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• Local corrosion and axial compression tests on 11 steel tubes were performed. • The stress development of a local corroded tube under load and the cause were analyzed. • An experimentally verified simulation method was used for parametric analysis. • The effects of various corrosion conditions on the degradation ratio of bearing capacity were quantitatively discussed. The sustainability of spatial structures, where the main bearing members are steel tubes, is becoming more and more prominent. In order to investigate the effect of local corrosion on the mechanical properties and ultimate compressive strength of circular steel tubes, outdoor accelerated corrosion tests on 11 steel tubes were conducted considering the effects of different corrosion locations and corrosion degrees. The experimental results showed that the ultimate bearing capacity of the specimens was significantly affected by local corrosion, and the corrosion in the middle of the tube was more unfavorable than that in the end. Moreover, local corrosion can change the failure phenomenon of circular steel tubes. Finite element analysis on the bearing capacity of circular steel tubes after local corrosion was carried out, and the reliability of the simulation method was verified by comparison with experimental findings. The stress evolution on different sections during axial compression was also analyzed. Finally, the effect of different corrosion conditions on the bearing capacity was studied using parametric analysis. The analysis results demonstrated that the circumferential corrosion ratio and corrosion depth are important indices to evaluate the corrosion effect. Meanwhile, it was found that the corrosion location has a significant impact on the residual bearing capacity of tubes; however, the impact decreases with the increase in circumferential corrosion ratio and corrosion depth. The research results of the present work can provide a technical reference for the study of the mechanical properties of building components, such as round steel tubes, after corrosion. [ABSTRACT FROM AUTHOR]

Corrosion-induced durability has become a critical issue for aging spatial structures using steel tubes as primary load-carrying structural components. Tremendous efforts have been made in predicting the ultimate strength of steel tubes under axial compression but understanding corrosion-induced buckling remains a challenge due to uncertainty of localized defects. To experimentally investigate the effect of localized corrosion on steel tubes, a modified galvanic method was developed to generate predefined corroded defects at targeted locations. A total of 24 tubes with different slenderness ratios were produced with various localized corroded defects, and then axially compressed to obtain ultimate strengths. Our experiments showed that the galvanic method could efficiently generate localized defects that could change the direction of buckling and significantly lower the ultimate strength of tubes. Further, the corrosion depth has the largest effect on the residual capacity of the tubes among three geometric characteristics of corroded patches. The influence of circumferential corrosion size is greater than that of longitudinal corrosion size due to the deviation of section centroid. From a practical perspective, our experiments indicate that the ultimate strengths of steel tubes can be lower than those estimated by both US and Chinese codes when the localized corrosion ratio exceeds 15%. Thus, the localized corrosion should be checked regularly during the maintenance routine such that buckling-induced failure can be avoided in advance. • A test method for simulating localized corrosion of construction tube was designed. • Both initial bending measurements and axial compression tests were conducted on 24 tubes. • Different corrosion shapes, depths and slenderness ratios of tubes are considered. • Circumferential corrosion ratio has significant influence on the residual bearing capacity. • Test results were compared with the calculations by the American and Chinese codes. [ABSTRACT FROM AUTHOR]

• Tensile tests of bolt-ball joint with insufficient bolt connection are done. • The detailed FEM with thread part is built and verified. • The consistent work of sleeve and bolt determine the bending behavior of joint. • Failure models of defective joint under tension and bending moment are obtained. • Stability of reticulated shell with insufficient bolt connection defect is studied. This paper is aimed at exploring the mechanical behavior of bolt-ball joint with insufficient screwing depth of bolt. Such insufficient bolt connection was quantified as the thread screwing error. Experimental work was conducted to investigate the tensile behavior of the bolt-ball joint with insufficient bolt connection. It was found that three failure modes occurred in the joint, including the tube failure, bolt rod failure and thread failure. The tensile capacity of joint with thread failure decreased in an approximate linear manner with respect to the thread screwing error. A detailed finite element model of bolt–ball joint with thread part was established and verified by the tension test and a previous bending test. The moment-rotation curves of bolt–ball joint with insufficient bolt connection were obtained via the detailed model. These curves were then used to study the stability of Kiewitt 8 single-layer reticulated shells considering bolt-ball joints with insufficient bolt connection. The results showed that the stability capacity of reticulated shells with different rise-span ratios exhibited varied decrease. An obvious decrease occurred on the reticulated shells with 1/8 rise-span ratio. The proposed finite element methods provide a basic for the further parameter analysis of single-layer reticulated shells. [ABSTRACT FROM AUTHOR]

[Display omitted] • Highly dispersed CeO x decorated mesoporous silica promotes Ni-catalyzed CO 2 methanation. • The catalyst exhibits a 3-fold increase in activity and enhanced CH 4 selectivity compared to the Ce-free catalyst. • The oxygen vacancy sites contributed by CeO x present high adsorption and dissociation ability of CO 2. • The in-situ FT-IR and kinetic isotope results indicate that CO 2 activation is the rate-determining step of the reaction. CO 2 methanation is a key step in the power-to-gas technology for storing and distributing renewable energy as energy vectors. Due to thermodynamic constraints, highly active catalysts below about 300 °C are necessary. We demonstrate that their preparation is possible by supporting Ni nanoparticles over highly dispersed CeO x species decorating mesopores silicate (mSiO 2) obtained by a template-free method. The CeO x decorated mSiO 2 exhibits a 3-fold increase in activity and enhanced CH 4 selectivity (98.7 % at 300 °C) compared to the Ni/mSiO 2 catalyst. The performances are superior compared to the literature data. A systematic characterisation by physisorption, XPS, XAFS, UV–Vis and HR-TEM shows a uniform dispersion of highly dispersed CeO x within the mesoporous silica framework. The CO 2 hydrogenation properties were investigated in a fixed-bed flow reactor and complemented by CO 2 -TPD, CO 2 -TPSR, in-situ FTIR, and D 2 kinetic isotope experiments. The results show that highly dispersed CeO x exhibits excellent CO 2 adsorption and dissociation abilities. The inverse kinetic isotope effect indicates that CO 2 activation is the rate-determining step of the reaction. CO 2 is strongly adsorbed on CeO x to form bidentate carbonate, which accelerates the generation of CO while avoiding the adsorption of CO 2 on Ni nanoparticles. [ABSTRACT FROM AUTHOR]

• Eccentric compression test of circular steel tube with bolt–ball joint was done. • The size of sleeve and bolt had an effect on stability capacity. • The detailed FEM with bolt thread was built and verified. • The degradation characteristics of the buckling stability is obtained. • Reference is provided for the tube with eccentricity in engineering design. An issue that frequently occurs during the installation of a spatial grid structure is that the tube exhibits bending under installation eccentricity, and the buckling stability of the tube significantly decreases. In the study, eccentric compression tests of circular steel tube with a bolt–ball joint are carried out, in which three types of joint specifications and three types of installation eccentricities are considered. The degradation characteristics of the buckling stability of circular steel tubes under different installation eccentricities are obtained via tests. Similar phenomena of tube buckling are observed under different installation eccentricities. Additionally, detailed finite element models with bolt threads are established via ANSYS. A comparison of simulation and test results indicate good agreement, and this confirms the validity of the numerical simulation method. Then, a total of eighteen simulation schemes for the buckling behavior of tube under different eccentricities are studied, regarding three different joint specifications with six tube specifications for each. The results indicate that the stability capacity decreases in an approximate linear manner with respect to the installation eccentricity in the range of 0–15 mm, which is consistent to the test results, and the decreasing speed slightly drops while the eccentricity goes large. A reduction factor is proposed as the reference for considering the reduction of stability capacity of the tube under different eccentricities in engineering design. [ABSTRACT FROM AUTHOR]

The antineoplastic gefitinib has a low aqueous solubility, leading to poor absorption rates. To overcome this problem, microparticles (MP) were prepared using solution‐enhanced dispersion by supercritical fluids (SEDS) with supercritical CO2 and the cosolvents dichloromethane and ethanol. The results showed that the use of SEDS resulted in the formation of smaller particles and rendered the usually heterogeneous crystals of the crude drug pure and uniform. Furthermore, the reduction in the MP size increased the dissolution rate of gefitinib, and in vitro cytotoxicity assays indicated that the MP inhibited the proliferation of A549 cells to a larger extent than did the crude drug. Given the beneficial properties of the MP, SEDS could potentially be used to micronize drugs for therapeutic applications. Microparticles (MP) of gefitinib prepared using solution‐enhanced dispersion by supercritical fluids resulted in the formation of smaller particles and pure and uniform crystals of the crude drug. The reduced MP size increased the dissolution rate of gefitinib and the MP inhibited A549 cell proliferation more effectively than the crude drug. [ABSTRACT FROM AUTHOR]

[Display omitted] • DP and DE were selected as the indexes of enhanced drug solubility. • Drug solubility related to clathrate compositions and operating conditions were collected. • Four excipients (PEG, PVP, HPMC and cyclodextrin) in the clathrates were studied. • DP and DE were predicted simultaneously by Random Forest firstly. Although complexation technique has been documented as a promising strategy to enhance the dissolution rate and bioavailability of water-insoluble drugs, prediction of the enhanced drug solubility related to clathrate compositions and operating conditions is still a challenge. Herein, clathrate compositions (drug content (DC), drug molecular weight (M) and molar ratio (Ratio)), operating conditions (drug concentration (C), pH, pressure (P), temperature (T) and dissolution time (t)) under the different excipients (PEG, PVP, HPMC and cyclodextrin) as main solubilizers of the clathrates condition as input parameters were used to predict two indexes (drug dissolved percentage and dissolution efficiency) simultaneously through machine learning method for the first time. The results show that PVP as the main solubilizer of clathrates had higher prediction accuracy to the drug dissolved percentage, and HPMC as the main solubilizer of clathrates had higher prediction accuracy to the drug dissolution efficiency. In addition, the influence of various factors and interactions on the target variables were analyzed. This study affords achievable hints to the quantitative prediction of the drug solubility affected by various compositions and different operating conditions. [ABSTRACT FROM AUTHOR]

Highlights • Mechanical behavior of containment during prestressing construction is studied. • A refined model of a prestressed concrete containment is established. • Accuracy of simulation method is verified by comparing with measured data on site. • A reasonable optimization scheme for prestressing construction is proposed. Abstract Taking a third generation nuclear power plant as the research background, a refined model of a prestressed concrete containment which consisted of 270 complex spatial prestressed tendons was accurately established, using FE software ABAQUS. The cooling method was adopted to simulate the tensioning process of tendons. The simulation method of the tensioning of tendons during the prestressing construction of containment was verified by comparing with the measured data on site of the practical project. The mechanical behavior of the containment during the prestressing construction according to the prestressing construction scheme on site was studied in detail. Then the influence of steel liner and reinforcement on mechanical behavior of the containment during the prestressing construction of prestressed tendons was discussed. Finally, four prestressing construction schemes were analyzed and a reasonable optimization scheme was obtained. [ABSTRACT FROM AUTHOR]

[Display omitted] • DES and CA were encapsulated jointly with a hydrophobic and permeable shell. • Specific surface area was increased by encapsulation to reduce transfer resistance. • Little water in CU was utilized via adding CA to intensify CO 2 capture. • Hydrophobicity of shell materialcan prevent water absorption during CO 2 absorption. • High absorption capacity, rate, selectivity and more recycles were achieved. Excessive carbon dioxide (CO 2) emissions from fossil fuel combustion have a profound impact on environment, leading to different associated climate disasters. Although deep eutectic solvents (DES) have the advantage of high absorption capacity of CO 2 , their high viscosities sharply decrease absorption performance due to the low absorption rates. Herein, one of DES choline chloride / urea (CU) and carbonic anhydrase (CA) was encapsulated jointly by microfluidics and crosslinked thermally (microcapsule@(CU + CA)), which was designed for high capture performance of CO 2. The absorption abilities of microcapsules have been significantly improved by the increase of specific surface area, in which the absorption capacity and absorption rate of microcapsule@(CU + CA) were 74 times and 253 times higher than that of neat CU. In addition, the selectivity of CO 2 /CH 4 also increased 62 times via encapsulation. The high cyclic performance of microcapsule@(CU + CA) was achieved for its high absorption performance and high ability to desorb CO 2 from microcapsule. DES and CA encapsulated jointly by microfluidics can realize high absorption capacity, high absorption rate and high absorption selectivity simultaneously, and it also provides a potential pathway for the efficient capture of various gases. [ABSTRACT FROM AUTHOR]

• A new type of flexible TCC scheme is proposed for low-temperature water treatment. • Thermal structure and pressure distribution of TCC in different month are analyzed. • Thermal structure in different month is significantly influenced by TCC. • Both static and dynamic pressure difference increase with thermal stratification. • Static pressure difference is significantly higher than the dynamic pressure difference. Stratified water temperature and low temperature outflow water caused by water storage characteristics in deep reservoirs are common practical problems. The temperature-control curtain (TCC) is a novel low-temperature water treatment technique, characterized by a simple structure and low cost. In the present paper, a new type of flexible TCC scheme is proposed. Moreover, its applicability in engineering is explored by analyzing the thermal structure and hydrodynamic characteristics of the TCC. The general notions and theoretical basis of Boussinesq approximation for thermal flow are first elaborated. Then, the three-dimensional TCC form is obtained through the structural nonlinear analysis method based on Vector Form Intrinsic Finite Element (VFIFE). In addition, using a reservoir which is under TCC construction in southwest China as the research object, the thermal structure change with and without TCC scenario is observed to evaluate the improvement effect of outflow temperature from April to June. Lastly, taking the flood situation from July to August as the most unfavorable condition, the hydrodynamic characteristics are investigated, including the static and the dynamic pressures applied on the curtain. These preliminary modeling works provide important theoretical references for further engineering operation. [ABSTRACT FROM AUTHOR]

This study investigated the fatigue behavior of fillet weld steel joints (including cruciform and T-welded joints) in marine structures based on experimental tests and finite element analysis (FEA). In cyclic tensile loading, fatigue failure of full-scale specimens consistent with in-plane failure mode of marine structures was validated with ultrasonic phased array testing (UPAT). The effect of incomplete penetration and weld profile on fatigue performance were analyzed based on traction structural stress method. The results showed that the failure mode of load-carrying cruciform joints would change when the incomplete penetration ratio p'/t r reached 0.91. And the concave weld profile is better choice for welded structures anti-fatigue design. In view of the complexity of fatigue performance evaluation of fillet weld joints in IIW and BS7608 standards, a unified master S–N curve covering different plate thicknesses, materials, and weld profiles was proposed. • 1.Fatigue tests and ultrasonic phased array testing of full-scale fillet weld joints. • 2.Fatigue behavior analysis of full-scale fillet weld joints with misalignments, incomplete penetration and different weld profile. • 3.A unified master S–N curve proposed for accurately evaluating fatigue performance of fillet weld joints. [ABSTRACT FROM AUTHOR]

[Display omitted] • The fatigue properties and failure modes of butt joints with backing plates are studied by conducting fatigue tests and UPAT. • A method for predicting failure modes of butt joints with backing plates is proposed. • The fatigue performance of butt joints with backing plates is evaluated based on the IIW and BS7608 standards. • The effect of angular misalignment on the failure modes of test specimens is investigated. • The effect of failure modes on the fatigue properties of the test specimens is studied. In this study, the fatigue behaviors and associated failure modes for a series of aluminum alloy butt joints with backing plates are investigated by conducting fatigue testing and Ultrasonic Phased Array Testing (UPAT). When the fatigue properties of butt joints are evaluated according to International Institute of Welding (IIW) and BS7608, the S-N curves of the corresponding welded joints cannot be determined due to irregular positioning of tack welds prepared, following typical manufacturing practices. To gain insights on how the fatigue test data can be correlated with different backing plate positions, traction structural stress method is used for determining both critical fatigue-critical location and corresponding stress value in the test specimens. It is found that the traction stress method is effective in identifying fatigue-critical location caused by backing plate welds and incorporating angular joint misalignment effects. [ABSTRACT FROM AUTHOR]

• Data of bio-oil characteristic related to pyrolysis were collected systematically. • Regression of viscosity, CV, H/C and O/C was realized via machine learning. • Bio-oil was analyzed from three aspects: quantity, quality and compositions. It is crucial to predict the characteristics of pyrolytic bio-oil accurately for its application, but the prediction results are greatly influenced by biomass compositions and pyrolysis conditions. In this work, different biomass compositions analysis (chemical compositions, ultimate and proximate analysis) and pyrolysis conditions (particle size, heating rate and pyrolysis temperature) were successfully used as input to analyze the characteristics of bio-oil by machine learning method. The model based on ultimate analysis is better for regression analysis of the yield, viscosity and oxygen-carbon ratio (O/C) of bio-oil. The model based on chemical compositions is better for regression analysis of calorific value and hydrogen-carbon ratio (H/C) of bio-oil. Moreover, relative error analysis and scatter diagrams were used to analyze the predicted results. In addition, the analysis of partial dependence diagram shows the influence of various factors and the interactions on the target variables. This study provides feasible thinking for the prediction of the characteristics of bio-oil obtained by biomass with different compositions under different pyrolysis conditions. [ABSTRACT FROM AUTHOR]

The water temperature of the deep dam reservoir is stratified in the vertical direction, which causes the water to have low temperatures at the intake throughout the year. The outflow of low-temperature water will bring problems into the ecological environment. Temperature-control curtain (TCC) is a treatment method for this problem with a low cost and simple structure. This paper presents and analyzes the new flexible TCC from the perspective of structural design and mechanical analysis. First, this paper presents the main mechanical components and the force transferring path of the new flexible TCC. Taking into account the deformations, stress, stability and construction convenience of the structure, three types of cable-net layout schemes have been proposed, namely the Plane TCC, the Elliptic Paraboloid TCC and the Conical Surface TCC. Then, a nonlinear structural analysis method based on the Vector Form Intrinsic Finite Element is proposed for the form evolution and internal force change of the TCC structure under the influence of water pressure. Finally, the mechanical properties of different schemes are also evaluated and compared. This provides a feasible analysis method and a preliminary scheme for practical engineering design. • A new flexible temperature-control curtain is presented for low-temperature water treatment. • Nonlinear analysis method is proposed for the form and force analysis of this TCC structure. • This method can realize large displacement motion tracking until to equilibrium state. • Mechanical properties and key parameters of different schemes are evaluated and compared. • Forms and force changes of Conical Surface TCC under different water levels are obtained. [ABSTRACT FROM AUTHOR]

• Monodisperse and spherical AgNPs were successfully prepared by UILM method. • The formation process of AgNPs was affected by fluid dynamics and chemical effects. • Uncontrolled secondary nucleation and particle growth processes could be inhibited. • Machine learning approach was available for quick evaluation. Due to the high reactivity of Ag+ and uncontrolled growth process, the AgNPs produced by conventional Lee-Meisel method always exhibited larger particle size (30–200 nm) and polydisperse morphology (including spherical, triangular, and rod-like shape). An ultrasound-intensified Lee-Meisel (UILM) method is developed in this study to environmental-friendly and controllable synthesize monodisperse spherical AgNPs (~3.7 nm). Effects of Ag:citrate ratio (1:3 or 5:4), ultrasound power (300 to 1200 W) and reaction time (4 to 24 min) on the physical–chemical properties of AgNPs are investigated systematically. The transmission electron microscope (TEM) images, UV–Vis spectra, average particle size, zeta potential and pH value all demonstrate that crystallization and digestive ripening processes are facilitated in the presence of ultrasound irradiation. Therefore, both chemical reaction rate and mass transfer rate are enhanced to accelerate primary nucleation and inhibit uncontrolled particle growth, leading to the formation of monodisperse spherical AgNPs. Moreover, a machine learning approach - Decision Tree Regressor in conjunction with Shapley value analysis reveal the concentration of reactants is a more important feature affecting the particle. [ABSTRACT FROM AUTHOR]

In the process of tumor metastasis, tumor cells can acquire invasion by excessive uptake of nutrients and energy and interact with the host microenvironment to shape a premetastatic niche (PMN) that facilitates their colonization and progression in the distal sites. Pyruvate is an essential nutrient that engages in both energy metabolism and remodeling of the extracellular matrix (ECM) in the lungs for PMN formation, thus providing a target for tumor metastasis treatment. There is a paucity of strategies focusing on PMN prevention, which is key to metastasis inhibition. Here, we design a bioresponsive nanoparticle (HP/GU) based on a disulfide-cross-linked hyperbranched polyethylenimine (D-PEI) core and a hyaluronic acid (HA) shell with a reactive oxygen species (ROS)-sensitive cross-linker between them to encapsulate glucose oxidase (GOX) and a mitochondrial pyruvate carrier (MPC) inhibitor via electrostatic interaction, which reinforces starvation therapy and reduces PMN formation in the lungs via inhibiting pyruvate metabolism. In tumor cells, GOX and MPC inhibitors can be rapidly released and synergistically reduce the energy supply of tumor cells by consuming glucose and inhibiting pyruvate uptake to decrease tumor cell invasion. MPC inhibitors can also reduce ECM remodeling by blocking cellular pyruvate metabolism to prevent PMN formation. Consequently, HP/GU achieves an efficient inhibition of both primary and metastatic tumors and provides an innovative strategy for the treatment of tumor metastases.

Despite the potential benefits of close-looped insulin delivery systems in regulating glycemic homeostasis and effectively alleviating diabetes, they still encounter challenges such as limited effectiveness in preventing low glycemic episodes due to sluggish glucose response, and issues with the instability of enzymes and carriers. In this study, dually-crosslinked and glucose oxidase (GOx)-immobilized insulin nanogels (DC-NGs@Ins) are developed for rapid-responsive and sustained hypoglycemic therapy. The DC-NGs@Ins with the phenylborate ester linker enabled the insulin release in a close-looped fashion, and moreover, immobilized GOx-generated hydrogen peroxide (H 2 O 2 ) by consuming the glucose, which can further bind to phenylborate ester for enhancing glucose response and accelerating the insulin release. The dually-crosslinked structure (phenylboronic ester and UV-crosslinking) effectively minimized the initial burst release of insulin, thus preventing the potential risk of hypoglycemia. More interestingly, GOx immobilized in the nanogels mitigated GOx leakage and enhanced its multiple utilization compared to free GOx. In vivo study demonstrated that DC-NGs@Ins effectively maintained glycemic levels (BGLs) below 200 mg dL -1 for at least 8 h compared to singly-crosslinked nanogels (SC-NGs@Ins). Therefore, this intelligent insulin delivery system shows potential applications in diabetes treatment., (© 2024 Wiley‐VCH GmbH.)

The formation of pre-metastatic niche (PMN) in a hospitable organ derived from the primary tumor requires the communication between the tumor cells and the host environment. Pyruvate is a fundamental nutrient by which the tumor cells metabolically reshape the extracellular matrix in the lung to facilitate their own metastatic development. Here we report a combination regimen by integrating the photo-sensitizer and the mitochondrial pyruvate carrier (MPC) inhibitor in a dendritic polycarbonate core-hyaluronic acid shell nano-platform with multivalent reversible crosslinker embedded in it (DOH-NI+L) to reinforce photodynamic therapy (PDT) toward the primary tumor and interrupt PMN formation in the lung via impeding pyruvate uptake. We show that DOH-NI+L mediates tumor-specific MPC inhibitor liberation, inhibiting the aerobic respiration for facilitated PDT and restraining ATP generation for paralyzing cell invasion. Remarkably, DOH-NI+L is demonstrated to block the metabolic crosstalk of tumor cell-host environment by dampening pyruvate metabolism, provoking a series of metabolic responses and resulting in the pulmonary PMN interruption. Consequently, DOH-NI+L realizes a significant primary tumor inhibition and an efficient pulmonary metastasis prevention. Our research extends nano-based anti-metastatic strategies aiming at PMN intervention and such a dendritic core-shell nano-inhibitor provides an innovative paradigm to inhibit tumor growth and prevent metastasis efficiently. STATEMENT OF SIGNIFICANCE: In the progression of cancer metastasis, the formation of a pre-metastatic niche (PMN) in a hospitable organ derived from the primary tumor is one of the rate-limiting stages. The current nano-based anti-metastatic modalities mainly focus on targeted killing of tumor cells and specific inhibition of tumor cell invasion, while nanomedicine-mediated interruption of PMN formation has been rarely reported. Here we report a combination regimen by integrating a photo-sensitizer and an inhibitor of mitochondrial pyruvate carrier in a dendritic core-shell nano-platform with a reversible crosslinker embedded in it to reinforce PDT toward the primary tumor and interrupt PMN formation via impeding the uptake of pyruvate that is a fundamental nutrient facilitating aerobic respiration and PMN formation. Our research proposed a nano-based anti-metastatic strategy aiming at PMN intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Glucose -sensitive delivery systems hold great promise as a therapeutic approach for high-incidence diabetes owing to their ability to release insulin whenever elevated glycemia is detected. However, they are unstable in a hyperglycemic environment, which leads to short-term sustained insulin release. Herein, we designed dually crosslinked insulin polyionic micelles (DCM@insulin) based on triblock polymers of o -glycol and phenylboronic acid-functionalized poly(ethylene glycol)-poly(dimethylamino carbonate)-poly(dimethylamino-trimethylene carbonate) (mPEG-P(AC- co -MPD)-PDMAC and mPEG-P(AC- co -MAPBA)-PDMATC, respectively) for sustained glucose-responsive insulin release. DCM@insulin with a phenylboronic acid ester structure (first crosslinking structure) enhanced glycemic responsiveness by regulating insulin release in a hyperglycemic environment. Additionally, the UV-crosslinking structure (second crosslinking structure) formed by the residual double bonds in AC units endowed DCM@insulin with the ability to effectively protect the loaded insulin against protease degradation and avoid burst release under multiple insulin release. The in vivo findings demonstrated that DCM@insulin effectively maintained glycemic levels (BGLs) within the normal range for 6 h in comparison to single-crosslinked micelles (SCM@insulin). Therefore, the glucose-responsive and dually crosslinked polyionic micelle system exhibits potential as a viable option for the treatment of diabetes.

Oral insulin therapies targeting the liver and further simulating close-looped secretion face significant challenges due to multiple trans-epithelial barriers. Herein, ursodeoxycholic acid (UDCA)-decorated zwitterionic nanoparticles (NPs) (UC-CMs@ins) are designed to overcome these barriers, target the liver, and respond to glycemia, thereby achieving oral one-time-per-day therapy. UC-CMs@ins show excellent mucus permeability through the introduction of zwitterion (carboxy betaine, CB). Furthermore, UC-CMs@ins possess superior cellular internalization via proton-assisted amino acid transporter 1 (PAT1, CB-receptor) and apical sodium-dependent bile acid transporter (ASBT, UDCA-receptor) pathways. Moreover, UC-CMs@ins exhibit excellent endolysosomal escape ability and improve the basolateral release of insulin into the bloodstream via the ileal bile acid-binding protein and the heteromeric organic solute transporter (OSTα- OSTβ) routes compared with non-UDCA-decorated C-CMs@ins. Therefore, CB and UDCA jointly overcome mucus and intestinal barriers. Additionally, UC-CMs@ins prevent insulin degradation in the gastrointestinal tract for crosslinked structure, improve insulin accumulation in the liver for UDCA introduction, and effectively regulate glycemia for "closed-loop" glucose control. Surprisingly, oral ingestion of UC-CMs@ins shows a superior effect on glycemia (≈22 h, normoglycemia) and improves postprandial glycemic levels in diabetic mice, illustrating the enormous potential of the prepared NPs as a platform for oral insulin administration in diabetes treatment., (© 2024 Wiley-VCH GmbH.)

Prodrug assembled nanoparticles integrate the merits of both prodrug and nanoparticle, which significantly improve pharmacokinetic parameters, enhance tumorous accumulation and decrease adverse effects, while they are challenged by disassembly upon dilution in blood, masking the superiority of nanoparticles (NPs). Herein, a reversibly "double locked" hydroxycamptothecin (HCPT) prodrug nanoparticle decorated with cyclic RGD peptide (cRGD) is developed for safe and efficient chemotherapy of orthotopic lung cancer in mice. HCPT prodrug is constructed from acetal (ace)-linked cRGD-PEG-ace-HCPT-ace-acrylate polymer, which is self-assembled into the nanoparticles with "the first lock" of HCPT. Then the nanoparticles undergo the in situ UV-crosslinking of the acrylate residues for constructing "the second lock" of HCPT. The obtained "double locked" nanoparticles (T-DLHN) with simple and well-defined construction are demonstrated to possess extremely high stability against 100-fold dilution and acid-triggered "unlock" including de-crosslinking and liberation of the pristine HCPT. In an orthotopic lung tumor of mouse model, T-DLHN reveals a prolonged circulation time of about 5.0 h, superb lung tumor-homing capacity with tumorous drug uptake of about 7.15%ID/g, resulting in significantly boosted anti-tumor activity and reduced adverse effects. Hence, these nanoparticles utilizing "double lock" and acid-triggered "unlock" strategies represent a unique and promising nanoplatform for safe and efficient drug delivery. STATEMENT OF SIGNIFICANCE: Prodrug assembled nanoparticles have the unique properties of the well-defined structure, systemic stability, improved pharmacokinetics, passive targeting and decreased adverse effects. However, prodrug assembled NPs would disassemble against extensive dilution in the blood circulation when intravenously injected into the body. Herein, we have designed a cRGD-directed reversibly "double-locked" HCPT prodrug nanoparticle (T-DLHN) for safe and efficient chemotherapy of orthotopic A549 human lung tumor xenografts. Upon intravenous injection, T-DLHN can overcome the shortcoming of disassembly against extensive dilution, prolong the circulation time due to the "double locked" configuration and then mediate targeted drug delivery into the tumors. After uptaken into the cells, T-DLHN undergoes concurrent de-crosslinking and liberation of HCPT under acidic condition for enhanced chemotherapeutic efficacy with negligible adverse effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Chemotherapy predominates in clinical treatment of prostate cancer (PCa), while irreversible resistance to chemotherapeutics and severe side effects hinder the therapeutic efficacy, especially in castration-resistant PCa (CRPC). Herein, a bombesin (BBN)-decorated two-in-one prodrug (T-NO/E 2 -PMs) incorporating a polymeric nitric oxide (NO) donor and acetal-linked 17β-estradiol (E 2 ) in one backbone is developed, aiming to inhibit androgen receptor (AR) expression, reprogram the tumor microenvironment of CRPC, and enhance estradiol-mediated hypoxic CRPC therapy. Following efficient internalization mediated by BBN, T-NO/E 2 -PMs releases estradiol and NO in response to the unique intracellular environments. Both in vitro and in vivo studies demonstrate that the T-NO/E 2 -PMs nano-prodrug along with NO release potently downregulates AR levels to reverse CRPC and further enhances the chemo-sensitization of estradiol to PCa PC-3 cell apoptosis and the inhibition of metastasis. Collectively, this two-in-one nano-prodrug strategy offers a promising platform for construction of advanced nanomedicine to boost the therapeutic efficacy.

Objective: To observe the correlation between early fluid resuscitation and prognosis in patients with severe acute pancreatitis (SAP)., Methods: SAP patients admitted to the department of critical care medicine of the People's Hospital of Chuxiong Yi Autonomous Prefecture of Yunnan Province from June 2018 to December 2020 were enrolled and analyzed retrospectively. All patients were given the routine treatment according to their condition and relevant diagnostic According to their different prognosis, enrolled patients were divided into death group and survival group. The differences in gender, age, acute physiology and chronic health evaluation II (APACHE II) and Ranson score on admission between the two groups were analyzed. Taking 24 hours as an observation day, the fluid inflow, outflow, and net balance at the first, second, and third 24 hours after admission were recorded, and the ratio of the fluid inflow at the first 24 hours to the total fluid inflow in 72 hours (FV 24 h-1 st ) was calculated as a study index. Using 33% as the standard, compare the proportion of patients in the two groups who achieved FV 24 h-1 st < 33%. The differences of various indicators between the two groups were compared, and the effect of early fluid balance on the prognosis of SAP patients was analyzed., Results: Eighty-nine patients were included in the study (41 in the death group, 48 in the survival group). There were no statistically significant differences on age (years old: 57.6±15.2 vs. 49.5±15.2), gender (male: 61.0% vs. 54.2%), APACHE II score (18.0±2.4 vs. 17.3±2.3), and Ranson score (6.3±1.4 vs. 5.9±1.2) between the death group and the survival group at the time of admission on the intensive care unit (ICU) (all P > 0.05). The fluid intake of the death group in the first 24 hours, the second 24 hours and the third 24 hours after admission to ICU was significantly higher than that of the survival group, and the difference was statistically significant (mL: 4 138±832 vs. 3 535±1 058, 3 883±729 vs. 3 324±516, 3 786±490 vs. 3 212±609, all P < 0.05), and the fluid inflow in the death group at the first 24 hours was greater than 4 100 mL. After treatment, the fluid outflow of the death group at the three 24-hour periods after admission on the ICU was an increasing trend, but it was still significantly less than that of the survival group at the three 24-hour periods (mL: 1 242±465 vs. 1 795±819, 1 536±579 vs. 2 080±524, 1 610±585 vs. 2 932±752, all P < 0.01). Due to the fact that the total fluid inflow and total fluid outflow in the three 24-hour periods in the death group were more than those in the survival group, the net fluid balances in the three 24-hour periods in the death group were still significantly more than those in the survival group finally (mL: 2 896±782 vs. 1 740±725, 2 347±459 vs. 1 243±795, 2 176±807 vs. 338±289, all P < 0.01). There was no difference in FV 24 h-1 st between the death group and survival group [FV 24 h-1 st > 33%: 56.1% (23/41) vs. 54.2% (26/48), P > 0.05]., Conclusions: Fluid resuscitation is an important method for early treatment of SAP, but it also has many adverse reactions. Fluid resuscitation indexes such as fluid inflow, outflow, net balance, and FV 24 h-1 st within 24 to 72 hours after admission are related to the prognosis of patients with SAP, and can be used as indicators to evaluate the prognosis of SAP. The optimized fluid resuscitation strategy can improve the prognosis of patients with SAP.

Poly (ethylene glycol) (PEG)-based nanomedicines are perplexed by the challenges of oxidation damage, immune responses after repeated injections, and limited excretion from the body. As an alternative to PEG, bioinspired zwitterions bearing an identical number of positive and negative ions, exhibit exceptional hydrophilicity, excellent biomimetic nature and chemical malleability, endowing zwitterionic nano-vectors with biocompatibility, non-fouling feature, extended blood circulation and multifunctionality. In this review, we innovatively classify zwitterionic nano-vectors into linear, hyperbranched, crosslinked, and hybrid nanoparticles according to different chemical architectures in rational design of zwitterionic nano-vectors for enhanced drug delivery with an emphasis on zwitterionic engineering innovations as alternatives of PEG-based nanomedicines. Through combination with other nanostrategies, the intelligent zwitterionic nano-vectors can orchestrate stealth and other biological functionalities together to improve the efficacy in the whole journey of drug delivery., (Copyright © 2022. Published by Elsevier B.V.)

Biomass utilization is facing great challenge mainly due to the low profit margin of biomass products. Bio-energy plants using gasification and liquefaction technologies are barely surviving, while biomass to activated carbon (AC) route has been demonstrated economically successful. In this work, spent mushroom substrate was used to produce AC and fuel gas with two different processes using internal flue gas and external air as activation agents, respectively. Experimental work was conducted to produce input data for Aspen Plus simulation including processing temperature, flue gas composition, AC yield, etc. Techno-economic analysis was performed, which reveals a great economic potential of integrating AC production in biomass processing. Air activation has obvious advantage in economic benefits, while the risk of precise temperature control and operation stability needs to be carefully evaluated in large-scale production. Flue gas activation is more reliable and it also generates less CO 2 that is beneficial for the long-term operation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

To study the salt effect of recovering N -methyl-2-pyrrolidone (NMP) from the waste liquid produced in the polyphenylene sulfide (PPS) synthesis process, this study presents vapor-liquid equilibrium (VLE) measurement and correlation for water + NMP, water + NMP + lithium chloride, and water + NMP + sodium chloride at p = 101.3 kPa. The salt effect is discussed and the salts follow the order of lithium chloride > sodium chloride. The NRTL model was used for the correlation with binary parameters of water + NMP, water + NMP + lithium chloride, and water + NMP + sodium chloride. The correlation showed good agreement with experimental data; root-mean-square deviations are less than 0.48 K for the equilibrium temperature and 0.005 for the vapor-phase mole fraction of water., Competing Interests: The authors declare no competing financial interest., (© 2020 The Authors. Published by American Chemical Society.)

We investigated the effects of different oxygen tension (21% and 2.5% O 2 ) on the chondrogenesis of different cell systems cultured in pH-degradable PVA hydrogels, including human articular chondrocytes (hACs), human mesenchymal stem cells (hMSCs), and their cocultures with a hAC/hMSC ratio of 20/80. These hydrogels were prepared with vinyl ether acrylate-functionalized PVA (PVA-VEA) and thiolated PVA-VEA (PVA-VEA-SH) via Michael-type addition reaction. The rheology tests determined the gelation of the hydrogels was controlled within 2-7 min, dependent on the polymer concentrations. The different cell systems were cultured in the hydrogel scaffolds for 5 weeks, and the safranin O and GAG assay showed that hypoxia (2.5% O 2 ) greatly promoted the cartilage matrix production with an order of hAC > hAC/hMSC > hMSC. The real time quantitative PCR (RT-PCR) revealed that the hMSC group exhibited the highest hypertrophic marker gene expression (COL10A1, ALPL, MMP13) as well as the dedifferentiated marker gene expression (COL1A1) under normoxia conditions (21% O 2 ), while these expressions were greatly inhibited by coculturing with a 20% amount of hACs and significantly further repressed under hypoxia conditions, which was comparative to the sole hAC group. The enzyme-linked immunosorbent assay (ELISA) also showed that coculture of hMSC/hAC greatly reduced the catabolic gene expression of MMP1 and MMP3 compared with the hMSC group. It is obvious that the hypoxia conditions promoted the chondrogenesis of hMSC by adding a small amount of hACs, and also effectively inhibited their hypotrophy. We are convinced that coculture of hAC/hMSC using in situ forming hydrogel scaffolds is a promising approach to producing cell source for cartilage engineering without the huge needs of primary chondrocyte harvest and expansion.