Foldback-crRNA-Enhanced CRISPR/Cas13a System (FCECas13a) Enables Direct Detection of Ultrashort sncRNA.

The CRISPR/Cas13a system has promising applications in clinical small noncoding RNA (sncRNA) detection because it is free from the interference of genomic DNA. However, detecting ultrashort sncRNAs (less than 20 nucleotides) has been challenging because the Cas13a nuclease requires longer crRNA-target RNA hybrids to be activated. Here, we report the development of a foldback-crRNA-enhanced CRISPR/Cas13a (FCECas13a) system that overcomes the limitations of the current CRISPR/Cas13a system in detecting ultrashort sncRNAs. The FCECas13a system employs a 3'-terminal foldback crRNA that hybridizes with the target ultrashort sncRNA, forming a double strand that "tricks" the Cas13a nuclease into activating the HEPN structural domain and generating trans-cleavage activity. The FCECas13a system can accurately detect miRNA720 (a sncRNA currently known as tRNA-derived small RNA), which is only 17 nucleotides long and has a concentration as low as 15 fM within 20 min. This FCECas13a system opens new avenues for ultrashort sncRNA detection with significant implications for basic biological research, disease prognosis, and molecular diagnosis.

The support dilemma of stroke inpatients and family caregivers under COVID-19 prevention and control: a qualitative study in China.

China has implemented a strict isolation system in hospitals since the COVID-19 pandemic, that adversely affected the psychology of inpatients and their caregivers. Face-to-face, semi-structured interviews with 22 stroke inpatients from two municipal hospitals were conducted to explore the psychological, emotional and related support needs of stroke inpatients and their family caregivers under this environment. Results which showed that external support for stroke inpatients and their family caregivers was insufficient highlight the necessity for developing specific nursing interventions that meet the psychological and emotional needs of inpatients and the caregivers.

Anti-Inflammatory Effects of Boldine and Reticuline Isolated from Litsea cubeba through JAK2/STAT3 and NF-κB Signaling Pathways.

The anti-inflammatory effects of boldine and reticuline isolated from Litsea cubeba were evaluated by using xylene-induced ear edema and carrageenan-induced paw edema in mice and rats. Our results demonstrated that intragastric administration with boldine and reticuline significantly mitigated ear weight in mice and decreased paw volume in rats. A combination administration of boldine (0.5 mg/kg) + reticuline (0.25 mg/kg) resulted in a potentiated inhibition in these two models. In parallel, boldine or reticuline reduce the infiltration of neutrophil leukocytes in rat paw tissue, respectively, and the combination of the two groups performed a better anti-inflammatory activity as shown in histopathologies. Boldine, reticuline, and their combination notably inhibited mRNA expressions of TNF-α, and IL-6 and reduced the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Beyond that, their combination also can reduce the phosphorylation levels of p65 and IκBα in the pathological tissues of animals, as observed by real-time PCR and western blot analyses, respectively. These findings indicate for the first time that boldine and reticuline have not only anti-inflammatory activity but also potential synergistic effects in vivo. The underlying mechanism may relate to the inhibition on the expression of pro-inflammatory cytokines, such as TNF-α and IL-6, which may be a consequence of JAK2/STAT3 and NF-κB pathway involvements. This study provides useful data for further exploration and application of boldine and reticuline as potential anti-inflammatory medicines.

Three new triterpenoid saponins from the stems of Ilex asprella.

Three new triterpenoid saponins, namely asprellinoids A-C (1-3), featuring a sulfate substitution in sugar moiety, were isolated from the stems of Ilex asprella (Hook. et Arn.) Champ. ex Benth. Their structures were elucidated by the spectroscopic data analyses including HR-ESI-MS, IR, and NMR spectra, and chemical method.

[Chemical and pharmacological progress on usnic acid and its derivatives].

Usnic acid and its derivatives, a group of organic molecules with great importance, are characteristic to lichens, possessing pharmacological activities such as anti-virus, anti-bacteria, anti-humor, anti-inflammatory, analgesic, and anaesthetic effects. Many of them have been widely used as medicine, but also bring side effects such as dermatitis and liver damages. In the past decades, great efforts by isolation, organic synthesis, and structure modification methods were put on discovery of UA derivatives with higher biological activities or less side effects. This paper describes herein the most progress on natural sources, isolation and structure elucidation, structural characteristics, synthesis and modification results, pharmacological activities and toxicities of UA and its derivatives, hopefully to provide valuable reference for further research.

Noralashinol B, a norlignan with cytotoxicity from stem barks of Syringa pinnatifolia.

One new norlignan, noralashinol B (1), and one new natural product, proposed noralashinol C (2), were isolated in a continuous phytochemical investigation on the stem barks of Syringa pinnatifolia. Their structures were elucidated based on the analysis of spectroscopic data, including mass spectrometry and 1D and 2D NMR spectroscopies, and the absolute configuration was determined by experimental and calculated electronic circular dichroism. Compound 1 showed a weak cytotoxicity against HepG2 hepatic cancer cells with its IC50 value of 31.7 µM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose-dependent manner at concentrations of 0-80.0 µM.

Anti-Proliferative Effect of Triterpenoidal Glycosides from the Roots of Anemone vitifolia through a Pro-Apoptotic Way.

A cytotoxicity-guided phytochemical investigation of Anemone vitifolia roots led to the isolation of six oleanane saponins (1-6), which were reported from the species for the first time. Their structures were determined by comparing its MS and NMR data with those in literature. Compounds 1-4 showed significant inhibitory effects on the proliferation of hepatocellular carcinoma HepG2 cells with IC50 values ranging from 2.0 to 8.5 µM, compared to positive control methotrexate with IC50 value of 15.8 µM. Flow cytometry analysis revealed that compounds 1-4 exerted anti-proliferative effects through a pro-apoptotic way of hepatocellular carcinoma cells.

[A phytochemical and pharmacological advance on Ilex asprella].

Ilex asprella is one of representative medicinal plants in South of the Five Ridges of China. The roots and rhizomes of I. asprella have the effects of clearing heat and detoxifying, stimulating salvia, and reducing thirst, which has been used to treat wind-heat cold, acute and chronic pharyngitis, and sore throat. Contemporary studies showed that I. asprella contains the major triterpenoids and glycosides, phenolic acids, and minor steroids. The extracts and compounds show activities of anti-inflammatory, antiviral, anti-tumor, and regulating lipid metabolism.The present paper summarizes a phytochemical and pharmacological advance on this species to provide reference for clarification of its pharmacologically active ingredients, quality evaluation, and further explorations.

[Chemical constituents from stems of Ilex asprella].

Phytochemical investigation on the stems of Ilex asprella by using various chromatographic techniques led to the isolation of 13 compounds. By spectroscopic analyses and comparisons the spectral data with those in literatures, these compounds were identified as salicifoneoliganol(1), rel-(7R,8S)-3,3',5-trimethoxy-4',7-epoxy-8,5'-neolignan-4,9,9'-triol 9-ß-D-glucopyranoside(2),(+)-cycloolivil(3),(+)-syringaresinol-4'-O-ß-D-monoglucoside(4), liriodendrin(5), caffeic acid (6), 3,4-dihydroxy-5-methoxybenzaldehyde(7), benzene-1,2,4-triol(8), 3,4,5-trimethoxyphenyl-1-O-ß-D-apiofuranosyl(1″→6')-glucopyranoside(9), aeculetin(10), cryptochlorogenic acid ethyl ester(11), chlorogenic acid ethyl ester(12), and rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo [3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid(13). Among them, compounds 7, 8, 11, and 13 were isolated from genus Ilex for the first time, and 1-3, 9, 10, and 12 were isolated from this speciesfor the first time. The anti-inflammatory assay results of these compounds showed that compounds 1 and 9 showed moderate inhibitory effect against NO production in RAW 267. 4 cells with IC50 values of 35.7 and 50.6 µmol•L⁻¹, in vitro respectively, whereas compound 10 showed weak inhibition(IC50 value 98.7 µmol•L⁻¹).

[Phenolic constituents from lichen Usnea longissima].

Sixteen compounds were isolated from lichen Usnea longissima using of various chromatographic techniques including silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC. By spectroscopic data analyses, their structures were identified by as useanol(1), lecanorin(2), 3-hydroxy-5-methylphenyl 2-hydroxy-4-methoxy-6-methylbenzoate(3), lecanorin E(4), 3'-methylevernic acid(5), evernic acid(6), barbatinic acid(7), 3,7-dihydroxy-1,9-dimethyldibenzofuran(8), orcinol(9), O-methylorcinol(10), methyl orsellinate(11), methyl everninate(12), 2,5-dimethyl-1,3-benzenediol(13), 2-hydroxy-4-methoxy-3,6-dimethyl benzoic acid(14), ethyl everninate(15), and ethyl 2,4-dihydroxy-6-methylbenzoate(16). Compound 1 was obtained as a natural product for the first time, and 3,4, 8,10,12, and 13 were isolated from Usneaceae family for the first time. Compound 1, 8, and 13 showed significant anti-inflammatory activity against NO production in RAW 267.4 cells with IC50 values of 6.8, 3.9 and 4.8 µmol•L⁻¹, respectively, compared with the positive controls curcumin(IC50 15.3 µmol•L⁻¹) and indomethacin(IC50 42.9 µmol•L⁻¹).

Interplay of Natural Organic Matter with Flow Rate and Particle Size on Colloid Transport: Experimentation, Visualization, and Modeling.

The investigation on factors that affect the impact of natural organic matter (NOM) on colloid transport in complex hydraulic flow systems remains incomplete. Using our previously established approach, the interplay of flow rate and particle size on the NOM effect was quantified, using flow rates of 1 and 2 mL/min and particle sizes of 50 and 200 nm to represent small nanoparticles (1-100 nm) and large non-nano-microspheres (100-1000 nm) in the low-flow groundwater environment. Latex particles, Suwannee River humic acid (SRHA), and iron oxide-coated sand were used as model particles, NOM, and the aquifer medium, respectively. The quantitative results show NOM blocked more sites for large particles at a high flow rate: 1 µg of SRHA blocked 5.95 × 10(9) microsphere deposition sites at 2 mL/min but only 7.38 × 10(8) nanoparticle deposition sites at 1 mL/min. The particle size effect dominated over the flow rate, and the overall effect of the two is antagonistic. Granule-scale visualization of the particle packing on the NOM-presented sand surface corroborates the quantification results, revealing a more dispersed status of large particles at a high flow rate. We interpret this phenomenon as a polydispersivity effect resulting from the differential size of the particles and NOM: high flow and a high particle size enlarge the ratio of particle-blocked to NOM-blocked areas and thus the NOM blockage. To our knowledge, this is the first model-assisted quantification on the interplay of NOM, flow rate, and particle size on colloid transport. These findings are significant for nanorisk assessment and nanoremediation practices.

A novel bismuth-activated Sr3NaSbO6 phosphor with multi-band switchable emission for NUV-pumped LEDs.

Multi-band emission characteristics open up more possibilities for the application of phosphors in LEDs. In this work, a novel Bi3+-activated Sr3NaSbO6 phosphor is developed. The Bi3+ occupation, luminescence properties and application in LEDs of the phosphor are investigated and discussed. There are Sr and Na sites in the crystal structure for Bi3+ substitution, corresponding to two different luminescence centers, which can be excited by commercial UV chips. By changing the excitation wavelength, Bi3+ in the two lattice sites can be excited separately, and a switchable multi-band emission can be obtained accordingly. The blue emission peaks at 450 nm, and the other emission has an ultra-wide full-width at half-maximum of 206 nm, which can cover a wider visible spectrum. All the results show that the phosphor has application prospects in LEDs.

Carbon quantum dots assisted BiFeO3@BiOBr S-scheme heterojunction enhanced peroxymonosulfate activation for the photocatalytic degradation of imidacloprid under visible light: Performance, mechanism and biotoxicity.

A novel S-scheme heterojunction photocatalyst carbon quantum dots (CQDs)/BiFeO3/BiOBr (CBB) was synthesized via a facile hydrothermal method, which was highly effective in activating peroxymonosulfate (PMS) to photodegrade imidacloprid (IMD) (one of the typical neonicotinoid insecticides (NEOs)) under visible light irradiation. Based on the physicochemical and photoelectrochemical analysis, the super photocatalytic performance of the CBB photocatalyst was contributed to the enhanced separation and transfer of photogenerated electrons (e-) and holes (h+), the activation of PMS by reactive species, and the wider light absorption range induced by CQDs. Moreover, the intermediate products and possible photodegradation pathways of IMD were confirmed through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) detection and density functional theory (DFT) calculations. Although the photodegradation of IMD in the CBB/PMS/Vis system can be affected by the water quality parameters (i.e., acid group anions, pH, and the presence of humic acid (HA)), the synthesized CBB photocatalyst showed excellent photocatalytic performance in multiple natural water samples. This study provides a new idea to construct an effective and efficient heterojunction photocatalyst, which may have great advantages in photocatalytic degradation of NEOs and possibly other emerging contaminants in the aquatic environment.

Decreased cadmium content in Solanum melongena induced by grafting was related to glucosinolates synthesis.

Grafting is an effective horticultural method to reduce Cd accumulation in crops. However, the mechanism of grafting inducing the decrease in Cd content in scions remains unclear. This study evaluated the effect of grafting on fruit quality, yield, and Cd content of Solanum melongena, and explored the potential mechanism of grafting reducing Cd content in scions. In the low Cd-contaminated soil, compared with un-grafted (UG) and self-grafted plants (SG), the fruit yield of inter-grafted plants (EG) increased by 38 %, and the fruit quality was not markedly affected. In EG, the decrease in total S and Cd content was not related to organic acids and thiol compounds. The decrease in total S and Cd content in EG leaves and fruits was closely related to the synthesis and transportation of glucosinolates (GSL). The genes encoding GSL synthesis in leaves, such as basic helix-loop-helix, myelocytomatosis proteins, acetyl-CoA, cytochrome P450, and glutathione S-transferases, were significantly downregulated. In EG leaves, the contents of five of the eight amino acids involved in GSL synthesis decreased significantly (P < 0.05). Notably, total GSL in EG stems, leaves, and fruits had a significant linear correlation with total S and Cd. In summary, the decrease in total S and Cd content in scions caused by grafting is closely related to GSL. Our findings provide a theoretical basis for the safe use of Cd-contaminated soil, exploring the long-distance transport of Cd in plants and cultivating crops with low Cd accumulation.

Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Objective: We aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Methods: MDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes. Results: Our findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC. Conclusion: MDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

A portable thermostatic molecular diagnosis device based on high-efficiency photothermal conversion material for rapid field detection of SARS-CoV-2.

The outbreak of the novel coronavirus (SARS-CoV-2) has seriously harmed human health and economic development worldwide. Studies have shown that timely diagnosis and isolation are the most effective ways to prevent the spread of the epidemic. However, the current polymerase chain reaction (PCR) based molecular diagnostic platform has the problems of expensive equipment, high operation difficulty, and the need for stable power resources support, so it is difficult to popularize in low-resource areas. This study established a portable (<300 g), low-cost (<$10), and reusable molecular diagnostic device based on solar energy photothermal conversion strategy, which creatively introduces a sunflower-like light tracking system to improve light utilization, making the device suitable for both high and low-light areas. The experimental results show that the device can detect SARS-CoV-2 nucleic acid samples as low as 1 aM within 30 min.

Bovine serum albumin adsorption to iron-oxide coated sands can change microsphere deposition mechanisms.

Particulate colloids often occur together with proteins in sewage-impacted water. Using Bovine Serum Albumin (BSA) as a surrogate for protein in sewage, column experiments investigating the capacity of iron-oxide coated sands to remove latex microspheres from water revealed that microsphere attenuation mechanisms depended on antecedent BSA coverage. Dual pulse experiment (DPE) results suggested that where all BSA was adsorbed, subsequent multiple pore volume microsphere breakthrough curves reflected progressively reduced colloid deposition rates with increasing adsorbed BSA content. Modeling colloid responses suggested adsorption of 1 µg BSA generated the same response as blockage by between 7.1 × 10(8) and 2.3 × 10(9) deposited microspheres. By contrast, microsphere responses in DPEs where BSA coverage of the deposition sites approached/reached saturation revealed the coated sand maintained a finite capacity to attenuate microspheres, even when incapable of further BSA adsorption. Subsequent microsphere breakthrough curves demonstrated the matrix's colloid attenuation capacity progressively increased with continued microsphere deposition. Experimental findings suggested BSA adsorption on the sand surface approaching/reaching saturation generated attractive deposition sites for colloids, which became progressively more attractive with further colloid deposition (filter ripening). Results demonstrate that adsorption of a single type of protein may either enhance or inhibit colloid mobility in saturated porous media.

Quantifying the influence of EDTA on polymer nanoparticle deposition and retention in an iron-oxide-coated sand column.

Ethylenediaminotetraacetic acid (EDTA) occurring in groundwater aquifers complicates the prediction of nanoparticle movement in the porous medium. This paper demonstrates an approach combining Triple Pulse Experiments (TPEs) and numerical modelling to quantify the influence of EDTA on the deposition and retention of polymer nanoparticles in a water-saturated column packed with iron-oxide-coated sand. TPEs injecting three successive pulses in the order of nanoparticle, EDTA, nanoparticle permit nanoparticle deposition in the absence and the presence of EDTA to be compared. Random Sequential Adsorption (RSA) modelling of the nanoparticle breakthrough curves combining mass balance calculation allows the influence of EDTA to be quantified. TPE results demonstrate that the injected EDTA eluted the oxide coatings (favorable deposition sites) from the sand surface and the resulting decline in sites led to enhanced nanoparticle mobility in the subsequent pulse. Quantification results suggest that at the experimental time-scale and under the controlled conditions, elution of one deposition site requires injection of 2.4 × 10(11) EDTA molecules. In total, 75 gram EDTA needs to be injected to remove all the column sites.

Denitrification using permeable reactive barriers with organic substrate or zero-valent iron fillers: controlling mechanisms, challenges, and future perspectives.

Nitrate as a diffusive agricultural contaminant has been causing substantial groundwater quality deterioration worldwide. In situ groundwater remediation techniques using permeable reactive barriers (PRBs) have attracted increasing interest. Particularly, PRBs based on biological denitrification, using the organic substrate as a biostimulator, and chemical nitrate reduction, using zero-valent iron (ZVI) as a reductant, are two major PRB approaches for groundwater denitrification. This review paper analyzed the published studies over the past 10 years (2010-2020) using laboratory, modeling, and field-scale approaches to explore the performance and mechanisms of these two types of PRBs. Important factors affecting the denitrification efficiencies as well as the influential mechanisms were discussed. Several research gaps have been identified and further research needs are discussed in the end.

Downward transport of naturally-aged light microplastics in natural loamy sand and the implication to the dissemination of antibiotic resistance genes.

Current understanding on the fate and behavior of microplastics (MPs) in complex soil media remains inadequate. We characterized the aging and hetero-aggregation of a MP sampled in farmland soil, and explored its vertical downward transport in natural loamy sand. The MP was identified with FTIR spectrum as polypropylene, a plastic lighter than water. FTIR spectrum combined with SEM imaging confirmed the MP was highly aged, generating colloidal plastic fibers and carbonyl groups. SEM imaging coupled with EDX analysis suggested hetero-aggregation of the MP with soil minerals. Soil leaching tests performed with the clean MP (without soil minerals) (CMP), the raw MP (RMP) (with soil minerals), and the RMP with humic acid (HA) (RMP + HA) demonstrated that the mobility was insignificant for the CMP, moderate for the RMP and highest for the RMP + HA, resulting in a maximal downward traveling distance of 0 cm, 3-4 cm, and 9-10 cm, respectively. Correlation between the maximal traveling distance and zeta potential of the CMP, RMP, and RMP + HA confirmed surface charge as a dominant control on the MP mobility; while the increasing density of the MP, due to hetero-aggregation with soil minerals, was identified as a driving mechanism for its downward transport, despite its intrinsic density lower than water. Occurrence of only the lower-sized rod-shaped plastic fibers at the maximal traveling distance suggested the natural aging, a process leading to plastic vibration and fragmentation, was conducive to plastic translocation. The three explored classes of antibiotic resistance genes (ARGs) (tetracycline, beta-lactam and sulfonamide) were all detected in the plastic surface, suggesting the MP may function as a potential pathway for the dissemination of ARGs to the deeper soil layer. These findings are important to understand the concentration distribution of both the MPs and ARGs in agriculture impacted soils, a natural reservoir of both emerging contaminants.