The Effect of Lipid Composition on the Liposomal Delivery of Camptothecin Developed by Active Click Loading.

In the present study, we investigated the role of lipid composition of camptothecin (CPT)-loaded liposomes (CPT-Lips) to adjust their residence time, drug distribution, and therefore the toxicities and antitumor activity. The CPT was loaded into liposomes using a click drug loading method, which utilized liposomes preloaded with GSH and then exposed to CPT-maleimide. The method produced CPT-Lips with a high encapsulation efficiency (>95%) and sustained drug release. It is shown that the residence times of CPT-Lips in the body were highly dependent on lipid compositions with an order of non-PEGylated liposomes of unsaturated lipids < non-PEGylated liposomes of saturated lipids < PEGylated liposomes of saturated lipids. Interestingly, the fast clearance of CPT-Lips resulted in significantly decreased toxicities but did not cause a significant decrease in their in vivo antitumor activity. These results suggested that the lipid composition could effectively adjust the residence time of CPT-Lips in the body and further optimize their therapeutic index, which would guide the development of a liposomal formulation of CPT.

Subdural effusion associated with COVID-19 encephalopathy: A case report.

BACKGROUND: The precise mechanism by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts the central nervous system remains unclear, with manifestations spanning from mild symptoms (e.g., olfactory and gustatory deficits, hallucinations, and headache) to severe complications (e.g., stroke, seizures, encephalitis, and neurally demyelinating lesions). The occurrence of single-pass subdural effusion, as described below, is extremely rare. CASE SUMMARY: A 56-year-old male patient presented with left-sided limb weakness and slurred speech as predominant clinical symptoms. Through comprehensive imaging and diagnostic assessments, he was diagnosed with cerebral infarction complicated by hemorrhagic transformation affecting the right frontal, temporal, and parietal regions. In addition, an intracranial infection with SARS-CoV-2 was identified during the rehabilitation process; consequently, an idiopathic subdural effusion developed. Remarkably, the subdural effusion underwent absorption within 6 d, with no recurrence observed during the 3-month follow-up. CONCLUSION: Subdural effusion is a potentially rare intracranial complication associated with SARS-CoV-2 infection.

Fast multi-view clustering via correntropy-based orthogonal concept factorization.

Owing to its ability to handle negative data and promising clustering performance, concept factorization (CF), an improved version of non-negative matrix factorization, has been incorporated into multi-view clustering recently. Nevertheless, existing CF-based multi-view clustering methods still have the following issues: (1) they directly conduct factorization in the original data space, which means its efficiency is sensitive to the feature dimension; (2) they ignore the high degree of factorization freedom of standard CF, which may lead to non-uniqueness factorization thereby causing reduced effectiveness; (3) traditional robust norms they used are unable to handle complex noises, significantly challenging their robustness. To address these issues, we establish a fast multi-view clustering via correntropy-based orthogonal concept factorization (FMVCCF). Specifically, FMVCCF executes factorization on a learned consensus anchor graph rather than directly decomposing the original data, lessening the dimensionality sensitivity. Then, a lightweight graph regularization term is incorporated to refine the factorization process with a low computational burden. Moreover, an improved multi-view correntropy-based orthogonal CF model is developed, which can enhance the effectiveness and robustness under the orthogonal constraint and correntropy criterion, respectively. Extensive experiments demonstrate that FMVCCF can achieve promising effectiveness and robustness on various real-world datasets with high efficiency.

Research Progress, Hotspots, and Trends of Using BIM to Reduce Building Energy Consumption: Visual Analysis Based on WOS Database.

With the development of engineering technology, building information modeling (BIM) has attracted more and more attention and has been studied by many experts on building energy consumption in recent years. It is necessary to analyze and forecast the application trend and prospect of BIM technology in building energy consumption. Based on 377 articles published in the WOS database, this study adopts the technique of combining scientometrics and bibliometrics to obtain relevant research hotspots and quantitative analysis results. The findings demonstrate that the building energy consumption field has made extensive use of BIM technology. However, there are still some limitations that can be improved, and the use of BIM technology in construction renovation projects should be emphasized. This study can help readers better understand the application status of BIM technology and its trajectory of development with regard to building energy consumption, providing a valuable reference for future research.

The intracortical myelin content of impulsive choices: results from T1- and T2-weighted MRI myelin mapping.

Delay discounting (DD) refers to a phenomenon that humans tend to choose small-sooner over large-later rewards during intertemporal choices. Steep discounting of delayed outcome is related to a variety of maladaptive behaviors and is considered as a transdiagnostic process across psychiatric disorders. Previous studies have investigated the association between brain structure (e.g. gray matter volume) and DD; however, it is unclear whether the intracortical myelin (ICM) influences DD. Here, based on a sample of 951 healthy young adults drawn from the Human Connectome Project, we examined the relationship between ICM, which was measured by the contrast of T1w and T2w images, and DD and further tested whether the identified associations were mediated by the regional homogeneity (ReHo) of brain spontaneous activity. Vertex-wise regression analyses revealed that steeper DD was significantly associated with lower ICM in the left temporoparietal junction (TPJ) and right middle-posterior cingulate cortex. Region-of-interest analysis revealed that the ReHo values in the left TPJ partially mediated the association of its myelin content with DD. Our findings provide the first evidence that cortical myelination is linked with individual differences in decision impulsivity and suggest that the myelin content affects cognitive performances partially through altered local brain synchrony.

Color-Tunable Binary Copolymers Manipulated by Intramolecular Aggregation and Hydrogen Bonding.

Construction of color-tunable luminescent polymeric materials with enhanced emission intensity and room-temperature phosphorescence (RTP) performance regulated by a single chromophore component is highly desirable in the scope of photoluminescent materials. Herein, a set of binary copolymers were facilely synthesized using free radical polymerization by selecting different types of polymer matrix and N-substituted naphthalimides (NPA) as chromophores. Surprisingly, the fluorescence emission of copolymers could be remarkably enhanced, because of the intramolecular aggregation of NPA manipulated by a single polymer chain in both solution and solid state. Moreover, RTP signals of binary copolymers were all clearly observed in the air without any processing procedure, because of the embedding of phosphors into hydrogen bonding networks after copolymerization with vinyl-based acrylamide monomers. Taking advantages of the synergistic effect of copolymerization-induced aggregation and copolymerization-induced rigidification to promote optical performance, UV stimulus-responsive luminescent polymer films with processability, flexibility, and adjustable emission wavelength were simply prepared using a drop-casting method in large scale, the setting of which is the basis for application in the fields of organic optoelectronics, information security, and bioimaging/sensing.

Tale of COF-on-MOF Composites with Structural Regulation and Stepwise Luminescence Enhancement.

Integrating metal-organic framework (MOF)-covalent organic framework (COF) allows versatile engineering of hybrid materials with properties superior to pristine components, especially COFs suffered from aggregation-caused quenching (ACQ), unlocking more possibilities to improve the luminescence of COFs. In this work, we prepared various MOF@COF composites with different COF layer thicknesses, in which stable UiO-66-NH2 served as the inner substrate and 1,3,5-benzenetricarboxaldehyde (BT), and 3,3'-dihydroxybenzidine (DH) were used to construct a COF layer. In addition to the conventional preparation method, we increased the ratio of BT and DH to be 1:2.5, and impressively, the morphologies of acquired UC (1:2.5) materials were quite different from the previous reticular structure and gradually extended from the spherical structure to the prickly structure with the increase of COF monomers. Remarkably, all of the UC materials possessed better luminescence properties than individual COF due to the limited COF layers. Meanwhile, UC-1 materials with an optimal COF layer displayed the strongest emission. In comparison with a single COF, the quantum yields of UC-1 and UC-1 (1:2.5) were increased nearly 7 times and 5 times, respectively. Moreover, the fluorescence of UC-1 materials was progressively enhanced via selective F- sensing. This work is expected to shed light on the potential hybridization of MOF-COF with structural adjustment, morphological design, and luminescence enhancement.

RNANetMotif: Identifying sequence-structure RNA network motifs in RNA-protein binding sites.

RNA molecules can adopt stable secondary and tertiary structures, which are essential in mediating physical interactions with other partners such as RNA binding proteins (RBPs) and in carrying out their cellular functions. In vivo and in vitro experiments such as RNAcompete and eCLIP have revealed in vitro binding preferences of RBPs to RNA oligomers and in vivo binding sites in cells. Analysis of these binding data showed that the structure properties of the RNAs in these binding sites are important determinants of the binding events; however, it has been a challenge to incorporate the structure information into an interpretable model. Here we describe a new approach, RNANetMotif, which takes predicted secondary structure of thousands of RNA sequences bound by an RBP as input and uses a graph theory approach to recognize enriched subgraphs. These enriched subgraphs are in essence shared sequence-structure elements that are important in RBP-RNA binding. To validate our approach, we performed RNA structure modeling via coarse-grained molecular dynamics folding simulations for selected 4 RBPs, and RNA-protein docking for LIN28B. The simulation results, e.g., solvent accessibility and energetics, further support the biological relevance of the discovered network subgraphs.

Tunable fluorescence emission based on multi-layered MOF-on-MOF.

Luminescent metal-organic frameworks (MOFs) have garnered considerable attention in various fields. Herein, we proposed a hierarchical confinement strategy based on MOF-on-MOF to tune luminescence emission ranging from blue to red including white light in a flexible way. The easily available ZIF-8 MOF was used as a host for the confinement of two kinds of size-matching dyes (perylene and rhodamine B) to obtain a layered ZIF-8@dye@ZIF-8@dye via in situ encapsulation and seed-mediated synthesis. ZIF-8@dye@ZIF-8@dye materials with different fluorescence emission in dispersed and solid states were both obtained by tuning the initial encapsulation concentration of dye and changing the structure of the inner and outer ZIF-8@dye layers. To our delight, ZIF-8@0.125perylene@ZIF-8@25RhB with white light emission in the dispersed state was obtained; meanwhile, ZIF-8@0.125perylene + 25RhB and mechanically mixed ZIF-8@0.125perylene + ZIF-8@25RhB could not realize white light emission under the same conditions, indicating that the proposed hierarchical confinement strategy facilitated white light regulation. Similarly, the emission of ZIF-8@dye@ZIF-8@dye in the solid state has also been investigated; ZIF-8@perylene@ZIF-8@3RhB with white light emission was obtained, while white light emission could not be achieved in ZIF-8@perylene + 3RhB and ZIF-8@perylene + ZIF-8@3RhB, which further indicated the importance of the hierarchical confinement strategy based on MOF-on-MOF. The proposed hierarchical confinement strategy may also inspire the development of other functional optical MOF materials.

Hepatoprotective effect and structural analysis of Hedysarum polysaccharides in vivo and in vitro.

The crude Hedysarum polysaccharides (HPS: HPS-50 and HPS-80) obtained from Radix Hedysari exhibited great pharmacological activities in our previous research. This study investigated the effects of HPS on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury (ALI) in mice and LPS-induced injury in LO2 cells, as well as the relationship between structural characteristics and hepatoprotective activities. The in vivo results showed that compared with HPS-80, HPS-50 showed stronger hepatoprotection, which improved histopathological changes to normal levels. HPS-50 significantly decreased the levels of ALT, AST, MPO, and MDA, increased the activities of SOD, CAT, and GSH, and suppressed the LPS/D-GalN-triggered production of TNF-α, IL-1ß, and IL-6 (p < .05). The results in vitro showed that HPS-50-P (HPS-50-1, HPS-50-2, and HPS-50-3) purified from HPS-50 played significant protective roles against LPS-induced injury in LO2 cells by reducing cell apoptosis and relieving cell cycle arrest. HPS-50-2 restored the percentage of normal cells from 54.8% to 94.7%, and reduced the S phase cells from 59.40% to 47.05% (p < .01). By analyzing the structure of HPS-50-P, including monosaccharide composition, molecular weight, chain conformation, and surface morphology, we speculated that the best protective effect of HPS-50-2 might be attributed to its beta configuration, highest molecular weight, and high glucose and galactose contents. These findings indicate that HPS-50 might be a promising source of functional foods for the protection and prevention of ALI. PRACTICAL APPLICATIONS: In this study, the protective effect of HPS on ALI was evaluated from multiple perspectives, and HPS-50-2 was screened as a potential active ingredient. This study has two practical applications. First, it provides a new way to improve ALI, and a new option for patients to prevent and treat ALI. Second, this work also complements the pharmacological activity of Radix Hedysari and provides a basis for the development of Radix Hedysari as a functional food.

Sensitive determination of tobramycin using homocystine capped gold nanoclusters as probe by second-order scattering.

A novel photoluminescent Hcy-AuNCs has been developed through one-pot reduction method, to establish a tobramycin sensing by second-order scattering (SOS). Hcy-AuNCs could spontaneously assemble to small-scaled aggregation, resulting in remarkable intensity enhancement of scattered luminescence signals. The luminescence of Hcy-AuNCs could be clearly observed under ultraviolet lamp, when excited at 365 nm, a significant luminescent intensity at 741 nm was monitored in SOS spectra. The introduction of AuNPs would cause large-scaled aggregation of Hcy-AuNCs that was rapidly settled in the solution, resulting in the decrease of SOS intensity. Besides, the non-radiative energy transfer between AuNPs and Hcy-AuNCs would also reduce the luminescent intensity. However, the addition of tobramycin would cause the aggregation of AuNPs due to the electrostatic and covalent bonding between AuNPs and tobramycin, thus eliminating the interference of AuNPs. The luminescence of Hcy-AuNCs reappeared, exhibiting an optical response toward tobramycin. The good linearity was obtained in a wide range from 4 nM to 300 nM with a low detection limit of 0.27 nM. The selectivity was acceptable toward different types of antibiotics. Finally, the proposed method was successfully applied to the widely used tobramycin eye drops.

Comparative stomach tissue distribution profiles of four major bio-active components of Radix Astragali in normal and gastric ulcer mice

Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-ß-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali

Structural characterization of a polysaccharide from Radix Hedysari and its protective effects against H2O2-induced injury in human gastric epithelium cells.

The gastroprotective effects of polysaccharides had become a hot topic in the field of functional polysaccharides research. Three polysaccharides, namely HPS-80-1, HPS-80-2, and HPS-80-3 were purified by DEAE-52 column chromatography. The thermodynamic characteristics, scanning electron microscopy, and Congo red experimental results of the above polysaccharides were greatly distinctive. Then a mature GES-1 oxidative stress cell model induced by H2O2 was established to screen out subsequent research subjects. It turned out that HPS-80-1 had a desirable protective effect, which was confirmed by analyses of cell cycle & apoptosis, and oxidative stress-related factors in the cell culture media, and so on. Furthermore, Structural features demonstrated that the backbone of HPS-80-1 appeared to mainly consist of →4)-α-D-Glcp-(1→, →4,6)-ß-L-Glcp-(1→, and →6)-α-D-Galp-(1→, with branches at O-1, O-4, and O-6 position consisting of →2,4)-ß-D-Rhap-(1→, →1)-α-D-Galp-(4→, and →3,4)-α-D-Manp-(1→. It was speculated that the excellent gastric mucosal protective activity of HPS-80-1 may be due to the high amount of glucose in the backbone. In addition, it was also related to the anti-inflammatory activity and antioxidant bases such as (1 â†’ 4)-Glcp and (1 â†’ 6)-Galp in the structure of HPS-80-1. These findings provide a scientific basis for further utilization of polysaccharides from Radix Hedysari.

Discovery of N-Phenylaminomethylthioacetylpyrimidine-2,4-diones as Protoporphyrinogen IX Oxidase Inhibitors through a Reaction Intermediate Derivation Approach.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an effective target for green herbicide discovery. In this work, we reported the unexpected discovery of a novel series of N-phenylaminomethylthioacetylpyrimidine-2,4-diones (2-6) as promising PPO inhibitors based on investigating the reaction intermediates of our initially designed N-phenyluracil thiazolidinone (1). An efficient one-pot procedure that gave 41 target compounds in good to high yields was developed. Systematic Nicotiana tabacum PPO (NtPPO) inhibitory and herbicidal activity evaluations led to identifying some compounds with improved NtPPO inhibition potency than saflufenacil and good post-emergence herbicidal activity at 37.5-150 g of ai/ha. Among these analogues, ethyl 2-((((2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)phenyl)amino)methyl)thio)acetate (2c) (Ki = 11 nM), exhibited excellent weed control at 37.5-150 g of ai/ha and was safe for rice at 150 g of ai/ha, indicating that compound 2c has the potential to be developed as a new herbicide for weed management in paddy fields. Additionally, our molecular simulation and metabolism studies showed that the side chains of compound 2c could form a hydrogen-bond-mediated seven-membered ring system; substituting a methyl group at R1 could reinforce the hydrogen bond of the ring system and reduce the metabolic rate of target compounds in planta.

Correction: Formononetin in Radix Hedysari extract-mediated green synthesis of gold nanoparticles for colorimetric detection of ferrous ions in tap water.

[This corrects the article DOI: 10.1039/D0RA05660J.].

The amelioration of ulcerative colitis induced by Dinitrobenzenesulfonic acid with Radix Hedysari.

Ulcerative colitis (UC) is a chronic inflammatory disease with an unknown precise etiology. This study proves that Radix Hedysari (RH) ameliorates UC. Four RH extracts were used to ameliorate UC induced by 2,4-Dinitrobenzenesulfonic acid by 7 days intervention in agreement to preliminary studies. Compared to treatment with RH extracts, the RH ethanol extract (EE) was found to be more effective in ameliorating UC. With EE, the DAI were significantly decreased. Macroscopic and histopathological assessments suggest that the colon mucosa was repaired, the organizational structure of the colon had been rebuilt. The levels of MPO, TNF-α, IL-1ß, and MDA were significantly decreased (p < .01), the levels of T-SOD and CAT were significantly increased (p < .01). Moreover, the compounds in EE were analyzed by HPLC. The results show that EE can ameliorate UC, and its anti-inflammatory capability probably plays an important role. RH can act as a functional food and ameliorate UC. PRACTICAL APPLICATIONS: In this work, the ameliorative effect of RH on UC was evaluated from multiple angles. There are two practical applications of this work. On the one hand, a new approach to ameliorating UC is provided by this work. In addition, UC patients have a new option for improving their symptoms. On the other hand, this work also provides information on how best to process RH for therapeutic use. In addition, we can utilize some compounds of RH that were once considered useless and reduce the waste of natural resources.

Chromatographic Fingerprint Analysis of Radix Hedysari Using Supercritical Fluid Chromatography Coupled with Diode Array Detector.

A newly and rapid supercritical fluid chromatography method for the simultaneous determination of 11 active compounds in Radix Hedysari samples has been developed and validated. Optimum separation was achieved on a HSS SB C18 column with a gradient elution at a flow rate of 1.5 mL/min, back pressure of 11.03 Mpa and diode array detector at 260 nm. The results from the quantitative data showed that contents of these 11 active compounds were different from plant regions. Especially the contents of formononetin in the Minxian county are ~6-fold than in wild Radix Hedysari. The chromatographic fingerprint of Radix Hedysari was recorded under the same chromatographic condition. Data analytic procedure was performed to differentiate the 25 batches of Radix Hedysari samples. Data from chromatographic fingerprint were also analyzed using hierarchical cluster analysis. The results showed that 23 batches of Radix Hedysari samples had a high similarity (> 0.90) and overall 25 batches of sample were divided into two clusters. Moreover, according to the comparison contents of active compounds in each Radix Hedysari samples, the cultivated location of Radix Hedysari was successfully distinguished. This method presented good stability, repeatability and precision and would be a useful and reliable approach for the quality control of Radix Hedysari. Moreover, all target compounds were quantified by ultra-high performance liquid chromatography-time-of-flight mass spectrometry.

Formononetin in Radix Hedysari extract-mediated green synthesis of gold nanoparticles for colorimetric detection of ferrous ions in tap water.

This study linked natural plant materials and nanomaterials; reporting an environmentally friendly, non-toxic and efficient method for the green synthesis of gold nanoparticles (AuNPs) using an ethyl acetate extract of Radix Hedysari (EAR). The components of the extract were identified using HPLC and it was found that formononetin accounted for more than 90% of the total contents. We predicted that formononetin in EAR plays a crucial role in green synthesis. Thus, formononetin was used as a standard reductant to synthesize AuNPs, and the result confirmed our prediction. The synthetic mechanism was also discussed in detail in the article. Moreover, EAR-AuNPs realized the sensitive and selective colorimetric detection of ferrous ions (Fe2+) among other metal ions, and were applied to spiked tap water with a low detection limit of 1.5 µM in a wide range from 10 µM to 500 µM. EAR-AuNPs were green synthesized using Radix Hedysari extract for the first time and were successfully applied in real sample detection.

Spectrum-effect relationship between HPLC fingerprints and bioactive components of Radix Hedysari on increasing the peak bone mass of rat.

The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for ascending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.

Design, Herbicidal Activity, and QSAR Analysis of Cycloalka[d]quinazoline-2,4-dione-Benzoxazinones as Protoporphyrinogen IX Oxidase Inhibitors.

In continuation of our search for potent protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) inhibitors, we designed and synthesized a series of novel herbicidal cycloalka[d]quinazoline-2,4-dione-benzoxazinones. The bioassay results of these synthesized compounds indicated that most of the compounds exhibited very strong Nicotiana tabacum PPO (NtPPO) inhibition activity. More than half of the 37 synthesized compounds displayed over 80% control of all three tested broadleaf weeds at 37.5-150 g ai/ha by postemergent application, and a majority of them showed no phytotoxicity toward at least one kind of crop at 150 g ai/ha. Promisingly, 17i (Ki = 6.7 nM) was 6 and 4 times more potent than flumioxazin (Ki = 46 nM) and trifludimoxazin (Ki = 31 nM), respectively. Moreover, 17i displayed excellent, broad-spectrum herbicidal activity, even at levels as low as 37.5 g ai/ha, and it was determined to be safe for wheat at 150 g ai/ha in postemergent application, indicating the great potential for 17i development as a herbicide for weed control in wheat fields.