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The analysis demonstrates the remarkable loop flexibility existing in the avian influenza N1, which is found to exhibit extremely rapid loop switching motion. The loop flexibility helps in the designing of various antiviral drugs that directly target the neuraminidase (NA) glycoprotein and facilitates the release of viral progeny from infected cells.

Research has been conducted on methyl protodiosin. The authors describe the synthesis of this compound carried out from diosgenin.

Cryo-electron tomography (cryo-ET) can provide insights into the structure and states of natural membrane environments to explore the role of SNARE proteins at membrane fusion and understand the relationship between their subcellular localization/formation and action mechanism. Nevertheless, the identification of individual molecules in crowded and low signal-to-noise ratio membrane environments remains a significant challenge. In this study, cryo-ET is employed to image near-physiological state 293T cell membranes, specifically utilizing in situ synthesized gold nanoparticles (AuNPs) bound with cysteine-rich protein tags to single-molecularly labeled synaptosomal-associated protein 25 (SNAP25) on the membrane surface. The high-resolution images reveal that SNAP25 is predominantly located in regions of high molecular density within the cell membrane and aggregates into smaller clusters, which may increase the fusion efficiency. Remarkably, a zigzag arrangement of SNAP25 is observed on the cell membrane. These findings provide valuable insights into the functional mechanisms of SNARE proteins.

Graphene chemical vapor deposition (CVD) growth directly on target using substrates presents a significant route toward graphene applications. However, the substrates are usually catalytic-inert and special-shaped; thus, large-scale, high-uniformity, and high-quality graphene growth is challenging. Herein, graphene-skinned glass fiber fabric (GGFF) was developed through graphene CVD growth on glass fiber fabric, a Widely used engineering material. A fluid dynamics rectification strategy was first proposed to synergistically regulate the distribution of carbon species in 3D space and their collisions with hierarchical-structured substrates, through which highly uniform deposition of high-quality graphene on fibers in large-scale 3D-woven fabric was realized. This strategy is universal and applicable to CVD systems using various carbon precursors. GGFF exhibits high electrical conductivity and photothermal conversion capability, based on which a natural energy harvester was first developed. It can harvest both solar and raindrop energy through solar heating and droplet-based electricity generating, presenting promising potentials to alleviate energy burdens.

In this work, a series of amphiphilic diblock copolymers poly( N -2-(methacryloyloxy) ethyl pyrrolidone)- b -poly(benzyl methacrylate) (PNMP m - b -PBzMA n ) were developed by the dispersion polymerization method in ethanol. The polymerization-induced self-assembly (PISA) behaviors were studied systematically, and a comprehensive structure-property relationship was also established. Two distinct PISA tendencies were observed, which was mainly depended on the polymerization degree m of PNMP segment. When m is small such as 39 and 55, morphological transitions from spherical to vesicle-like assemblies via wormlike ones upon increasing n commonly happen regardless of the solid content. Alternatively, spherical assemblies became the sole morphology for PNMP 64 - b -PBzMA n block copolymers because of the excellent solvophilicity of the PNMP 64 segment. Attributing to the amphiphilicity of PNMP m - b -PBzMA n block copolymers, PNMP m - b -PBzMA n assemblies by PISA are a type of excellent Pickering emulsifiers. These assemblies prefer to stabilize O/W Pickering emulsions as confirmed by the confocal laser scanning microscopy method, and the effects of polymerization degree of PBzMA segment or morphologies of PNMP m - b -PBzMA n assemblies are finite., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Domestic monitoring devices make real-time and long-term health monitoring possible, allowing people to track their health status regularly. Uric acid (UA), creatinine, and urea in urine are three important biomarkers for various diseases, especially kidney diseases. This work proposed a 10-channel potentiometric sensing array containing a UA electrode group, a creatinine electrode group, a urea electrode group, a pH electrode group, and one pair of reference channels, which could be connected with a portable potentiometric analyzer, realizing the simultaneous detection of UA, creatinine, urea, and pH in urine. The prepared Pt/carbon nanotubes (CNTs)-uricase, creatinine deiminase, Au@urease, and polyaniline were employed as the sensing materials, showing responses to four targets with high sensitivity and selectivity. To improve the accuracy of domestic monitoring, a calibration channel was integrated into each electrode group to calibrate the basic potential of the sensing channels, and the influences of pH and temperature on the responses were investigated through the pH electrode group and an external temperature probe to calibrate the slope and intercept. With the preset of the deduced calibration parameters and computational formula for the four targets in the analyzer in Lab Mode, the concentrations of UA, creatinine, and urea and the pH of the human urine samples were directly displayed on the screen of the analyzer in Practical Mode. The agreement of these results with those obtained from commercial kits and pH meters reveals the high potential of these methods for developing domestic devices to facilitate health monitoring.

Recently, Liu et al. reported 1,4-dithiazole-5,10-dihydrophenazine ( DTDHP ) and its B ← N-fused derivative ( DTHDHP-BF 2 ), which were expected to show excellent optoelectronic properties ( Angew. Chem. Int. Ed. 2022 , 61, e202205893). However, their charge-transport performance and luminescence emission mechanisms have not been revealed. In this work, we used density functional theory (DFT) calculations to investigate the optoelectronic properties of DTDHP and DTHDHP-BF 2 and analyzed the influence of the introduction of -BF 2 on the basic parameters governing charge transport and injection in detail. Our calculation results showed that adding -BF 2 could stabilize the frontier molecular orbitals and decrease the reorganization energies associated with electron transport due to the formation of B ← N bonds, and the intermolecular electronic couplings are greatly enhanced owing to the strong intermolecular F···H interactions. Based on the master equation coupled with the Marcus-Hush electron transfer theory, we theoretically predicted the charge transport properties of DTDHP S DTHDHP-BF 2 . The optimum hole mobility (3.87 cm 2 S -1 S -1 ) and electron mobility (1.52 cm 2 . Moreover, the assignments of multiple fluorescence bands in the experiment were confirmed by time-dependent density functional theory (TDDFT) calculations. The simulated emission spectra indicate that the experimental fluorescence maxima at 687 nm originates from the S -1 → S -1 ) of DTHDHP-BF 2 are, respectively, 3 and 9 times as high as the corresponding optimum values of compound DTDHP . Moreover, the assignments of multiple fluorescence bands in the experiment were confirmed by time-dependent density functional theory (TDDFT) calculations. The simulated emission spectra indicate that the experimental fluorescence maxima at 687 nm originates from the S 1 → S 0 transition of the double proton transfer phototautomer ( T 2H ) of DTDHP, and the shoulder peak at ∼660 nm may be related to the excited-state single-proton transfer phototautomer ( T 1H ); for DTHDHP-BF 2 , the experimental fluorescence maxima at 687 nm should be attributed to normal Stokes shifted emission, and the shifted fluorescence with a peak at 751 nm originates from the emission of the photodissociation product of DTHDHP-BF 2 .

Physical vapor deposition (PVD) is widely utilized for the production of organic semiconductor devices due to its ability to form thin layers with exceptional properties. Although the layers in the device usually consist of two or more components, there is limited understanding about the fundamental characteristics of such multicomponent vapor-deposited glasses. Here, spectroscopic ellipsometry was employed to characterize the densities, thermal stabilities, and optical properties of covapor deposited NPD and TPD glasses across the entire range of composition. We find that codeposited NPD and TPD form high density glasses with enhanced thermal stability. The dependences of density and stability upon substrate temperature are correlated, and the birefringence of the codeposited glasses is determined by the reduced substrate temperature of mixtures. Additionally, we observe that the transformation of a highly stable and dense two-component glass into its supercooled liquid initiates from the free surface and propagates into the bulk at a constant velocity, like single component PVD glasses. All of these features are consistent with the surface equilibration mechanism.

Helicity-dependent photocurrent (HDPC) and its modulation in topological insulator Bi 2 Te 3 nanowires have been investigated. It is revealed that when the incident plane of a laser is perpendicular to the nanowire, the HDPC is an odd function of the incident angle, which is mainly contributed by the circular photogalvanic effect originating from the surface states of Bi 2 Te 3 nanowire. When the incident plane of a laser is parallel to the nanowire, the HDPC is approximately an even function of the incident angle, which is due to the circular photon drag effect coming from the surface states. It is found that the HDPC can be effectively tuned by the back gate and the ionic liquid top gate. By analyzing the substrate dependence of the HDPC, we find that the HDPC of the Bi 2 Te 3 nanowire on the Si substrate is an order of magnitude larger than that on SiO 2 , which may be due to the spin injection from the Si substrate to the Bi 2 Te 3 nanowire. In addition, by applying different biases, the Stokes parameters of a polarized light can be extracted by arithmetic operation of the photocurrents measured in the Bi 2 Te 3 nanowire. This work suggests that topological insulator Bi 2 Te 3 nanowires may provide a good platform for opto-spintronic devices, especially in chirality and polarimtry detection.

The unique optical properties of graphene, with broadband absorption and ultrafast response, make it a critical component of optoelectronic and spintronic devices. Using time-resolved momentum microscopy with high data rate and high dynamic range, we report momentum-space measurements of electrons promoted to the graphene conduction band with visible light and their subsequent relaxation. We observe a pronounced nonthermal distribution of nascent photoexcited electrons with lattice pseudospin polarization in remarkable agreement with results of simple tight-binding theory. By varying the excitation fluence, we vary the relative importance of electron-electron vs electron-phonon scattering in the relaxation of the initial distribution. Increasing the excitation fluence results in increased noncollinear electron-electron scattering and reduced pseudospin polarization, although up-scattered electrons retain a degree of polarization. These detailed momentum-resolved electron dynamics in graphene demonstrate the capabilities of high-performance time-resolved momentum microscopy in the study of 2D materials and can inform the design of graphene devices.

Defective metal-organic frameworks (MOFs) have shown great potential for catalysis due to abundant active sites and adjustable physical and chemical properties. A series of Ce-based MOFs with different defect contents were synthesized via a modulator-induced defect engineering strategy with the aid of the cell pulverization technique. The effects of modulators on the pore structure, morphology, valence distribution of Ce, and Lewis acidity of Ce-MOF-801 were systematically investigated. Among the different samples studied, the optimal Ce-MOF-801-50eq sample exhibited remarkable catalytic activity for DCPD hydrogenation, achieving a conversion rate of 100%, which is significantly higher compared to other Ce-MOF-801- n eq samples as well as the Zr-MOF-801-50eq and Hf-MOF-801-50eq samples. The enhanced catalytic performance of Ce-MOF-801-50eq can be attributed to advantages provided by defect engineering, such as the high specific surface area, proper pore size distribution, abundant unsaturated metal sites, and Ce 3+ /Ce 4+ atom ratio, which have been supported by various characterizations. This study provides important insights into the rational design of Ce-MOFs in the field of catalytic DCPD hydrogenation.

Obesity is becoming a worldwide pandemic. Interfacial engineering of food lipid is expected to inhibit diet-induced obesity without damage to the eating enjoyment brought by high-fat diets. Unfortunately, this strategy has not been achieved yet. After screening different plant proteins, bromelain and papain were found to form wormlike and long-straight protein fibrils, respectively. The conversion of long-straight amyloid-like fibrils to wormlike fibrils was demonstrated in the fibrillation of bromelain. Using oil-in-water high internal phase emulsions (HIPEs) as a proof of concept, bromelain fibrils showed dramatically stronger interfacial stabilization capabilities than papain fibrils with high application potentials in the real-world formulation of high-fat food products such as mayonnaise. Compared with papain fibrils, oral administration of HIPEs stabilized by bromelain fibrils resulted in substantially higher fecal lipid contents and significantly decreased expression levels of the genes related to lipid absorption and transport in the intestine, including CD36 , FATP-2 , FATP-4, and APOA-4 , without a difference in intervening gut microbiota. Consequently, dramatically less lipid absorption in the small intestine, markedly smaller chylomicron particles in the plasma, lower serum triglycerides, and controlled energy and lipid metabolism, as well as the inhibition of adipose expansion and overweight, were observed in the group with gavage of HIPEs stabilized by the bromelain fibrils rather than the papain fibrils. Furthermore, with the same calorie, substitution of all the fat in the standard high-fat feed of mice with the HIPEs emulsified by the bromelain fibrils showed a significantly stronger effect than the ones prepared by the papain fibrils on preventing high-fat-diet (HFD)-induced obesity including alleviation of adipose expansion and inflammation as well as fatty liver, also via inhibiting the absorption and transport of lipid in the intestine. The effect is ascribed to the suppressed lipolysis caused by a more compact and elastic interfacial layer formed by the wormlike fibrils than that of the long-straight fibrils, which are resistant to gastric environments and replacement by bile acids in digestion. Therefore, we provide an appealing and general strategy for controlling obesity by reducing the supply of free fatty acids (FAs) for absorption in the enteric lumen through protein fibril polymorphisms at the interface.

Layered sodium transition-metal oxides generally encounter severe capacity decay and inferior rate performance during cycling, especially at a high state of charge. Herein, defect concentration is rationally modulated to explore the impact on electrochemical behavior in NaNi 1/3 Fe 1/3 Mn 1/3 O 2 layered oxides. Bulk vacancies are increased through annealing in an oxygen-rich atmosphere, demonstrated by electron paramagnetic resonance measurement. It is found that the cathode with enriched oxygen vacancies exhibits significantly enhanced reversibility of redox reactions with a higher initial Coulombic efficiency of 90.0%. Furthermore, the reduced volume variations during the initial charge/discharge process are also confirmed by in situ X-ray diffraction. As a result, the oxygen-vacancy-rich cathode shows great cycling stability and superior rate performances. Also, full cells deliver a specific capacity of approximately 145.2 mAh g -1 at 0.5 C, with a high capacity retention of 78.3% after 100 cycles. This work presents a viable strategy for designing Na + intercalated cathodes with a high-energy density.

In this study, we designed an artificial pathway composed of tyramine β-hydroxylase (TBH) and phenylethanolamine N -methyltransferase (PNMT) for the biosynthesis of both octopamine and synephrine. As most TBH and PNMT originate from eukaryotic animals and plants, the heterologous expression and identification of functional TBH and PNMT are critical for establishing the pathway in mode microorganisms like Escherichia coli . Here, three TBHs were evaluated, and only TBH from Drosophila melanogaster was successfully expressed in the soluble form in E. coli . Its expression was promoted by evaluating the effects of different expression strategies. The specific enzyme activity of TBH was optimized up to 229.50 U·g -1 , and the first step in the biosynthetic pathway was successfully established and converted tyramine to synthesize 0.10 g/L of octopamine. Furthermore, the second step to produce synephrine from octopamine was developed by screening PNMT, enhancing enzyme activity, and optimizing reaction conditions, with a maximum synephrine production of 2.02 g/L. Finally, based on the optimization of the reaction conditions for each individual reaction, the one-pot cascade reaction for synthesizing synephrine from tyramine was constructed by combining the TBH and PNMT. The synthetic synephrine reached 30.05 mg/L with tyramine as substrate in the two-step enzyme cascade system. With further optimization and amplification, the titers of octopamine and synephrine were increased to 0.45 and 0.20 g/L, respectively, with tyramine as substrate. This work was the first achievement of the biosynthesis of octopamine and synephrine to date.

Betanin is a water-soluble red-violet pigment belonging to the betacyanins family. It has become more and more attractive for its natural food colorant properties and health benefits. However, the commercial production of betanin, typically extracted from red beetroot, faces economic and sustainability challenges. Microbial heterologous production therefore offers a promising alternative. Here, we performed combinatorial engineering of plant P450 enzymes and precursor metabolisms to improve the de novo production of betanin in Saccharomyces cerevisiae . Semirational design by computer simulation and molecular docking was used to improve the catalytic activity of CYP76AD. Alanine substitution and site-directed saturation mutants were screened, with a combination mutant showing an approximately 7-fold increase in betanin titer compared to the wild type. Subsequently, betanin production was improved by enhancing the l-tyrosine pathway flux and UDP-glucose supply. Finally, after optimization of the fermentation process, the engineered strain BEW10 produced 134.1 mg/L of betanin from sucrose, achieving the highest reported titer of betanin in a shake flask by microbes. This work shows the P450 enzyme and metabolic engineering strategies for the efficient microbial production of natural complex products.

Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by self-assembly of epigallocatechin gallate (EGCG) and FeCl 3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo , NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.

As a typical carbon-based material electrode, graphene fiber exhibits many advantages, such as good electrical conductivity, lightweight, and strong structural designability. Its demand is increasing in the wearable display field. With the help of fine denier fiber spinning combined with multistranded graphene fibers prepared via twisting and drafting, their petal-like twisted structure endows the fibers with a high specific surface area, enabling them to complete dye adsorption within 30 min. Simultaneously, compared with that of a single fiber with the same thickness, the volume specific resistance of a multistranded twisted graphene fiber is reduced by 2.4 times. During force sensing, the twisted structure of multistranded fibers exhibits varying simultaneity of fiber fracture with excellent resistance sensitivity reaching up to 55%. The multistranded twisted flexible graphene fibers demonstrate excellent robustness. Electroluminescent flexible devices prepared with graphene fibers and fiber braided fabrics with different organizational structures as electrodes emit highly saturated short-wave blue light during long-term multiple use. Therefore, multistranded twisted graphene fibers exhibit considerable potential for future applications in wearable multicolor smart displays and flexible optical signal electronics.

The development of Fe-based catalysts for the selective catalytic reduction of NO x by NH 3 (NH 3 -SCR of NO x ) has garnered significant attention due to their exceptional SO 2 resistance. However, the influence of different sulfur-containing species (e.g., ferric sulfates and ammonium sulfates) on the NH 3 -SCR activity of Fe-based catalysts as well as its dependence on exposed crystal facets of Fe 2 O 3 has not been revealed. This work disclosed that nanorod-like α-Fe 2 O 3 (Fe 2 O 3 -NR) predominantly exposing (110) facet performed better than nanosheet-like α-Fe 2 O 3 (Fe 2 O 3 -NS) predominantly exposing (001) facet in NH 3 -SCR reaction, due to the advantages of Fe 2 O 3 -NR in redox properties and surface acidity. Furthermore, the results of the SO 2 /H 2 O resistance test at a critical temperature of 250 °C, catalytic performance evaluations on Fe 2 O 3 -NR and Fe 2 O 3 -NS sulfated by SO 2 + O 2 or deposited with NH 4 HSO 4 (ABS), and systematic characterization revealed that the reactivity of ammonium sulfates on Fe 2 O 3 catalysts to NO(+O 2 ) contributed to their improved catalytic performance, while ferric sulfates showed enhancing and inhibiting effects on NH 3 -SCR activity on Fe 2 O 3 -NR and Fe 2 O 3 -NS, respectively; despite this, Fe 2 O 3 -NR showed higher affinity for SO 2 + O 2 . This work set a milestone in understanding the NH 3 -SCR reaction on Fe 2 O 3 catalysts in the presence of SO 2 from the aspect of crystal facet engineering.

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

Atherosclerosis (AS) is characterized by the accumulation of substantial low-density lipoprotein (LDL) and inflammatory response. Hemoperfusion is commonly employed for the selective removal of LDL from the body. However, conventional hemoperfusion merely focuses on LDL removal and does not address the symptom of plaque associated with AS. Based on the LDL binding properties of acrylated chondroitin sodium sulfate (CSA), acrylated beta-cyclodextrin (CD) and acrylic acid (AA), along with the anti-inflammatory property of rosiglitazone (R), the fabricated AA-CSA-CD-R microspheres could simultaneously release R and facilitate LDL removal for hemoperfusion. The AA and CSA offer electrostatic adsorption sites for LDL, while the CD provides hydrophobic adsorption sites for LDL and weak binding sites for R. According to the Sips model, the maximum static LDL adsorption capacity of AA-CSA-CD-R is determined to be 614.73 mg/g. In dynamic simulated perfusion experiments, AA-CSA-CD-R exhibits an initial cycle LDL adsorption capacity of 150.97 mg/g. The study suggests that the weakened inflammatory response favors plaque stabilization. The anti-inflammatory property of the microspheres is verified through an inflammation model, wherein the microsphere extracts are cocultured with mouse macrophages. Both qualitative analysis of iNOS\TNF-α and quantitative analysis of IL-6\TNF-α collectively demonstrate the remarkable anti-inflammatory effect of the microspheres. Therefore, the current study presents a novel blood purification treatment of eliminating pathogenic factors and introducing therapeutic factors to stabilize AS plaque.

PTP1B, a promising target for insulin sensitizers in type 2 diabetes treatment, can be effectively degraded using proteolysis-targeting chimera (PROTAC). This approach offers potential for long-acting antidiabetic agents. We report potent bifunctional PROTACs targeting PTP1B through the E3 ubiquitin ligase cereblon. Western blot analysis showed significant PTP1B degradation by PROTACs at concentrations from 5 nM to 5 μM after 48 h. Evaluation of five highly potent PROTACs revealed compound 75 with a longer PEG linker (23 atoms), displaying remarkable degradation activity after 48 and 72 h, with DC 50 values of 250 nM and 50 nM, respectively. Compound 75 induced selective degradation of PTP1B, requiring engagement with both the target protein and CRBN E3 ligase, in a ubiquitination and proteasome-dependent manner. It significantly reduced blood glucose AUC 0-2h to 29% in an oral glucose tolerance test and activated the IRS-1/PI3K/Akt signaling pathway in HepG2 cells, showing promise for long-term antidiabetic therapy.

Marine biodiversity offers a wide array of active ingredient resources. Gadus morhua peptides (GMPs) showed excellent osteoprotective effects in ovariectomized mice. However, the potential osteogenesis mechanisms of key osteogenic peptides in GMP were seldom reported. In this study, a novel osteogenic peptide (GETNPADSKPGSIR, P-GM-2) was screened from GMP. P-GM-2 has a high stability coefficient and a strong interaction with epidermal growth factor receptor. Cell culture experiments showed that P-GM-2 stimulated the expression of osteogenic differentiation markers to promote osteoblast proliferation, differentiation, and mineralization. Additionally, P-GM-2 phosphorylates GSK-3β, leading to the stabilization of β-catenin and its translocation to the nucleus, thus initiating the activation of the Wnt/β-catenin signaling pathway. Meanwhile, P-GM-2 could also regulate the osteogenic differentiation of preosteoblasts by triggering the BMP/Smad and mitogen-activated protein kinase signaling pathways. Further validation with specific inhibitors (ICG001 and Noggin) demonstrated that the osteogenic activity of P-GM-2 was revealed by the activation of the BMP and Wnt/β-catenin pathways. In summary, these results provide theoretical and practical insights into P-GM-2 as an effective antiosteoporosis active ingredient.

Direct air capture (DAC) of CO 2 is a carbon-negative technology to mitigate carbon emissions, and it requires low-cost sorbents with high CO 2 sorption capacity that can be easily manufactured on a large scale. In this work, we develop highly porous membrane adsorbents comprising branched polyethylenimine (PEI) impregnated in low-cost, porous Solupor supports. The effect of the PEI molecular mass and loading on the physical properties of the adsorbents is evaluated, including porosity, degradation temperature, glass transition temperature, and CO 2 permeance. CO 2 capture from simulated air containing 400 ppm of CO 2 in these sorbents is thoroughly investigated as a function of temperature and relative humidity (RH). Polymer dynamics was examined using differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS), showing that CO 2 sorption is limited by its diffusion in these PEI-based sorbents. A membrane adsorbent containing 48 mass% PEI (800 Da) with a porosity of 72% exhibits a CO 2 sorption capacity of 1.2 mmol/g at 25 °C and RH of 30%, comparable to the state-of-the-art adsorbents. Multicycles of sorption and desorption were performed to determine their regenerability, stability, and potential for practical applications.

Sepsis is a systemic inflammatory response syndrome caused by pathogen infection, while the current antibiotics mainly utilized in clinical practice to combat infection result in the release of pathogen-associated molecular patterns (PAMPs) in the body. Herein, we provide an innovative strategy for controlling sepsis, namely, capturing active pathogens by means of extracorporeal blood purification. Carbon nanotubes (CNTs) were modified with dimethyldiallylammonium chloride (DDA) through γ-ray irradiation-induced graft polymerization to confer a positive charge. Then, CNT-DDAs are blended with polyurethane (PU) to prepare porous microspheres using the electro-spraying method. The obtained microspheres with a pore diameter of 2 μm served as pathogen traps and are termed as PU-CNT-DDA microspheres. Even at a high flow rate of 50 mL·min -1 , the capture efficiencies of the PU-CNT-DDAs for Escherichia coli and Staphylococcus aureus remained 94.7% and 98.8%, respectively. This approach circumvents pathogen lysis and mortality, significantly curtails the release of PAMPs, and hampers the production of pro-inflammatory cytokines. Therefore, hemoperfusion using porous PU-CNT-DDAs as pathogen traps to capture active pathogens and alleviate inflammation opens a new route for sepsis therapy.

Aqueous zinc-bromine batteries (ZBBs) are highly promising because of the advantages of safety and cost. Compared with flow ZBBs, static ones without the assistance of pumping and tank components possess decreased cost and increased energy density and efficiency. Yet, the issues of Zn dendrites and shuttle effect of polybromide ions (Br n - ) are more serious in nonflow ZBBs. Meanwhile, the hydrogen evolution reaction (HER) and the sluggish kinetics of the Br 2 /Br - couple are also in-negligible. Herein, a compressive approach, the cation-exchange membrane (CEM) coating on Zn anodes and N-defect decoration toward carbon felt cathodes, is developed. The CEM with cation-only function can inhibit the formation of Zn dendrites via tuning the Zn 2+ flow at the interface, block the noncationic substances, and hence prevent the shuttle of Br 2 /Br n - and the water decomposition-concerned HER. The optimized nonflow ZBBs can deliver high Coulombic, voltage, and energy efficiencies of 94.1, 92.8, and 87.4%, respectively, which can be well remained in 1000 cycles. Meanwhile, the output voltage is as high as 1.7 V at 10 mA cm -2 with a high areal capacity of 2 mA h cm -2 , and a LED with a rated voltage of 1.6 V can be powered successfully, exhibiting high application value.

We demonstrate the application of a recurrent neural network (RNN) to perform multistep and multivariate time-series performance predictions for stirred and static mixers as exemplars of complex multiphase systems. We employ two network architectures in this study, fitted with either long short-term memory and gated recurrent unit cells, which are trained on high-fidelity, three-dimensional, computational fluid dynamics simulations of the mixer performance, in the presence and absence of surfactants, in terms of drop size distributions and interfacial areas as a function of system parameters; these include physicochemical properties, mixer geometry, and operating conditions. Our results demonstrate that while it is possible to train RNNs with a single fully connected layer more efficiently than with an encoder-decoder structure, the latter is shown to be more capable of learning long-term dynamics underlying dispersion metrics. Details of the methodology are presented, which include data preprocessing, RNN model exploration, and methods for model performance visualization; an ensemble-based procedure is also introduced to provide a measure of the model uncertainty. The workflow is designed to be generic and can be deployed to make predictions in other industrial applications with similar time-series data., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The skeletal transformations of diterpenoid forskolin were achieved by employing an oxidative rearrangement strategy. A library of 36 forskolin analogues with structural diversity was effectively generated. Computational analysis shows that 12 CTD compounds with unique scaffolds and ring systems were produced during the course of this work.

ConspectusSince their commercialization in the 1990s, lithium-ion batteries (LIBs) have been increasingly used in applications such as portable electronics, electric vehicles, and large-scale energy storage. The increasing use of LIBs in modern society has necessitated superior-performance LIB development, including electrochemical reversibility, interfacial stability, efficient kinetics, environmental adaptability, and intrinsic safety, which is difficult to simultaneously achieve in commercialized electrolytes. Current electrolyte systems contain a solution with Li salts (e.g., LiPF 6 ) and solvents (e.g., ethylene carbonate and dimethyl carbonate), in which the latter dissolves Li salts and strongly interacts with Li + (lithiophilic feature). Only lithiophilic agents can be functionally modified (e.g., additives and solvents), altering the bulk and interfacial behaviors of Li + solvates. However, such approaches alter pristine Li + solvation and electrochemical processes, making it difficult to strike a balance between the electrochemical performance and other desired electrolyte functions. This common electrolyte design in lithiophilic solvents shows strong coupling among formulation, coordination, electrochemistry, and electrolyte function. The invention of lithiophobic cosolvents (e.g., multifluorinated ether and fluoroaromatic hydrocarbons) has expanded the electrolyte design space to lithiophilic (interacts with Li + ) and lithiophobic (interacts with solvents but not with Li + ) dimensions. Functional modifications switch to lithiophobic cosolvents, affording superior properties (carried by lithiophobic cosolvents) with little impact on primary Li + solvation (dictated by lithiophilic solvents). This electrolyte engineering technique based on lithiophobic cosolvents is the 2D electrolyte (TDE) principle, which decouples formulation, coordination, electrochemistry, and function. The molecular-scale understanding of TDEs is expected to accelerate electrolyte innovations in next-generation LIBs.This Account provides insights into recent advancements in electrolytes for superior LIBs from the perspective of lithiophobic agents (i.e., lithiophobic additives and cosolvents), establishing a generalized TDE principle for functional electrolyte design. In bulk electrolytes, a microsolvating competition emerges because of cosolvent-induced dipole-dipole and ion-dipole interactions, forming a loose solvation shell and a kinetically favorable electrolyte. At the electrode/electrolyte interface, the lithiophobic cosolvent affords reliable passivation and efficient desolvation, with interfacial compatibility and electrochemical reversibility even under harsh conditions. Based on this unique coordination chemistry, functional electrolytes are formulated without significantly sacrificing their electrochemical performance. First, lithiophobic cosolvents are used to tune Li + -solvent affinity and anion mobility, promoting Li + diffusion and electrochemical kinetics of the electrolyte to benefit high-rate and low-temperature applications. Second, the lithiophobic cosolvent undergoes less thermally induced decomposition and constructs a thermally stable interphase in TDEs, affording electrolytes with high-temperature adaptability and cycling stability. Third, the lithiophobic cosolvent modifies the local Li + -solvent-anion topography, controlling electrolyte electrochemical reversibility to afford numerous promising solvents that cannot be used in common electrolyte design. Finally, the lithiophobic cosolvent mitigates detrimental crosstalk between flame retardants and carbonate solvents, improving the intrinsic electrolyte safety without compromising electrochemical performance, which broadens the horizons of electrolyte design by optimizing versatile cosolvents and solvents, inspiring new ideas in liquid electrochemistry in other battery systems.

Inflammatory bowel disease (IBD) is a common disease of the digestive system, and an excessive immune response mediated by the nuclear factor κ-B (NF-κB) signaling pathway is an essential etiology. Recent studies have found that bovine milk exosomes can improve intestinal mucosal health by delivering microRNA (miRNA), but the mechanism of action is so far unknown. In the present study, we analyzed the differential expression profiles of miRNA in colostrum and mature milk exosomes using high-throughput sequencing, based on the demonstration that colostrum exosomes inhibit the lipopolysaccharide (LPS)-induced intestinal epithelial NF-κB inflammatory pathway better than mature milk exosomes. The bta-miR-30a-5p, which is specifically highly expressed in colostrum, was screened, and its predicted target gene TRAM was found to be closely related to the NF-κB signaling pathway by functional enrichment analysis. Further, we used gene overexpression and silencing techniques and found that the bta-miR-30a-5p transfection treatment was confirmed to inhibit LPS-induced NF-κB signaling pathway activation and downstream pro-inflammatory factor expression, while the expression of its potential target gene, TRAM, was also suppressed. It is hypothesized that the high expression of bta-miR-30a-5p in colostrum, which targets TRAM to inhibit the downstream NF-κB inflammatory pathway, may be one of the molecular mechanisms responsible for its superior effect on resisting inflammatory attack compared to mature milk.

Alleviating the injury of type II alveolar epithelial cells (AEC 2s) and inhibiting the activation and differentiation of fibroblasts are significant for improving the therapeutic effect of idiopathic pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles (ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small interfering RNA targeting transforming growth factor β1 (si TGF-β 1) were developed for enhanced IPF therapy. ASNPs showed high loading and intracellular delivery efficiency for AST and si TGF-β 1. After the injection of ASNPs in an IPF mice model, the loaded AST largely scavenged reactive oxygen species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby ensuring the integrity of the alveolar epithelium. Meanwhile, si TGF-β 1, delivered by ASNPs, significantly silenced the expression of TGF-β1 in fibroblasts, inhibiting the differentiation of fibroblasts into myofibroblasts as well as reducing the excessive deposition of extracellular matrix (ECM). The combined use of the two drugs exhibited an excellent synergistic antifibrotic effect and was conducive to minimizing alveolar epithelial damage. This work provides a codelivery strategy of AST and si TGF-β 1, which shows great promise for the treatment of IPF by simultaneously reducing alveolar epithelial damage and inhibiting fibroblast activation.

Ferritin nanocages possess remarkable structural properties and biological functions, making them highly attractive for applications in functional materials and biomedicine. This comprehensive review presents an overview of the molecular characteristics, extraction and identification of ferritin, ferritin receptors, as well as the advancements in the directional design of high-order assemblies of ferritin and the applications based on its unique structural properties. Specifically, this Review focuses on the regulation of ferritin assembly from one to three dimensions, leveraging the symmetry of ferritin and modifications on key interfaces. Furthermore, it discusses targeted delivery of nutrition and drugs through facile loading and functional modification of ferritin. The aim of this Review is to inspire the design of micro/nano functional materials using ferritin and the development of nanodelivery vehicles for nutritional fortification and disease treatment.

Artificial synaptic devices are emerging as contenders for next-generation computing systems due to their combined advantages of self-adaptive learning mechanisms, high parallel computation capabilities, adjustable memory level, and energy efficiency. Optoelectronic devices are particularly notable for their responsiveness to both voltage inputs and light exposure, making them attractive for dynamic modulation. However, engineering devices with reconfigurable synaptic plasticity and multilevel memory within a singular configuration present a fundamental challenge. Here, we have established an organic transistor-based synaptic device that exhibits both volatile and nonvolatile memory characteristics, modulated through gate voltage together with light stimuli. Our device demonstrates a range of synaptic behaviors, including both short/long-term plasticity (STP and LTP) as well as STP-LTP transitions. Further, as an encoding unit, it delivers exceptional read current levels, achieving a program/erase current ratio exceeding 10 5 , with excellent repeatability. Additionally, a prototype 4 × 4 matrix demonstrates potential in practical neuromorphic systems, showing capabilities in the perception, processing, and memory retention of image inputs.

Thrombus and cardiovascular diseases pose a significant health threat, and dietary interventions have shown promising potential in reducing the incidence of these diseases. Marine bioactive proteins and peptides have been extensively studied for their antithrombotic properties. They can inhibit platelet activation and aggregation by binding to key receptors on the platelet surface. Additionally, they can competitively anchor to critical enzyme sites, leading to the inhibition of coagulation factors. Marine microorganisms also offer alternative sources for the development of novel fibrinolytic proteins, which can help dissolve blood clots. The advancements in technologies, such as targeted hydrolysis, specific purification, and encapsulation, have provided a solid foundation for the industrialization of bioactive peptides. These techniques enable precise control over the production and delivery of bioactive peptides, enhancing their efficacy and safety. However, it is important to note that further research and clinical studies are needed to fully understand the mechanisms of action and therapeutic potential of marine bioactive proteins and peptides in mitigating thrombotic events. The challenges and future application perspectives of these bioactive peptides also need to be explored.

Fractured gas condensate reservoirs (FGCR) are a complex, special, and highly valuable type of gas reservoir, accounting for a significant proportion of gas reservoir development. In recent years, with the continuous advancement of horizontal well technology, it has become the main approach for the development of FGCR. The current model is unable to accurately represent the fluid distribution in the near-well area of horizontal wells due to the unique retrograde condensation phenomenon in GCR. Additionally, the presence of fractures complicates the solution of traditional analytical models. In response to this issue, this paper proposes a novel semianalytical model for horizontal wells in FGCR, which incorporates natural fractures, multiphase flow, and the influence of stress sensitivity on pressure response. A dual-porosity model is employed to simulate fractured reservoirs, and a four-region radial composite model is developed to characterize multiphase flow resulting from retrograde condensation in GCR. The pseudopressure transform, Pedrosa transform, Laplace transform, and Finite Cosine transform are utilized to address the nonlinear partial differential equation. A systematic verification of the semianalytical solution is confirmed through a comparison with the numerical solution from computer modeling group (CMG). We thoroughly explain the physical significance of the various features by identifying the 12 flow regimes of the typical curve. Furthermore, we offer a method for assessing the extent of retrograde condensation and the size of the retrograde condensate region based on the curve's characteristics. Finally, the pressure measurements recorded from the Bohai field are carried out to validate the accuracy of the proposed model. The results show that the predictions of the new model are in good agreement with the actual production data, demonstrating the proposed solution's applicability., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Enantioenriched 2-azabicyclo[3.1.0]hexanes are accessed from readily available allyl substituted α-isocyanoesters by intramolecular (1 + 2) cycloaddition with the olefinic moiety and isocyano carbon as the respective C2 and C1 units. Cyclopropanation is initiated by 1,1-hydrocupration of isocyanide followed by formimidoylcopper to copper α-aminocarbenoid equilibration and subsequent (1 + 2) cycloaddition. The unprecedented copper/chiral phosphoric acid (CPA) catalytic system can be operated in the presence of water under air, delivering a variety of 2-azabicyclo[3.1.0]hexanes containing an angular all-carbon quaternary stereocenter in good to excellent yields and enantioselectivity.

High-performance dielectric nanocomposites are promising candidates for thin-film dielectric capacitors for high-power pulse devices. However, the existing nanocomposites suffer from low charge-discharge efficiency (η), which results in severe generation and accumulation of Joule heat and subsequently the failure of the devices. In this work, we report nacre-inspired dielectric nanocomposites with outstanding η, which are enabled by superspreading shear flow-induced highly aligned two-dimensional (2D) nanofillers. Taking boron nitride nanosheets (BNNS) as an example, the highly aligned BNNS in the poly(vinylidene fluoride) (PVDF)-based nanocomposites contributes to a highly efficient Coulomb blockade effect for the injected charge carriers. Therefore, the bioinspired nanocomposites with highly aligned BNNS show significantly reduced dielectric loss (tan δ) (63.3%) and improved η (144.8%), compared to the ones with partially aligned nanosheets fabricated by solution casting. Furthermore, the optimized loading content of BNNS is as low as 3.6 wt %. The resulting nanocomposites exhibit reduced tan δ (0.018) and enhanced E b (687 kV/mm), η (71%), and U e (16.74 J/cm 3 ). Our work demonstrates that the realization of high alignment of 2D nanofillers enabled by the superspreading shear flow is a promising way for the development of high-performance dielectric nanocomposites.

Sodium-ion batteries (SIBs) are considered as an alternative to and even replacement of lithium-ion batteries in the near future in order to address the energy crisis and scarcity of lithium resources due to the wide distribution and abundance of sodium resources on the earth. The exploration and development of high-performance anode materials are critical to the practical applications of advanced SIBs. Among various anode materials, bimetallic oxides (BMOs) have attracted special research attention because of their abundance, easy access, rich redox reactions, enhanced capacity and satisfactory cycling stability. Although many BMO anode materials have been reported as anode materials in SIBs, very limited studies summarized the progress and prospect of BMOs in practical applications of SIBs. In this review, recent progress and challenges of BMO anode materials for SIBs have been comprehensively summarized and discussed. First, the preparation methods and sodium storage mechanisms of BMOs are discussed. Then, the challenges, optimization strategies, and sodium storage performance of BMO anode materials have been reviewed and summarized. Finally, the prospects and future research directions of BMOs in SIBs have been proposed. This review aims to provide insight into the efficient design and optimization of BMO anode materials for high-performance SIBs.

This study explored the effectiveness of hydrothermal liquefaction (HTL) in converting sewage sludge (SS) into high-quality biocrude. It scrutinized the influence of various solvents, including conventional choices like dichloromethane (DCM) and hexane, alongside environmentally friendly alternatives, such as ethyl butyrate (EB) and ethyl acetate (EA). HTL experiments, conducted at 350 °C for 60 min in a 20 mL batch reactor, include solvent-based biocrude extraction. Notably, EB showed the highest extraction yield (50.1 wt %), the lowest nitrogen distribution (5.4% with 0.32 wt %), and a remarkable 74% energy recovery (ER), setting a noteworthy benchmark in nitrogen reduction. GCMS analysis reveals EB-derived biocrude's superiority in having the least heteroatoms and nitrogenous compounds compared to hexane, EA, and DCM. Solid residues from hexane, EB, and EA displayed the highest nitrogen distribution range (62-68%), hinting at potential applications in further processes. These findings significantly inform solvent selection for efficient and sustainable waste-to-energy conversion. While promising, the study emphasizes the need to explore solvent-solute interactions further to optimize biocrude quality, highlighting the pivotal role of solvent choice in advancing clean, cost-effective waste-to-energy technologies., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Dendritic cells (DCs) play a crucial role in HIV-1 infection of CD4+ T cells. DC-SIGN, a lectin expressed on the surface of DCs, binds to the highly mannosylated viral membrane protein gp120 to capture HIV-1 virions and then transport them to target T cells. In this study, we modified peptide C34, an HIV-1 fusion inhibitor, at different sites using different sizes of the DC-SIGN-specific carbohydrates to provide dual-targeted HIV inhibition. The dual-target binding was confirmed by mechanistic studies. Pentamannose-modified C34 inhibited virus entry into both DC-SIGN+ 293T cells (52%-71% inhibition at 500 μM) and CD4+ TZM-b1 cells (EC 50 = 0.7-1.7 nM). One conjugate, NC-M5, showed an extended half-life relative to C34 in rats ( T 1/2 : 7.8 vs 1.02 h). These improvements in antiviral activity and pharmacokinetics have potential for HIV treatment and the development of dual-target inhibitors for pathogens that require the involvement of DC-SIGN for infection.

Excited triplet states of wastewater effluent organic matter ( 3 EfOM*) are known as important photo-oxidants in the degradation of extracellular antibiotic resistance genes (eArGs) in sunlit waters. In this work, we further found that 3 EfOM* showed highly selective reactivity toward 2'-deoxyguanosine (dG) sites within eArGs in irradiated EfOM solutions at pH 7.0, while it showed no photosensitizing capacity toward 2'-deoxyadenosine, 2'-deoxythymidine, and 2'-deoxycytidine (the basic structures of eArGs). The 3 EfOM* contributed to the photooxidation of dG primarily via one-electron transfer mechanism, with second-order reaction rate constants of (1.58-1.74) × 10 8 M -1 s -1 , forming the oxidation intermediates of dG (dG(-H) • ). The formed dG(-H) • could play a significant role in hole hopping and damage throughout eArGs. Using the four deoxynucleosides as probes, the upper limit for the reduction potential of 3 EfOM* is estimated to be between 1.47 and 1.94 V NHE . Compared to EfOM, the role of the triplet state of terrestrially natural organic matter ( 3 NOM*) in dG photooxidation was minor (∼15%) mainly due to the rapid reverse reactions of dG(-H) • by the antioxidant moieties of NOM. This study advances our understanding of the difference in the photosensitizing capacity and electron donating capacity between NOM and EfOM and the photodegradation mechanism of eArGs induced by 3 EfOM*.