Revolutionizing animal husbandry: Breakthroughs in gene editing delivery systems.

Gene editing technology has become an essential tool for advancing breeding practices, enhancing disease resistance, and boosting productivity in animal husbandry. Despite its potential, the delivery of gene editing reagents into cells faces several challenges, including low targeting efficiency, immunogenicity, and cytotoxicity, which have hindered its wider application in the field. This review discusses the evolution of gene editing technologies and highlights recent advancements in various delivery methods used in animal husbandry. It critically evaluates the strengths and weaknesses of these different delivery approaches while identifying potential directions for future development. The goal is to equip researchers with effective strategies to optimize delivery methods, ultimately facilitating the implementation and progress of gene editing technologies in animal husbandry.

Characterization of Escherichia coli strains producing Shiga Toxin 2f subtype from domestic Pigeon.

Shiga toxin-producing Escherichia coli (STEC) can cause mild diarrhea even severe hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is the primary virulence factor. Two Stx types and several subtypes have been identified. STEC strains encoding stx2f (Stx2f-STECs) are frequently identified from pigeons. Stx2f was initially considered to be associated with mild symptoms, more recently Stx2f-STECs have been isolated from HUS cases, indicating their pathogenic potential. Here, we investigated the prevalence of Stx2f-STECs among domestic pigeons in two regions in China, characterized the strains using whole-genome sequencing (WGS), and assessed the Stx2f transcriptions. Thirty-two Stx2f-STECs (4.36%) were culture-positive out of 734 fecal samples (one strain per sample). No other stx subtype-containing strain was isolated. Four serotypes and two sequence types were determined, and a novel sequence type ST15057 was identified. All strains harbored the E. coli attaching and effacing gene eae. Two types of Stx2f prophages were assigned. Stx2f-STECs showed variable Stx transcription levels induced by mitomycin C. Whole genome single-nucleotide polymorphism (wgSNP) analysis revealed different genetic backgrounds between pigeon-derived strains and those from diarrheal or HUS patients. In contrast, pigeon-derived Stx2f-STECs from diverse regions exhibited genetic similarity. Our study reports the prevalence and characteristics of Stx2f-STECs from pigeons in China. The pigeon-derived strains might pose low public health risk.

Chloroplast mini-barcodes combined with high resolution melting analysis to identify herbal medicine Difengpi (Illicium difengpi).

Difengpi, derived from the air-dried stem bark of Illicium difengpi and enlisted in the Chinese Pharmacopoeia for its therapeutic effect against common ailments, confronts challenges due to dwindling wild resources and intentional substitution with potentially harmful botanical relatives. The imperative need to authenticate this herbal remedy has led to the development of robust methods. Here, we integrated chloroplast mini-barcoding and high resolution melting (HRM) analysis to distinguish Difengpi from the reported adulterants. We assembled the complete chloroplast (cp) genomes of I. difengpi and substituted close relatives I. jiadifengpi and I. majus, and conducted an in-depth comparative analysis to screen divergent regions for exploiting as DNA mini-barcodes. Despite the conservativeness characterizing the whole cp genomes among these Illicium species, we identified some highly variable regions with promising potential as molecular markers for species identification. Subsequently, we designed DNA mini-barcodes and subjected them to HRM analysis to assess their efficacy in species discrimination. Melting profiles unveiled that mini-barcodes designed from four divergence regions trnL-trnF, trnF-ndhJ, ycf1-ndhF and rpl32-trnL exhibited substantial discriminatory power, distinctly differentiated I. difengpi from I. jiadifengpi, I. majus and I. verum. We tested ten commercially available Difengpi products from online stores and local traditional markets using these four mini-barcodes. All ten samples clustered closely with the reference I. difengpi with genotype confidence higher than 93 %, indicating the presence of the claimed species in these samples, sans any reported toxic adulterants. Consequently, we simulated Difengpi mimic samples utilizing I. jiadifengpi, I. majus and I. verum and subjected them to evaluate the practicability of these mini-barcodes. The outcomes confirmed the precision of the four mini-barcodes in accurately discerning the mimic samples. In conclusion, integrating taxon-specific DNA mini-barcodes with HRM analysis is an efficient strategy for the authentication of species identity within commercial herbal products.

Highly Efficient Organic/Silicon Hybrid Solar Cells with a MoO3 Capping Layer.

Organic/Si hybrid solar cells have attracted considerable attention for their uncomplicated fabrication process and superior device efficiency, making them a promising candidate for sustainable energy applications. However, the efficient collection and separation of charge carriers at the organic/Si heterojunction interface are primarily hindered by the inadequate work function of poly (3,4-ethylenedioxythiophene): poly (styrenesulfonate) (PEDOT:PSS). Here, the application of a high-work-function MoO3 film onto the n-Si/PEDOT:PSS surface leads to a notable enhancement in the device's built-in potential. This enhancement results in the creation of an inversion layer near the n-Si surface and facilitates charge separation at the interface. Simultaneously, it inhibits charge recombination at the heterojunction interface. As a result, the champion PEDOT:PSS/Si solar cell, which incorporates a MoO3 interface layer, demonstrates an efficiency of 16.0% and achieves a high fill factor of 80.8%. These findings provide a straightforward and promising strategy for promoting the collection and transmission of charge carriers at the interface of photovoltaic devices.

Influence of Electrostatic Field on Optical Rotation of D-Glucose Solution: Experimental Research for Electric Field-Induced Biological Effect.

At present, the effects of environmental electromagnetic irradiation on the metabolism of organisms have attracted extensive attention, but the mechanism is still not clear. D-glucose plays an important role in the metabolism of organisms. In this work, the change in the optical rotation of D-glucose solution under an electrostatic field is measured experimentally, so as to explain the mechanism of the electric field-induced biological effect. The experimental results show that the electrostatic field can alter the optical rotation of D-glucose solution at different temperatures. Under the different strengths of electrostatic field, the specific rotation of D-glucose solution increases at different temperatures; the maximum increase can reach 2.07%, but the effect of temperature and electric field strength on the rotation increment is nonlinear and very complex. Further, it turns out that the proportion of α-D-glucose in solution increases by up to 3.25% under the electrostatic field, while the proportion of ß-D-glucose decreases by as much as 1.75%. The experimental study confirms that electrostatic field can change the proportion of two conformation molecules (α and ß-D-glucose) in D-glucose solution, which can provide a novel explanation for the mechanism of the electric field-induced biological effect.

Se-Rich Multinuclear Er-Containing Dawson-type Poly(selenotungstate).

A multinuclear Er-containing Dawson-type poly(selenotungstate) (poly(ST)) [H2N(CH3)2]12Na8Cs6H26 [Er12Se14W12O72(H2O)6(Se2W14O52)6]·78H2O (1) was made by the one-pot assembly with an excess SeO32- source in the reaction system. The polyoxoanion consists of an extremely rare Er12Se14W12O72(H2O)6 ({Er12Se14W12}) cluster core surrounded by six tetravacant Dawson-type Se2W14O52 ({Se2W14}) fragments, representing the most Se-containing Dawson-type structure so far. Notably, the {Er12Se14W12} cluster exhibits an interesting trefoil-shaped configuration, formed by the condensation of a central Er3Se2O6 ({Er3Se2}) cage with three Er3Se4W4O22(H2O)2 ({Er3Se4W4}) clusters. The catalytic performance of 1 was evaluated by the oxidative decontamination of 2-chloroethyl ethyl sulfide (CEES) into nontoxic 2-chloroethyl ethyl sulfoxide (CEESO), showing remarkable conversion and selectivity, as well as excellent reusability.

ROS/pH dual-responsive quercetin-loaded guanosine borate supramolecular hydrogel enema in dextran sulfate sodium-induced colitis in mice.

Ulcerative colitis (UC) is an inflammatory bowel disease that predominantly impacts the colon, typically starting in the rectum. A significant characteristic of UC is its propensity to affect the distal colon, which is particularly beneficial for targeted treatments such as enemas. This localized approach ensures that the medication is delivered directly to the affected areas, resulting in minimal systemic absorption. In this research, we have formulated a novel stimuli-responsive quercetin-loaded guanosine borate supramolecular hydrogel (named GBQ hydrogel), designed to prolong the residence time of the drug and protect the ulcerated intestinal tissues. The GBQ hydrogel has exhibited excellent injectability, self-healing capabilities, and biocompatibility, rendering it an ideal candidate for enema administration. In vitro studies have highlighted its ROS/pH dual-responsive release profile, which mimics the microenvironment of intestinal inflammation. Furthermore, we assessed the efficacy of the GBQ hydrogel on dextran sulfate sodium (DSS)-induced colitis, a common animal model for UC. Our findings indicate that the GBQ hydrogel significantly reduces disease activity, mitigates oxidative stress, restores the intestinal mucosal barrier, and prevents colonic cell apoptosis. Collectively, this study underscores the therapeutic potential of the GBQ hydrogel in managing inflammatory bowel conditions and paves the way for a novel hydrogel enema-based treatment strategy for UC.

Ultrasonic-assisted membrane processes for the systematic purification of glycyrrhiza wastewater.

A significant amount of glycyrrhiza wastewater is generated in the cleaning process of glycyrrhiza. The wastewater contains polysaccharide, glycyrrhizic acid, liquiritin, and other polyphenols, which is expensive for cleanup and wastes medical resources. To reduce environmental pollution from glycyrrhiza wastewater and increase the resource usage efficiency of glycyrrhiza components. According to the physicochemical properties of the component in glycyrrhiza wastewater, the ultrasonic assisted membrane separation mode was adopted to regulate the micellar state of glycyrrhizic acid and enhance the differences in membrane separation of polysaccharides, saponins, and flavones, in order to achieve the classification and separation of polysaccharides, saponins, and flavones while removing organic matter in glycyrrhiza wastewater. However, the efficiency, application, and mechanism of ultrasonic-assisted membrane technology for the separation of polysaccharides, saponins, and flavonoids from glycyrrhiza wastewater remain unclear. This study presents a green and feasible technical strategy for glycyrrhiza wastewater treatment that was developed by adjusting the parameters of ultrasonic assisted membrane separation. In this study, the systematic separation mode of ultrasonic enhanced ultrafiltration combined with nanofiltration is provided. The SCQ-9200E ultrasonic system was provided for the study with adjustable ultrasonic power, and the ultrasonic frequency was 40 kHz. The glycyrrhizic acid micelle was changed using ultrasonic power, pH, and molecular weight cut off (MWCO), and the separation differences among polysaccharide, glycyrrhizic acid, and liquiritin were enhanced. The optimal polysaccharide separation parameters used in the first step: MWCO 30 kDa, ultrasonic power 500 W and pH 5.00, and the rejections of polysaccharide, glycyrrhizic acid, and liquiritin were 87.72 %, 8.01 %, and 6.57 %, respectively. The second step included the following parameters for the separation of liquiritin and glycyrrhizic acid: MWCO 10 kDa, ultrasonic power 100 W and pH 8.00, the rejections of liquiritin and glycyrrhizic acid were 9.22 % and 40.65 %, respectively. The third step is to remove the low molecular sugar in liquiritin by nanofiltration: MWCO 800 Da, pH 8.00, retention solution diluted and separated twice, the rejection of liquiritin and total sugar were 95.72 % and 3.70 %, respectively. Ultrasonic may regulate the microtopography of glycyrrhiza wastewater with the power intensity of 50 W/L, improving the mass transfer efficiency of glycyrrhizic acid and liquiritin in the ultrafiltration separation process. As the separation volume of wastewater increased from 2.00 L to 20.00 L, the concentrations of polysaccharide, glycyrrhizic acid, and liquiritin increased by 2.5-35.4 times, 0.6-15.2 times, and 2.4-32.8 times, respectively, significantly increasing the content of index components in wastewater and solving the problem of recycling and resource utilization in glycyrrhiza wastewater.

Tailoring Fumaric Acid Delivery: The Role of Surfactant-Enhanced Solid Lipid Microparticles via Spray-Congealing.

Fumaric acid, a naturally occurring preservative with antimicrobial properties, has been widely used in the baking industry. However, its direct addition interferes with yeast activity and negatively impacts the gluten structure. This study investigates the potential of spray-congealing as a method for encapsulating fumaric acid within solid lipid microparticles. The selection of lipid carriers and surfactants is critical, so hydrogenated palm stearin, hydrogenated rapeseed oil, and Compritol ATO 888 (glyceryl behenate) were chosen as lipid carriers, and propylene glycol monostearate and glyceryl monolaurate were utilised as surfactants with varying concentrations. Rheological properties, encapsulation efficiency, particle size, moisture content, and thermal behaviour were assessed, along with the release profiles under different temperature conditions simulating the baking process. The findings indicate that the addition of surfactants significantly impacts the viscosity and stability of the molten mixtures, which in turn affects the spray-congealing process and the release of fumaric acid. The temperature-dependent and time-dependent release profiles demonstrate the potential for customising release kinetics to suit specific applications, such as the baking industry. This study may contribute to the development of a controlled-release system that synchronises with the baking process, thereby optimising fumaric acid's functionality while preserving the quality of baked goods.

Empagliflozin attenuating renal interstitial fibrosis in diabetic kidney disease by inhibiting lymphangiogenesis and lymphatic endothelial-to-mesenchymal transition via the VEGF-C/VEGFR3 pathway.

Renal interstitial fibrosis (RIF) is a significant pathological change in diabetic kidney disease (DKD) that can be induced by endothelial-to-mesenchymal transition (EndMT). Lymphangiogenesis, mediated by the vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3) pathway, plays a crucial role in the development of RIF in DKD. Although numerous studies have demonstrated the efficacy of empagliflozin in treating renal injury, its effects on lymphangiogenesis in DKD-related RIF and the underlying mechanisms remain unclear. In the present study, significant lymphangiogenesis was assessed in the renal interstitium of patients with DKD. We subsequently explored the relationship between DKD-related RIF and lymphangiogenesis in mouse models, high-glucose (HG)-stimulated renal HK-2 cell lines, and human lymphatic endothelial cells (hLECs). Additionally, we evaluated the effects of empagliflozin on these processes. The results revealed that HG induces lymphangiogenesis, which exacerbates RIF by promoting inflammatory responses. Furthermore, hLECs directly contributed to the progression of DKD-related RIF through EndMT. Further analysis revealed that tubular epithelial cells (TECs) act as effector cells for VEGF-C, with the epithelial-to-mesenchymal transition (EMT) of TECs occurring concurrently with the EndMT of lymphatic vessels. Empagliflozin inhibited RIF in DKD by suppressing the VEGF-C/VEGFR3 pathway and reducing lymphangiogenesis. In conclusion, this study elucidates the interplay between lymphangiogenesis, EndMT, and RIF in DKD and provides new insights into the mechanism by which empagliflozin treats DKD.

Sodium Alkyl(trimethylsilyl)amides: Substituent- and Solvent-dependent Solution Structures and Reactivities.

The preparation of sodium isopropyl(trimethylsilyl)amide (NaPTA), sodium (1-phenylethyl)(trimethylsilyl)amide (NaPETA), sodium tert-butyl(trimethylsilyl)amide (NaBTA), and isotopologues [15N]NaPTA and [15N]NaBTA are described. Solution structural studies using a combination of 29Si NMR spectroscopy, the Method of Continuous Variations, and density functional theory computations provided insights into aggregation and solvation in a range of solvents including toluene, N,N-dimethylethylamine, triethylamine, MTBE, THF, 1,2-dimethoxyethane (DME), diglyme, N,N,N',N'-tetramethylethylenediamine (TMEDA), N,N,N',N'-tetramethylcyclohexanediamine (TMCDA), N,N,N',N″,N″-pentamethyldiethylenetriamine (PMDTA). 12-crown-4, 15-crown-5, and 18-crown-6 revealed solvent- and substituent-dependent dimer-monomer mixtures with affiliated solvation numbers. Complexation of the three crown ethers documented both crown and substituent dependencies. Qualitative studies of reactivity showed a variety of reactions of NaPETA. Aminolysis of methyl benzoate with dialkylamines mediated by NaPTA afforded high yields of benzamides. Quantitative rate studies of aminolysis of methyl benzoate by NaPTA revealed a 47,000-fold range of rates. Detailed rate studies in toluene and THF showed dimer-based mechanisms. The role of primary- and secondary-shell solvation by THF is discussed, including nuances of methods used to separate the two contributions. PMDTA-solvated NaPTA monomer reacts as a monomer whereas bis-diglyme solvated monomer reacts as a dimer. Rate studies exploring the structure-reactivity correlations of the three crown ethers show mono- and bis-crown-based pathways in which 15-crown-5─the crown ether often said to be of choice for sodium─was decidedly inferior as an accelerant.

Crucial role of a takeout protein in white-backed planthopper Sogatella furcifera (Horváth) orientation towards its host rice plants.

The takeout (TO) gene family impacts diverse physiological and behavioral functions in insects, yet specific olfactory-associated roles for the family have yet to be fully elucidated. To provide insights into TO function in rice planthoppers, the genomes of three rice planthoppers (white-backed planthopper, brown planthopper and small brown planthopper) were searched for TO homologs and their degree of conservation assessed via chromosomal localization, exon-intron boundaries, phylogenetic relationships and protein domains/motifs. We performed a tissue-specific expression analysis of the 20 TO genes in the white-backed planthopper (WBPH, Sogatella furcifera) and found that SfTO17 is enriched in adult antennae. RNAi-mediated knockdown of SfTO17 impaired WBPH olfaction and reduced host-seeking responses following exposure to rice plants. The binding profile of ß-ionone, hexyl benzoate and benzyl benzoate with recombinant SfTO17 was evaluated via competitive fluorescence binding assays. Conformational prediction of SfTO17 coupled with molecular docking analyses revealed several amino acid residues potentially critical for odorant binding. This study demonstrates the olfactory function of SfTO17 in WBPH and highlights its potential as a target for controlling this rice pest. © 2024 Society of Chemical Industry.

Spatial resolved transcriptomics reveals distinct cross-talk between cancer cells and tumor-associated macrophages in intrahepatic cholangiocarcinoma.

BACKGROUND: Multiple studies have shown that tumor-associated macrophages (TAMs) promote cancer initiation and progression. However, the reprogramming of macrophages in the tumor microenvironment (TME) and the cross-talk between TAMs and malignant subclones in intrahepatic cholangiocarcinoma (iCCA) has not been fully characterized, especially in a spatially resolved manner. Deciphering the spatial architecture of variable tissue cellular components in iCCA could contribute to the positional context of gene expression containing information pathological changes and cellular variability. METHODS: Here, we applied spatial transcriptomics (ST) and digital spatial profiler (DSP) technologies with tumor sections from patients with iCCA. RESULTS: The results reveal that spatial inter- and intra-tumor heterogeneities feature iCCA malignancy, and tumor subclones are mainly driven by physical proximity. Tumor cells with TME components shaped the intra-sectional heterogenetic spatial architecture. Macrophages are the most infiltrated TME component in iCCA. The protein trefoil factor 3 (TFF3) secreted by the malignant subclone can induce macrophages to reprogram to a tumor-promoting state, which in turn contributes to an immune-suppressive environment and boosts tumor progression. CONCLUSIONS: In conclusion, our description of the iCCA ecosystem in a spatially resolved manner provides novel insights into the spatial features and the immune suppressive landscapes of TME for iCCA.

Nuciferine analogs block voltage-gated sodium, calcium and potassium channels to regulate the action potential and treat arrhythmia.

Dysfunction of the Nav1.5, Cav1.2, and Kv channels could interfere with the AP and result in arrhythmias and even heart failure. We herein present a novel library of nuciferine analogs that target ion channels for the treatment of arrhythmias. Patch clamp measurements of ventricular myocytes revealed that 6a dramatically blocked both the INa and ICa without altering the currentvoltage relationship (including the activation potential and peak potential), accelerated the inactivation of Nav and Cav channels and delayed the resurrection of these channels after inactivation. Additionally, 6a significantly decreased the APA and RMP without affecting the APD30 or APD50. The IC50 values of 6a against Nav1.5 and Cav1.2 were 4.98 µM and 4.62 µM, respectively. Furthermore, 6a (10 µM) blocked IKs, IK1, and Ito with values of 17.01 %±2.54 %, 9.09 %±2.78 %, and 11.15 %±3.52 %, respectively. Surprisingly, 6a weakly inhibited hERG channels, suggesting a low risk of proarrhythmia. The cytotoxicity evaluation of 6a with the H9c2 cell line indicated that this compound was noncytotoxic. In vivo studies suggested that these novel nuciferine analogs could shorten the time of arrhythmia continuum induced by BaCl2 and normalize the HR, QRS, QT and QTc interval and the R wave amplitude. Moreover, 6a dose-dependently affected aconitine-induced arrhythmias and notably improved the cumulative dosage of aconitine required to evoke VP, VT, VF and CA in rats with aconitine-induced arrhythmia. In conclusion, nuciferine analogs could be promising ion channel blockers that could be further developed into antiarrhythmic agents.

Screening of mtr-miR156a from exosomes of dairy cow blood to milk and its regulatory effect on milk protein synthesis in BMECs.

MicroRNA (miRNA) is a type of endogenous non-coding small RNA, which is abundant in living organisms. miRNAs play an important role in regulating gene expression and myriad cellular processes by binding to target messenger RNAs through complementary base pairing, and cross-species regulation mammalian cells by plant-derived xeno-miRNAs has been described. Here, we examined the miRNA species in two alfalfa (Medicago sativa, lucerne) cultivars commonly grown in Ningxia, China: cv. Zhongmu 1 and cv. Xinyan 52. Both cultivars have good salt and drought resistance. We found that the miRNA profiles were similar between the cultivars, with a slightly higher number of miRNAs present in the newer cv. Xinyan 52, which may contribute to its improved salt and drought tolerance. miRNAs were stable during drying, and some miRNAs were increased in dry versus fresh alfalfa, suggesting some miRNAs may be upregulated during drying. Alfalfa-derived miRNAs could be detected in exosomes from serum and whey collected from dairy cows, confirming the ability of the exogenous miRNAs (xeno-miRNAs) to enter the circulation and reach the mammary epithelium. In vitro studies confirmed that overexpression of mtr-miR156a could downregulate expression of Phosphatase 2 Regulatory Subunit B'gamma ( PPP2R5D) and Phosphoinositide-3-kinase Regulatory Subunit 2 (PIK3R2). Overexpression of mtr-miR156a also modulated PI3K-AKT-mTOR signaling as well as the casein content of milk produced by bovine mammary epithelial cells. Based on the known roles of PPP2R5D and PIK3R2 in regulating the PI3K-AKT-mTOR pathway as well as the effect of PI3K-AKT-mTOR on milk protein content, our findings implicate alfalfa-derived miR156a as a new cross-species regulator of milk quality in dairy cows.

An ultra-dense linkage map identified quantitative trait loci corresponding to fruit quality- and size-related traits in red goji berry.

Goji berries are a small-fruited shrub with industrial importance whose fruit considered beneficial in both fresh and dried forms. Current germplasms of goji berries include small fruits with a short shelf life, less sweet and bitter taste, and a lack of appropriate genetic information. This study aimed to employ whole genome resequencing to generate an ultra-dense bin linkage map and to elucidate the genetic basis of goji fruit quality and size using quantitative trait loci (QTL) mapping analysis in a cross-pollinated hybrid population. To achieve this goal, human sensory tests were carried out to determine the bitter taste (BT) and sweet taste (ST), and to quantify the soluble solid content (SSC), fruit firmness (FF), and fruit size-related traits of fresh goji fruits over three or four years. The results revealed that the goji bin linkage map based on resequencing spanned a total length of 966.42 cM and an average bin interval of 0.03 cM. Subsequent variant calling and ordering resulted in 3,058 bins containing 35,331 polymorphic markers across 12 chromosomes. A total of 99 QTLs, with individual loci in different environments explaining a phenotypic variance of 1.21-16.95% were identified for the studied traits. Ten major effects, including colocalized QTLs corresponding to different traits, were identified on chromosomes 1, 3, 5, 6, 7, and 8, with a maximum Logarithm of Odds (LOD) of 29.25 and 16.95% of explained phenotypic variance (PVE). In addition, four stable loci, one for FF, one for fruit weight (FW), and two for fruit shape index (FSI), were mainly mapped on chromosomes 5, 6, and 7, elucidating 2.10-16.95% PVE. These findings offer valuable insights into the genetic architecture of goji fruit traits along with identified specific loci and markers to further improve and develop sweeter, less bitter and larger fruited goji berry cultivars with extended shelf life.

Effects of integrated traditional Chinese and Western medicine for acute pancreatitis: A real-world study in a tertiary teaching hospital.

AIM: This study aimed to evaluate whether integrated traditional Chinese medicine (TCM) and Western medicine (WM) is more effective than WM for acute pancreatitis (AP). METHODS: Patients with AP were enrolled and divided into the TCM and WM (TCM&WM) and WM groups according to the therapeutic protocol in real clinical settings. We applied 1:3 propensity score matching, which was to adjust confounding factors. The primary outcome was mortality, whereas the secondary outcomes were organ failure, organ supportive therapies, local complications, hospitalization cost, and length of hospital stay. Sensitivity and subgroup analyses were also performed. RESULTS: Of 5442 patients with AP, 4691 and 751 were included in the TCM&WM and WM groups, respectively. After PSM, patient baseline characteristics were well balanced. Compared with the WM group (n = 734), the TCM&WM group (n = 2096) had lower overall mortality rate (1.7% vs. 3.4%; risk ratio, 0.482; 95% confidence interval, 0.286-0.810; p = 0.005). The TCM&WM group was associated with lower risk of persistent renal failure, multiple organ failure, and infection, lower utilization of organ supportive therapies, shortened lengths of hospital and intensive care unit stay, and lower hospital costs. Sensitivity analyses showed similar results. Subgroup analysis favored TCM&WM treatment for patients aged < 60 years, with hypertriglyceridic etiology, and with admission interval between 24 and 48 h. CONCLUSION: TCM&WM treatment can achieve lower risks of mortality and organ failure and better economic effectiveness in patients with AP than WM treatment. This study provides a promising alternative of TCM&WM treatment for AP in the real-world setting.

Quercetin-primed BMSC-derived extracellular vesicles ameliorate chronic liver damage through miR-136-5p and GNAS/STAT3 signaling pathways.

BACKGROUND: Chronic liver damage (CLD) is a long-term and progressive liver condition characterized by inflammation, fibrosis, and impaired liver function, which ultimately lead to severe complications such as cirrhosis or liver cancer. Quercetin (Que), a flavonoid in various plants, possesses anti-inflammatory, antiviral, anti-ischemic, and anticancer properties. Recently, extracellular vesicles (EVs) derived from pretreated bone marrow mesenchymal stem cells (BMSCs) have shown immense potential in treating various diseases, including CLD. Thus, this study evaluated the regulatory effects of Que-preconditioned BMSC-derived EVs (Que-EVs) on LPS-stimulated RAW264.7 cells and their therapeutic effects on mice with CLD. METHODS: Que-EVs and control-EVs were harvested from the cell culture supernatant of BMSCs. The EVs were characterized using western blot, transmission electron microscopy, and nanoparticle tracking analysis. Further, the DIR labeling of EVs was used to detect in vitro and in vivo uptake. Next, LPS pre-stimulated RAW264.7 cells were treated with Que-EVs and control-EVs for 24 h. The relative expression of inflammatory cytokines and macrophage polarization markers genes was assessed using RT-qPCR, and western blot was conducted to evaluate the GNAS, PI3K, ERK, and STAT3 gene and protein expressions in RAW264.7 cells. Furthermore, transfection techniques were employed to induce miR-136-5p inhibition and GNAS overexpression in RAW264.7 cells to validate the role of miR-136-5p in alleviating inflammation through the GNAS/PI3K/ERK/STAT3 pathway. Subsequently, the outcomes were validated via in vitro experiments. RESULTS: Que enhanced miR-136-5p expression in BMSC-EVs. Furthermore, it was shown that EVs delivered miR-136-5p to macrophages, thereby attenuating M1-type macrophage polarisation through the GNAS/PI3K/ERK/STAT3 pathway, reducing liver inflammation, improving liver function and treating CLD.

Programmable Persistent Room Temperature Phosphorescence Switches through Wavelength-Selective Photoactivation.

Controlling multicolor persistent room-temperature phosphorescence (RTP) through photoirradiation holds fundamental significance but remains a significant challenge. In this study, we engineered a wavelength-selective photoresponsive system utilizing the Förster resonance energy transfer strategy. This system integrates a photoactivated long-lived luminescent material as the energy donor with a fluorescent photoswitch as the energy acceptor, facilitating programmable persistent luminescence switches. Distinct afterglow color states, such as initial nonemissive, green, yellow, and orange, were achieved through irradiation at 400 nm, 365 nm, and 254 nm, respectively. Based on this capability, we established an interacting network for multistate afterglow color switching among these four emissive states. In addition, we demonstrate the potential of this wavelength-selective photoresponsive system in the photo-controlled rewritable printing of multicolor afterglow images on a single thin film. This work represents a substantial step towards the fabrication of sophisticated wavelength-selective photoresponsive systems, potentially revolutionizing applications in optical data storage, security labeling, and smart displays by enabling precise control over photoresponsive behaviors under various photoirradiation wavelengths.

Nervonic acid improves depression like behaviors and demyelination of medial prefrontal cortex in chronic restraint stress mice.

Major depressive disorder (MDD) is a psychiatric disorder characterized by depressed mood, behavioral despair and anhedonia. Demyelination in specific brain regions underlies the pathology of MDD, raising the alleviating demyelination as a potential strategy for MDD therapy. Nervonic acid (NA) has the potential to improve brain demyelination, offering benefits for various neurological disorders. However, its effects on depression remain undetermined. Mice were subjected to 14 days of chronic restraint stress (CRS) to induce depression-like behaviors, and were injected with NA (70 mg/kg) daily. The administration of NA significantly improved depressive-like behaviors in CRS mice. CRS led to significant demyelination in the medial prefrontal cortex (mPFC), which were reversed by NA treatment. In addition, NA ameliorated the upregulation of inflammatory cytokines and downregulation of brain-derived neurotrophic factor, improved the alternations in axonal spines observed in the mPFC of CRS mice. Our results highlighted the potential of NA as an antidepressant, with its benefits likely attributed to its effects in alleviating demyelination in the mPFC.