This study delves into the physicochemical properties of inorganic hydroxyapatite (HAp) and hybrid hydroxyapatite–chitosan (HAp-CTS) granules, also gold-enriched, which can be used as aggregates in biomicroconcrete-type materials. The impact of granules’ surface modifications with citric acid (CA) or polyethylene glycol (PEG) was assessed. Citric acid modification induced increased specific surface area and porosity in inorganic granules, contrasting with reduced parameters in hybrid granules. PEG modification resulted in a slight increase in specific surface area for inorganic granules and a substantial rise for hybrid granules with gold nanoparticles. Varied effects on open porosity were observed based on granule type. Microstructural analysis revealed increased roughness for inorganic granules post CA modification, while hybrid granules exhibited smoother surfaces. Novel biomicroconcretes, based on α-tricalcium phosphate (α-TCP) calcium phosphate cement and developed granules as aggregates within, were evaluated for compressive strength. Compressive strength assessments showcased significant enhancement with PEG modification, emphasizing its positive impact. Citric acid modification demonstrated variable effects, depending on granule composition. The incorporation of gold nanoparticles further enriched the multifaceted approach to enhancing calcium phosphate-based biomaterials for potential biomedical applications. This study demonstrates the pivotal role of surface modifications in tailoring the physicochemical properties of granules, paving the way for advanced biomicroconcretes with improved compressive strength for diverse biomedical applications. Full article

Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern. Full article

The Drinking Water Directive (EU) 2020/2184 includes the parameter microcystin LR, a cyanotoxin, which drinking water producers need to analyze if the water source has potential for cyanobacterial blooms. In light of the increasing occurrences of cyanobacterial blooms worldwide and given that more than 50 percent of the drinking water in Sweden is produced from surface water, both fresh and brackish, the need for improved knowledge about cyanotoxin occurrence and cyanobacterial diversity has increased. In this study, a total of 98 cyanobacterial blooms were sampled in 2016–2017 and identified based on their toxin production and taxonomical compositions. The surface water samples from freshwater lakes throughout Sweden including brackish water from eight east coast locations along the Baltic Sea were analyzed for their toxin content with LC-MS/MS and taxonomic composition with 16S rRNA amplicon sequencing. Both the extracellular and the total toxin content were analyzed. Microcystin’s prevalence was highest with presence in 82% of blooms, of which as a free toxin in 39% of blooms. Saxitoxins were found in 36% of blooms in which the congener decarbamoylsaxitoxin (dcSTX) was detected for the first time in Swedish surface waters at four sampling sites. Anatoxins were most rarely detected, followed by cylindrospermopsin, which were found in 6% and 10% of samples, respectively. As expected, nodularin was detected in samples collected from the Baltic Sea only. The cyanobacterial operational taxonomic units (OTUs) with the highest abundance and prevalence could be annotated to Aphanizomenon NIES-81 and the second most profuse cyanobacterial taxon to Microcystis PCC 7914. In addition, two correlations were found, one between Aphanizomenon NIES-81 and saxitoxins and another between Microcystis PCC 7914 and microcystins. This study is of value to drinking water management and scientists involved in recognizing and controlling toxic cyanobacteria blooms. Full article

Carbon dot (CD) nanozymes have enzyme-like activity. Compared with natural enzymes, CD nanozymes offer several advantages, including simple preparation, easy preservation, good stability and recycling, which has made them a popular research topic in various fields. In recent years, researchers have prepared a variety of CD nanozymes for biosensing detection, medicine and tumor therapy, and many of them are based on oxidative stress regulation and reactive oxygen species clearance. Particularly to expand their potential applications, elemental doping has been utilized to enhance the catalytic capabilities and other properties of CD nanozymes. This review discusses the prevalent techniques utilized in the synthesis of CD nanozymes and presents the diverse applications of CD nanozymes based on their doping characteristics. Finally, the challenges encountered in the current utilization of CD nanozymes are presented. The latest research progress of synthesis, application and the challenges outlined in the review can help and encourage the researchers for the future research on preparation, application and other related researches of CD nanozymes. Full article

(1) Background: Alzheimer’s disease (AD) is an irreversible disorder of the central nervous system associated with beta-amyloid protein (Aβ) deposition and accumulation. Current treatments can only act on symptoms and not the etiologic agent. Neprilysin and α-bisabolol have been shown to reduce the aggregation of Aβ, suggesting a potential interaction between both molecules, leading to increased proteolytic activity on Aβ aggregates. (2) Methods: Computational simulations were conducted to explore the interaction between murine neprilysin [NEP(m)] and α-bisabolol and their effects on enzymatic activity. NEP(m) structure was predicted using comparative modeling, and the binding pattern to α-bisabolol and its effects on leu-enkephalin binding were explored through docking calculations and molecular dynamics simulations, respectively. (3) Results: The findings suggest that α-bisabolol stabilizes the Val⁴⁸¹-Pro⁴⁸⁸ segment of NEP2(m), which directly interacts with the peptide substrate, enabling an optimized alignment between the catalytic residue Glu⁵²⁵ and leu-enkephalin. (4) Conclusions: This computational evidence strongly supports the notion that α-bisabolol stabilizes peptide substrates at the NEP2(m) catalytic site, leading to the positive modulation of enzymatic activity. Full article

Calcitonin gene-related peptide (CGRP) has long been implicated in both the physiology and pathophysiology of the respiratory tract. The objective of our study was to determine the serum concentration of alpha CGRP (αCGRP) in cystic fibrosis (CF) that arises from mutations in the gene responsible for encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Currently, there are not many data in the literature about the role of CGRP in CF. The serum level of αCGRP was estimated using the enzyme-linked immunosorbent assay among 64 patients with CF and 31 healthy controls. The αCGRP concentration in the CF group was 62.51 ± 15.45 pg/mL, while in the control group it was 47.43 ± 8.06 pg/mL (p < 0.001). We also compared the level of αCGRP in CF patients according to the type of CFTR mutation. Homozygotes for ΔF508 had higher αCGRP levels than heterozygotes (67.9 ± 10.2 vs. 54.5 ± 18.3 pg/mL, p < 0.01). The level of this neuropeptide was statistically higher in patients with severe disease than in those with mild CF (p = 0.003) when patients were divided into three groups by spirometry results. αCGRP concentration was not correlated with age, sex, clinical parameters, and pulmonary function test results in the study participants. The results of our study suggest a significant increase in the concentration of αCGRP in the serum of patients with CF compared to the control group. This observation opens interesting possibilities for understanding the role of αCGRP in the context of CF pathophysiology. Full article

With the continuous development of rural revitalization and urbanization in China, the sustainable transformation of traditional rural architecture has become increasingly important. This study takes the Thangka exhibition hall in rural Malkang, Sichuan Province, as the research object and proposes a Thangka exhibition hall architectural design centered around solar heating and aiming for near-zero energy consumption. The research method involves establishing a solar energy system model on the roof of the exhibition hall and utilizing solar angle and area calculation formulas along with simulation software to calculate the optimal installation angle and area of solar panels, with the aim of achieving indoor temperatures that meet Thangka protection requirements while achieving zero-energy heating. Preliminary results indicate that this solar-centric near-zero energy architectural design can effectively promote the increase in indoor temperature through solar thermal conversion. Additionally, through calculation and simulation, the optimal installation angle for the solar panels achieving zero-energy heating is determined to be 24.25 with an azimuth angle of −1.2. The optimum installation area for solar panels is 8.2 square meters in the showroom and 2.7 square meters in the storeroom. Among these, the solar panel area for the Thangka exhibition hall constitutes 4.12% of the total area and is required for maintaining Thangka protection temperature requirements throughout the year, while the solar panel area for the storage room constitutes 1.88% and is also needed for the same purpose. Studying the optimal installation angle and area of solar panels can transform the exhibition hall into a near-zero-energy building, meeting the temperature requirements for Thangka preservation and human thermal comfort, while also achieving optimal economic benefits. This provides guidance and a reference for promoting near-zero-energy buildings in rural areas. Full article

We study the properties of the constructive linear programming problems. The parameters of linear functions in such problems are constructive real numbers. Solving such a problem involves finding the optimal plan with the constructive real number components. We show that it is impossible to have an algorithm that solves an arbitrary constructive real programming problem. Full article

Borane–trimethylamine complex (Me₃N·BH₃; BTM) is the most stable of the amine–borane complexes that are commercially available, and it is cost-effective. It is a valuable reagent in organic chemistry with applications in the reduction of carbonyl groups and carbon–nitrogen double bond reduction, with considerable examples in the reduction of oximes, hydrazones and azines. The transfer hydrogenation of aromatic N-heterocycles and the selective N-monomethylation of primary anilines are further examples of recent applications, whereas the reduction of nitrobenzenes to anilines and the reductive deprotection of N-tritylamines are useful tools in the organic synthesis. Moreover, BTM is the main reagent in the regioselective cleavage of cyclic acetals, a reaction of great importance for carbohydrate chemistry. Recent innovative applications of BTM, such as CO₂ utilization as feedstock and radical chemistry by photocatalysis, have extended their usefulness in new reactions. The present review is focused on the applications of borane–trimethylamine complex as a reagent in organic synthesis and has not been covered in previous reviews regarding amine–borane complexes. Full article

This study sought to investigate the vertical distribution pattern of the soil faunal community in a low-altitude mountain area. On 8 July 2022, a low hill was selected as the study area, and soil arthropods were collected through traps. The leaf litter, vegetation type, and distribution quantity of each sampling site were investigated while the soil faunae were collected. In addition, the soil’s physical and chemical parameters were measured. The results of a one-way ANOVA showed that there were significant differences (p < 0.05) in the soil properties, leaf litter, and plant quantities at different altitudes within the research area. A total of 1086 soil arthropods, belonging to five classes and ten orders, were collected during the study period. The dominant species of soil arthropods at different altitudes were significantly different. The dominant species in low-altitude areas were Armadillidium sp. and Aethus nigritus. However, Eupolyphaga sinensis and Philodromidae were the dominant species in high-altitude areas. The results of a non-metric multidimensional scaling (NMDS) analysis showed that the soil faunae at different altitudes were clustered into two communities: a high-altitude community and a low-altitude community. With the increase in altitude, the species richness of the soil arthropods gradually decreased, and their abundance showed a decreasing trend. A redundancy analysis (RDA) of the soil arthropods and environmental factors showed that soil moisture (p < 0.01), pH (p < 0.01) and defoliation (p < 0.05) had significant effects on the distribution of the soil fauna. The results of a Pearson correlation analysis indicated that different environmental factors had interactive effects on the distribution of the soil arthropods. The quantity and species richness of the soil arthropods in different sample lines were tested using a variance analysis. The results showed that there were significantly smaller quantities of soil arthropods in the sampling line closer to the trekking ladder. This indicates that human tourism, namely mountaineering activities, had a direct impact on the soil fauna. This study can provide a reference for and data support in the development of biodiversity conservation measures for forest parks in low mountain areas. Full article

Emotional eating, the act of consuming food to cope with negative emotions rather than responding to hunger cues, can lead to overeating in an attempt to regulate and alleviate these emotions. This study aimed to assess emotional eating among college students in Israel, specifically during times of war, which present unique and heightened stressors that accumulate on top. A total of 575 participants from the Ashkelon Academic College completed an online questionnaire examining background information, stress levels, and emotional eating symptoms. Our findings indicate that factors, such as being female, not having children, younger age, lower body satisfaction, higher BMI, and increased stress, are predictors of heightened emotional eating. These results highlight risk factors predisposing college students to engage in emotional eating. Developing targeted interventions, particularly campus-based programs to address emotional eating by promoting healthy coping strategies, a positive body image, and stress management skills is needed. In addition, raising awareness concerning emotional eating risks during challenging life transitions and distressing situations is necessary. The college leadership, led by the departments of Nutrition, Psychology, and Public Health, in collaboration with stakeholders in the Israeli Ministry of Health, must consider the mental effects of war on students and their involvement in emotional eating. Full article

Virtual simulation offers a powerful educational tool with considerable, albeit underexplored potential. This technology immerses students in lifelike digital scenarios, fostering the acquisition of knowledge and skills necessary for their future careers. This study aimed to assess knowledge acquisition and satisfaction outcomes among students using a virtual simulation teaching approach. The specific objectives were (1) to compare pre-and posttest knowledge acquisition, (2) to investigate the influence of prior professional experience on knowledge, and (3) to explore satisfaction levels with virtual simulation. One hundred and fifty-nine nursing students participated in a virtual simulation-based clinical intervention, entailing the resolution of a virtual adult patient hospitalized with respiratory pathology. Sociodemographic data and prior professional experience were collected, and knowledge was evaluated through pre-to-post tests. Satisfaction levels were assessed using open-ended questions. Quantitative data were analyzed using descriptive statistics, Wilcoxon, Mann–Whitney U, and Cohen’s tests, while qualitative data underwent keyword-in-context analysis. Significant differences were noted between pre- and posttest knowledge levels, with prior experience showing no significant impact on knowledge acquisition. Participants reported high levels of satisfaction. Lexicometric analysis identified four clusters of words related to the key terms “simulation”, “learn”, “activity”, and “knowledge”. Virtual clinical simulation effectively enhances knowledge acquisition and fosters satisfaction, with students recognizing the positive impact of this approach on their learning. Consequently, virtual simulation contributes to the training of competent health professionals. Full article

Polyunsaturated fatty acids (PUFAs) can alter adipose tissue function; however, the relative effects of plant and marine n3-PUFAs are less clear. Our objective was to directly compare the n3-PUFAs, plant-based α-linolenic acid (ALA) in flaxseed oil, and marine-based eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in high-purity oils versus n6-PUFA containing linoleic acid (LA) for their effects on the adipose tissue and oral glucose tolerance of obese rats. Male fa/fa Zucker rats were assigned to faALA, faEPA, faDHA, and faLA groups and compared to baseline fa/fa rats (faBASE) and lean Zucker rats (lnLA). After 8 weeks, faEPA and faDHA had 11–14% lower body weight than faLA. The oral glucose tolerance and total body fat were unchanged, but faEPA had less mesenteric fat. faEPA and faDHA had fewer large adipocytes compared to faLA and faALA. EPA reduced macrophages in the adipose tissue of fa/fa rats compared to ALA and DHA, while faLA had the greatest macrophage infiltration. DHA decreased (~10-fold) T-cell infiltration compared to faBASE and faEPA, whereas faALA and faLA had an ~40% increase. The n3-PUFA diets attenuated tumour necrosis factor-α in adipose tissue compared to faBASE, while it was increased by LA in both genotypes. In conclusion, EPA and DHA target different aspects of inflammation in adipose tissue. Full article

The traditional PID controller in quadrotor UAVs has poor performance, a large overshoot, and a long adjustment time, which limit its stability and accuracy in practical applications. In order to solve this problem, an improved whale optimization fuzzy PID control strategy based on CRICLE chaos map initialization is proposed, and a detailed simulation analysis was carried out using MATLAB software (MATLAB R2022B). Firstly, to more realistically reflect quadrotor UAVs’ flight behavior, a dynamic simulation model was established, and the dynamics and kinematic characteristics of the aircraft were considered. Then, CRICLE chaotic mapping initialization was introduced to improve the global search ability of the whale optimization algorithm and to effectively initialize the parameters of the fuzzy PID controller. This improved initialization method helped to speed up the convergence process and improve the stability of the control system. In the simulation experiments, we compared the performance indicators of the improved CRICLE chaotic mapping initialization whale optimization fuzzy PID controller to the traditional PID and fuzzy PID controllers, including overshoot, adjustment time, etc. The results show that the proposed control strategy has better performance than the traditional PID and fuzzy PID controllers, significantly reduces overshoot, and achieves a significant improvement in adjustment time. Therefore, the improved CRICLE chaotic mapping initialization whale optimization fuzzy PID control strategy proposed in this study provides an effective solution for improving the performance of the quadrotor control system and has practical application potential. Full article

Background: Indoleamine 2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO) are the two principals enzymes involved in the catabolization of tryptophan (Trp) into kynurenine (Kyn). Despite their well-established role in the immune escape, their involvement in angiogenesis remains uncertain. We aimed to characterize TDO and IDO1 in human umbilical venular endothelial cells (HUVECs) and human endothelial colony-forming cells (ECFCs). Methods: qRT-PCR and immunofluorescence were used for TDO and IDO1 expression while their activity was measured using ELISA assays. Cell proliferation was examined via MTT tests and in in vitro angiogenesis by capillary morphogenesis. Results: HUVECs and ECFCs expressed TDO and IDO1. Treatment with the selective TDO inhibitor 680C91 significantly impaired HUVEC proliferation and 3D-tube formation in response to VEGF-A, while IDO1 inhibition showed no effect. VEGF-induced mTor phosphorylation and Kyn production were hindered by 680C91. ECFC morphogenesis was also inhibited by 680C91. Co-culturing HUVECs with A375 induced TDO up-regulation in both cell types, whose inhibition reduced MMP9 activity and prevented c-Myc and E2f1 upregulation. Conclusions: HUVECs and ECFCs express the key enzymes of the kynurenine pathway. Significantly, TDO emerges as a pivotal player in in vitro proliferation and capillary morphogenesis, suggesting a potential pathophysiological role in angiogenesis beyond its well-known immunomodulatory effects. Full article

Background and Objectives: Neonates born from thawed embryo transfers tend to have a significantly higher birthweight compared to those from fresh embryo transfers. The aim of this study was to compare the crown-rump length (CRL) between thawed and fresh embryos to investigate the potential causes of different growth patterns between them. Materials and Methods: This was a retrospective study (July 2010–December 2023) conducted at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. In total, 3082 assisted reproductive technology (ART) pregnancies (4044 embryos) underwent a routine scan at 11⁺⁰–13⁺⁶ gestational weeks and were included in the study. Maternal age, the type of embryo transfer (thawed vs. fresh, donor vs. their own oocytes), CRL, twin and singleton gestations were analyzed. Results: The mean maternal age in thawed was significantly higher than in fresh embryos (39.8 vs. 35.8 years, p-value < 0.001). The mean CRL z-score was significantly higher in thawed compared to fresh embryo transfers (0.309 vs. 0.199, p-value < 0.001). A subgroup analysis on singleton gestations showed that the mean CRL z-score was higher in thawed blastocysts compared to fresh (0.327 vs. 0.215, p-value < 0.001). Accordingly, an analysis on twins revealed that the mean CRL z-score was higher in thawed blastocysts (0.285 vs. 0.184, p-value: 0.015) and in oocytes’ recipients compared to own oocytes’ cases (0.431 vs. 0.191, p-value: 0.002). Conclusions: The difference in CRL measurements between thawed and fresh embryos may be a first indication of the subsequent difference in sonographically estimated fetal weight and birthweight. This finding highlights the need for additional research into the underlying causes, including maternal factors and the culture media used. Full article

Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facilitative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 located on the maternal-facing apical trophoblast membrane and SLC2A1 located on the fetal-facing basolateral trophoblast membrane. We have previously reported that impaired placental SLC2A3 glucose transport resulted in smaller, hypoglycemic fetuses with reduced umbilical artery insulin and glucagon concentrations, in addition to diminished pancreas weights. These findings led us to subject RNA derived from SLC2A3-RNAi (RNA interference) and NTS-RNAi (non-targeting sequence) fetal pancreases to qPCR followed by transcriptomic analysis. We identified a total of 771 differentially expressed genes (DEGs). Upregulated pathways were associated with fat digestion and absorption, particularly fatty acid transport, lipid metabolism, and cholesterol biosynthesis, suggesting a potential switch in energetic substrates due to hypoglycemia. Pathways related to molecular transport and cell signaling in addition to pathways influencing growth and metabolism of the developing pancreas were also impacted. A few genes directly related to gluconeogenesis were also differentially expressed. Our results suggest that fetal hypoglycemia during the first half of gestation impacts fetal pancreas development and function that is not limited to β cell activity. Full article

Morphological changes in canals are greatly influenced by sediment load dynamics, whose estimation is a challenging task because of the non-linear behavior of the sediment concentration variables. This study aims to compare different techniques including Artificial Intelligence Models (AIM) and empirical equations for estimating sediment load in Upper Chenab Canal based on 10 years of sediment data from 2012 to 2022. The methodology involves utilization of a newly developed empirical equation, the Ackers and White formula and AIM including 20 neural networks with 10 training functions for both Double and Triple Layers, two Artificial Neuro-Fuzzy Inference System (ANFIS), Particle Swarm Optimization, and Ensemble Learning Random Forest models. Sensitivity analysis of sediment concentration variables has also been performed using various scenarios of input combinations in AIM. A state-of-the-art optimization technique has been used to identify the parameters of the empirical equation, and its performance is tested against AIM and the Ackers and White equation. To compare the performance of various models, four types of errors—correlation coefficient (R), T-Test, Analysis of Variance (ANOVA), and Taylor’s Diagram—have been used. The results of the study show successful application of Artificial Intelligence (AI) and empirical equations to capture the non-linear behavior of sediment concentration variables and indicate that, among all models, the ANFIS outperformed in simulating the total sediment load with a high R-value of 0.958. The performance of various models in simulating sediment concentration was assessed, with notable accuracy achieved by models AIM11 and AIM21. Moreover, the newly developed equation performed better (R = 0.92) compared to the Ackers and White formula (R = 0.88). In conclusion, the study provides valuable insights into sediment concentration dynamics in canals, highlighting the effectiveness of AI models and optimization techniques. It is suggested to incorporate other AI techniques and use multiple canals data in modeling for the future. Full article

The mechanism of ethylene (ET)–regulated salinity stress response remains largely unexplained, especially for semi-halophytes and halophytes. Here, we present the results of the multifaceted analysis of the model semi-halophyte Mesembryanthemum crystallinum L. (common ice plant) ET biosynthesis pathway key components’ response to prolonged (14 days) salinity stress. Transcriptomic analysis revealed that the expression of 3280 ice plant genes was altered during 14-day long salinity (0.4 M NaCl) stress. A thorough analysis of differentially expressed genes (DEGs) showed that the expression of genes involved in ET biosynthesis and perception (ET receptors), the abscisic acid (ABA) catabolic process, and photosynthetic apparatus was significantly modified with prolonged stressor presence. To some point this result was supported with the expression analysis of the transcript amount (qPCR) of key ET biosynthesis pathway genes, namely ACS6 (1-aminocyclopropane-1-carboxylate synthase) and ACO1 (1-aminocyclopropane-1-carboxylate oxidase) orthologs. However, the pronounced circadian rhythm observed in the expression of both genes in unaffected (control) plants was distorted and an evident downregulation of both orthologs’ was induced with prolonged salinity stress. The UPLC-MS analysis of the ET biosynthesis pathway rate-limiting semi-product, namely of 1-aminocyclopropane-1-carboxylic acid (ACC) content, confirmed the results assessed with molecular tools. The circadian rhythm of the ACC production of NaCl-treated semi-halophytes remained largely unaffected by the prolonged salinity stress episode. We speculate that the obtained results represent an image of the steady state established over the past 14 days, while during the first hours of the salinity stress response, the view could be completely different. Full article

Access to rural primary healthcare services has been broadly studied in the past few decades. However, most earlier studies that focused on examining access to rural healthcare services have conventionally treated spatial and non-spatial access as separate factors. This research aims to measure access to primary healthcare services in rural areas with the consideration of both spatial and non-spatial dimensions. The methodology of study is threefold. First, the Gaussian two-step floating catchment area (G-2SFCA) method was adopted to measure spatial access to primary healthcare services. Then, a questionnaire survey was conducted to investigate non-spatial access factors, including demographic condition, patient’s household income, healthcare insurance, education level, and patient satisfaction level with the services. After that, a comprehensive evaluation index system was employed to integrate both spatial and non-spatial access. The empirical study showed a remarkable disparity in spatial access to primary healthcare services. In total, 78 villages with 185,137 local people had a “low” or “very low” level of spatial access to both clinics and hospitals. For the non-spatial dimension, the results depicted that Songzi had significant inequalities in socioeconomic status (e.g., income, education) and patient satisfaction level for medical service. When integrating both spatial and non-spatial factors, the disadvantaged areas were mainly located in the eastern and middle parts. In addition, this study found that comprehensively considering the spatial and non-spatial access had a significant impact on results in healthcare access. In conclusion, this study calls for policymakers to pay more attention to primary healthcare inequalities within rural areas. The spatial and non-spatial access should be considered comprehensively when the long-term rural medical support policy is designated. Full article

Psychostimulants alter cellular morphology and activate neuroimmune signaling in a number of brain regions, yet few prior studies have investigated their persistence beyond acute abstinence or following high levels of voluntary drug intake. In this study, we examined the effects of the repeated binge-like self-administration (96 h/week for 3 weeks) of methamphetamine (METH) and 21 days of abstinence in female and male rats on changes in cell density, morphology, and cytokine levels in two addiction-related brain regions—the prefrontal cortex (PFC) and dorsal striatum (DStr). We also examined the effects of similar patterns of intake of the cocaine-like synthetic cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV) or saline as a control. Robust levels of METH and MDPV intake (~500–1000 infusions per 96 h period) were observed in both sexes. We observed no changes in astrocyte or neuron density in either region, but decreases in dendritic spine densities were observed in PFC pyramidal and DStr medium spiny neurons. The microglial cell density was decreased in the PFC of METH self-administering animals, accompanied by evidence of microglial apoptosis. Changes in microglial morphology (e.g., decreased territorial volume and ramification and increased cell soma volume) were also observed, indicative of an inflammatory-like state. Multiplex analyses of PFC and DStr cytokine content revealed elevated levels of various interleukins and chemokines only in METH self-administering animals, with region- and sex-dependent effects. Our findings suggest that voluntary binge-like METH or MDPV intake induces similar cellular perturbations in the brain, but they are divergent neuroimmune responses that persist beyond the initial abstinence phase. Full article