Standardized framework for assessing soil quality at antimony smelting site by considering microbial-induced resilience and heavy metal contamination.

Antimony smelting activities damage the soil and vegetation surroundings while generating economic value. However, no standardized methods are available to diagnose the extent of soil degradation at antimony smelting sites. This study developed a standardized framework for assessing soil quality by considering microbial-induced resilience and heavy metal contamination at Xikuangshan antimony smelting site. The soil resilience index (SRI) and soil contamination index (SCI) were calculated by Minimum Data Set and geo-accumulation model, respectively. After standardized by a multi-criteria quantitative procedure of modified Nemerow's pollution index (NPI), the integrated assessment of soil quality index (SQI), which is the minimum of SRINPI and SCINPI, was achieved. The results showed that Sb and As were the prominent metal(loid) pollutants, and significant correlations between SQI and SRI indicated that the poor soil quality was mainly caused by the low level of soil resilience. The primary limiting factors of SRI were Fungi in high and middle contaminated areas, and Skermanella in low contaminated area, suggesting that the weak soil resilience was caused by low specific microbial abundances. Microbial regulation and phytoremediation are greatly required to improve the soil quality at antimony smelting sites from the perspectives of pollution control and resilience improvement. This study improves our understanding of ecological effects of antimony smelting sites and provides a theoretical basis for ecological restoration and sustainable development of mining areas.

The Synthesis of Functionalized Carbonized Polymer Dots via Reversible Assembly of Oligomers for Anti-Counterfeiting, Catalysis, and Gas storage.

Carbonized polymer dots (CPDs) have shown exceptional potential across a wide range of applications. However, their practical utilization is significantly greatly impeded by the lack of precise control over their structures and functionalities. Consequently, the development of controlled synthesis strategies for CPDs with well-defined structures and tailored functionalities remains a critical challenge in the field. Here, the controlled synthesis of functional CPDs with reversible assembly properties via airflow-assisted melt polymerization, followed by a one-step post-synthetic doping strategy, is reported. This synthetic approach achieves high product yield, uniform and tunable structures, as well as customized functionalities including solid-state emission, enhanced catalytic performance (3.5-45 times higher than conventional methods), and selective gas storage in the resulting CPDs. The ability to tailor the properties of CPDs through controlled synthesis opens up new opportunities for their practical application in photocatalysis and gas storage.

Ternary Logic Circuit and Neural Network Integration via Small Molecule-Based Antiambipolar Vertical Electrochemical Transistor.

Circuits based on organic electrochemical transistors (OECTs) have great potential in the fields of biosensors and artificial neural computation due to their biocompatibility and neural similarity. However, the integration of OECT-based circuits lags far behind other emerging electronics. Here, ternary inverters based on antiambipolar vertical OECTs (vOECTs) and their integration with the establishment of neural networks are demonstrated. Specifically, by adopting a small molecule (t-gdiPDI) as the channel of vOECT, high antiambipolar performance, with current density of 33.9 ± 2.1 A cm-2 under drain voltage of 0.1 V, peak voltage ≈0 V, low driving voltage < ± 0.6 V, and current on/off ratio > 106, are realized. Consequently, vertically stacked ternary circuits based solely on OECTs are constructed for the first time, showing three distinct logical states and high integration density. By further developing inverter array as the internal fundamental units of ternary weight network hardware circuits for ternary processing and computation, it demonstrates excellent data classification and recognition capabilities. This work demonstrates the possibility of constructing multi-valued logic circuits by OECTs and promotes a new strategy for high-density integration and multivalued computing systems based on organic circuits.

Ensemble Learning Improves the Efficiency of Microseismic Signal Classification in Landslide Seismic Monitoring.

A deep-seated landslide could release numerous microseismic signals from creep-slip movement, which includes a rock-soil slip from the slope surface and a rock-soil shear rupture in the subsurface. Machine learning can effectively enhance the classification of microseismic signals in landslide seismic monitoring and interpret the mechanical processes of landslide motion. In this paper, eight sets of triaxial seismic sensors were deployed inside the deep-seated landslide, Jiuxianping, China, and a large number of microseismic signals related to the slope movement were obtained through 1-year-long continuous monitoring. All the data were passed through the seismic event identification mode, the ratio of the long-time average and short-time average. We selected 11 days of data, manually classified 4131 data into eight categories, and created a microseismic event database. Classical machine learning algorithms and ensemble learning algorithms were tested in this paper. In order to evaluate the seismic event classification performance of each algorithmic model, we evaluated the proposed algorithms through the dimensions of the accuracy, precision, and recall of each model. The validation results demonstrated that the best performing decision tree algorithm among the classical machine learning algorithms had an accuracy of 88.75%, while the ensemble algorithms, including random forest, Gradient Boosting Trees, Extreme Gradient Boosting, and Light Gradient Boosting Machine, had an accuracy range from 93.5% to 94.2% and also achieved better results in the combined evaluation of the precision, recall, and F1 score. The specific classification tests for each microseismic event category showed the same results. The results suggested that the ensemble learning algorithms show better results compared to the classical machine learning algorithms.

Advancements in understanding the role of ferroptosis in hypoxia-associated brain injury: a narrative review.

Background and Objective: Ferroptosis, a form of programmed cell death driven by lipid peroxidation and dependent on iron ions, unfolds through a sophisticated interplay of multiple biological processes. These include perturbations in iron metabolism, lipid peroxidation, aberrant amino acid metabolism, disruptions in hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) axis, and endoplasmic reticulum (ER) stress. Recent studies indicate that ferroptosis may serve as a promising therapeutic target for hypoxia-associated brain injury such as hypoxic-ischemic brain damage (HIBD) and cerebral ischemia-reperfusion injury (CIRI). HIBD is a neonatal disease that can be fatal, causing death or mental retardation in newborns. HIBD is a kind of diffuse brain injury, which is characterized by apoptosis of nerve cells and abnormal function and structure of neurons after cerebral hypoxia and ischemia. At present, there are no fundamental prevention and treatment measures for HIBD. The brain is the most sensitive organ of the human body to hypoxia. Cerebral ischemia will lead to the damage of local brain tissue and its function, and CIRI will lead to a series of serious consequences. We hope to clarify the mechanism of ferroptosis in hypoxia-associated brain injury, inhibit the relevant targets of ferroptosis in hypoxia-associated brain injury to guide clinical treatment, and provide guidance for the subsequent treatment of disease-related drugs. Methods: Our research incorporated data on "ferroptosis", "neonatal hypoxic ischemia", "hypoxic ischemic brain injury", "hypoxic ischemic encephalopathy", "brain ischemia-reperfusion injury", and "therapeutics", which were sourced from Web of Science, PubMed, and comprehensive reviews and articles written in English. Key Content and Findings: This review delineates the underlying mechanisms of ferroptosis and the significance of these pathways in hypoxia-associated brain injury, offering an overview of therapeutic strategies for mitigating ferroptosis. Conclusions: Ferroptosis involves dysregulation of iron metabolism, lipid peroxidation, amino acid metabolism, dysregulation of HIF-PHD axis and endoplasmic reticulum stress (ERS). By reviewing the literature, we identified the involvement of the above processes in HIBD and CIRI, and summarized a series of therapeutic measures for HIBD and CIRI by inhibiting ferroptosis. We hope this study would provide guidance for the clinical treatment of HIBD and CIRI in the future.

Differential absorption and metabolic characteristics of organic acid components in pudilan xiaoyan oral liquid between young rats and adult rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood. AIM OF THE STUDY: The differential absorption and metabolism characteristics of the main pharmacological components in PDL in young and adult rats were investigated with a view to providing a reference for preclinical data of PDL in medication for children. MATERIALS AND METHODS: This study utilized UPLC-Q-TOF-MS to investigate the pharmacodynamic material basis of PDL. The focus was on the gastrointestinal digestion and absorption characteristics of organic acid components in PDL (PDL-OAC), known as the primary pharmacodynamic components in this formulation. The research combined in vitro dynamic simulation and a Quadruple single-pass intestinal perfusion model to examine these characteristics. The permeability properties of PDL-OAC were evaluated using an artificial parallel membrane model. Additionally, an acute pharyngitis model was established to evaluate the histopathological condition of the pharynx in young rats using H&E staining. The levels of IL-1ß, TNF-α, IL-6, and IL-10 in blood and pharyngeal tissue homogenates of young rats were quantified using ELISA kits. RESULTS: A total of 91 components were identified in PDL, including 33 organic acids, 24 flavonoids, 14 alkaloids, 5 terpenoids and coumarins, 3 sugars, and 12 amino acids. The PDL-OAC exhibited a significant reduction in IL-1ß, TNF-α, IL-6, and IL-10 levels in the pharyngeal tissues of young rats with acute pharyngitis. Results from dynamic simulation studies of gastrointestinal fluids revealed that the PDL-OAC (Specifically chlorogenic acid (CGA), gallic acid (GA), chicoric acid (CRA), and caffeic acid (CA)) were effectively stabilized in the gastrointestinal fluids of both children and adults in vitro. Young rats, characterized by thinner intestinal walls and higher permeability, efficiently absorbed the four organic acids across the entire intestinal segment. The absorption of CGA, GA, and CRA followed a concentration-dependent pattern, with CGA and GA absorption being influenced by exocytosis. CONCLUSION: The efficacy of the PDL-OAC in treating acute pharyngitis was demonstrated in young rats. The absorption rate of these components was observed to be faster in young rats compared to adult rats, underscoring the need for dedicated studies on the drug's usage in children. This research provides valuable insights for the appropriate clinical use of PDL in pediatric patients.

Chromosome-level genome assembly of the two-spotted spider mite Tetranychus urticae.

The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is a notorious pest in agriculture that has developed resistance to almost all chemical types used for its control. Here, we assembled a chromosome-level genome for the TSSM using Illumina, Nanopore, and Hi-C sequencing technologies. The assembled contigs had a total length of 103.94 Mb with an N50 of 3.46 Mb, with 87.7 Mb of 34 contigs anchored to three chromosomes. The chromosome-level genome assembly had a BUSCO completeness of 94.8%. We identified 15,604 protein-coding genes, with 11,435 genes that could be functionally annotated. The high-quality genome provides invaluable resources for the genetic and evolutionary study of TSSM.

A microchip gas chromatography column assembly with a 3D metal printing micro column oven and a flexible stainless-steel column.

In this work, a microchip gas chromatography (GC) column assembly utilizing a three-dimensional (3D) printed micro oven and a flexible stainless steel capillary column was developed. The assembly's performance and separation capabilities were characterized. The key components include a 3D printed aluminum plate (7.50 × 7.50 × 0.16 cm) with a 3-meter-long circular spiral channel, serving as the oven, and the column coiled on the channel with an inner diameter of 320 µm and a stationary phase of OV-1. A heating ceramic plate was affixed on the opposite side of the plate. The assembly weighed 40.3 g. The design allows for easy disassembly, or stacking of heating devices and columns, enabling flexibility in adjusting column length. When using n-C13 as the test analyte at 140 °C, a retention factor (k) was 8.5, and 7797 plates (2599 plates/m) were obtained. The assembly, employing resistance heating, demonstrated effective separation performance for samples containing alkanes, aromatics, alcohols and ketones, with good reproducibility. The reduction in theoretical plates compared to oven heating was only 2.95 %. In the boiling point range of C6 to C18, rapid temperature programming (120 °C/min) was achieved with a power consumption of 119.512 W. The assembly was successfully employed to separate benzene series compounds, gasoline and volatile organic compounds (VOCs), demonstrating excellent separation performance. This innovative design addresses the challenges of the complexity and low repeatability of the fabrication process and the high cost associated with microchip columns. Furthermore, its versatility makes it suitable for outdoor analysis applications.

The carrier function and inhibition effect on benign prostatic hyperplasia of a glucan from Epimedium brevicornu Maxim.

Epimedium, a traditional Chinese medicine commonly used as a dietary supplement, contains polysaccharides and flavonoids as its main bioactive ingredients. In this study, a neutral homogeneous polysaccharide (EPSN-1) was isolated from Epimedium brevicornu Maxim. EPSN-1 was identified as a glucan with a backbone of →4)-α-D-Glcp-(1→, branched units comprised α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Glcp-(1→6)-ß-D-Glcp-(1→ and α-D-Glcp-(1→ connected to the C6 position of backbone. The conformation of EPSN-1 in aqueous solution indicated its potential to form nanoparticles. This paper aims to investigate the carrier and pharmacodynamic activity of EPSN-1. The findings demonstrated that, on the one hand, EPSN-1, as a functional ingredient, may load Icariin (ICA) through non-covalent interactions, improving its biopharmaceutical properties such as solubility and stability, thereby improving its intestinal absorption. Additionally, as an effective ingredient, EPSN-1 could help maintain the balance of the intestinal environment by increasing the abundance of Parabacteroides, Lachnospiraceae UGG-001, Anaeroplasma, and Eubacterium xylanophilum group, while decreasing the abundance of Allobaculum, Blautia, and Adlercreutzia. Overall, this dual action of EPSN-1 sheds light on the potential applications of natural polysaccharides, highlighting their dual role as carriers and contributors to biological activity.

Kinetic Resolution Polymerization Enabled Chemical Synthesis of Perfectly Isotactic Polythioesters.

Isotactic polythioesters (PTEs) that are thioester analogs to natural polyhydroxyalkanoates (PHAs) have attracted growing attention due to their distinct properties. However, the development of chemically synthetic methods for preparing isotactic PTEs has long been an intricate endeavour. Herein, we report the successful synthesis of perfectly isotactic PTEs via stereocontrolled ring-opening polymerization. This binaphthalene-salen aluminium (SalBinam-Al) catalyst promoted a robust polymerization of rac-α-substituted-ß-propiothiolactones (rac-BTL and rac-PTL) with highly kinetic resolution, affording perfectly isotactic P(BTL) and P(PTL) with Mn up to 276 kDa. Impressively, the isotactic P(BTL) formed a supramolecular stereocomplex with improved thermal property (Tm=204 °C). Ultimately, this kinetic resolution polymerization enabled the facile isolation of enantiopure (S)-BTL, which could efficiently convert to an important pharmaceutical building block (S)-2-benzyl-3-mercapto-propanoic acid. Isotactic P(PTL) served as a tough and ductile material comparable to the commercialized polyolefins. This synthetic system allowed to access of isotactic PTEs, establishing a powerful platform for the discovery of sustainable plastics.

Precisely Patterned Channels in a Vertical Organic Electrochemical Transistor with a Diazirine Photo-Crosslinker.

Organic electrochemical transistors (OECTs) rely on both efficient ionic doping/de-doping process and carrier transport in the mixed ionic-electronic channel under the modulation of gate bias. Moreover, channels that hold photopatterning capability are highly desired to minimize parasitic capacitance and simplify the fabrication process/cost. However, yielding photo-patternable channels with both precise/robust patterning capability and controllable ionic-electronic coupling is still challenging. Herein, double-end trifluoromethyl diazirines (DtFDA) with different chain lengths are introduced in the OECT channel to act as both photo-crosslinker and medium to regulate ionic-electronic transport. Specifically, high-resolution patterns with a minimum line width/gap of 2 µm are realized in p(g2T-T) or Homo-gDPP based channels by introducing DtFDA. Maximum transconductances of 68.6 mS and 81.6 mS, current on/off ratio of 106 and 107 (under a drain voltage of only ±0.1 V), are achieved in p- and n-type vertical OECTs (vOECTs), respectively, along with current densities exceeding 1 kA cm-2 and good cycling stability of more than 100,000 cycles (2000 seconds). This work provides a new and facile strategy for the fabrication of vOECT channels with high resolution and high performance via the introduction of a simple and efficient crosslinker.

A novel strategy for the multi-components division and discovering pharmacodynamic material basis of Chinese herbal compounds: A case study of Xian-Ling-Gu-Bao capsule.

The therapeutic effects of Chinese herbal compounds are often achieved through the synergistic interactions of multiple ingredients. However, current research predominantly focuses on individual ingredients, neglecting the holistic nature of Chinese herbal compounds. This study proposes a novel strategy to elucidate the pharmacodynamic material basis of Chinese herbal compounds based on their multi-components (components named 'ZuFen' in China, it refers to multiple ingredients with similar chemical structures) composition, using the Xian-Ling-Gu-Bao (XLGB) capsule as a case study. Cheminformatics-based components partitioning was conducted after sourcing ingredients from various databases, resulting in a total of 856 ingredients which were categorized into nine major components. Furthermore, the pharmacodynamic ingredients of XLGB capsule were determined by analyzing the ingredients that were absorbed into the bloodstream. Through a combination of these ingredients and screening for absorption, the Dipsacus asper saponin components, Psoralea corylifolia coumarin components, and Epimedium flavonoid polyglycosides components were isolated. The anti-osteoporosis efficacy of these components were evaluated in zebrafish, demonstrating their capability to reverse mineralization reduction caused by prednisolone. These findings further support the idea that these components serve as the material basis for the pharmacological efficacy of XLGB capsule. This study provides a novel systematic strategy for discovering the pharmacodynamic material basis of the efficacy of Chinese herbal compounds based on a 'multi-components' perspective.

Does county financial marketization promote high-quality development of agricultural economy?: Analysis of the mechanism of county urbanization.

China's agricultural economy has been hindered by insufficient accumulation of agricultural capital and credit constraints. It is worth investigating whether China's county financial marketization reform policy can alleviate these constraints and promote high-quality development of the agricultural economy (HQDAE). This paper presents an empirical analysis of the impact of county financial marketization reform on the HQDAE, based on county panel data. The focus is on the mechanism of county urbanization in the above relationship. The results show that county financial marketization has a significant non-linear impact on the HQDAE. Specifically, it has a 'U-shaped' impact on the overall growth of the agricultural economy and an inverted 'N-shaped' impact on the quality improvement of the agricultural economy. Secondly, the relationship between county financial marketization and the HQDAE is influenced by a threshold effect based on the level of county urbanization. As the level of county urbanization increases, the promoting effect of county financial marketization on HQDAE also increases significantly. Additionally, county financial marketization helps to promote county urbanization and accelerate urban-rural integration, which in turn leads to HQDAE. The research in this paper suggests that county-level local governments should promote a differentiated county financial system. In the early stages of financial market-oriented reform, the government should enhance the capacity of financial services in rural areas through tax breaks, policy incentives, and other measures to prevent financial leakage from agriculture. In the later stages of financial marketization reform, the government should strengthen financial supervision to prevent financial resources from being diverted from industry to capital. Moreover, to achieve the HQDAE, it is necessary to promote county financial market-oriented reform and accelerate the construction of county urbanization. This will help break the dual economic structure of urban and rural areas and promote the flow of financial capital, technology, and human capital from county cities to rural areas.

Mg2+-promoted high-efficiency DNA conjugation on polydopamine surfaces for aptamer-based ochratoxin A detection.

BACKGROUND: Surface immobilization of DNA is the foundation of a broad range of applications in biosensing and specific DNA extraction. Polydopamine (PDA) coatings can serve as intermediate layers to immobilize amino- or thiol-labelled molecules, including DNA, onto various materials through Michael addition and/or Schiff base reactions. However, the conjugation efficiency is limited by electrostatic repulsion between negatively charged DNA and PDA. Recently, it has been reported that polyvalent metal ions (such as Mg2+ and Ca2+) can mediate the adsorption of DNA on PDA surfaces. Inspired by this, in this work we aimed to exploit polyvalent metal ions to facilitate the conjugation of DNA on PDA. RESULTS: Mg2+ was used to promote the conjugation of amino-terminated DNA complementary to ochratoxin A (OTA) aptamer (cDNA-NH2) on PDA-coated magnetic nanoparticles (Fe3O4@PDA). After the reaction, the unlinked cDNA-NH2 adsorbed on Fe3O4@PDA mediated by Mg2+ was removed with EDTA. In the presence of 20 mM Mg2+, the amount of covalently linked cDNA-NH2 increased approximately 11-fold compared to that in the absence of Mg2+. The resulting Fe3O4@PDA@cDNA conjugates exhibited superior hybridization capacity towards OTA aptamers, minimal nonspecific adsorption, and excellent chemical stability. The conjugates combined with fluorophore-labelled aptamers were employed for OTA detection, achieving a limit of detection (LOD) of 2.77 ng mL-1. To demonstrate versatility, this conjugation method was extended to Ca2+-promoted conjugation of cDNA-NH2 on Fe3O4@PDA nanoparticles and Mg2+-promoted conjugation of cDNA-NH2 on PDA-coated 96-well plates. SIGNIFICANCE: The conjugation efficiency of DNA on PDA was significantly improved with the assistance of polyvalent metal ions (Mg2+ and Ca2+), providing a facile and efficient method for DNA immobilization. Due to the substrate-independent adhesion property of PDA, this method demonstrates versatility in DNA surface modification and holds great potential for applications in target extraction, biosensing, and other fields.

Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury.

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.

Pharmacists as clinical care partners: How a pharmacist-led intervention is associated with improved medication adherence in older adults with common chronic conditions.

BACKGROUND: Hypertension, hyperlipidemia, and type 2 diabetes (T2D) are 3 of the most common chronic conditions, but related medication adherence rates are far below 80%. Consequences of poor adherence include high health care utilization/costs and increased mortality. There is accumulating evidence in support of the benefits of affording pharmacists the opportunity to practice at the full scope of their licensure by engaging in patients' clinical care. OBJECTIVE: To examine the impact of a large national pharmacy chain's pharmacist-led interventions to improve medication adherence among older adults with hypertension, hyperlipidemia, or T2D. A secondary objective was to estimate the potential cost savings associated with improved adherence. METHODS: Participants were Medicare patients aged 18 years or older who had 2 or more prescription fills in at least 1 of the 3 therapeutic classes. The primary outcome, optimal adherence, was defined as proportion of days covered (PDC) of 80% or higher. A difference-in-differences (DID) design with a generalized linear model analytical approach was applied to examine differences between intervention participants and controls. The study period spanned from 2020 to 2022. RESULTS: Intervention participants (n = 317,613, age 70.1 years, female sex 57.0%) had lower baseline optimal adherence than controls (n = 943,389, age 73.3, female sex 56.1%) for diabetes (76.9% vs 79.8%), hypertension (79.0% vs 83.0%), and cholesterol (78.6% vs 82.1%). The DID results showed that between 2020 and 2022, optimal adherence had significant absolute increases for intervention participants (diabetes: +4.0%, hypertension: +6.3%, cholesterol: +6.1%) vs controls who declined in adherence (diabetes: -1.6%, hypertension: -0.4%, cholesterol: -1.4%). All DID models were significant at P < 0.0001. Total cost of care was projected based on improvements in adherence. Based on PDC improvements for the test population, we estimate that the pharmacist consultations were associated with annual total health care cost savings of $10,329,284 ($109 per capita), $31,640,660 ($122 per capita), and $21,589,875 ($75 per capita) for test population patients with diabetes, hypertension, and hyperlipidemia, respectively. CONCLUSIONS: The study found that the pharmacist-led interventions were significantly associated with increased optimal adherence over 2 years. These findings demonstrate the potential of pharmacist-led interventions to improve medication adherence among older adults with chronic conditions. Strategies to expand pharmacist-provided care must be further examined.

Semisynthesis of homogeneous spike RBD glycoforms from SARS-CoV-2 for profiling the correlations between glycan composition and function.

Vaccines have been the primary remedy in the global fight against coronavirus disease 2019 (COVID-19). The receptor-binding domain (RBD) of the spike protein, a critical viral immunogen, is affected by the heterogeneity of its glycan structures and relatively low immunogenicity. Here, we describe a scalable synthetic platform that enables the precise synthesis of homogeneously glycosylated RBD, facilitating the elucidation of carbohydrate structure-function relationships. Five homogeneously glycosylated RBDs bearing biantennary glycans were prepared, three of which were conjugated to T-helper epitope (Tpep) from tetanus toxoid to improve their weak immune response. Relative to natural HEK293-derived RBD, synthetic RBDs with biantennary N-glycan elicited a higher level of neutralising antibodies against SARS-CoV-2 in mice. Furthermore, RBDs containing Tpep elicited significant immune responses in transgenic mice expressing human angiotensin-converting enzyme 2. Our collective data suggest that trimming the N-glycans and Tpep conjugation of RBD could potentially serve as an effective strategy for developing subunit vaccines providing efficient protection.

Progress in the study of mechanisms and pathways related to the survival of random skin flaps.

The clinical application of random flaps in wound repair has been a topic of discussion. Random flaps are prone to necrosis due to the lack of well-defined vascular blood supply during transfer surgery. Their clinical utility is restricted, financial and psychological burdens is imposed on patients due to this limitation. The survival of random skin flaps depends on factors such as ischemia-reperfusion injury, oxidative stress, local inflammatory response, and neovascularization. This review aims to provide an overview of the evidence supporting the use of random flaps in clinical practice. In addition, this review explores the impact of different medications on signaling pathways within the flap's local microcirculation and investigates the interconnections between these pathways.

Novel nano-encapsulated limonene: Utilization of drug-in-cyclodextrin-in-liposome formulation to improve the stability and enhance the antioxidant activity.

Drug-in-cyclodextrin-in-liposome (DCL) combines advantages of cyclodextrin and liposome. Here, DCL formulation was successfully prepared to encapsulate limonene (Lim), whose characterization revealed that particle size was 147.5 ± 1.3 nm and zeta potential was -48.7 ± 0.8 mV. And the complexation mechanism of Lim/HP-ß-CD inclusion complex (the intermediate of DCL) was analyzed by molecular dynamics simulation, showing that Lim was entrapped into the cavity of HP-ß-CD through electrostatic and hydrophobic interaction with a molar ratio of 1:1. Notably, DCL formulation not only reduced Lim volatilization in 25℃, but also enhanced the free radical (DPPH· and ABTS·+) scavenging ability of Lim. In summary, Lim-DCL formulation improved the stability and enhanced the antioxidant activity of Lim. DCL nanocarrier system is suitable to preserve volatile and hydrophobic compounds, enlarging their application in pharmaceutics industries.