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Bioorthogonal reactions involving transition metals have diversified applications in imaging, drug development, chemical catalysis and other fields. Transition metals used to catalyze the bioorthogonal reaction mainly include ruthenium, palladium, copper, and gold. However, the great potential for translational applications of bioorthogonal reaction needs to be further expanded and their reaction efficiency should be improved. Therefore, it is an urgent need for the development of this field to find more suitable catalysts to efficiently catalyze existing biological orthogonal reactions and expand the types of biological orthogonal reactions. Thus, this review not only summarizes those transition metal complexes-based catalysts participating in bioorthogonal reaction and some bioorthogonal reactions involving transition metals inside the cells, but also sheds light into the discovery of new transition metal complexes and their future development in applications.

Polydimethylsiloxane (PDMS) has been widely used to improve the antifouling properties of polyurethane (PU) coatings due to its low surface energy. Herein, a novel type of waterborne polyurethane (WPU) coating with good antifouling and self-healing abilities was synthesized by incorporating PDMS and disulfide bonds. The effects of PDMS and the disulfide content on the thermal, mechanical and surface properties of the coatings were investigated. Benefiting from a rational structural design, the obtained WPU coating manifested superior antifouling properties. In addition, the WPU coating exhibited good healing capabilities owing to the collaboration between dynamic disulfide bonds. Interestingly, the self-healing of an experimental crack occurred at a temperature above 60°C, and the coating recovered its mechanical properties to 95%. This finding has great significance for the design of multifunctional smart coatings for diverse applications.

ABSTRACTConsidering the determining role of TGFβ signaling in the tumor microenvironment (TME) on immune evasion, the inhibition of signaling is expected to enhance the therapeutic efficacy of immunotherapies, especially immune checkpoint blockade (ICB), which is confirmed in preclinical data. However, successive failures in clinical translation occur at the initial stage. To provide a better understanding of TGFβ signaling within the TME and its relation to the individual immunological status, we performed a pan-cancer analysis comparing the activation of TGFβ pathway among different TMEs based on multi-omics data. Compared with non-inflamed tumors, increased TGFβ signaling activity appeared in four non-cancer cell types within TME in inflamed tumors. Significant correlations were revealed between TGFβ signaling and reliable biomarkers for ICB therapy, as well as between TGFβ signaling and HPV status. Our findings contribute to explain the inconsistency between preclinical and clinical research, and are crucial to optimizing upcoming clinical trial design and improving patient stratification for personalized prediction.

Omics applications in nephrology may have relevance in the future to improve clinical care of kidney disease patients. In a short term, patients will benefit from specific measurement and computational analyses around biomarkers identified at various omics-levels. In mid term and long term, these approaches will need to be integrated into a holistic representation of the kidney and all its influencing factors for individualized patient care. Research demonstrates robust data to justify the application of omics for better understanding, risk stratification, and individualized treatment of kidney disease patients. Despite these advances in the research setting, there is still a lack of evidence showing the combination of omics technologies with artificial intelligence and its application in clinical diagnostics and care of patients with kidney disease.

Analysis of medical images, such as radiological or tissue specimens, is an indispensable part of medical diagnostics. Conventionally done manually, the process may sometimes be time-consuming and prone to interobserver variability. Image classification and segmentation by deep learning strategies, predominantly convolutional neural networks, may provide a significant advance in the diagnostic process. In renal medicine, most evidence has been generated around the radiological assessment of renal abnormalities and histological analysis of renal biopsy specimens' segmentation. In this article, the basic principles of image analysis by convolutional neural networks, brief descriptions of convolutional neural networks, and their system architecture for image analysis are discussed, in combination with examples regarding their use in image analysis in nephrology.

· 2D Ti 3 C 2 /3D ZnIn 2 S 4 composites were prepared via a one-pot solvothermal method. · There's no need to peel off the MXene multilayers before its combination with ZnIn 2 S 4. · TAA served as both an intercalator of the Ti 3 C 2 MXene and a sulfur source of ZnIn 2 S 4. · The Ti 3 C 2 /ZnIn 2 S 4 composite performed well in photocatalytic hydrogen production. Herein, a novel strategy was exploited to achieve the delamination of Ti 3 C 2 MXene multilayers into ultrathin flakes by blossom of ZnIn 2 S 4 microflowers via a one-pot solvothermal method. There is no need to peel off the MXene bulk ahead of its combination with the semiconductor. The obtained ZnIn 2 S 4 /Ti 3 C 2 binary composites were applied for visible-light-driven photocatalytic hydrogen production without noble metal cocatalyst, and the optimized sample exhibited a hydrogen-production efficiency of 978.7 μmol h −1 g −1 with the corresponding apparent quantum efficiency of 24.2% at 420 nm, which was 2.7 times higher than bare ZnIn 2 S 4. Through the comprehensive analysis based on spectroscopy measurements, electrochemical techniques and energy band theory, such enhancement was mainly attributed to (1) the highly-exposed surface that was beneficial for the adequate exposure of reactive sites and (2) the intimate contact interface that favored the transfer of photogenerated carriers. This study provides a new way of thinking for synthesizing ultrathin MXene-based composite materials for noble-metal-free and highly-efficient photocatalysis applications. [ABSTRACT FROM AUTHOR]

Articular cartilage has very poor intrinsic healing ability and its repair remains a significant clinical challenge. To promote neocartilage regeneration, we fabricated two collagen (Col) scaffolds functionalized with a porcine decellularized extracellular matrix (dECM) in the forms of particle and solution named pE-Col and sE-Col, respectively. Their differences were systematically compared, including the biochemical compositions, scaffold properties, cell–material interactions, and in situcartilage regeneration. While it is demonstrated that both forms of dECM could enhance the cell recruitment, proliferation, and chondrogenesis of bone marrow stem cells (BMSCs) in vitro, better performance was seen in the sE-Col group, which could quickly provide a more favorable chondrogenic microenvironment for endogenous BMSCs. The superiority of sE-Col was also proved by our in vivostudy, which showed that the sE-Col scaffold achieved better structural hyaline-like neocartilage formation and subchondral bone repair compared to the pE-Col scaffold, according to the gross morphology, biological assessment, and micro-CT imaging analysis. Together, this study suggests that the sE-Col scaffold holds great potential in developing the one-step microfracture-based strategy for cartilage repair and also reminds us that despite dECM being a promising biomaterial in tissue engineering, the optimization of the proper processing methodology would be a crucial consideration in the future design of dECM-based scaffolds in articular cartilage regeneration.

A piezo-photocatalytic therapy based on thermally treated natural sphalerite nanosheet (NSH700 NS) heterojunction was applied to efficiently induce intracellular ROS burst and apoptosis of cancer cells. Upon ultrasound and laser irradiation, the formation of a polarized electric field and band bending of NSH700 NSs allow the directional separation of charges both in the bulk and their interface, thereby minimizing the probability of charge recombination. The piezo-photocatalytic effect leads to an efficient catalytic performance, exhibiting high-performance superoxide radical (O2−) and hydroxyl radical (OH) generation and glutathione (GSH) depletion, which results in a intracellular ROS burst-triggered apoptosis of cancer cells both in vitroand in vivo.

In the past few decades, countless organic and inorganic pollutants caused serious environmental problems all over the world. One way to remove or degrade pollutants in the environment is to use oxidizing agents. Photocatalytic technology uses unlimited solar energy to efficiently oxidize and remove organic pollutants. Recently, perylene diimide (PDI)-based nanomaterials have been widely used in photocatalytic degradation. However, there are no reviews on the use of PDI-based composites to remove organic pollutants from contaminated water. Therefore, a review paper is needed to fully understand the current status and prospects of this field. The main purpose of this work is to highlight the recent progress of PDI-based photocatalysts in the removal of organic pollutants. In this review, the basic molecular design and properties of PDI molecules are first described. Then, strategies to improve the photocatalytic activity of PDI are summarized. The system factor and water chemistry affecting the photocatalytic activity for organic pollutant removal are also discussed. Lastly, the stability and future challenges of PDI-based composites are briefly discussed.

The rising diversity of food preferences and the desire to provide better personalized care provide challenges to renal dietitians working in dialysis clinics. To address this situation, we explored the use of a large language model, specifically, ChatGPT using the GPT-4 model (openai.com), to support nutritional advice given to dialysis patients.

Bufalin is a promising active ingredient in traditional Chinese medicine but has shown limited anticancer applications due to its toxicity. Here, we report BCNPs@gel, a bufalin-containing CaCO3nanoparticle hydrogel, for enhancing cancer treatment through inducing cellular pyroptosis. Under the tumor microenvironment’s low pH conditions, bufalin and Ca2+are released from the delivery system. Bufalin serves as a direct anticancer drug and a Na+/K+-ATPase inhibitor by forcing the Na+/Ca2+exchanger to reverse its function, which transfers Ca2+into cytoplasm and ultimately causes Ca2+overload-triggered pyroptosis. Meanwhile, we found that bufalin can upregulate PD-L1 in tumor cells. In combination with the PD-1 antibody, the delivery system showed a greater performance during the cancer treatment. BCNPs@gel enhances antitumor efficiency, reduces systemic side effects, extends antitumor mechanism of bufalin, and provides new strategies for inducing pyroptosis and calcium overload in cancer immunotherapy via Na+/K+-ATPase inhibitor. This work provides an application model for numerous other traditional Chinese medicine ingredients.

The distance dependence of localized surface plasmon (LSP)-coupled Förster resonance energy transfer (FRET) between Si quantum dots (QDs) is experimentally and theoretically investigated utilizing core–shell nanostructures. The dependence of the energy transfer efficiency, rate, and characteristic distance, as well as the enhancement of the acceptor emission, on the shell thickness is examined. Compared to the structure without assistance of LSP from silver nanoparticles (Ag NPs), the FRET rate is enhanced by a factor of 15, and the Förster radius increases by 50% as a result of plasmon-coupling to the Si QDs and the FRET-assisted exciton transfer from the donors to the acceptors. The potential to tune the characteristic energy transfer distance has implications for applications in nanophotonic devices or sensors.

Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with sustained effects on the brain and behavior in offspring. However, the mechanisms have yet to be determined. We hypothesized that prenatal exposure to ambient PAH in mice would be associated with impaired neurocognition, increased anxiety, altered cortical expression of Bdnfand Grin2b, and greater DNA methylation of Bdnf. Our results indicated that during open-field testing, prenatal PAH–exposed offspring spent more time immobile and less time exploring. Females produced more fecal boli. Offspring prenatally exposed to PAH displayed modest reductions in overall exploration of objects. Further, prenatal PAH exposure was associated with lower cortical expression of Grin2band Bdnfin males and greater Bdnf IVpromoter methylation. Epigenetic differences within the BdnfIV promoter correlated with Bdnfgene expression but not with the observed behavioral outcomes, suggesting that additional targets may account for these PAH-associated effects.

The free vibration analysis of cracked thin plates via a quasi-convex coupled isogeometric-meshfree method is presented. This formulation employs the consistently coupled isogeometric-meshfree strategy where a mixed basis vector of the convex B-splines is used to impose the consistency conditions throughout the whole problem domain. Meanwhile, the rigid body modes related to the mixed basis vector and reproducing conditions are also discussed. The mixed basis vector simultaneously offers the consistent isogeometric-meshfree coupling in the coupled region and the quasi-convex property for the meshfree shape functions in the meshfree region, which is particularly attractive for the vibration analysis. The quasi-convex meshfree shape functions mimic the isogeometric basis function as well as offer the meshfree nodal arrangement flexibility. Subsequently, this approach is exploited to study the free vibration analysis of cracked plates, in which the plate geometry is exactly represented by the isogeometric basis functions, while the cracks are discretized by meshfree nodes and highly smoothing approximation is invoked in the rest of the problem domain. The efficacy of the present method is illustrated through several numerical examples.

Hydrogels have blossomed as superstars in various fields, owing to their prospective applications in tissue engineering, soft electronics and sensors, flexible energy storage, and biomedicines. Two-dimensional (2D) nanomaterials, especially 2D mono-elemental nanosheets (Xenes) exhibit high aspect ratio morphology, good biocompatibility, metallic conductivity, and tunable electrochemical properties. These fascinating characteristics endow numerous tunable application-specific properties for the construction of Xene-based hydrogels. Hierarchical multifunctional hydrogels can be prepared according to the application requirements and can be effectively tuned by different stimulation to complete specific tasks in a spatiotemporal sequence. In this review, the synthesis mechanism, properties, and emerging applications of Xene hydrogels are summarized, followed by a discussion on expanding the performance and application range of both hydrogels and Xenes.

An ultra-accurate isogeometric dynamic analysis is presented. The key ingredient of the proposed methodology is the development of isogeometric higher order mass matrix. A new one-step method is proposed for the construction of higher order mass matrix. In this approach, an adjustable mass matrix is formulated through introducing a set of mass parameters into the consistent mass matrix under the element mass conservation condition. Then the semi-discrete frequency derived from the free vibration equation with the adjustable mass matrix is served as a measure to optimize the mass parameters. In 1D analysis, it turns out that the present one-step method can perfectly recover the existing reduced bandwidth mass matrix and the higher order mass matrix by choosing different mass parameters. However, the employment of the proposed one-step method to the 2D membrane problem yields a remarkable gain of solution accuracy compared with the higher order mass matrix generated by the original two-step method. Subsequently a full-discrete isogeometric transient analysis algorithm is presented by using the Newmark time integration scheme and the higher order mass matrix. The full-discrete frequency is derived to assess the accuracy of space-time discretization. Finally a set of numerical examples are presented to evaluate the accuracy of the proposed method, which show that very favorable solution accuracy is achieved by the present dynamic isogeometric analysis with higher order mass formulation compared with that obtained from the standard consistent mass approach.

Elevations in the intracellular Ca2+concentration are a phenomena commonly observed during stem cell differentiation but cease after the process is complete. The transient receptor potential melastatin 4 (TRPM4) is an ion channel that controls Ca2+signals in excitable and nonexcitable cells. However, its role in stem cells remains unknown. The aim of this study was to characterize TRPM4 in rat dental follicle stem cells (DFSCs) and to determine its impact on Ca2+signaling and the differentiation process. We identified TRPM4 gene expression in DFSCs, but not TRPM5, a closely related channel with similar function. Perfusion of cells with increasing buffered Ca2+resulted in a concentration‐dependent activation of currents typical for TRPM4, which were also voltage‐dependent and had Na+conductivity. Molecular suppression with shRNA decreased channel activity and cell proliferation during osteogenesis but not adipogenesis. As a result, enhanced mineralization and phosphatase enzyme activity were observed during osteoblast formation, although DFSCs failed to differentiate into adipocytes. Furthermore, the normal agonist‐induced first and secondary phases of Ca2+signals were transformed into a gradual and sustained increase which confirmed the channels' ability to control Ca2+signaling. Using whole genome microarray analysis, we identified several genes impacted by TRPM4 during DFSC differentiation. These findings suggest an inhibitory role for TRPM4 on osteogenesis while it appears to be required for adipogenesis. The data also provide a potential link between the Ca2+signaling pattern and gene expression during stem cell differentiation. STEMCells2013;31:167–177

Abstract: A strain smoothing formulation for NURBS (non-uniform rational B-splines) based isogeometric finite element analysis is presented. This approach is formulated within the framework of assumed strain methods and strain smoothing operations. The strain smoothing is defined through strain averaging in the element sub-domains which are subsequently used for numerical integration of the Galerkin weak form. This formulation satisfies the orthogonality condition of the assumed strain methods. Meanwhile the present formulation totally avoids the gradient computation of the rational NURBS basis functions in the formulation of stiffness matrix. A transformation method is employed to accurately enforce the displacement boundary conditions. Numerical results demonstrate that the present formation gives very satisfactory solution accuracy simultaneously with improved computational efficiency.

Application of nitrification inhibitors (NIs) has been widely used to inhibit nitrification and reduce N2O emissions. However, the impacts of NI addition on soil carbon transformation and carbon-degrading microbial communities have not been well explored. Here, a microcosm experiment was carried out, and four treatments were designed: (i) unfertilized control, (ii) urea alone, (iii) urea plus cattle manure, and (iv) urea plus cattle manure with nitrapyrin. The influence of nitrapyrin on soil CO2emissions, carbon-degrading extracellular enzyme activities, and the abundance and diversity of the cbhI community was investigated. Compared to the treatment of urea plus cattle manure, nitrapyrin significantly decreased cumulative CO2emissions by 51.8%. Moreover, cbhI community gene copies and their α-diversities (P< 0.05) were also significantly reduced by nitrapyrin application. A partial least squares path model showed that CO2emission was positively associated with cbhI community α-diversity but negatively associated with nitrapyrin addition. We conclude that the mitigation of soil CO2emissions by nitrapyrin can be ascribed to its effects on decreasing of cellulose-degrading gene community diversity. Our findings provide new insights into the side-effects of nitrapyrin on abating CO2emission.

In management of metabolic syndrome, the traditional Chinese medicine (TCM) is an excellent representative in alternative and complementary medicines with a complete theory system and substantial herb remedies. In this article, basic principle of TCM is introduced and 25 traditional Chinese herbs are reviewed for their potential activities in the treatment of metabolic syndrome. Three herbs, ginseng, rhizoma coptidis (berberine, the major active compound) and bitter melon, were discussed in detail on their therapeutic potentials. Ginseng extracts made from root, rootlet, berry and leaf of Panax quinquefolium (American ginseng) and Panax ginseng (Asian ginseng), are proved for anti-hyperglycemia, insulin sensitization, islet protection, anti-obesity and anti-oxidation in many model systems. Energy expenditure is enhanced by ginseng through thermogenesis. Ginseng-specific saponins (ginsenosides) are considered as the major bioactive compounds for the metabolic activities of ginseng. Berberine from rhizoma coptidis is an oral hypoglycemic agent. It also has anti-obesity and anti-dyslipidemia activities. The action mechanism is related to inhibition of mitochondrial function, stimulation of glycolysis, activation of AMPK pathway, suppression of adipogenesis and induction of low-density lipoprotein (LDL) receptor expression. Bitter melon or bitter gourd (Momordica charantia) is able to reduce blood glucose and lipids in both normal and diabetic animals. It may also protect β cells, enhance insulin sensitivity and reduce oxidative stress. Although evidence from animals and humans supports the therapeutic activities of ginseng, berberine and bitter melon, multi-center large-scale clinical trials have not been conducted to evaluate the efficacy and safety of these herbal medicines.

Intradialytic hypotension (IDH) is a common complication of hemodialysis, but there is no data about the time of onset during treatment. Here we describe the incidence of IDH throughout hemodialysis and associations of time of hypotension with clinical parameters and survival by analyzing data from 21 dialysis clinics in the United States to include 785682 treatments from 4348 patients. IDH was defined as a systolic blood pressure of 90 mmHg or under while IDH incidence was calculated in 30-minute intervals throughout the hemodialysis session. Associations of time of IDH with clinical and treatment parameters were explored using logistic regression and with survival using Cox-regression. Sensitivity analysis considered further IDH definitions. IDH occurred in 12% of sessions at a median time interval of 120-149 minutes. There was no notable change in IDH incidence across hemodialysis intervals (range: 2.6-3.2 episodes per 100 session-intervals). Relative blood volume and ultrafiltration volume did not notably associate with IDH in the first 90 minutes but did thereafter. Associations between central venous but not arterial oxygen saturation and IDH were present throughout hemodialysis. Patients prone to IDH early as compared to late in a session had worse survival. Sensitivity analyses suggested IDH definition affects time of onset but other analyses were comparable. Thus, our study highlights the incidence of IDH during the early part of hemodialysis which, when compared to later episodes, associates with clinical parameters and mortality.

Fixture locators are used to precisely locate and stably support a workpiece so that the desired position and orientation (pose) of the workpiece relative to the cutting tool can be maintained during machining or inspection process. It is believed that manufacturing errors of locators and locating datum surfaces are key factors for the pose error between the workpiece and the cutting tool. Optimizing the layout of locators is helpful to reduce the pose error so as to improve machining accuracy of the workpiece. In order to minimize the pose error, we introduced, for the first time, a singular value decomposition (SVD) technique for the location matrix to derive error amplification factors (EAF) in six degrees-of-freedom of the workpiece. The EAF principle defines the maximal singular value, the condition number, the product of all singular values and the manipulability as the maximal error amplification factor, the relative error amplification factor, the error ellipsoid volume and the location stability, respectively. The four defined indices taken as objective functions are optimized, by a nondominated sort genetic algorithm (NSGA-II), so that an optimal layout of locators is obtained due to the minimization of the pose error. Also, the feasibility of the proposed method was comprehensively validated by simulation and machining experiments.