Fucoidan alleviated autoimmune diabetes in NOD mice by regulating pancreatic autophagy through the AMPK/mTOR1/TFEB pathway.

Objectives: The present study investigated the effect and its underlying mechanisms of fucoidan on Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice. Materials and Methods: Twenty 7-week-old NOD mice were used in this study, and randomly divided into two groups (10 mice in each group): the control group and the fucoidan treatment group (600 mg/kg. body weight). The weight gain, glucose tolerance, and fasting blood glucose level in NOD mice were detected to assess the development of diabetes. The intervention lasted for 5 weeks. The proportions of Th1/Th2 cells from spleen tissues were tested to determine the anti-inflammatory effect of fucoidan. Western blot was performed to investigate the expression levels of apoptotic markers and autophagic markers. Apoptotic cell staining was visualized through TdT-mediated dUTP nick-end labeling (TUNEL). Results: The results suggested that fucoidan ameliorated T1DM, as evidenced by increased body weight and improved glycemic control of NOD mice. Fucoidan down-regulated the Th1/Th2 cells ratio and decreased Th1 type pro-inflammatory cytokines' level. Fucoidan enhanced the mitochondrial autophagy level of pancreatic cells and increased the expressions of Beclin-1 and LC3B II/LC3B I. The expression of p-AMPK was up-regulated and p-mTOR1 was inhibited, which promoted the nucleation of transcription factor EB (TFEB), leading to autophagy. Moreover, fucoidan induced apoptosis of pancreatic tissue cells. The levels of cleaved caspase-9, cleaved caspase-3, and Bax were up-regulated after fucoidan treatment. Conclusion: Fucoidan could maintain pancreatic homeostasis and restore immune disorder through enhancing autophagy via the AMPK/mTOR1/TFEB pathway in pancreatic cells.

Membranes based on Covalent Organic Frameworks through Green and Scalable Interfacial Polymerization using Ionic Liquids for Antibiotic Desalination.

Covalent organic framework (COF) membranes featuring uniform topological structures and devisable functions, show huge potential in water purification and molecular separation. Nevertheless, the inability of uniform COF membranes to be produced on an industrial scale and their nonenvironmentally friendly fabrication method are the bottleneck preventing their industrial applications. Herein, we report a new green and industrially adaptable scraping-assisted interfacial polymerization (SAIP) technique to fabricate scalable and uniform TpPa COF membranes. The process used non-toxic and low-volatility ionic liquids (ILs) as organic phase instead of conventional organic solvents for interfacial synthesis of TpPa COF layer on a support membrane, which can simultaneously achieve the purposes of (i) improving the greenness of membrane-forming process and (ii) fabricating a robust membrane that can function beyond the conventional membranes. This approach yields a large-area, continuous COF membrane (19×25 cm2 ) with a thickness of 78 nm within a brief period of 2 minutes. The resulting membrane exhibited an unprecedented combination of high permeance (48.09 L m-2 h-1 bar-1 ) and antibiotic desalination efficiency (e.g., NaCl/adriamycin separation factor of 41.8), which is superior to the commercial benchmarking membranes.

Anhydrous interfacial polymerization of sub-1 Å sieving polyamide membrane.

Highly permeable polyamide (PA) membrane capable of precise ionic sieving can be utilized for many energy-efficient chemical separations. To fulfill this target, it is crucial to innovate membrane-forming process to induce a narrow pore-size distribution. Herein, we report an anhydrous interfacial polymerization (AIP) at a solid-liquid interface where the amine layer sublimated is in direct contact with the alkane containing acyl chlorides. In such a heterophase interface, water-caused side reactions are eliminated, and the amines in compact arrangement enable an intensive and orderly IP reaction, leading to a unique PA layer with an ionic sieving accuracy of 0.5 Å. The AIP-PA membrane demonstrates excellent separation selectivities of monovalent and divalent cations such as Mg2+/Li+ (78.3) and anions such as Cl-/SO42- (29.2) together with a high water flux up to 13.6 L m-2 h-1 bar-1. Our AIP strategy may provide inspirations for engineering high-precision PA membranes available in various advanced separations.

Stretchable Thermoelectric Fibers with Three-Dimensional Interconnected Porous Network for Low-Grade Body Heat Energy Harvesting.

Electricity generation from body heat has garnered significant interest as a sustainable power source for wearable bioelectronics. In this work, we report stretchable n-type thermoelectric fibers based on the hybrid of Ti3C2Tx MXene nanoflakes and polyurethane (MP) through a wet-spinning process. The proposed fibers are designed with a 3D interconnected porous network to achieve satisfactory electrical conductivity (σ), thermal conductivity (κ), and stretchability simultaneously. We systematically optimize the thermoelectric and mechanical traits of the MP fibers and the MP-60 (with 60 wt % MXene content) exhibits a high σ of 1.25 × 103 S m-1, an n-type Seebeck coefficient of -8.3 µV K-1, and a notably low κ of 0.19 W m-1 K-1. Additionally, the MP-60 fibers possess great stretchability and mechanical strength with a tensile strain of 434% and a breaking stress of 11.8 MPa. Toward practical application, a textile thermoelectric generator is constructed based on the MP-60 fibers and achieves a voltage of 3.6 mV with a temperature gradient between the body skin and ambient environment, highlighting the enormous potential of low-grade body heat energy harvesting.

Folic Acid Protects against Ethanol-Induced Hepatic Mitophagy Imbalance by ROS Scavenging and Attenuating the Elevated Hcy Levels.

Ample evidence indicates that ethanol-induced oxidative stress and mitochondrial dysfunction are central to the pathogenesis of alcoholic liver disease (ALD). As an adaptive quality control mechanism, mitophagy removes dysfunctional mitochondria to avert hepatic lesions in ALD. Folic acid exhibits potential radical scavenging properties and has been proven to ameliorate mitochondrial disorder in oxidative stress-related diseases. In this study, we aimed to uncover the mitophagy regulatory effects of folic acid in a 10w alcohol C57BL/6J mice feeding model (56% v/v) and L02 cells model cultured with ethanol (2.5% v/v). The results showed that folic acid alleviates ethanol-induced liver injury, decreasing oxidative stress and restoring liver enzyme. Furthermore, folic acid improved the mitochondrial function and inhibited ethanol-activated mitophagy through decreasing PINK1-Parkin and Drp1 expression, which inhibited the release of mitochondrial cytochrome C to the cytoplasm, preventing hepatocyte apoptosis. Intriguingly, folic acid attenuates the elevated hepatic homocysteine (Hcy) level. Additionally, the pretreatment of L02 cells with folic acid also ameliorated Hcy-induced oxidative damage, mitochondrial fission, and mitophagy. In summary, these results suggest that folic acid has beneficial effects in mitophagy remodeling by ROS scavenging and facilitating Hcy metabolism and could be developed as a potential therapeutic agent against ALD.

Influence of intestinal microecology in the development of gout or hyperuricemia and the potential therapeutic targets.

Gout and hyperuricemia are common metabolic diseases. Patients with purine metabolism disorder and/or decreased uric acid excretion showed increased uric acid levels in the blood. The increase of uric acid in the blood leads to the deposition of urate crystals in tissues, joints, and kidneys, and causes gout. Recent studies have revealed that imbalance of the intestinal microecology is closely related to the occurrence and development of hyperuricemia and gout. Disorder of the intestinal flora often occurs in patients with gout, and high purine and high fructose may induce the disorder of intestinal flora. Short-chain fatty acids and endotoxins produced by intestinal bacteria are closely related to the inflammatory response of gout. This article summarizes the characteristics of intestinal microecology in patients or animal models with hyperuricemia or gout, and explores the relationship between intestinal microecology and gout or hyperuricemia from the aspect of the intestinal barrier, intestinal microorganisms, intestinal metabolites, and intestinal immune system. We also review the current status of hyperuricemia treatment by targeting intestinal microecology.

A Polyzwitterion-Mediated Polymer Electrolyte with High Oxidative Stability for Lithium-Metal Batteries.

To achieve high-performance solid-state lithium-metal batteries (SSLMBs), solid electrolytes with high ionic conductivity, high oxidative stability, and high mechanical strength are necessary. However, balancing these characteristics remains dramatically challenging and is still not well addressed. Herein, a simple yet effective design strategy is presented for the development of high-performance polymer electrolytes (PEs) by exploring the synergistic effect between dynamic H-bonded networks and conductive zwitterionic nanochannels. Multiple weak intermolecular interactions along with ample nanochannels lead to high oxidative stability (over 5 V), improved mechanical properties (strain of 1320%), and fast ion transport (ionic conductivity of 10-4 S cm-1 ) of PEs. The amphoteric ionic functional units also effectively regulate the lithium ion distribution and confine the anion transport to achieve uniform lithium ion deposition. As a result, the assembled SSLMBs exhibit excellent capacity retention and long-term cycle stability (average Coulombic efficiency: 99.5%, >1000 cycles with LiFePO4 cathode; initial capacity: 202 mAh g-1 , average Coulombic efficiency: 96%, >230 cycles with LiNi0.8 Co0.1 Mn0.1 O2 cathode). It is exciting to note that the corresponding flexible cells can be cycled stably and can withstand severe deformation. The resulting polyzwitterion-mediated PE therefore offers great promise for the next-generation safe and high-energy-density flexible energy storage devices.

Bio-Inspired Aerobic-Hydrophobic Janus Interface on Partially Carbonized Iron Heterostructure Promotes Bifunctional Nitrogen Fixation.

Competition from hydrogen/oxygen evolution reactions and low solubility of N2 in aqueous systems limited the selectivity and activity on nitrogen fixation reaction. Herein, we design an aerobic-hydrophobic Janus structure by introducing fluorinated modification on porous carbon nanofibers embedded with partially carbonized iron heterojunctions (Fe3 C/Fe@PCNF-F). The simulations prove that the Janus structure can keep the internal Fe3 C/Fe@PCNF-F away from water infiltration and endow a N2 molecular-concentrating effect, suppressing the competing reactions and overcoming the mass-transfer limitations to build a robust "quasi-solid-gas" state micro-domain around the catalyst surface. In this proof-of-concept system, the Fe3 C/Fe@PCNF-F exhibits excellent electrocatalytic performance for nitrogen fixation (NH3 yield rate up to 29.2 µg h-1 mg-1 cat. and Faraday efficiency (FE) up to 27.8 % in nitrogen reduction reaction; NO3 - yield rate up to 15.7 µg h-1 mg-1 cat. and FE up to 3.4 % in nitrogen oxidation reaction).

Polyzwitterion-SiO2 Double-Network Polymer Electrolyte with High Strength and High Ionic Conductivity.

The key to developing high-performance polymer electrolytes (PEs) is to achieve their high strength and high ionic conductivity, but this is still challenging. Herein, we designed a new double-network PE based on the nonhydrolytic sol-gel reaction of tetraethyl orthosilicate and in situ polymerization of zwitterions. The as-prepared PE possesses high strength (0.75 Mpa) and high stretchability (560%) due to the efficient dissipation energy of the inorganic network and elastic characteristics of the polymer network. In addition, the highest ionic conductivity of the PE reaches 0.44 mS cm-1 at 30 °C owning to the construction of dynamic ion channels between the polyzwitterion segments and between the polyzwitterion segments and ionic liquids. Furthermore, the inorganic network can act as Lewis acid to adsorb trace impurities, resulting in a prepared electrolyte with a high electrochemical window over 5 V. The excellent interface compatibility of the as-prepared PE with a Li metal electrode is also confirmed. Our work provides new insights into the design and preparation of high-performance polymer-based electrolytes for solid-state energy storage devices.

Protective effect of fucoidan against iron overload and ferroptosis-induced liver injury in rats exposed to alcohol.

This study was aimed to explore the effects of fucoidan on iron overload and ferroptosis-induced liver injury, and the underlying mechanisms in rats exposed to alcohol. Sprague-Dawley rats were used to establish alcoholic liver injury model by intragastric administration with alcohol for 16 weeks. The results showed that fucoidan treatment reversed alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and increased glutathione peroxidase and glutathione levels, thus protecting against liver damage. Long-term alcohol feeding resulted in abnormal increase of serum ferritin, liver total iron and the "free" iron levels. Fucoidan treatment reduced serum ferritin level and alleviated liver iron deposition. Fucoidan reversed the reduction of hepcidin induced by alcohol exposure and decreased divalent metal transporter 1 (DMT1) and ferroportin1 (FPN1) expressions in the duodenum. Electron microscope observation of liver tissues showed that alcohol exposure induced ferroptosis changes in the liver. However, fucoidan treatment could alleviate alcohol-induced ferroptosis via upregulating the expressions of p62, Nrf2, SLC7A11 and GPX4. The liver endogenous metabolites analysis by liquid chromatography and mass spectrometry showed that after fucoidan intervention, mineral absorption, biosynthesis of amino acids pathways and lipid metabolism were changed. Fucoidan intervention reduced the levels of oxidized glutathione and regulated the levels of phosphatidylethanolamines in liver tissues. Our data showed that fucoidan supplementation could inhibit iron load via regulating hepcidin-intestinal DMT1/FPN1 axis, alleviate the liver oxidative damage and protect hepatocytes from ferroptosis induced by long-term alcohol exposure through upregulating p62/Nrf2/SLC7A11 pathway in rats.

Beyond the Pore Size Limitation of a Nanoporous Graphene Monolayer Membrane for Water Desalination Assisted by an External Electric Field.

One efficient strategy for addressing the global water shortage is advanced membrane separation, which depends on the precise pore size being close to the hydrated ion size and other surface properties like charge and polarity. However, it is very difficult to fabricate uniform pores with diameters of <1 nm on monolayer membranes. By applying an electric field (bias voltage) perpendicular to the direction of the pressure difference, herein we demonstrate for the first time that a monolayer nanoporous graphene membrane with pores much larger than hydrated ions exhibits high salt rejection and allows a high rate of water transport. This theoretical proposal goes beyond the pore size limitation and shows promise for the design of high-performance reverse osmosis membranes.

A portable triboelectric spirometer for wireless pulmonary function monitoring.

Coronavirus disease 2019 (COVID-19) as a severe acute respiratory syndrome infection has spread rapidly across the world since its emergence in 2019 and drastically altered our way of life. Patients who have recovered from COVID-19 may still face persisting respiratory damage from the virus, necessitating long-term supervision after discharge to closely assess pulmonary function during rehabilitation. Therefore, developing portable spirometers for pulmonary function tests is of great significance for convenient home-based monitoring during recovery. Here, we propose a wireless, portable pulmonary function monitor for rehabilitation care after COVID-19. It is composed of a breath-to-electrical (BTE) sensor, a signal processing circuit, and a Bluetooth communication unit. The BTE sensor, with a compact size and light weight of 2.5 cm3 and 1.8 g respectively, is capable of converting respiratory biomechanical motions into considerable electrical signals. The output signal stability is greater than 93% under 35%-81% humidity, which allows for ideal expiration airflow sensing. Through a wireless communication circuit system, the signals can be received by a mobile terminal and processed into important physiological parameters, such as forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). The FEV1/FVC ratio is then calculated to further evaluate pulmonary function of testers. Through these measurement methods, the acquired pulmonary function parameters are shown to exhibit high accuracy (>97%) in comparison to a commercial spirometer. The practical design of the self-powered flow spirometer presents a low-cost and convenient method for pulmonary function monitoring during rehabilitation from COVID-19.

Nanoscale Venturi-Bernoulli Pumping of Liquids.

We use molecular dynamics simulations to show that the Venturi-Bernoulli effect can pump liquids at the nanoscale. In particular, we found that water flowing in an open reservoir close to a static substrate experiences a friction which converts its kinetic energy into breaking of hydrogen bonds. This water flowing under friction acquires a lower density, which can be used in pumping fluids positioned under a nanoporous substrate.

Selectivity of ion transport in narrow carbon nanotubes depends on the driving force due to drag or drive nature of their active hydration shells.

Molecular dynamics simulations have revealed the important roles of hydration shells of ions transported through ultrathin carbon nanotubes (CNTs). In particular, ions driven by electric fields tend to drag their hydration shells behind them, while for ions transported by pressure, their hydration shells can actively drive them. Given the different binding strengths of hydration shells to ions of different sizes, these active roles of hydration shells affect the relative entry rates and driving speeds of ions in CNTs.

Theoretically designed two-dimensional γ-C4O as an effective gas separation membrane for hydrogen purification.

A high-performance gas separation membrane for hydrogen (H2) purification is still highly desirable for the sustainable development of our society. Based on the structure of γ-graphyne, we theoretically designed the two-dimensional nanomaterials γ-C4X (X = O, S or Se) with intrinsic pores that may be suitable for gas separation. By first-principles calculations, we obtained the geometric structures of γ-C4X, and confirmed that γ-C4O and γ-C4S are stable at room temperature. Due to the moderate size of the intrinsic pores, γ-C4O exhibits a lower diffusion barrier and higher permeance for H2 than those of γ-C4S. It is worth noting that at room temperature, the high selectivity (1019) for separating H2 from a H2/CH4 mixture by γ-C4O shows great potential for H2 purification. Moreover, the classic molecular dynamics simulations at 300 K demonstrate that H2 can easily permeate through the intrinsic pores of γ-C4O membranes with high permeability and selectivity, which supports our first-principles calculations.

Endothelial cell-derived small extracellular vesicles suppress cutaneous wound healing through regulating fibroblasts autophagy.

Diabetic foot ulcer is a life-threatening clinical problem in diabetic patients. Endothelial cell-derived small extracellular vesicles (sEVs) are important mediators of intercellular communication in the pathogenesis of several diseases. However, the exact mechanisms of wound healing mediated by endothelial cell-derived sEVs remain unclear. sEVs were isolated from human umbilical vein endothelial cells (HUVECs) pretreated with or without advanced glycation end products (AGEs). The roles of HUVEC-derived sEVs on the biological characteristics of skin fibroblasts were investigated both in vitro and in vivo We demonstrate that sEVs derived from AGEs-pretreated HUVECs (AGEs-sEVs) could inhibit collagen synthesis by activating autophagy of human skin fibroblasts. Additionally, treatment with AGEs-sEVs could delay the wound healing process in Sprague-Dawley (SD) rats. Further analysis indicated that miR-106b-5p was up-regulated in AGEs-sEVs and importantly, in exudate-derived sEVs from patients with diabetic foot ulcer. Consequently, sEV-mediated uptake of miR-106b-5p in recipient fibroblasts reduces expression of extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in fibroblasts autophagy activation and subsequent collagen degradation. Collectively, our data demonstrate that miR-106b-5p could be enriched in AGEs-sEVs, then decreases collagen synthesis and delays cutaneous wound healing by triggering fibroblasts autophagy through reducing ERK1/2 expression.

Nanoporous MoS2 monolayer as a promising membrane for purifying hydrogen and enriching methane.

We present a theoretical prediction of a highly efficient membrane for hydrogen purification and natural gas upgrading, i.e. laminar MoS2 material with triangular sulfur-edged nanopores. We calculated from first principles the diffusion barriers of H2 and CO2 across monolayer MoS2 to be, respectively, 0.07 eV and 0.17 eV, which are low enough to warrant their great permeability. The permeance values for H2 and CO2 far exceed the industrially accepted standard. Meanwhile, such a porous MoS2 membrane shows excellent selectivity in terms of H2/CO, H2/N2, H2/CH4, and CO2/CH4 separation (>103, > 103, > 106, and > 104, respectively) at room temperature. We expect that the findings in this work will expedite theoretical or experimental exploration on gas separation membranes based on transition metal dichalcogenides.

Graphdiyne as a High-Efficiency Membrane for Separating Oxygen from Harmful Gases: A First-Principles Study.

We theoretically explored the adsorption and diffusion properties of oxygen and several harmful gases penetrating the graphdiyne monolayer. According to our first-principles calculations, the oxidation of the acetylenic bond in graphdiyne needs to surmount an energy barrier of ca. 1.97 eV, implying that graphdiyne remains unaffected under oxygen-rich conditions. In a broad temperature range, graphdiyne with well-defined nanosized pores exhibits a perfect performance for oxygen separation from typical noxious gases, which should be of great potential in medical treatment and industry.

Cell membrane-inspired polymeric micelles as carriers for drug delivery.

In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.