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Demonstration of a colorimetric approach for nucleic acid detection represents an attractive educational experiment for chemistry undergraduate students in the time of coronavirus pandemic. Herein, a rapid and vivid detection method that visualizes the presence of a specific DNA sequence is described. The plasmon resonance of gold nanoparticles (AuNPs) (∼20 nm in diameter) endows a red color to DNA-functionalized gold nanoparticles (DNA-AuNPs) in a colloidal solution. Simply upon addition of a sample containing the complementary DNA sequence, the DNA-AuNPs dispersed in a strong ionic solution can spontaneously aggregate in minutes and turn to be purple in color, which can be detected using UV–visible spectroscopy as well as the naked eye. In contrast, the DNA-AuNPs remain highly dispersed as a reddish colloid even at high ionic strength when the DNA sequence is terminally mismatched or overhung. According to the teaching experience, this DNA testing experiment can be accomplished by students in pairs or groups under instruction in a three-day lab session. Given the rapid and fail-proof DNA testing, the testing method is also well-suited for hands-on introduction of analytical chemistry and nanotechnology to chemistry freshman and high school students.

Quaternary nonlinear optical single crystals AgxGaxGe1-xSe2 (x = 0.250, 0.167) were grown by the Bridgman method in a four-zone furnace. The thermal expansion behavior of AgxGaxGe1-xSe2 (x = 0.25, 0.167) was studied by the method of single-crystal X-ray diffraction from 150 to 295 K and powder X-ray diffraction in the range of 298-773 K. Both results show the crystals have positive linear thermal expansion coefficients in different directions and a positive volume thermal expansion coefficient, and it is observed that they satisfy the relationship of αa > αc > αb and αV ≈ αa + αb + αc for the orthorhombic structure. It is found that the AgxGaxGe1-xSe2 (x = 0.25, 0.167) unit cells varying with temperature were mainly dominated by variations in framework geometry (AgSe4 tetrahedron), and the thermal motion of Ag atoms in the AgSe4 tetrahedron. As it was revealed, according to the powder X-ray diffraction, it is found that the isotropic thermal atomic displacement parameter of the Ag atoms is much larger than those of the Se and Ga(Ge) atoms in the AgSe4 tetrahedron. Furthermore, anisotropic atomic displacement parameters (ADPs) of Ag atoms are extracted from the single-crystal diffraction; the ADPs along the a axis, b axis, and c axis have a significant difference, which means the thermal vibration of Ag atoms is anisotropic. It is of great significance for improving crystal growth technology and understanding the thermal properties of this kind of crystals.

Peptide/protein therapeutics have been significantly applied in the clinical treatment of various diseases such as cancer, diabetes, etc. owing to their high biocompatibility, specificity, and therapeutic efficacy. However, due to their immunogenicity, instability stemming from its complex tertiary and quaternary structure, vulnerability to enzyme degradation, and rapid renal clearance, the clinical application of protein/peptide therapeutics is significantly confined. Though nanotechnology has been demonstrated to prevent enzyme degradation of the protein therapeutics and thus enhance the half-life, issues such as initial burst release and uncontrollable release kinetics are still unsolved. Moreover, the traditional administration method results in poor patient compliance, limiting the clinical application of protein/peptide therapeutics. Exploiting the sustained-release formulations for more controllable delivery of protein/peptide therapeutics to decrease the frequency of injection and enhance patient compliance is thus greatly meaningful. In this review, we comprehensively summarize the substantial advancements of protein/peptide sustained-release systems in the past decades. In addition, the advantages and disadvantages of all these sustained-release systems in clinical application together with their future challenges are also discussed in this review.

Second-harmonic generation (SHG) is a kind of nonlinear optical phenomenon which has been widely used in optical devices, and factors influencing its signal are very complex. Here, taking advantage of excellent structural designability and overcoming the limitations of various coordinations of lanthanide metals, for the first time a series of lanthanide metal-organic frameworks (Ln-MOFs) with one particular ligand were synthesized and structurally characterized to study the interference of the SHG signal. The optical performance including single-photon fluorescence and SHG was collected and analyzed. It is found that all 13 kinds of Ln-MOFs can be divided into 2 crystal configurations by their individual space groups and Ln-MOFs with coordinated metal atoms from La to Tb possessing the noncentrosymmetric C2 space group exhibit the SHG property, the intensity of which depends on the type of metal atoms, the pumping wavelength, and the size of the single-crystal particles. This is the first time that the relationship between the nonlinear optical properties and the structure, metal atoms, pumping wavelength, crystal size of the whole series of Ln-MOFs is studied systematically, providing a lot of interesting results and enriching the research scope of nonlinear optics and materials science.

Quality control of food products requires the development of powerful analytical tools and regulations to avoid fraud to consumers and ineffective product recalls. DNA barcoding represents a potent...

Various spectroscopic properties of Yb3+-doped Y2SiO5 crystal have been extensively investigated due to its promising application in quantum information processing. However, the local structure, electronic structure of Yb3+:Y2SiO5 crystal, and its optical and magnetic properties have not been comprehensively studied from a theoretical viewpoint. In this work, the geometric and electronic structures of Yb3+ that replaces two crystallographic Y3+ sites in the Y2SiO5 crystal are first obtained by the method of density functional theory (DFT). Then, the optical, electron paramagnetic resonance (EPR), and optically detected magnetic resonance (ODMR) spectra for 171Yb3+ (nuclear spin I = 1/2) at such two sites are simultaneously calculated in the framework of the complete diagonalization (of energy) matrix (CDM) based on the optimized local structure around 171Yb3+ ion by DFT. The various calculated spectroscopic properties by such combined theoretical approach are consistent with the experimental ones, which demonstrates that CDM is effective and particularly suitable for calculating hyperfine A-tensors under zero, low, and intermediate magnetic field. More importantly, based on the obtained accurate hyperfine structure of 171Yb3+ in Y2SiO5 crystal, the possible "clock transitions", which can enhance the optical coherence time, can be assigned or predicted by the present approach. This study successfully explains the spectroscopic properties of 171Yb3+-doped Y2SiO5 and provides a feasible method to design and search for practical rare-earth-doped quantum information materials for the community.

The thermal properties of orthorhombic AgGaGeS4 and chalcopyrite AgGaS2 crystals, including thermal expansion, specific heat, and thermal conductivity, have been investigated. For the AgGaS2 crysta...

In the past few decades, intracellular calcium overload has been shown to induce cell death through multiple signaling pathways. In this study, we used BAPTA-AM, a well-known membrane-permeable Ca2+ chelator, to prevent cell injury by allaying the intracellular calcium overload. We explored the clinical potentials of BAPTA-AM-loaded liposome (BAL) in the treatment of the acute liver failure (ALF) mouse model, which is characterized by severe hepatic necrosis and apoptosis. We discovered that BAL can significantly inhibit D-GalN-induced LO2 cell damage as it increased cell viability by 60% and downregulated the LPS-stimulated inflammatory response in RAW 264.7 macrophages by reversing the morphological change and modulating TNF-α and NF-κB expressions. Through systemic administration, BAL can rapidly accumulate in damaged liver tissue and exhibit excellent treatment effects on the D-GalN/LPS-induced ALF mouse model, including elevation of the survival rate (from 10 to 80%), recovery of normal liver indexes and liver health indicators, improvement of liver blood microcirculation (increased the blood flow volume by 80% and flow rate by 60%), and blood coagulation. The underlying hepatoprotective effect of BAL is presumably based on the antinecrosis and antiapoptosis abilities attributed to its inhibition on oxidative stress, restriction on TNF-α receptor, and mitochondria-mediated apoptotic pathway by effectively clearing the overloaded intercellular calcium. BAL holds great potential as a new therapeutic strategy for ALF treatment, and its prominent cell rescue ability provides ample opportunities for the treatment of many other diseases that are characterized by rapid and massive cell damage.

Polyelectrolyte complex (PEC) nanoparticles assembled from plasmid DNA (pDNA) and polycations such as linear polyethyleneimine (lPEI) represent a major non-viral delivery vehicle for gene therapy tested thus far. Efforts to control the size, shape and surface properties of pDNA/polycation nanoparticles have been primarily focused on fine-tuning the molecular structures of the polycationic carriers and on assembly conditions such as medium polarity, pH, and temperature. However, reproducible production of these nanoparticles hinges on the ability to control the assembly kinetics, given the non-equilibrium nature of the assembly process and nanoparticle composition. Here we adopt a kinetically controlled mixing process, termed flash nanocomplexation (FNC), that accelerates the mixing of pDNA solution with polycation lPEI solution to match the PEC assembly kinetics through turbulent mixing in a microchamber. This achieves explicit control of the kinetic conditions for pDNA/lPEI nanoparticle assembly as demonstrated by the tunability of nanoparticle size, composition, and pDNA payload. Using a combined experimental and simulation approach, we prepared pDNA/lPEI nanoparticles having an average of 1.3 to 21.8 copies of pDNA per nanoparticle and average size of 35 to 130 nm in a more uniform and scalable manner than bulk mixing methods. Using these nanoparticles with well-defined compositions and sizes, we showed the correlation of pDNA payload and nanoparticle formulation composition with the transfection efficiencies in vitro and in vivo. These nanoparticles exhibited long-term stability at −20°C for at least 9 months in a lyophilized formulation, validating scalable manufacture of an off-the-shelf nanoparticle product with well-defined characteristics as a gene medicine.

AgGaGeS4 is a new promising nonlinear-optical crystal for frequency-shifting a 1.064 μm laser into mid-IR. This quaternary compound single crystal has been successfully grown by a modified vertical...

Oral delivery of nucleic acid therapy is a promising strategy in treating various diseases because of its higher patient compliance and therapeutic efficiency compared to parenteral routes of administration. However, its success has been limited by the low transfection efficiency resulting from nucleic acid entrapment in the mucus layer and epithelial barrier of the gastrointestinal (GI) tract. Herein, we describe an approach to overcome this phenomenon and improve oral DNA delivery in the context of treating type II diabetes (T2D). Linear PEI (lPEI) was used as a carrier to form complexes with plasmid DNA encoding glucagon-like peptide 1 (GLP-1), a common target in T2D treatments. These nanoparticles were then coated with a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-rac-glycero-3-methoxy poly(ethylene glycol)-2000 (DMG-PEG) to render the nanoparticle surface hydrophilic and electrostatically neutral. The surface-modified lPEI/DNA nanoparticles showed higher diffusivity and transport in the mucus layer of the GI tract and mediated high levels of transfection efficiency in vitro and in vivo. Moreover, these modified nanoparticles demonstrated high levels of GLP-1 expression for more than 24 h in the liver, lungs, and intestine in a T2D murine model after a single dose, as well as controlled blood glucose levels within a normal range for at least 18 h with repeatable therapeutic effects upon multiple dosages. Taken together, this work demonstrates the feasibility of an oral plasmid DNA delivery approach in the treatment of T2D through a facile surface modification to improve the mucus permeability and delivery efficiency of the nanoparticles.

AgGaGe nS2( n+1) crystal is a series of quaternary nonlinear optical materials for mid-IR laser applications of converting a 1.064 μm pump signal (Nd:YAG laser) to 4-11 μm laser output, but only AgGaGeS4 has attracted the most attention, remaining the other promising AgGaGe nS2( n+1) crystal whose physicochemical properties can be modulated by n value. In this work, AgGaGe nS2( n+1) ( n = 2, 3, 4, and 5) polycrystals are synthesized by vapor transport and mechanical oscillation method with different cooling processes. High-resolution X-ray diffraction analysis and refinement have revealed that all the four compounds are crystallized in the noncentrosymmetric orthorhombic space group Fdd2, resulting in the excellent nonlinear optical property, and the distortion of tetrahedron with the variation of n value causes the discrepancy of physicochemical property. Besides, using the modified Bridgman method, AgGaGe nS2( n+1) single crystals with 15 mm diameter and 20-40 mm length have been grown. We have discussed the structure and composition of AgGaGe nS2( n+1) by XPS spectra and analyzed the three kinds of vibration modes of tetrahedral clusters by the Raman spectra. The Hall measurement indicates that the AgGaGe nS2( n+1) single crystals are p-type semiconductor, and the carrier concentration decreases with the increasing n value. All the transmittances of as-grown AgGaGe nS2( n+1) samples exceeds 60% in the transparent range, especially the transmittance of AgGaGe2S6, is up to 70% at 1064 nm, and the band gap of as-grown crystal increases from 2.85 eV for AgGaGe2S6 to 2.92 eV for AgGaGe5S12. After a thermal annealing treatment, the absorptions at 2.9, 4, and 10 μm have been eliminated, and the band gap changed into the range of 2.89-2.96 eV.

Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Currently, nanoparticulate drug delivery systems (NDDS) exhibit many unique advantages in mediating oral drug delivery; however, many anticancer drugs that were susceptible in hostile gastrointestinal (GI) environment showed poor permeability across intestinal epithelium, and most materials used as drug carriers are nonactive excipients and displayed no therapeutically relevant function, which leads to low oral bioavailability and therapeutic efficacy of anticancer drugs (e.g., paclitaxel). Inspired by these, in this study, paclitaxel (PTX) was used as a model drug, depending on intermolecular hydrogen-bonded interactions, PTX-loaded tannic acid/poly( N-vinylpyrrolidone) nanoparticles (PTX-NP) were produced by a flash nanoprecipitation (FNP) process. The optimized PTX-NP showed an average diameter of 54 nm with a drug encapsulation efficiency of 80% and loading capacity of 14.5%. Molecular dynamics simulations were carried out to illuminate the assembling mechanism of hydrogen-bonded PTX-NP. In vitro and in vivo results confirmed that PTX-NP showed pH-dependent intestinal site-specific drug release, P-gp inhibitory function by tannic acid (TA), prolonged intestinal retention, and improved trans-epithelial transport properties. Oral administration of PTX-NP generated a high oral delivery efficiency and relative oral bioavailability of 25.6% in rats, and further displayed a significant tumor-inhibition effect in a xenograft breast tumor model. These findings confirmed that our PTX-NP might be a promising oral drug formulation for chemotherapy.

Hyaluronic-acid (HA)-coated LOX-1-specific siRNA-condensed cell-penetrating peptide (CPP) nanocomplexes (NCs) were developed for targeted gene delivery to macrophages and suppression of lipid accumulation. The HA coating facilitated the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors and was further degraded by hyaluronidase (HAase) intraplaques for exposing the naked CPP NCs and achieving the ultimate location into macrophages. The surface coating of HA was verified by the increased particle size, inverted zeta potential, and TEM images. The targeting mechanism was studied on the established injured endothelium-macrophage coculture system, which revealed that modification of higher molecular weight HA and higher HA coating density on NCs, termed as NPs-3, improved the intracellular uptake of nanoparticles by macrophages. Macrophages internalized NCs via caveolae-mediated endocytosis pathway. Moreover, NPs-3 exhibited better cellular drug efficacy in preventing macrophage-derived foam cell formation than other preparations. Compared with NCs, HA decoration showed enhanced atherosclerotic-lesion-targeting efficiency, proven by results from ex vivo imaging. Furthermore, atheroprotective efficacy study in apoE-deficient mice showed that NPs-3 had the best potent efficacy, which was demonstrated by the fewest atherosclerotic lesions sizes and lipid accumulation, the lowest macrophage infiltration, and the lowest expression of monocyte chemoattractant protein-1 (MCP-1), respectively. Collectively, the HA-coated CPP NCs were promising nanocarriers for efficient macrophage-targeted gene delivery and antiatherogenic therapy.