Synthesis and Characterization of Sulfonamide-Containing Naphthalimides as Fluorescent Probes.

A tumor-targeting fluorescent probe has attracted increasing interest in fluorescent imaging for the noninvasive detection of cancers in recent years. Sulfonamide-containing naphthalimide derivatives (SN-2NI, SD-NI) were synthesized by the incorporation of N-butyl-4-ethyldiamino-1,8-naphthalene imide (NI) into sulfonamide (SN) and sulfadiazine (SD) as the tumor-targeting groups, respectively. These derivatives were further characterized by mass spectrometry (MS), nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV), and a fluorescence assay. In vitro properties, including cell cytotoxicity and the cell uptake of tumor cells, were also evaluated. Sulfonamide-containing naphthalimide derivatives possessed low cell cytotoxicity to B16F10 melanoma cells. Moreover, SN-2NI and SD-NI can be taken up highly by B16F10 cells and then achieve good green fluorescent images in B16F10 cells. Therefore, sulfonamide-containing naphthalimide derivatives can be considered to be the potential probes used to target fluorescent imaging in tumors.

Engineering and Characterization of a Biomimetic Microchip for Differentiating Mouse Adipocytes in a 3D Microenvironment.

Although two-dimensional (2D) cell cultures are the standard in cell research, one pivotal disadvantage is the lack of cell-cell and cell-extracellular matrix (ECM) signaling in the culture milieu. However, such signals occur in three-dimensional (3D) in vivo environments and are essential for cell differentiation, proliferation, and a range of cellular functions. In this study, we developed a microfluidic device to proliferate and differentiate functional adipose tissue and adipocytes by utilizing 3D cell culture technology. This device was used to generate a tissue-specific 3D microenvironment to differentiate 3T3-L1 preadipocytes into either visceral white adipocytes using visceral adipose tissue (VAT) or subcutaneous white adipose tissue (SAT). The microchip has been tested and validated by functional assessments including cell morphology, inflammatory response to a lipopolysaccharide (LPS) challenge, GLUT4 tracking, and gene expression analyses. The biomimetic microfluidic chip is expected to mimic functional adipose tissues that can replace 2D cell cultures and allow for more accurate analysis of adipose tissue physiology.

Direct monitoring of protease activity using an integrated microchip coated with multilayered fluorogenic nanofilms.

Proteases play an essential role in the four sequential but overlapping phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. In chronic wounds, excessive protease secretion damages the newly formed extracellular matrix, thereby delaying or preventing the normal healing process. Peptide-based fluorogenic sensors provide a visual platform to sense and analyze protease activity through changes in the fluorescence intensity. Here, we have developed an integrated microfluidic chip coated with multilayered fluorogenic nanofilms that can directly monitor protease activity. Fluorogenic protease sensors were chemically conjugated to polymer films coated on the surface of parallel microfluidic channels. Capillary flow layer-by-layer (CF-LbL) was used for film assembly and combined with subsequent sensor modification to establish a novel platform sensing technology. The benefits of our platform include facile fabrication and processing, controllable film nanostructure, small sample volume, and high sensitivity. We observed increased fluorescence of the LbL nanofilms when they were exposed to model recombinant proteases, confirming their responsiveness to protease activity. Increases in the nanofilms' fluorescence intensity were also observed during incubation with liquid extracted from murine infected wounds, demonstrating the potential of these films to provide real-time, in situ information about protease activity levels.

Vip3Aa from Bacillus thuringiensis subsp. kurstaki HD1 is toxic to Aedes aegypti (Diptera: Culicidae).

Bacillus thuringensis (Bt) vegetative insecticidal proteins share no sequence or structural homology with the known Cry proteins. The activity of Vip3Aa is generally considered to be restricted to lepidopteran insects. In this paper, the vip3Aa gene was cloned from Bt subsp. kurstaki HD1 and expressed in E. coli. It was found to be toxic to Aedes aegypti larvae - the first time that dipteran activity has been reported. Furthermore, the potential synergism of Vip3Aa with the Cry toxins was investigated. Although no significant synergism was observed, Vip3Aa could be used in combination with Cry toxins to prevent or delay the onset of resistance.

Dendrimers as carriers for siRNA delivery and gene silencing: a review.

RNA interference (RNAi) was first literaturally reported in 1998 and has become rapidly a promising tool for therapeutic applications in gene therapy. In a typical RNAi process, small interfering RNAs (siRNA) are used to specifically downregulate the expression of the targeted gene, known as the term "gene silencing." One key point for successful gene silencing is to employ a safe and efficient siRNA delivery system. In this context, dendrimers are emerging as potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have attracted intense interest since their emanating research in the 1980s and are extensively studied as efficient DNA delivery vectors in gene transfer applications, due to their unique features based on the well-defined and multivalent structures. Knowing that DNA and RNA possess a similar structure in terms of nucleic acid framework and the electronegative nature, one can also use the excellent DNA delivery properties of dendrimers to develop effective siRNA delivery systems. In this review, the development of dendrimer-based siRNA delivery vectors is summarized, focusing on the vector features (siRNA delivery efficiency, cytotoxicity, etc.) of different types of dendrimers and the related investigations on structure-activity relationship to promote safe and efficient siRNA delivery system.

A three-dimensional supramolecular framework of silver(I), 2-phenylquinoline-4-carboxylate and 4,4'-bipyridine.

A novel supramolecular framework, catena-poly[[[aqua(2-phenylquinoline-4-carboxylato-κO)silver(I)]-µ-4,4'-bipyridine-κ(2)N:N'] dihydrate], {[Ag(C16H10NO2)(C10H8N2)(H2O)]·2H2O}n, has been synthesized and structurally characterized. The Ag(I) centres are four-coordinated and bridged by 4,4'-bipyridine (4,4'-bipy) ligands to form a one-dimensional Ag-bipy chain. The Ag-bipy chains are further linked together by intermolecular O-H···O and O-H···N hydrogen-bonding interactions between adjacent chains, resulting in a three-dimensional framework.

Study on macro-meso mechanical properties of cemented tailings backfill with high fly ash content.

The use of cement and fly ash (FA) to prepare cemented tailings backfill (CTB) lowers backfill mining costs while also reducing pollution caused by the accumulation of waste materials like tailings and FA, making it a green backfill mining process. While adding FA to CTB may reduce costs, too much FA might weaken CTB's strength property. Mechanical tests were used to explore the effects of FA content and curing time on the uniaxial compressive strength (UCS) and deformation modulus of CTB in this research. The effects of FA content on failure modes, strain energy, and crack evolution of CTB were studied using a numerical model that considered FA content and particle contact mode. The influence mechanism of different FA contents on CTB was also revealed at the microscopic level. The results demonstrate that the UCS of CTB has a quadratic polynomial and a linear relationship with FA content and curing time respectively, and that the elasticity modulus and secant modulus of CTB increase and then decrease with FA content under different curing times. The peak strain energy of CTB increases and subsequently declines with the FA content, and crack propagation inside CTB may be limited by regulating the FA content. A reasonable content of FA can optimize the size and distribution of CTB microscopic defects, enabling them to exhibit superior strength property. This study systematically explores the mechanism of different FA contents on the strength property of CTB from a macro-micro perspective, providing an essential reference value for improving the recycling of FA and waste residues such as tailings.

Analysis of influencing factors of postoperative myasthenic crisis in 564 patients with myasthenia gravis in a single center.

OBJECTIVE: To study the influencing factors of myasthenic crisis in patients with myasthenia gravis during perioperative period. METHODS: A total of 564 myasthenia gravis (MG) patients who underwent standard expanded resection of thymoma/thymoma in the Department of Thoracic Surgery of Beijing Hospital from January 2011 to March 2022 were retrospectively included in the study. Clinical indicators such as gender, age, thymoma, American Society of Anesthesiologists (ASA) score, operation time, intraoperative blood loss, and some others were recorded. RESULTS: Osserman-stages IIB + III + IV (odds ratio [OR] 16.091, 95% confidence interval [CI] 5.170-50.076, p value < 0.001), the dosage of pyridostigmine bromide more than 240 mg (OR 6.462, 95% CI 3.110-13.427, p value < 0.001), ASA score 2 and 3 (OR 3.203, 95% CI 1.461-7.020, p value = 0.004), low diffusion lung capacity for carbon monoxide (DLCO%) (OR 0.981, 95% CI 0.963-1.000 p value = 0.049), and blood loss greater than 1000 ml (OR 16.590, 95% CI 1.911-144.011, p value = 0.011) were independent risk factors for myasthenic crisis. CONCLUSIONS: Patients with poor Osserman stages, higher preoperative dosage of pyridostigmine bromide, higher ASA score, poor pulmonary function (low DLCO%), and more intraoperative bleeding should be highly vigilant for the occurrence of postoperative myasthenic crisis.

Analysis of influencing factors of perioperative myasthenic crisis in 387 myasthenia gravis patients without thymoma in a single center.

OBJECTIVE: To study the influencing factors of myasthenic crisis in non-thymoma myasthenia gravis (MG) patients during perioperative period. METHODS: We retrospectively analyzed a total of 387 non-thymoma MG patients who underwent extended thymoma resection in the Department of Thoracic Surgery of Beijing Hospital from February 2011 to December 2021, recorded ASA score, Osserman classification, preoperative course, pyridostigmine dosage, operation method, operation time, and intraoperative blood loss, then analyzed the factors associated with postoperative myasthenic crisis by univariate and multivariate logistic regression. RESULTS: Osserman classification IIB + III + IV (P < 0.001), history of myasthenic crisis (P = 0.013), pyridostigmine dosage greater than 240 (P < 0.001), ASA score 2 and 3 (P = 0.001) are independent risk factors for myasthenic crisis. CONCLUSION: Patients with poor Osserman classification, history of myasthenic crisis before surgery, larger preoperative dosage of pyridostigmine, and higher ASA scores should be highly alert to the occurrence of postoperative myasthenic crisis.

Surgical safety analysis and clinical experience sharing of myasthenia gravis patients aged 65 and over.

BACKGROUND: To evaluate the surgical safety in myasthenia gravis (MG) patients aged 65 and over. METHODS: A total of 564 patients with MG who underwent surgery in the Department of Thoracic Surgery of Beijing Hospital from November 2011 to March 2022 were included in the study and divided into two groups taking the age of 65 as the boundary. Perioperative data of patients were recorded and statistically analyzed. RESULTS: Compared with young patients, FEV1, FEV1% and MVV in lung function of elderly MG patients were worse (p < 0.001, p < 0.001, p = 0.002). Postoperative drainage time was longer (p < 0.001), combined with more drainage volume (p = 0.002). The American Society of Anesthesiologists (ASA) score of elderly MG patients was higher (p < 0.001). Complications were more likely to occur (p = 0.008) after surgery and Clavien-Dindo classification (CDC) of postoperative complications was also higher (p = 0.003). Meanwhile, postoperative myasthenic crisis (POMC) was more likely to occur (p = 0.038). Logistic regression showed that lower DLCO% (p = 0.049) was an independent risk factor for postoperative complications. CONCLUSIONS: Surgical indications should be considered in each elderly MG patient on an individual basis. Moreover, most elderly MG patients safely survive the perioperative period and benefit from surgery through individualized consideration.

Postoperative clinical outcomes of patients with thymic epithelial tumors after over-3-year follow-up at a single-center.

BACKGROUND: To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation. METHODS: Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0. RESULTS: A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2-137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications. CONCLUSIONS: The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy.

Biochemical investigation of the formation of three-dimensional networks from DNA-grafted large silica particles.

DNA is used to rationally build up networks of silica nanoparticles (SiNPs) based on the molecular recognition properties of complementary sequences. Network self-assembly is controlled from DNA covalently grafted at the surface of chemically modified SiNPs. Two strategies are compared, where grafted DNA sequences are designed in a three-strand system using noncomplementary sequences and an extra DNA linker, or in a two-strand approach for direct hybridization. In this paper, both systems are compared in terms of DNA hybridization stability, network size, and three-dimensional organization using a combination of dynamic light scattering and electron microscopy. The observed differences are discussed in terms of hybridization interactions between DNA sequences in particle-free systems through fluorescence, circular dichroism, and UV spectroscopy techniques.

Effect of calcium formate as an accelerator on dilatancy deformation, strength and microstructure of cemented tailings backfill.

Recycling mining wastes to produce cemented tailings backfill (CTB) is the optimal approach to eliminate the environmental pollution caused by their accumulation. However, its low strength limits its application. Using calcium formate (CF) as an accelerator for improving its mechanical properties is of great significance to promote sustainable development. The effects of CF dosage and curing time on dilatancy deformation, compressive strength and microstructure of CTB were investigated through mechanical compression, scanning electron microscope (SEM) and energy dispersive spectrometer (EDS) tests. The strengthening and deterioration mechanisms of CF dosage on CTB were revealed, and its engineering practicability was systematically evaluated. The results show that the variation of volumetric strain in the dilatancy deformation stage firstly increase and then decrease with the increases of CF dosage and curing time. The relationship between CF dosage and compressive strength can be characterized by quadratic polynomial, and the optimal CF dosage characterizing the superior mechanical property of CTB is between 1.60 and 1.84. The supplement of CF reduces the size and distribution of microcracks and micropores, thereby optimizing the microstructure of CTB. Nevertheless, the excessive dosages of CF deteriorate the microstructure of CTB and produce serious defects, which cannot be effectively filled by hydration products, thus weakening the strength property of CTB. This study provides an effective accelerator for improving the mechanical properties of CTB, which is of great significance to promote the recycling of tailings.

Mechanical property and microstructure of cemented tailings backfill containing fly ash activated by calcium formate.

Cemented tailings backfill (CTB) is the most economical and environmental method to recycle tailings and fly ash (FA) for filling mining, but the high content of FA will weaken its strength property. This paper aims to use calcium formate (CF) as an activator to stimulate the activity of FA, thereby enhancing the mechanical property of CTB. The influence of FA and CF content on the stress-strain behavior, dilatancy deformation, and compressive strength of CTB was investigated using uniaxial compression test and scanning electron microscope. The coupling effect mechanism of FA and CF content on the compressive strength of CTB was revealed. The results show that increasing the content of FA and CF can enhance the bearing capacity of CTB during the dilatancy deformation stage, but the excessive content of FA and CF will lead to the attenuation of peak stress. The relations between FA content, CF content, and the compressive strength of CTB can be characterized by quadratic polynomial. Adding CF can stimulate the activity of insoluble FA, increasing the utilization of FA in CTB and producing rich hydration products to fill the internal defects of CTB. The microstructure of CTB is effectively improved by adding CF, including the size and distribution of microcracks and micropores, so that the strength property of CTB is optimized. However, too much CF will make the microstructure of CTB loose and porous, resulting in more microcracks and micropores. Microcracks propagate and connect with micropores to form defects, which deteriorate the microstructure of CTB, thus weakening the strength parameters of CTB. This study provides a method to increase the utilization of FA in CTB, which is of great significance for strengthening the mechanical properties of CTB and improving engineering economic benefits.

Coupled effects of fly ash and calcium formate on strength development of cemented tailings backfill.

Cemented tailings backfill (CTB) is widely adopted to ensure the safety of underground goafs and mitigate environmental risks. Fly ash (FA) and calcium formate (CF) are common industrial by-products that improve the mechanical performance of CTB. How the coupling of the two components affects the strength development is not yet well-understood. Neural network modelling was conducted to predict the strength development, including the static indicator of uniaxial compressive strength (UCS) and the dynamic indicator of ultrasonic pulse velocity (UPV). Sobol' sensitivity analysis was carried out to reveal the contributions of FA, CF and curing time to CTB strength. SEM microstructure investigation on CTB samples was implemented to reveal the mechanism of strength development and justify the predictions by neural network modelling and sensitivity analysis. Results show that the combination of FA content, CF content and curing time can be used to predict both UCS and UPV while providing adequate accuracy. The maximum of UCS of 6.1215 MPa is achieved at (FA content, CF content, curing time) = (13.78 w%, 3.76 w%, 28 days), and the maximum of UPV of 2.9887 km/s is arrived at (FA content, CF content, curing time) = (11.67 w%, 3.08 w%, 10 days). It is also implicated that prediction of UCS using UPV alone, although common in field application is not recommended. However, UPV measurement, in combination with the information of FA dosage, CF dosage and curing time, could be used to improve UCS prediction. The rank of variable significance for UCS is curing time > FA content > CF content, and for UPV is FA content > curing time > CF content; variable interaction is strongest for FA with CF for UCS development, and for FA with curing time for UPV evolution. Influence of FA on CTB strength development is due to improved polymerisation and consumption of Ca(OH)2. Influence of CF on strength development is a result of accelerated hydration and increased combined-water content in calcium silicate hydrate (CSH). Effect of curing time is attributed to the evolution of CSH product and pore-water content during cement hydration.

Structurally flexible triethanolamine core PAMAM dendrimers are effective nanovectors for DNA transfection in vitro and in vivo to the mouse thymus.

With the aim of developing dendrimer nanovectors with a precisely controlled architecture and flexible structure for DNA transfection, we designed PAMAM dendrimers bearing a triethanolamine (TEA) core, with branching units pointing away from the center to create void spaces, reduce steric congestion, and increase water accessibility for the benefit of DNA delivery. These dendrimers are shown to form stable nanoparticles with DNA, promote cell uptake mainly via macropinocytosis, and act as effective nanovectors for DNA transfection in vitro on epithelial and fibroblast cells and, most importantly, in vivo in the mouse thymus, an exceedingly challenging organ for immune gene therapy. Collectively, these results validate our rational design approach of structurally flexible dendrimers with a chemically defined structure as effective nanovectors for gene delivery, and demonstrate the potential of these dendrimers in intrathymus gene delivery for future applications in immune gene therapy.

Particle size distribution of aggregates effects on mesoscopic structural evolution of cemented waste rock backfill.

The most economical, environmental, and friendly method for recycling gangue is filling mining with cemented waste rock backfill (CWRB), which solves the environmental problems caused by gangue discharge and reduces the mining damages. Evaluating the mesoscopic structure of CWRB is of great significance for maximizing the utilization of gangue recycling and improving the economic benefits of filling mining. This paper constructed the particle flow model of cemented waste rock backfill (CWRB) considering particle size distribution (PSD) of aggregates and hydration of cementing material to investigate the effect of the PSD of aggregates on its mesoscopic structural evolution. The strain energy, crack, force chain, and particle fragment of CWRB during the whole loading were discussed. The binary processing and calculation on the crack image were performed to analyze the fractal dimension of crack distribution by compiling program. The influencing mechanism of the PSD of aggregates on the strength of CWRB is revealed from the mesoscopic levels of crack evolution, force chain structure, and particle fragment. The results show that the strain energy increases firstly and then decreases with the PSD fractal dimension, while the crack number decreases firstly and then increases with that. The cracks with less number and more uniform distribution present the smaller fractal dimension, CWRB with a low fractal dimension of crack distribution has higher strength, the fractal dimension of crack distribution exhibits a correlation with the PSD of aggregates. CWRBs with the PSD fractal dimensions of 2.4-2.6 have the largest strain energy and the smallest crack number, performing the superior structural evolution during loading. This study presents the huge potential of optimizing PSD in CWRB application from a new perspective, it is of great significance for strengthening the internal structure of CWRB and reducing engineering cost.

Assessment of cemented waste rock backfill for recycling gangue and controlling strata: creep experiments and models.

Filling mining with cemented waste rock backfill (CWRB) is an optimal approach to eliminate the gangue waste pollution. To efficiently evaluate the gangue recycling and its advantage in structure protection, the effects of the confining pressure, cement dosage, and aggregate particle size distribution (PSD) on the creep behavior of CWRB were investigated. Burgers creep model was used to characterize the visco-elastic characteristics of CWRB, a visco-elastic-plastic creep model was established to describe its creep behavior on this basis. A genetic algorithm (GA) for optimizing the model parameters was constructed to verify the creep model. The time-varying evolutions of strata movements were discussed to evaluate the effect of the creep behavior of CWRB on the structural safeties. The results show that the creep load levels and times are positively correlated with the confining pressure and cement dosage, indicating that the consideration of roof load without confining pressure of surrounding rock causes an increase in the design parameters of CWRB to waste the cementing material. The creep load levels and times firstly increase and then decrease with the Talbot gradation index, revealing that CWRB with superior aggregate PSD performs the strong anti-deformation capacity under creep condition. The confining pressure, cement dosage, and aggregate PSD are comprehensively considered to optimize CWRB, and its stability under creep condition causes the strata movement to gradually slow down, thereby protecting underground aquifers and surface buildings.

Characterization of a novel Bacillus thuringiensis toxin active against Aedes aegypti larvae.

Some Bacillus thuringiensis (Bt) strains produce dipteran-active toxins and can control larval mosquitoes. We identified a novel mosquitocidal toxin named Xpp81Aa1 with the thioredoxin domain from Bt strain HSY204. This toxin has very little sequence similarity to the three-domain Cry toxin and Cyt toxins and has significant toxicity to Aedes aegypti larvae. A safety assessment indicated that the Xpp81Aa1 toxin has no cytocidal activity against red blood cells and did not induce allergic reactions. The Xpp81Aa1 toxin exhibited a synergistic effect in combination with Cry2Aa and Cry4Aa protein toxins. Thus, the Xpp81Aa1 toxin could be a good candidate for mosquito control applications to reduce the mosquito-borne disease.

Synthesis and characterization of gold nanoparticles based on low generational triethylene glycol-polyamidoamine dendrimers.

Low generational polyamidoamine (PAMAM) dendrimers with triethylene glycol (TEG) core and ester groups at the surface have been synthesized and investigated as templates for preparation of gold nanoparticles (AuNPs), by reducing chloroauric acid (HAuCl4) with potassium borohydride (KBH4) in N,N-dimethylformamide (DMF). UV-vis absorption spectroscopy, fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) were used to confirm the formation of AuNPs. Stable gold nanoparticles with particle size around 10 nm were obtained and the interaction between the dendrimers and Au moieties is discussed.