons, myelin thickness, and axonal diameters. Additionally, JAT markedly elevated the expression of myelination-associated proteins (MBP, MPZ, and Pmp22). The screening of histone deacetylases (HDAC) determined that histone deacetylase 3 (HDAC3) is an excellent target for JAT-induced myelination enhancement. Liquid chromatography-mass spectrometry-(MS)/MS and coimmunoprecipitation analyses further confirmed that HDAC3 antagonizes the NRG1-ErbB2-PI3K-AKT signaling axis by interacting with Atxn2l to augment SCs myelination. Thus, JAT ameliorates SCs myelination in DPN mice via inhibiting the recruitment of Atxn2l by HDAC3 to regulate the NRG1-ErbB2-PI3K-AKT pathway.

Synthesis and anti-inflammatory activity of paeonol derivatives with etherized aryl urea by regulating TLR4/MyD88 signaling pathway in RAW264.7 cell.

Thirty-three novel paeonol etherized aryl urea derivatives (PEUs) were synthesized via a bromination-Williamson Ether Synthesis-deprotection-nucleophilic addition reaction sequence. The structures of PEUs were characterized by LC-MS, HRMS, 1H NMR and 13C NMR spectra. The levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages were initially employed to evaluate the anti-inflammatory effects of all compounds. Remarkably, b16 exhibited a good anti-inflammatory activity at 2.5 µm which is the same as the potency of paeonol at 20 µm. The results of mechanism research displayed that the anti-inflammatory effect of b16 was ascribed to the inhibition of the TLR4/MyD88 signaling pathway and inflammatory factors. Additionally, b16 distinctly reduced the generation of free radicals in macrophages and strikingly increased the mitochondrial membrane potential. According to the structure-activity relationships (SAR) of PEUs, the incorporation of halogens on the benzene ring and the hydrogen of phenol hydroxyl substituted by aryl urea, were beneficial to enhance the anti-inflammatory activities. Molecular docking results illustrated that the binding ability of b16 to TLR4 was stronger than that of paeonol. In summary, the novel aryl urea-derivied paeonol b16 could be a new promising candidate for the treatment of inflammation-related diseases.

Downregulation of PER2 Promotes Tumor Progression by Enhancing Glycolysis via the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway in Oral Squamous Cell Carcinoma.

PURPOSE: PER2 gene expression is downregulated in oral squamous cell carcinoma (OSCC) and may have a pivotal role in tumor suppression. However, the biological function and mechanism of action of PER2 in OSCC remain unclear. In this study, the biological functions and anticancer mechanisms of PER2 in OSCC were investigated. MATERIALS AND METHODS: Both stably overexpressed and silenced PER2 OSCC cells were established as an experimental group; empty vector lentivirus and scramble short hairpin RNA lentivirus transfected-cells, as negative control groups; and untreated OSCC cells, as a blank group. Cell proliferation, apoptosis, and glycolysis potential assays were conducted. In addition, the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylation of protein kinase B, hexokinase 2 (HK2), pyruvate kinase M (PKM2), and lactate dehydrogenase A (LDHA) was quantified by real-time quantitative polymerase chain reaction and Western blotting. Rescue experiments were performed by the addition of AKT activators in the overexpressed cell line and by the addition of glycolysis inhibitor in the silenced cell line. These findings were verified in vivo using stably transfected OSCC cells overexpressing PER2 implanted in nude mice. RESULTS: PER2 overexpression significantly inhibited OSCC cell proliferation and glycolysis, promoted cell apoptosis, and reduced the expression of PI3K, phosphorylation of protein kinase B, HK2, PKM2, and LDHA. The converse was observed in PER2-silenced OSCC cells. After the addition of AKT activator to cultures of PER2-overexpressed OSCC cells, reduced glucose uptake, lactic acid production, and cell proliferation, combined with increased apoptosis, were substantially reversed. In addition, after the addition of HK2 inhibitor to PER2-silenced OSCC cells to inhibit glycolysis, the reduction in apoptosis and increased proliferation were significantly countermanded. Tumorigenesis experiments in vivo also confirmed that PER2 overexpression suppressed OSCC growth and decreased the expression of HK2, PKM2, and LDHA. CONCLUSIONS: PER2 heightened glycolysis via the PI3K/AKT pathway, heightened cell proliferation and inhibited apoptosis via glycolysis, thereby promoting the development of OSCC.

Synthesis and anti-inflammatory activity of paeonol analogues in the murine model of complete Freund's adjuvant induced arthritis.

A new series of paeonol alkyl ether analogues were synthesized and confirmed with IR, 1H NMR, 13C NMR and HRMS spectra. They have shown anti-inflammatory activities by scavenging mediator of free radicals and inhibiting lipid mediator of inflammation on complete Freund's adjuvant (CFA) induced arthritis in mice. The in vitro and in vivo scavenging ability of free radicals was determined by using chemical analysis and commercial assay kits, respectively. The in vivo inhibiting lipid mediator of inflammation was examined by ELISA. Our results indicated that the substitution of the hydrogen in hydroxyl group at C2 position of paeonol 1 by short carbon chain, in the presence or absence of bromo atom at C5 position, decreased its scavenging ability on radicals (3a or 4a vs 1), while the long alkyl substitution (Cn>14) increased the activity. Compared with 3a or 4a, scavenging abilities of 3a-h or 4a-h gradually increased following the length elongation of alkyl carbon chain. Compounds 3h and 4h showed great scavenging ability on OH, O2-, DPPH, ATBS+ and MDA, and good promotion on T-AOC and SOD. The results of the in vivo inhibiting lipid mediator of inflammation also demonstrated that 3h, 4h exhibited substantial inhibition on enzyme activity of COX-2, PGE2. Therefore, 3h and 4h have great potential to be the novel anti-inflammatory drug candidates for the therapy of arthritis.

Structural elucidation and anti-psoriasis activity of a novel polysaccharide from Saussurea Costus.

PSCP, a novel water-soluble polysaccharide, was extracted from the root of Saussurea costus and subsequently purified using DEAE-52 cellulose and Sephadax G-50 columns. The elucidation of its structure involved various techniques including HPGPC, FT-IR, HPLC-ELSD, GC-MS, NMR, AFM, and SEM. The results show that PSCP was a homogeneous heteropoly saccharide having molecular weight of 4131 Da and mainly composed of 1-α-D-Glcp-(-2-ß-D-Fruf-1-)23-2-ß-D-Fruf. The anti-psoriasis activity of PSCP was evaluated in imiquimod-induced psoriasis in Balb/C mice. This study revealed that treatment with PSCP resulted in a significant improvement in the pathological morphology of the skin and a reduction in the PASI score. Analysis of liver RNA-Seq data indicated that the MAPK signaling pathway may play a crucial role in the ability of PSCP to ameliorate psoriasis. PSCP was found to effectively inhibit the phosphorylation of JNK, ERK, and p38, as well as down-regulate the expression of the transcription factor AP-1 (c-fos and c-jun) in the nucleus, thereby reducing the expression of inflammatory factors. These findings suggest that PSCP holds promise as a novel therapeutic approach for the treatment of psoriasis.

Detachable Dual-Targeting Nanoparticles for Improving the Antitumor Effect by Extracellular Matrix Depletion.

In the tumor microenvironment (TME), the extracellular matrix (ECM) produced by cancer-associated fibroblasts (CAFs) forms a dense barrier that prevents nanodrugs from penetrating into deep tumor sites, leading to unsatisfactory therapeutic effects. Recently, it has been found that ECM depletion and using small-sized nanoparticles are effective strategies. Herein, we reported a detachable dual-targeting nanoparticle (HA-DOX@GNPs-Met@HFn) based on reducing ECM for enhancing penetration. When these nanoparticles reached the tumor site, the nanoparticles were divided into two parts in response to matrix metalloproteinase-2 overexpressed in TME, causing a decrease in the nanoparticle size from about 124 to 36 nm. One part was Met@HFn, which was detached from the surface of gelatin nanoparticles (GNPs), which effectively targeted tumor cells and released metformin (Met) under acidic conditions. Then, Met downregulated the expression of the transforming growth factor ß by the adenosine monophosphate-activated protein kinase pathway to inhibit the activity of CAFs, thereby suppressing the production of ECM including α-smooth muscle actin and collagen I. The other was the small-sized hyaluronic acid-modified doxorubicin prodrug with autonomous targeting ability, which was gradually released from GNPs and internalized into deeper tumor cells. Intracellular hyaluronidases triggered the release of doxorubicin (DOX), which killed tumor cells by inhibiting DNA synthesis. The combination of size transformation and ECM depletion enhanced the penetration and accumulation of DOX in solid tumors. Therefore, the tumor chemotherapy effect was greatly improved.

High-Performance Liquid-Repellent and Thermal-Wet Comfortable Membranes Using Triboelectric Nanostructured Nanofiber/Meshes.

Skin-like functional membranes with liquid resistance and moisture permeability are in growing demand in various applications. However, the membranes have been facing a long-term dilemma in balancing waterproofness and breathability, as well as resisting internal liquid sweat transport, resulting in poor thermal-wet comfort. Herein, a novel electromeshing technique, based on manipulating the ejection and phase separation of charged liquids, is developed to create triboelectric nanostructured nano-mesh consisting of hydrophobic ferroelectric nanofiber/meshes and hydrophilic nanofiber/meshes. By combining the true nanoscale diameter (≈22 nm), small pore size, and high porosity, high waterproofness (129 kPa) and breathability (3736 g m-2 per day) for the membranes are achieved. Moreover, the membranes can break large water clusters into small water molecules to promote sweat absorption and release by coupling hydrophilic wicking and triboelectric field polarization, exhibiting a satisfactory water evaporation rate (0.64 g h-1 ) and thermal-wet comfort (0.7 °C cooler than the cutting-edge poly(tetrafluoroethylene) protective membranes). This work may shed new light on the design and development of advanced protective textiles.

Berberine promotes IGF2BP3 ubiquitination by TRIM21 to induce G1/S phase arrest in colorectal cancer cells.

The increasing incidence of colorectal cancer (CRC) has become a major global public health burden. The natural drug Berberine (BBR) has shown potential in preventing CRC, and IGF2 mRNA binding protein 3 (IGF2BP3) may be a target of BBR. This study aims to investigate the mechanisms of BBR acting on IGF2BP3 to improve CRC. The results showed that IGF2BP3 played an important role in the development of CRC. BBR down-regulated IGF2BP3 expression and inhibited CRC growth in mice. Cell thermodynamic stability analysis (CETSA) and drug affinity responsive target stability (DARTS) analysis showed BBR may bind to IGF2BP3. BBR may induce structural changes in IGF2BP3 and decrease its protein stability in cytoplasm. The results from Co-Immunoprecipitation (Co-IP) suggested that BBR promoted the ubiquitination of IGF2BP3 by tripartite motif-containing protein 21 (TRIM21). Through RNA binding protein Immunoprecipitation (RIP) assay, it was found BBR inhibited the stabilization of CDK4/CCND1 mRNA by IGF2BP3 and promoted G1/S phase arrest in CRC cells. Overexpression of IGF2BP3 in vitro and in vivo attenuated the inhibition of CRC growth by BBR. This work demonstrated the potential of BBR targeting to IGF2BP3 in improving CRC and provided a new strategy for clinical treatment on CRC as well as novel anticancer drug design based on IGF2BP3 and TRIM21.

Environmentally Friendly Polyamide Nanofiber Membranes with Interconnective Amphiphobic Channels for Seawater Desalination.

Seawater desalination is a promising and sustainable solution to alleviate freshwater scarcity; however, most existing desalination membranes suffer from poor channel interconnectivity and toxic solvent processing and encounter a tradeoff dilemma of salt rejection and water flux. Herein, we report a unique and facile one-step green solvent/nonsolvent spinning methodology to assemble environmentally friendly polyamide nanofiber membranes with a precisely designed interconnective/stable channel structure and surface anti-wettability for seawater desalination. Direct electrospinning without any post-treatments via in situ introduction of fluorinated chemicals enables highly interconnective amphiphobic channels within polyamide membranes, and the incorporation of nonsolvent (diacetone alcohol) into polyamide/solvent (ethanol) spinning solutions endows the green alcohol-based polyamide membranes with a stable bonding structure and small pore size. The resultant green solvent/nonsolvent-spun polyamide nanofiber membranes show impressive liquid entry pressure (120.5 kPa) and vapor permeation (12.5 kg m-2 d-1), achieving robust seawater desalination performance with a salt rejection of 99.97% and permeate flux of 47.4 kg m-2 h-1. The facile one-step solvent/nonsolvent spinning strategy, highly interconnective amphiphobic channels, and green solvent-based environmental friendliness in this work can open opportunities for future polyamide membranes for practical applications in water purification.

Cascade nanozymes based on the "butterfly effect" for enhanced starvation therapy through the regulation of autophagy.

Although tumor starvation therapy has been proven to be an excellent method for tumor therapy, its efficiency may be weakened by autophagy, a self-protection mechanism exerted by tumors under starvation stress. Interestingly, over-activated autophagy not only improves the efficacy of starvation therapy, but also induces autophagic death. Herein, we report cascade nanozymes for enhanced starvation therapy by inducing over-activated autophagy. First, glucose oxidase (GOx) modified metal-organic frameworks (NH2-MIL88, MOF) were constructed (MOF-GOx). After loading with curcumin (Cur), Cur@MOF-GOx was further decorated with tumor-targeting hyaluronic acid (HA) to obtain Cur@MOF-GOx/HA nanozymes. GOx can catalyze glucose into H2O2 and gluconic acid, which not only leads to tumor starvation, but also provides reactants for the Fenton reaction mediated by the MOF to generate hydroxyl radicals (˙OH) for chemo-dynamic therapy. Most importantly, protective autophagy caused by tumor starvation can be over-activated by Cur to convert autophagy from pro-survival to pro-death, realizing augmented anticancer therapy efficacy. With these cascade reactions, the synergistic action of starvation, autophagy and chemo-dynamic therapy was realized. Generally, the introduction of Cur@MOF-GOx/HA into tumor cells leads to a "butterfly effect", which induces enhanced starvation therapy through subsequent autophagic cell death to completely break the self-protective mechanism of cancer cells, and generate ˙OH for chemo-dynamic therapy. Precise design allows for the use of cascade nanozymes to realize efficient cancer treatment and restrain metastasis.

Highly Transparent Nanofibrous Membranes Used as Transparent Masks for Efficient PM0.3 Removal.

Currently, the quest for highly transparent and flexible fibrous membranes with robust mechanical characteristics, high breathability, and good filtration performance is rapidly rising because of their potential use in the fields of electronics, energy, environment, medical, and health. However, it is still an extremely challenging task to realize transparent fibrous membranes due to serious surface light reflection and internal light scattering. Here, we report the design and development of a simple and effective topological structure to create porous, breathable, and high visible light transmitting fibrous membranes (HLTFMs). The resultant HLTFMs exhibit good optical performance (up to 90% transmittance) and high porosities (>80%). The formation of such useful structure with high light transmittance has been revealed by electric field simulation, and the mechanism of fibrous membrane structure to achieve high light transmittance has been proposed. Moreover, transparent masks have been prepared to evaluate the filtration performance and analyze their feasibility to meet requirement of facial recognition systems. The prepared masks display high transparency (>80%), low pressure drop (<100 Pa) and high filtration efficiency (>90%). Furthermore, the person wearing this mask can be successfully identified by facial recognition systems. Therefore, this work provides an idea for the development of transparent, breathable, and high-performance fibrous membranes.

Cordycepin attenuates high-fat diet-induced non-alcoholic fatty liver disease via down-regulation of lipid metabolism and inflammatory responses.

Cordycepin (CRD), an adenosine analog derived from traditional Chinese medicine, is an active component in Cordyceps militaris. It has been shown to have many protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). This study aims to explore the effects of CRD on obesity-induced NAFLD. In this experiment, C57BL/6 J mice were randomly assigned into normal control group (NC), high fat diet group (HFD) and HFD + CRD group for 8 weeks. The body weights were recorded weekly, at the end of the experiments, the liver and serum samples were collected. We found that CRD administration reduced body weight and decreased the weight of adipose and liver, and CRD relieved liver injure through diminishing of histopathological changes and decreasing serum levels of AST, ALT, TG, TC, LDL-C and increased the level of HDL-C. Furthermore, treatment with CRD significantly alleviated expression of inflammatory factors (TNF-α, IL-6 and Il-1ß) and macrophage markers (MCP1, MIP2, mKC and VCAM1). On the other hand, compared with HFD group, the CRD treated group markedly down-regulated relative proteins of lipid anabolism (SREBP1-c, ACC, SCD-1, LXRα and CD36) and up-regulated relative proteins of ß-oxidation (p-AMPK, AMPK, CPT-1 and PPARα). In summary, our results suggest that CRD can be a potential therapeutic agent in the prevention and treatment of NAFLD, which may be closely related to its effect on lipid metabolism and inflammatory responses.

Diosmetin ameliorate type 2 diabetic mellitus by up-regulating Corynebacterium glutamicum to regulate IRS/PI3K/AKT-mediated glucose metabolism disorder in KK-Ay mice.

BACKGROUND AND PURPOSE: Diosmetin (Dios), a flavonoid compound with multiple pharmacological activities. However, fewer studies have reported its effects on type 2 diabetic mellitus (T2DM). Here, we address the effect of Dios on glucose metabolism and gut microbiota in KK-Ay diabetic mice. METHOD: Wild type C57BL/6 J mice or diabetic KK-Ay mice were treated with vehicle or Dios for one month. The ELISA kit and fluorescence microscope system were respectively employed to the evaluation of serum biochemical indicators and histopathological changes. Liver RNA-Seq and western blot were used to reveal the key signaling pathway. The effects of Dios on gut microbiota was investigated by the 16S rRNA gene sequencing, as well as the relationship between Dios and C. glu on glucose metabolism was explored with the C. glu transplantation. RESULTS: Dios treatment significantly decreased blood glucose and increased serum insulin concentrations. RNA-Seq analysis found that the underlying action mechanism of Dios on T2DM was via modulating glucose metabolism, which was proved by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. Besides, Dios treatment reshaped the unbalanced gut microbiota by suppressing the ratio of Firmicutes/Bacteroidetes and markedly increasing the richness of C. glu. Moreover, treatment with C. glu and Dios together could markedly ameliorate glucose metabolism by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. CONCLUSIONS: Dios treatment remarkably ameliorated glucose metabolism in KK-Ay diabetic mice by the regulation of C. glu via IRS/PI3K/AKT signaling pathway and reshaped the unbalanced gut microbiota. Our study provided evidence for the application of Dios to the treatment of T2DM.

PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma via the PER1/RACK1/PI3K signaling complex.

There is increasing evidence that the core clock gene Period 1 (PER1) plays important roles in the formation of various tumors. However, the biological functions and mechanism of PER1 in promoting tumor progression remain largely unknown. Here, we discovered that PER1 was markedly downregulated in oral squamous cell carcinoma (OSCC). Then, OSCC cell lines with stable overexpression, knockdown, and mutation of PER1 were established. We found that PER1 overexpression significantly inhibited glycolysis, glucose uptake, proliferation, and the PI3K/AKT pathway in OSCC cells. The opposite effects were observed in PER1-knockdown OSCC cells. After treatment of PER1-overexpressing OSCC cells with an AKT activator or treatment of PER1-knockdown OSCC cells with an AKT inhibitor, glycolysis, glucose uptake, and proliferation were markedly rescued. In addition, after treatment of PER1-knockdown OSCC cells with a glycolysis inhibitor, the increase in cell proliferation was significantly reversed. Further, coimmunoprecipitation (Co-IP) and cycloheximide (CHX) chase experiment demonstrated that PER1 can bind with RACK1 and PI3K to form the PER1/RACK1/PI3K complex in OSCC cells. In PER1-overexpressing OSCC cells, the abundance of the PER1/RACK1/PI3K complex was significantly increased, the half-life of PI3K was markedly decreased, and glycolysis, proliferation, and the PI3K/AKT pathway were significantly inhibited. However, these effects were markedly reversed in PER1-mutant OSCC cells. In vivo tumorigenicity assays confirmed that PER1 overexpression inhibited tumor growth while suppressing glycolysis, proliferation, and the PI3K/AKT pathway. Collectively, this study generated the novel findings that PER1 suppresses OSCC progression by inhibiting glycolysis-mediated cell proliferation via the formation of the PER1/RACK1/PI3K complex to regulate the stability of PI3K and the PI3K/AKT pathway-dependent manner and that PER1 could potentially be a valuable therapeutic target in OSCC.

Waterborne electrospinning of fluorine-free stretchable nanofiber membranes with waterproof and breathable capabilities for protective textiles.

HYPOTHESIS: Smart membranes with robust liquid water resistance and water vapor transmission capabilities have attracted growing attentions in personal protective equipment and environmental protection. However, current fluorine-free waterproof and breathable nanofibrous membranes are usually prepared through toxic solvent-based electrospinning, which raises great concerns about their environmental impacts. EXPERIMENTS: We develop environmentally friendly fluorine-free polyurethane nanofibrous membranes with robust waterproof and breathable performances via waterborne electrospinning without post-coating treatment. The incorporation of the low surface energy long-chain alkyls and polycarbodiimide crosslinker imparts the interconnective porous channels with high hydrophobicity to waterborne fluorine-free polyurethane nanofibrous membranes. FINDINGS: The waterborne fluorine-free nanofibrous membranes show high water contact angle of 137.1°, robust hydrostatic pressure of 35.9 kPa, desirable water vapor transmission rate of 4885 g m-2 d-1, excellent air permeability of 19.9 mm s-1, good tensile elongation of 372.4%, and remarkable elasticity of 56.9%, thus offering strong potential for protective textiles and leaving no toxic solvent residues. This work could also serve as a guide for the design of green and high-performance fibrous materials used for medical hygiene, wearable electronics, water desalination, and oil/water separation.

An integrated network pharmacology and transcriptomic method to explore the mechanism of the total Rhizoma Coptidis alkaloids in improving diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Coptidis (RC) is a traditional Chinese medicine (TCM) used for treating diabetes (Xiao Ke Zheng), which is firstly recorded in Shennong Bencao Jing. Modern pharmacological studies have confirmed that RC has beneficial effects on diabetes and its complications. Alkaloids are the main active pharmacological component of RC. However, the effect and molecular mechanism of total Rhizoma Coptidis alkaloids (TRCA) in improving diabetic nephropathy (DN) are still unclear. AIM OF THE STUDY: To verify the effect of TRCA in the treatment of DN and clarify the molecular mechanism by combining network pharmacology and transcriptomic. MATERIALS AND METHODS: Eight-week-old db/db mice were orally administered with normal saline, 100 mg/kg TRCA, and 100 mg/kg berberine (BBR) for 8 weeks. Serum, urine, and kidney samples were collected to measure biological indicators and observe renal pathological changes. Then, the molecular mechanism of TRCA improving DN was predicted by the network pharmacology. Briefly, the main active alkaloids components of TRCA and their targets were collected from the database, as well as the potential targets of DN. Using the Cytoscape software to visualize the interactive network diagram of "ingredient-target". The GO and KEGG pathways enrichment analysis of the core targets were executed by Metascape. Furthermore, RNA-seq was used to get whole transcriptomes from the kidneys of db/m mice, db/db mice, and db/db mice treated with TRCA. The key differentially expressed genes (DEGs) were gathered to conduct the GO and KEGG pathways enrichment analysis. Finally, the potential pathways were validated by western blotting. RESULTS: The administration of BBR or TRCA for 8 weeks significantly reduced the fasting blood glucose (FBG) and body weight of db/db mice, and improved their renal function and lipid disorders. According to H&E, PAS, and Masson staining, both the BBR and TRCA could alleviate renal damage and fibrosis. The Venn diagram had shown that seven alkaloids ingredients collected from TRCA regulated 85 common targets merged in the TRCA and DN. The results of RNA-seq indicated that there are 121 potential targets for TRCA treatment on DN. Intriguingly, both the AGE-RAGE signaling pathway and the PI3k-Akt signaling pathway were included in the KEGG pathways enrichment results of network pharmacology and RNA-seq. Moreover, we verified that TRCA down-regulated the expression of related proteins in the AGEs-RAGE-TGFß/Smad2 and PI3K-Akt pathways in the kidney tissues. CONCLUSIONS: In summary, the renal protection of TRCA on DN may be related to activation of the AGEs-RAGE-TGFß/Smad2 and PI3K-Akt signaling pathways.