Conjugated polymers of an oxa[5]helicene-derived polycyclic heteroaromatic: tailoring energy levels and compatibility for high-performance perovskite solar cells.

In the quest to enhance the efficiency and durability of n-i-p perovskite solar cells (PSCs), engineering hole-transporting conjugated polymers with well-matched energy levels, exceptional film-forming properties, rapid hole transport, and superior moduli is paramount. Here, we present a novel approach involving the customization of a conjugated polymer, designated as p-DTPF4-EBEH, comprising alternating units of an oxa[5]helicene-based polycyclic heteroaromatic (DTPF4) and 5,5'-(2,5-di(hexyloxy)-1,4-phenylene)bis(3,4-ethylenedioxythiophene) (EBEH), synthesized through palladium-catalyzed direct arylation. Relative to homopolymers p-DTPF4 and p-EBEH, p-DTPF4-EBEH demonstrates a proper HOMO energy level, hole density, and hole mobility, alongside superior film-forming capabilities. Remarkably, compared to the commonly used hole transport material spiro-OMeTAD, p-DTPF4-EBEH not only exhibits superior film-forming property and hole mobility but also offers increased modulus and improved waterproofing. Incorporating p-DTPF4-EBEH as the hole transport material in PSCs results in an average power conversion efficiency of 25.8%, surpassing the 24.3% achieved with spiro-OMeTAD. Importantly, devices utilizing p-DTPF4-EBEH demonstrate enhanced thermal storage stability at 85 °C, along with operational robustness.

Effect of the intraoperative head hypsokinesis on sore throat after thyroid surgery: a randomized controlled trial.

PURPOSE: Postoperative sore throat (POST) after thyroidectomy is a major concern.A roll is typically inserted under the shoulder to achieve head hypsokinesis and neck extension to better expose the surgical site during thyroid surgery. However, POST and impaired voice function have been attributed to neck overextension. This study aimed to explore the rational angle of head hypsokinesis that both reduced sore throat intensity and protects voice function after thyroid surgery. METHODS: A total of 210 patients who underwent thyroidectomy were enrolled and randomized into high-tilt (Group H) and low-tilt angle groups (Group L). The primary outcome was the incidence of POST 6 h after surgery. Secondary outcomes included the severity of postoperative pharyngeal pain, voice function, swallowing pain, and coughing. RESULTS: The incidence of POST 6 h after thyroidectomy was significantly lower in Group L than that in Group H. In addition, the intensity of postoperative sore throat and swallowing pain was more severe in Group H. A lower degree of head hypsokinesis in Group L prevented transient postoperative voice injury. CONCLUSIONS: A lower degree of head hypsokinesis effectively mitigated sore throat severity after thyroidectomy and improved postoperative voice function. REGISTER INFORMATION: The trial was registered in the Chinese Clinical Trial Registry on 21 June 2022 (ChiCTR2200061329). The trial is registered at https://www.chictr.org.cn/showproj.html?proj=166254 .

Comparative efficacy of bilateral mesh sacrospinous ligament suspension versus laparoscopic sacrocolpopexy in patients with metroptosis.

This study assesses the efficacy of bilateral mesh sacrospinous ligament suspension (MSSLS) compared to laparoscopic sacrocolpopexy (LSC) in patients with uterine prolapse. Ninety-eight patients with uterine prolapse were evaluated at our hospital from January 2021 to January 2023. Patients were equally divided into two groups: the study group (undergoing MSSLS) and the control group (undergoing LSC) using a random number table. Various parameters including operation time, bleeding volume, indwelling catheter time, exhaust time, hospital stay, pelvic organ prolapse stage, postoperative recurrence rate, pain severity, quality of life, pelvic floor function, impact on sexual life, complications, and recurrence rate were recorded. The study group showed significant reductions in operation time, bleeding volume, indwelling catheter time, exhaust time, and hospital stay compared to the control group (P < 0.05). There were no significant differences in Aa, Ba, Ap, Bp, and C between the two groups before surgery (P > 0.05), but six months postoperatively, these indexes were significantly lower in the study group (P < 0.05). Pain severity did not differ significantly between the two groups before surgery (P > 0.05), but was significantly lower in the study group six months postoperatively (P < 0.05). Quality of life, pelvic floor function, and sexual life quality did not significantly differ before surgery, at 6 months, and at 12 months postoperatively (P > 0.05). All patients were followed up for 12-14 months, with an average follow-up time of (13.02 ± 1.36) months. The incidence of complications was significantly lower in the study group (P < 0.05), but there were no recurrences in either group, thus the difference was not statistically significant (P > 0.05). MSSLS emerges as a safe and efficacious treatment for uterine prolapse, notably reducing both complications and recurrence rates, rendering it suitable for broad clinical application.

Postbiotics are a candidate for new functional foods.

Accumulating studies have highlighted the great potential of postbiotics in alleviating diseases and protecting host health. Compared with traditional functional foods (such as probiotics and prebiotics), postbiotics have the advantages of a single composition, high physiological activity, long shelf life, easy absorption, and high targeting, etc. The development of postbiotics has led to a wide range of potential applications in functional food and drug development. However, the lack of clinical trial data, mechanism analyses, safety evaluations, and effective regulatory frameworks has limited the application of postbiotic products. This review describes the definition, classification, sources, and preparation methods of postbiotics, the progress and mechanism of preclinical and clinical research in improving host diseases, and their application in food. Strengthen understanding of the recognition and development of related products to lay a theoretical foundation.

Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway.

The probability of cardiovascular events has been reported lower in rheumatoid arthritis (RA) patients treated with leflunomide. However, the anti-atherosclerotic and cardiovascular protective effects and metabolism of leflunomide are not explored. In this study, we assessed the potential benefits of leflunomide on atherosclerosis and revealed the underlying mechanism. ApoE-/- mice were fed a western diet (WD) alone or supplemented with leflunomide (20 mg/kg, oral gavage, once per day) for 12 weeks. Samples of the aorta, heart, liver, serum, and macrophages were collected. We found that leflunomide significantly reduced lesion size in both en-face aortas and aortic root in WD-fed ApoE-/- mice. Leflunomide also obviously improved dyslipidemia, reduced hepatic lipid content, and improved disorders of glucose and lipid metabolism in vivo. RNA-Seq results showed that leflunomide effectively regulated the genes' expression involved in the lipid metabolism pathway. Importantly, leflunomide significantly increased the phosphorylation levels of AMPKα and acetyl-CoA carboxylase (ACC) in vivo. Furthermore, leflunomide and its active metabolite teriflunomide suppressed lipid accumulation in free fatty acid (FFA)-induced AML12 cells and improved endothelial dysfunction in palmitic acid (PA)-induced HUVECs through activating AMPK signaling and inhibiting dihydroorotate dehydrogenase (DHODH) signaling pathway. We present evidence that leflunomide and teriflunomide ameliorate atherosclerosis by regulating lipid metabolism and endothelial dysfunction. Our findings suggest a promising use of antirheumatic small-molecule drugs leflunomide and teriflunomide for the treatment of atherosclerosis and related cardiovascular diseases (CVDs).

Multi-omics analysis unravels chemical roadmap and genetic basis for peach fruit aroma improvement.

Selection of fruits with enhanced health benefits and superior flavor is an important aspect of peach breeding. Understanding the genetic interplay between appearance and flavor chemicals remains a major challenge. We identify the most important volatiles contributing to consumer preferences for peach, thus establishing priorities for improving flavor quality. We quantify volatiles of a peach population consisting of 184 accessions and demonstrate major reductions in the important flavor volatiles linalool and Z-3-hexenyl acetate in red-fleshed accessions. We identify 474 functional gene regulatory networks (GRNs), among which GRN05 plays a crucial role in controlling both red flesh and volatile content through the NAM/ATAF1/2/CUC (NAC) transcription factor PpBL. Overexpressing PpBL results in reduced expression of PpNAC1, a positive regulator for Z-3-hexenyl acetate and linalool synthesis. Additionally, we identify haplotypes for three tandem PpAATs that are significantly correlated with reduced gene expression and ester content. We develop genetic resources for improvement of fruit quality.

Characteristics of Bacteria in Urine and Stones from Patients Treated with Percutaneous Nephrolithotomy and Association with Postoperative Infection.

Background: The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS). Methods: Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed. Results: Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients. Conclusion: The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.

A high-fat diet induced depression-like phenotype via hypocretin-HCRTR1 mediated inflammation activation.

Background: A high-fat diet (HFD) is generally associated with an increased risk of mental disorders that constitute a sizeable worldwide health. A HFD results in the gut microbiota-brain axis being altered and linked to mental disorders. Hypocretin-1, which can promote appetite, has been previously confirmed to be associated with depression. However, no exact relationship has been found for hypocretin between depression and HFDs. Methods: Adult male SD rats were randomly assigned to either a HFD or a normal diet for eight weeks, followed by behavioral tests and plasma biochemical analyses. Then, we investigated the protein and mRNA levels of inflammation-related factors in the hippocampus. We also observed morphological changes in brain microglia and lipid accumulation. Additionally, metagenomic and metabolomic analyses of gut microbiomes were performed. 3T3-L1 cells were utilized in vitro to investigate the impact of hypocretin receptor 1 antagonists (SB334867) on lipid accumulation. To consider the connection between the brain and adipose tissue, we used a conditioned medium (CM) treated with 3T3-L1 cells to observe the activation and phagocytosis of BV2 cells. Following a 12-week period of feeding a HFD to C57BL/6 mice, a three-week intervention period was initiated during which the administration of SB334867 was observed. This was followed by a series of assessments, including monitoring of body weight changes and emotional problems, as well as attention to plasma biochemical levels and microglial cell phenotypes in the brain. Results: The HFD rats displayed anxiety and depressive-like behaviors. HFD rats exhibited increased plasma HDL, LDL, and TC levels. A HFD also causes an increase in hypocretin-1 and hypocretin-2 in the hypothalamus. Metagenomics and metabolomics revealed that the HFD caused an increase in the relative abundance of associated inflammatory bacteria and decreased the abundance of anti-inflammatory and bile acid metabolites. Compared with the CTR group, hippocampal microglia in the HFD group were significantly activated and accompanied by lipid deposition. At the same time, protein and mRNA expression levels of inflammation-related factors were increased. We found that SB334867 could significantly reduce lipid accumulation in 3T3-L1 cells after differentiation. The expression of inflammatory factors decreased in the SB334867 group. The administration of SB334867 was found to reverse the adverse effects of the HFD on body weight, depressive-like behaviour and anxiety-like mood. Furthermore, this treatment was associated with improvements in plasma biochemical levels and a reduction in the number of microglia in the brain. Conclusions: In summary, our results demonstrated that a HFD induced anxiety and depressive-like behaviors, which may be linked to the increased hypocretin-1 level and lipid accumulation. Supplementation with SB334867 improved the above. These observations highlight the possibility of hypocretin-1 inducing the risk of HFD-associated emotional dysfunctions.

Constructing a Ready-to-Use mRNA Vaccine Delivery System for the Prevention of Influenza A virus, Utilizing FDA-Approved Raw Materials.

Messenger ribonucleic acid (mRNA) vaccines, serving as a rapid and easily scalable emergency preventive measure, have played a pivotal role in preventing infectious diseases. The effectiveness of mRNA vaccines heavily relies on the delivery carrier, but the current market options are predominantly lipid nanoparticles. Their intricate preparation process and high transportation costs pose challenges for widespread use in remote areas. In this study, we harnessed FDA-approved polymer PLGA and lipid components widely employed in clinical experiments to craft a ready-to-use mRNA vaccine delivery system known as lipid-polymer hybrid nanoparticles (LPP). Following formulation optimization, the PDCD nanoparticles emerged as the most effective, showcasing exceptional mRNA delivery capabilities both in vitro and in vivo. Loading PDCD nanoparticles with mRNA encoding the H1N1 influenza virus HA antigen-fused M2e peptide enabled the successful induction of M2e-specific antibodies and T cell immune responses in immunized mice. After three rounds of vaccine immunization, the mice demonstrated weight recovery to normal levels and maintained a survival rate exceeding 80% following an encounter with the H1N1 influenza virus. The innovative mRNA delivery system that we designed demonstrates outstanding effectiveness in preventing infectious diseases, with the potential to play an even more significant role in future clinical applications.

Activation and modulation of the AGEs-RAGE axis: Implications for inflammatory pathologies and therapeutic interventions - A review.

Chronic inflammation is a common foundation for the development of many non-communicable diseases, particularly diabetes, atherosclerosis, and tumors. The activation of the axis involving Advanced Glycation End products (AGEs) and their receptor RAGE is a key promotive factor in the chronic inflammation process, influencing the pathological progression of these diseases. The accumulation of AGEs in the body results from an increase in glycation reactions and oxidative stress, especially pronounced in individuals with diabetes. By binding to RAGE, AGEs activate signaling pathways such as NF-κB, promoting the release of inflammatory factors, exacerbating cell damage and inflammation, and further advancing the formation of atherosclerotic plaques and tumor development. This review will delve into the molecular mechanisms by which the AGEs-RAGE axis activates chronic inflammation in the aforementioned diseases, as well as strategies to inhibit the AGEs-RAGE axis, aiming to slow or halt the progression of chronic inflammation and related diseases. This includes the development of AGEs inhibitors, RAGE antagonists, and interventions targeting upstream and downstream signaling pathways. Additionally, the early detection of AGEs levels and RAGE expression as biomarkers provides new avenues for the prevention and treatment of diabetes, atherosclerosis, and tumors.

Primary Cutaneous Cryptococcosis in an Elderly Patient: A Case Report and Review of Literature.

ABSTRACT: This article reports an elderly male patient with nodules and ulcers on the face and behind the left ear after trauma. Primary cutaneous cryptococcosis was confirmed using pathological biopsy, special staining, tissue culture, and fungal sequencing. The patient received a therapeutic intervention involving the administration of the antifungal agent itraconazole. Substantial amelioration of cutaneous manifestations was observed after a 3-month course of treatment. After an elapsed interval, the patient was diagnosed with esophageal tumor. Moreover, the literature on 33 patients with primary cutaneous cryptococcosis published in the past 10 years was also reviewed.

Early Postoperative Rapid Rehabilitation Yields More Favorable Short-term Outcomes in Patients Undergoing Patellar Realignment Surgery for Recurrent Patellar Dislocation: A Prospective Randomized Controlled Study.

BACKGROUND: Use of a rapid rehabilitation protocol for postoperative recovery after recurrent patellar dislocation (RPD) has gradually gained attention; nonetheless, evidence of its safety and effectiveness is lacking. PURPOSE: To compare the short-term postoperative outcomes of early rapid rehabilitation with those of conservative rehabilitation in patients with RPD. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 50 patients with RPD who underwent tibial tubercle osteotomy combined with medial patellofemoral ligament reconstruction were enrolled between January 2018 and February 2019. Postoperatively, the patients were randomly assigned to either the early rapid group (rapid group; n = 25 patients) or the conservative group (control group; n = 25 patients) for rehabilitation training. The rapid group underwent faster progression in weightbearing and range of motion (ROM) training. Knee joint functional scores, ROM, bilateral thigh circumference differences, and imaging data were recorded preoperatively and at 6 weeks and 3, 6, 12, and 24 months postoperatively for comparison. Postoperative complications were recorded over the 24-month follow-up period. RESULTS: The baseline data did not significantly differ between the 2 groups. Postoperatively, compared with the control group, the rapid group had higher Tegner scores at 6 weeks and 3 months; higher Lysholm scores at 3 and 6 months; higher International Knee Documentation Committee scores at 6 weeks, 3 months, and 12 months; better ROM; and smaller bilateral thigh circumference differences at 24 months (P < .05 for all). However, no differences were observed in the Tegner, Lysholm, and International Knee Documentation Committee scores at 24 months postoperatively. At the 6-week and subsequent follow-up visits, the Caton and Insall indices were lower in the control group than in the rapid group (P < .01 for all). Moreover, compared with the control group, the rapid group had a lower incidence of patella baja at 24 months (0% vs 17%) and fewer complications during the whole follow-up period (P < .01). CONCLUSION: Early rapid postoperative rehabilitation appears to be safe and effective for patients who undergo tibial tubercle osteotomy combined with medial patellofemoral ligament reconstruction to treat RPD. In the short term, this approach was shown to be more advantageous than conservative rehabilitation in improving functional scores, allowing an earlier return to daily activities, although the lack of difference at 24 months implies no long-term benefits. In addition, it potentially helped to prevent the occurrence of complications, including patella baja. REGISTRATION: ChiCTR1800014648 (ClinicalTrials.gov identifier).

A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 µM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 µM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

Dynamic behaviors of protein and water associated with fresh noodle quality during processing based on different HMW-GSs at Glu-D1.

In this study, dynamic behaviors of proteins and water during fresh noodles processing associated with the quality of fresh noodles were systematically investigated by using wheat near-isogenic lines carrying high-molecular-weight glutenin subunits (HMW-GS) 2 + 12, 3 + 12 or 5 + 10 at the Glu-D1 locus. The results showed that subunits 5 + 10 tend to form a complex gluten network and had a poorly hydrated ability, that prevent the intrusion of external water during cooking; subunits 3 + 12 formed a moderate strength gluten network that generated a medium ability to resist the hydrated and mechanical treatment, which explained the highest water absorption and less cooking loss of cooked noodles; while subunits 2 + 12 formed fragile protein aggregates that had a poor ability to resist mechanical. The findings demonstrated that subunits 3 + 12 provided a suitable gluten network which was crucial for intrusion and hydration of external water thus formed a uniform gluten network and excellent fresh noodle quality.

Durable Perovskite Solar Cells with 24.5% Average Efficiency: The Role of Rigid Conjugated Core in Molecular Semiconductors.

Efficient and robust n-i-p perovskite solar cells necessitate superior organic hole-transport materials with both mechanical and electronic prowess. Deciphering the structure-property relationship of these materials is crucial for practical perovskite solar cell applications. Through direct arylation, two high glass transition temperature molecular semiconductors, DBC-ETPA (202 °C) and TPE-ETPA (180 °C) are synthesized, using dibenzo[g,p]chrysene (DBC) and 1,1,2,2-tetraphenylethene (TPE) tetrabromides with triphenylene-ethylenedioxythiophene-dimethoxytriphenylamine (ETPA). In comparison to spiro-OMeTAD, both semiconductors exhibit shallower HOMO energy levels, resulting in increased hole densities (generated by air oxidation doping) and accelerated hole extraction from photoexcited perovskite. Experimental and theoretical studies highlight the more rigid DBC core, enhancing hole mobility due to reduced reorganization energy and lower energy disorder. Importantly, DBC-ETPA possesses a higher cohesive energy density, leading to lower ion diffusion coefficients and higher Young's moduli. Leveraging these attributes, DBC-ETPA is employed as the primary hole-transport layer component, yielding perovskite solar cells with an average efficiency of 24.5%, surpassing spiro-OMeTAD reference cells (24.0%). Furthermore, DBC-ETPA-based cells exhibit superior operational stability and 85 °C thermal storage stability.

The novel small molecule E0924G dually regulates bone formation and bone resorption through activating the PPARδ signaling pathway to prevent bone loss in ovariectomized rats and senile mice.

Osteoporosis is particularly prevalent among postmenopausal women and the elderly. In the present study, we investigated the effect of the novel small molecule E0924G (N-(4-methoxy-pyridine-2-yl)-5-methylfuran-2-formamide) on osteoporosis. E0924G significantly increased the protein expression levels of osteoprotegerin (OPG) and runt-related transcription factor 2 (RUNX2), and thus significantly promoted osteogenesis in MC3T3-E1 cells. E0924G also significantly decreased osteoclast differentiation and inhibited bone resorption and F-actin ring formation in receptor activator of NF-κB ligand (RANKL)-induced osteoclasts from RAW264.7 macrophages. Importantly, oral administration of E0924G in both ovariectomized (OVX) rats and SAMP6 senile mice significantly increased bone mineral density and decreased bone loss compared to OVX controls or SAMR1 mice. Further mechanistic studies showed that E0924G could bind to and then activate peroxisome proliferator-activated receptor delta (PPARδ), and the pro-osteoblast effect and the inhibition of osteoclast differentiation induced by E0924G were significantly abolished when PPARδ was knocked down or inhibited. In conclusion, these data strongly suggest that E0924G has the potential to prevent OVX-induced and age-related osteoporosis by dual regulation of bone formation and bone resorption through activation of the PPARδ signaling pathway.

Dual-Stimuli-Responsive Gut Microbiota-Targeting Nitidine Chloride-CS/PT-NPs Improved Metabolic Status in NAFLD.

Background and Purpose: Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease. Methods: The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing. Results: The nanoparticles prepared in this study have an average particle size of (255.9±5.10) nm, with an encapsulation rate of (72.83±2.13) % and a drug loading of (4.65±0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice. Conclusion: This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.

Application of membrane separation technology in the purification of pharmaceutical components.

Traditional Chinese medicine (TCM) is often composed of a variety of natural medicines. Its composition is complex, and many of its components can not be analyzed and identified. The first step in the rational application of TCM is to successfully separate the effective components which is also a great inspiration for the development of new drugs. Among the many separation technologies of TCM, the traditional heating concentration separation technology has high energy consumption and low efficiency. As a new separation technology, membrane separation technology has the characteristics of simple operation, high efficiency, environment-friendly and so on. The separation effect of high molecular weight difference solution is better. The applications of several main membrane separation technologies such as microfiltration, nanofiltration, ultrafiltration and reverse osmosis are reviewed, the methods of restoring membrane flux after membrane fouling are discussed, and their large-scale industrial applications in the future are prospected and summarized.

A polyamino acid-based phosphatidyl polymer library for in vivo mRNA delivery with spleen targeting ability.

A qualified delivery system is crucial for the successful application of messenger RNA (mRNA) technology. While lipid nanoparticles (LNPs) are currently the predominant platform for mRNA delivery, they encounter challenges such as high inflammation and difficulties in targeting non-liver tissues. Polymers offer a promising delivery solution, albeit with limitations including low transfection efficiency and potential high toxicity. Herein, we present a poly(L-glutamic acid)-based phosphatidyl polymeric carrier (PLG-PPs) for mRNA delivery that combines the dual advantages of phospholipids and polymers. The PLGs grafted with epoxy groups were firstly modified with different amines and then with alkylated dioxaphospholane oxides, which provided a library of PLG polymers grafted with various phosphatidyl groups. In vitro studies proved that PLG-PPs/mRNA polyplexes exhibited a significant increase in mRNA expression, peaking 14 716 times compared to their non-phosphatidyl parent polymer. Impressively, the subset PA8-PL3 not only facilitated efficient mRNA transfection but also selectively delivered mRNA to the spleen instead of the liver (resulting in 69.73% protein expression in the spleen) once intravenously administered. This type of phosphatidyl PLG polymer library provides a novel approach to the construction of mRNA delivery systems especially for spleen-targeted mRNA therapeutic delivery.