Evaluation of Graphene Oxide as a Thermal Ionization Enhancer for Plutonium in TIMS Measurement.

Thermal ionization mass spectrometry (TIMS) has been extensively employed for the assessment of plutonium (Pu) isotopes in nuclear forensics and environmental monitoring. Recently, great efforts have been made to improve the ionization efficiency (IE) of Pu to achieve better accuracy and precision for trace-level analysis. Herein, the thermal ionization enhancement effect for plutonium of graphene oxide (GO) was investigated and the corresponding mechanism was discussed. The GO layers were homogeneously mounted on the filament's central surface to promote pg-level Pu ion emission. With the excellent structural property of GO, a greatly promoted ionization efficiency of 0.44% for Pu was obtained, and the initial ionization temperature for Pu was remarkably reduced from 1610 to 1390 °C. Average boosts in IE compared to the classical double-filament mode and graphite-loaded single-filament mode were 1640 and 520%, respectively. The analytical accuracy and precision based on the GO-loaded single-filament mode were validated using Pu isotopic certified reference materials. This work demonstrates the excellent property of GO as an ion source additive for Pu ionization, as it provided an interface for the promotion of energy transfer and Pu carbide formation. The operation of GO loading is quite simple and can be finished within 5 min. This rapid filament carburization approach has great potential for improving the measurement precision of trace-level plutonium isotopes and can be applied in nuclear safeguards, nuclear forensics, and environmental monitoring.

Co-amorphous Systems of Sinomenine with Platensimycin or Sulfasalazine: Physical Stability and Excipient-Adjusted Release Behavior.

There is strong interest to develop affordable treatments for the infection-associated rheumatoid arthritis (RA). Here, we present a drug-drug co-amorphous strategy against RA and the associated bacterial infection by the preparation and characterization of two co-amorphous systems of sinomenine (SIN) with platensimycin (PTM) or sulfasalazine (SULF), two potent antibiotics. Both of them were comprehensively characterized using powder X-ray diffraction, temperature-modulated differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The co-amorphous forms of SIN-PTM and SIN-SULF exhibited high Tgs at 139.10 ± 1.0 and 153.3 ± 0.2 °C, respectively. After 6 months of accelerated tests and 1 month of drug-excipient compatibility experiments, two co-amorphous systems displayed satisfactory physical stability. The formation of salt and strong intermolecular interactions between SIN and PTM or SULF, as well as the decreased molecular mobility in co-amorphous systems, may be the intrinsic mechanisms underlying the excellent physical stability of both co-amorphous systems. In dissolution tests, two co-amorphous systems displayed distinct reduced SIN-accumulative releases (below 20% after 6 h of release experiments), which may lead to its poor therapeutic effect. Hence, we demonstrated a controlled release strategy for SIN by the addition of a small percentage of polymers and a small-molecule surfactant to these two co-amorphous samples as convenient drug excipients, which may also be used to improve the unsatisfactory dissolution behaviors of the previously reported SIN co-amorphous systems. Several hydrogen bonding interactions between SIN and PTM or SULF could be identified in NMR experiments in DMSO-d6, which may be underlying reasons of decreased dissolution behaviors of both co-amorphous forms. These drug-drug co-amorphous systems could be a potential strategy for the treatment of infection-associated RA.

Determination of tautomeric preference of fenobam in solution by high-resolution NMR spectroscopy.

In this work, tautomeric preference of fenobam in solution was investigated by homonuclear and heteronuclear solution nuclear magnetic resonance (NMR) spectroscopy. 1 H-1 H nuclear Overhauser effect spectroscopy (NOESY) spectrum revealed that fenobam in liquid state exists exclusively in one of the two possible tautomeric structures, which was confirmed by 1 H-13 C HSQC and heteronuclear multiple bond correlation (HMBC) spectra. Moreover, difference between the two tautomeric structures was studied by theoretical calculations, which further proved the result obtained by the NMR experiments.

Combined Intrinsic and Extrinsic Proton Conduction in Robust Covalent Organic Frameworks for Hydrogen Fuel Cell Applications.

Developing new materials for the fabrication of proton exchange membranes (PEMs) for fuel cells is of great significance. Herein, a series of highly crystalline, porous, and stable new covalent organic frameworks (COFs) have been developed by a stepwise synthesis strategy. The synthesized COFs exhibit high hydrophilicity and excellent stability in strong acid or base (e.g., 12 m NaOH or HCl) and boiling water. These features make them ideal platforms for proton conduction applications. Upon loading with H3 PO4 , the COFs (H3 PO4 @COFs) realize an ultrahigh proton conductivity of 1.13×10-1  S cm-1 , the highest among all COF materials, and maintain high proton conductivity across a wide relative humidity (40-100 %) and temperature range (20-80 °C). Furthermore, membrane electrode assemblies were fabricated using H3 PO4 @COFs as the solid electrolyte membrane for proton exchange resulting in a maximum power density of 81 mW cm-2 and a maximum current density of 456 mA cm-2 , which exceeds all previously reported COF materials.

Graphene Oxide Carburization Enhanced Ionization Efficiency for TIMS Isotope Ratio Analysis of Uranium at Trace Level.

Isotope analysis of trace uranium is important in nuclear safeguards and nuclear forensics, which requires the analytical methodologies with high sensitivity, accuracy, and precision. As one of the most powerful techniques in isotopic measurement, thermal ionization mass spectrometry (TIMS) usually suffers from its relatively low sensitivity in ultratrace measurements. To overcome this limitation, we have developed a new filament carburization technique for TIMS, with graphene oxide (GO) as the ionization enhancer. A high and steady ionization efficiency of ∼0.2% for uranium was achieved in single-filament mode, which was 10× the classical double-filament method. With total evaporation (TE) measurements, this method was validated with certified reference materials (CRMs) at the picogram level, and the relative uncertainties for n(235U)/ n(238U) were as low as the ∼1% level. The enhancement mechanism of GO's promoting effect on uranium ionization was attributed to the uniform microstructure facilitating energy transfer and formation of carbides. This approach provides an alternative simple and rapid method for trace uranium isotope analysis with high sensitivity and excellent repeatability. Filament carburization and uranium loading could be accomplished within 10 min. This technique has great advantage in analysis of trace uranium isotope ratios and can be applied in the researches of environmental analysis and nuclear forensics.

Phase transformation induced reversible modulation of upconversion luminescence of WO3:Yb3+, Er3+ phosphor for switching devices.

The upconverting luminescence properties of phosphors are dependent on the hosts. In this work, the WO3:Yb3+, Er3+ phosphor was prepared, and the reversible phase transformation from the WO3 to the WO2 was obtained by alternating the sintering in a reducing atmosphere or in air. The influence of reversible phase transformation on the upconversion luminescence was investigated first. The WO3:Yb3+, Er3+ phosphor exhibits the visible upconversion luminescence, while no upconversion luminescence was observed in the WO2:Yb3+, Er3+ phosphor. The reversible modulation of upconversion luminescence of the WO3:Yb3+, Er3+ phosphor retains the excellent reproducibility, exhibiting the potential applications in data storage and optical switches.

Cell-assembled nanoclusters of MSC-targeting Gd-DOTA-peptide as a T2 contrast agent for MRI cell tracking.

A cyclic peptide CC9 that targets cell membrane of mesenchymal stem cells (MSCs) is coupled with Gd-DOTA to yield a Gd-DOTA-CC9 complex as MRI contrast agent. It is used to label human MSCs (hMSCs) via electroporation. Electroporation-labeling of hMSCs with Gd-DOTA-CC9 induces cell-assembly of Gd-DOTA-CC9 nanoclusters in the cytoplasm, significantly promotes cell-labeling efficacy and intracellular retention time of the agent. In vitro MRI of labeled hMSCs exhibits significant signal reduction under T2 -weighted MRI, which can allow long-term tracking of labeled cell transplants in in vivo migration. The labeling strategy is safe in cytotoxicity and differentiation potential.

Ultrasmall graphene oxide based T1 MRI contrast agent for in vitro and in vivo labeling of human mesenchymal stem cells.

Herein, we report on development of a two-dimensional nanomaterial graphene oxide (GO)-based T1 magnetic resonance imaging (MRI) contrast agent (CA) for in vitro and in vivo labeling of human mesenchymal stem cells (hMSCs). The CA was synthesized by PEGylation of ultrasmall GO, followed by conjugation with a chelating agent DOTA and then gadolinium(III) to form GO-DOTA-Gd complexes. Thus-prepared GO-DOTA-Gd complexes exhibited significantly improved T1 relaxivity, and the r1 value was 14.2 mM-1s-1 at 11.7 T, approximately three times higher than Magnevist, a commercially available CA. hMSCs can be effectively labeled by GO-DOTA-Gd, leading to remarkably enhanced cellular MRI effect without obvious adverse effects on proliferation and differentiation of hMSCs. More importantly, in vivo experiment revealed that intracranial detection of 5×105 hMSCs labeled with GO-DOTA-Gd is achieved. The current work demonstrates the feasibility of the GO-based T1 MRI CA for stem cell labeling, which may find potential applications in regenerative medicine.

Oligoethylenimine-grafted chitosan as enhanced T1 contrast agent for in vivo targeted tumor MRI.

PURPOSE: To synthesize and characterize an effective macromolecular magnetic resonance imaging (MRI) contrast agent based on oligoethylenimine-grafted chitosan with targeting capability. MATERIALS AND METHODS: In this study we synthesized and characterized oligoethylenimine-grafted chitosan copolymers, followed by conjugating with Gd-DTPA and folic acid. The toxicity was evaluated by WST assay, and in vitro MRI studies were performed in comparison with Gd-DTPA. Finally, the contrast enhancement of the new macromolecular MRI contrast agent was then evaluated in the mice bearing KB xenografts. RESULTS: Compared to Gd-DTPA (4.3 mM(-1) s(-1) ), this macromolecular contrast agent (mCA) exhibited much higher T1 relaxivity (14.4 mM(-1) s(-1) ), up to 3.3 times higher. Meanwhile, the WST assay illustrated that the viability of KB cells remained at 90% even when the Gd concentration was 1 mM. During the in vivo study, the image contrast produced by FA-mCA was higher than one produced by mCA, up to 2.5 times higher. CONCLUSION: Our results showed this macromolecular contrast agent has potential for developing sensitive and biocompatible MRI probe with targeting capability. J. Magn. Reson. Imaging 2016;44:23-29.

Aptamer-Modified Temperature-Sensitive Liposomal Contrast Agent for Magnetic Resonance Imaging.

A novel aptamer modified thermosensitive liposome was designed as an efficient magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an optimized thermosensitive liposome (TSL) formulation, followed by conjugation with AS1411 for specific targeting against tumor cells that overexpress nucleolin receptors. The resulting liposomes were extensively characterized in vitro as a contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious cytotoxicity was observed from MTT assay, which illustrated that the liposomes exhibited excellent biocompatibility. Compared to the control incubation at 37 °C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity in MCF-7 cells incubated at 42 °C. These data indicate that the Gd-encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis.

Tranilast-matrine co-amorphous system: Strong intermolecular interactions, improved solubility, and physiochemical stability.

There is a great interest to develop co-amorphous drug delivery systems to enhance the solubility of biopharmaceutics classification system (BCS) class II and IV drugs. However, most reported systems only resulted in severalfold solubility improvement. Tranilast (TRA) is an anti-allergic drug used to treat bronchial asthma and allergic rhinitis. It is a BCS class II drug and its poor aqueous solubility affects its absorption in vivo. To address this issue, a natural alkaloid matrine (MAR) with interesting biological activities was chosen to form a co-amorphous system with TRA, based on the solubility parameter and phase solubility experiment. The TRA-MAR drug-drug co-amorphous system was prepared by the solvent evaporation method, and further characterized by powder X-ray diffraction and modulated temperature differential scanning calorimetry. Fourier transform infrared spectroscopy, FT-Raman, and X-ray photoelectron spectroscopy revealed the formation of salt and the presence of strong intermolecular interactions in the TRA-MAR co-amorphous system, which are also supported by molecular dynamics simulations, showing ionic and hydrogen bonding interactions. This co-amorphous system exhibited excellent physical stability at both 25 °C and 40 °C under anhydrous silica gel condition. Finally, co-amorphous TRA-MAR showed greatly enhanced solubility (greater than 100-fold) and rapid release behavior in the vitro release experiments. NMR spectroscopy revealed the strong intermolecular interactions between TRA and MAR in both DMSO­d6 and D2O. Our study resulted in a TRA-MAR co-amorphous drug system with significant solubility improvement and showcased the great potential to improve the dissolution behaviors of BCS class II and IV drugs through the co-amorphization approach.

Sustainable planning in Wuhan City during COVID-19: an analysis of influential factors, risk profiles, and clustered patterns.

The outbreak of novel coronavirus pneumonia (COVID-19) is closely related to the intra-urban environment. It is important to understand the influence mechanism and risk characteristics of urban environment on infectious diseases from the perspective of urban environment composition. In this study, we used python to collect Sina Weibo help data as well as urban multivariate big data, and The random forest model was used to measure the contribution of each influential factor within to the COVID-19 outbreak. A comprehensive risk evaluation system from the perspective of urban environment was constructed, and the entropy weighting method was used to produce the weights of various types of risks, generate the specific values of the four types of risks, and obtain the four levels of comprehensive risk zones through the K-MEANS clustering of Wuhan's central urban area for zoning planning. Based on the results, we found: ①the five most significant indicators contributing to the risk of the Wuhan COVID-19 outbreak were Road Network Density, Shopping Mall Density, Public Transport Density, Educational Facility Density, Bank Density. Floor Area Ration, Poi Functional Mix ②After streamlining five indicators such as Proportion of Aged Population, Tertiary Hospital Density, Open Space Density, Night-time Light Intensity, Number of Beds Available in Designated Hospitals, the prediction accuracy of the random forest model was the highest. ③The spatial characteristics of the four categories of new crown epidemic risk, namely transmission risk, exposure risk, susceptibility risk and Risk of Scarcity of Medical Resources, were highly differentiated, and a four-level integrated risk zone was obtained by K-MEANS clustering. Its distribution pattern was in the form of "multicenter-periphery" gradient diffusion. For the risk composition of the four-level comprehensive zones combined with the internal characteristics of the urban environment in specific zones to develop differentiated control strategies. Targeted policies were then devised for each partition, offering a practical advantage over singular COVID-19 impact factor analyses. This methodology, beneficial for future public health crises, enables the swift identification of unique risk profiles in different partitions, streamlining the formulation of precise policies. The overarching goal is to maintain regular social development, harmonizing preventive measures and economic efforts.

Sustained Release of Co-Amorphous Matrine-Type Alkaloids and Resveratrol with Anti-COVID-19 Potential.

Matrine (MAR), oxymatrine (OMAR), and sophoridine (SPD) are natural alkaloids with varying biological activities; matrine was recently used for the treatment of coronavirus disease 2019 (COVID-19). However, the short half-lives and rapid elimination of these matrine-type alkaloids would lead to low oral bioavailability and serious side effects. Herein, resveratrol (RES) was selected as a co-former to prepare their co-amorphous systems to improve the therapeutic index. The formation of co-amorphous MAR-RES, OMAR-RES, and SPD-RES was established through powder X-ray diffraction and modulated temperature differential scanning calorimetry. Furthermore, Fourier transform infrared spectroscopy and NMR studies revealed the strong molecular interactions between resveratrol and these alkaloids, especially OMAR-RES. Matrine, oxymatrine, and sophoridine in the co-amorphous systems showed sustained release behaviors in the dissolution experiments, due to the recrystallization of resveratrol on the surface of co-amorphous drugs. The three co-amorphous systems exhibited excellent physicochemical stability under high relative humidity conditions. Our study not only showed that minor structural changes of active pharmaceutical ingredients may have distinct molecular interactions with the co-former, but also discovered a new type of sustained release mechanism for co-amorphous drugs. This promising co-amorphous drug approach may present a unique opportunity for repurposing these very promising drugs against COVID-19.

Impacts of Social Inequality, Air Pollution, Rural-Urban Divides, and Insufficient Green Space on Residents' Health in China: Insight from Chinese General Social Survey Data Analysis.

Attention to physical and mental health is becoming more intensive. In China, factors and mechanisms are now a focus of research. We used dynamic air quality monitoring data and the Chinese General Social Survey (CGSS) to assess the spatial differences and the coupling between subjective and objective air pollution. In addition, a logistic model was used to explore the impact mechanisms of social inequality, air pollution, food safety, and lack of green space on health. The results show that (1) the impact of subjective and objective air pollution on the health level of the population is significant; (2) income inequality, air pollution, food pollution, and travel behavior significantly affect the residents' health; and (3) environmental health has a significant differentiation mechanism between urban and rural areas. The negative health effects of air pollution and insufficient green space are more significant in cities; food pollution is more likely in rural areas. In terms of socioeconomic inequality, gender, family size, travel, and physical exercise had no significant effect on rural health. Health improvement was higher in the low-income group than in the high-income group. The adverse effect of travel behavior on environmental pollution is conducive to improving health. Therefore, social equality, strictly controlled environmental pollution, exercise, and travel can help narrow the gap between rich and poor, promote urban-rural health equity, and improve human health.

Platensimycin-berberine chloride co-amorphous drug system: Sustained release and prolonged half-life.

Co-amorphous technology is an emerging approach for pharmaceutical engineering of drugs and drug leads with improved physicochemical properties and bioavailability. Platensimycin (PTM) is a promising natural antibiotic lead that acts on bacterial fatty acid synthase and exhibits excellent antibacterial activity. Despite great strides to improve its poor pharmacokinetics by medicinal chemistry and nanotechnology, there are no convenient oral delivery systems developed. Here, a co-amorphous system of PTM and berberine chloride (BCL) was developed for oral delivery of PTM. Co-amorphous PTM-BCL was prepared by rotary vacuum evaporation method, and systematically characterized by powder X-ray diffraction, temperature modulated differential scanning calorimetry, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Compared with PTM or BCL alone, the equilibrium solubility and dissolution rate of both of them in the co-amorphous systems decreased significantly, showing the characteristics of sustained release. The molecular interactions between PTM and BCL were mediated by strong charged-mediated hydrogen bonds, based on FTIR, XPS, and NMR-based techniques. The co-amorphous PTM-BCL system showed excellent physiochemical stability at room and elevated (40 °C) temperature under dry conditions. The combination of PTM and BCL showed increased killing of a clinical isolated methicillin-resistant Staphylococcus aureus strain in killing checkerboard assays. Finally, co-amorphous PTM-BCL exhibited 2- or 3-fold longer half-life in rats than that of crystalline and amorphous PTM upon oral administration, respectively. Our study suggests a rational approach to realize the full potential of potent antibiotic PTM, which may be conveniently adapted for engineering of other important pharmaceutics.

Influencing Factors and Risk Assessment of Precipitation-Induced Flooding in Zhengzhou, China, Based on Random Forest and XGBoost Algorithms.

Due to extreme weather phenomena, precipitation-induced flooding has become a frequent, widespread, and destructive natural disaster. Risk assessments of flooding have thus become a popular area of research. In this study, we studied the severe precipitation-induced flooding that occurred in Zhengzhou, Henan Province, China, in July 2021. We identified 16 basic indicators, and the random forest algorithm was used to determine the contribution of each indicator to the Zhengzhou flood. We then optimised the selected indicators and introduced the XGBoost algorithm to construct a risk index assessment model of precipitation-induced flooding. Our results identified four primary indicators for precipitation-induced flooding in the study area: total rainfall for three consecutive days, extreme daily rainfall, vegetation cover, and the river system. The Zhengzhou storm and flood risk evaluation model was constructed from 12 indicators: elevation, slope, water system index, extreme daily rainfall, total rainfall for three consecutive days, night-time light brightness, land-use type, proportion of arable land area, gross regional product, proportion of elderly population, vegetation cover, and medical rescue capacity. After streamlining the bottom four indicators in terms of contribution rate, it had the best performance, with an accuracy rate reaching 91.3%. Very high-risk and high-risk areas accounted for 11.46% and 27.50% of the total area of Zhengzhou, respectively, and their distribution was more significantly influenced by the extent of heavy rainfall, direction of river systems, and land types; the medium-risk area was the largest, accounting for 33.96% of the total area; the second-lowest-risk and low-risk areas together accounted for 27.09%. The areas with the highest risk of heavy rainfall and flooding in Zhengzhou were in the Erqi, Guanchenghui, Jinshui, Zhongyuan, and Huizi Districts and the western part of Xinmi City; these areas should be given priority attention during disaster monitoring and early warning and risk prevention and control.

Co-amorphous systems of sinomenine with nonsteroidal anti-inflammatory drugs: A strategy for solubility improvement, sustained release, and drug combination therapy against rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune joint disorder that affects about 1% of the world population and may lead to severe disability and comorbidity. Despite breakthroughs in past decades to understand its pathogenesis and the development of transforming disease-modifying antirheumatic drugs, the symptoms of many patients are not substantially improved. Sinomenine (SIN), a natural alkaloid with poor solubility, has been used to treat RA in China for years because of its unique immunoregulative activity. However, its commercial hydrochloride form has a short half-time, which may cause huge fluctuations of blood drug concentration leading to severe adverse reactions. In this study, co-amorphous systems of SIN with three nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin, naproxen, and sulindac, were prepared for the combination therapy, as well as the improvement of its aqueous solubility and controlled release. Each co-amorphous sample was characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), and Fourier transform infrared spectroscopy (FTIR). The CO2- and N+H stretching vibration in the three co-amorphous samples appears in FTIR spectra, suggesting the formation of salts between SIN and NSAIDs. SIN also exhibits sustained release rates in all three co-amorphous samples. These co-amorphous systems show excellent physicochemical stability because no recrystallization was observed at 25 °C and 75% relative humidity (RH) after four months. Our study suggests that SIN-NSAIDs co-amorphous systems represent an affordable and promising treatment against RA.

Sinomenine-phenolic acid coamorphous drug systems: Solubilization, sustained release, and improved physical stability.

Sinomenine (SIN), isolated from Caulis sinomenii, is a benzyltetrahydroisoquinoline-type alkaloid with potent anti-inflammatory and analgesic effects. SIN-HCl has been used in the forms of tablets or enteric-coated tablets in the treatment of rheumatoid arthritis in China for years, while its short half-life leads to attenuated therapeutic effects and serious side effects. In the current study, three phenolic acids, including salicylic acid (SAA), 2,3-dihydroxybenzoic acid (23DHB), and 2,4-dihydroxybenzoic acid (24DHB), were firstly employed as coamorphous coformers to prepare three binary SIN-phenolic acid coamorphous systems. These new coamorphous systems were characterized by powder X-ray diffraction (PXRD), modulated temperature differential scanning calorimetry (mDSC), and Fourier transform infrared spectroscopy (FTIR). The formation of SIN-phenolic acid coamorphous systems are supported by the absence of diffraction peaks in their PXRD spectra, as well as the single Tgs of three samples (i.e., SIN-SAA, SIN-23DHB, and SIN-24DHB) at 109.5 °C, 124.9 °C, and 135.3 °C. Importantly, the salt formation between SIN and phenolic acids was observed in FTIR. In three coamorphous systems, coamorphous SIN-24DHB shows superior physicochemical stability under both low humidity and accelerated storage conditions. They were also more soluble than crystalline SIN, while were released slower than the commercial SIN-HCl in dissolution experiments. Therefore, our study suggests that phenolic acids may be used as a new type of coformers in the preparation of coamorphous systems for active pharmaceutical ingredients.

Naphthalene-facilitated self-assembly of a Gd-chelate as a novel T2 MRI contrast agent for visualization of stem cell transplants.

Naphthalene is coupled with DOTA via a peptide sequence to yield an amphipathic MRI probe Nap-CFGKTG-DOTA-Gd (Nap-Gd) that can self-assemble into nanofibers. Incubation of NSCs, hMSCs and L929 cells in the presence of Nap-Gd in the µM level can introduce a significant amount of Nap-Gd into the cells as nanoclusters or nanofibers. The resultant intracellular Gd content is 10-60 times that achieved by incubation with Dotarem at the same concentration. The labelled cells exhibit a significant hyperintensive effect under T1-weighted MRI and a significant hypointensive effect under T2-weighted MRI. The hypointensive effect is more persistent than the hyperintensive effect, which allows in vivo tracking of labelled hMSCs for over 12 days under T2-weighted MRI. A comprehensive interpretation of the MRI signal intensity and the associated relaxation times reveals the structure-function relationship between the binding status of Nap-Gd in cells (structure) and the magnetic relaxation processes (function) toward a full understanding of the observed hyperintensive and hypointensive effects.

Phase solubility diagrams and energy surface calculations support the solubility enhancement with low hygroscopicity of Bergenin: 4-Aminobenzamide (1: 1) cocrystal.

Herein, we reported a new bergenin: 4-aminobenzamide (BGN-4AM) cocrystal with significantly enhanced solubility and low hygroscopicity probed from two aspects such as phase solubility diagrams and theoretical calculations. Compared with anhydrous BGN, BGN-4AM solubilities in water and different buffer solutions (pH = 1.2, 4.5, 6.8) increase significantly. It is noted that BGN-4AM solubility in pH = 6.8 buffer solution presents 32.7 times higher than anhydrous BGN. Interestingly, BGN-4AM (0.31 ± 0.07%) showcases lower hygroscopicity than anhydrous BGN (9.31 ± 0.16%). The predicted and experimental solubilities agree with each other when considering solubility product (Ksp) and solution binding constant (K11) in phase solubility diagrams, indicating the solution complexes formation occurs. Further crystal surface-water interactions and Bravais, Friedel, Donnay-Harker (BFDH) analyses based on Density Functional Theory with dispersion correction (DFT-d) methods support the enhanced solubility. The water probe demonstrates an average interaction energy of -6.48 kcal/mol on the 002 plane of BGN-4AM, and only -5.47 kcal/mol on the 011 plane of BGN monohydrate. The lower lattice energy of BGN-4AM guarantees its lower hygroscopicity than BGN monohydrate. BGN-4AM with enhanced solubility and low hygroscopicity can be a potential candidate for further formulation development.