Valuating the efficiency of social security and healthcare in OECD countries from a sustainable development.

Under the goal of sustainable development, coping with the increase in social security and healthcare expenses caused by population aging is becoming increasingly important, but it is rare in the literature to evaluate the impact of social security efficiency on healthcare efficiency. This research uses the dynamic SBM two-stage model to observe the efficiencies of social security and healthcare in OECD countries. There are two findings as follows. First, the higher social security efficiency is, the better is the healthcare efficiency of countries with lower per capita GDP. Second, higher social security efficiency of National Health Service (NHS) countries denote better healthcare efficiency. When the financial source of the social security system is taxation, then it is more likely to bring higher efficiency to healthcare.

Injectable hemostatic hydrogel adhesive with antioxidant, antibacterial and procoagulant properties for hemorrhage wound management.

In emergencies, uncontrolled severe bleeding can result in undesired complications and even death of the injured. Designing advanced hemostatic agents is a potential solution for emergency hemostasis, yet it remains challenging to realize the persistent adhesion in a wet wound environment. In this study, based on dynamic reversible Schiff base bond and photo-initiated double-bond polymerization, a novel injectable hemostatic hydrogel (L-COC) consisting of methacrylated carboxymethyl chitosan (CMCSMA), oxidized konjac glucomannan (OKGM) and (+)-catechin hydrate (CH) was synthesized for emergency hemostasis. To our delight, the incorporated CH imparted enhanced blood procoagulantion to the L-COC hydrogel by intensifying the hydrogel-red blood cell interactions. As a result, the hemostatic effect of the engineered L-COC hydrogel was significantly superior to that of fluid gelatin SurgifloTM for liver bleeding wounds in rats (Blood loss: 0.62 ± 0.11 g (L-COC), 0.90 ± 0.08 g (SurgifloTM); hemostasis time: 69.0 ± 2.9 s (L-COC), 84.0 ± 2.2 s (SurgifloTM)). With the favorable antioxidant and antibacterial activities, as well as multifunctional properties, the bio-adhesive L-COC hydrogel and the underlying design principles may facilitate further development of practical hemostatic hydrogels.

STAT3-induced lncRNA GNAS-AS1 accelerates keloid formation by mediating the miR-196a-5p/CXCL12/STAT3 axis in a feedback loop.

Keloids are pathological scar tissue resulting from skin trauma or spontaneous formation, often accompanied by itching and pain. Although GNAS antisense RNA 1 (GNAS-AS1) shows abnormal upregulation in keloids, the underlying molecular mechanism is unclear. The levels of genes and proteins in clinical tissues from patients with keloids and human keloid fibroblasts (HKFs) were measured using quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay. The features of HKFs, including proliferation and migration, were evaluated using cell counting kit 8 and a wound healing assay. The colocalization of GNAS-AS1 and miR-196a-5p in HKFs was measured using fluorescence in situ hybridization. The relationships among GNAS-AS1, miR-196a-5p and C-X-C motif chemokine ligand 12 (CXCL12) in samples from patients with keloids were analysed by Pearson correlation analysis. Gene interactions were validated by chromatin immunoprecipitation and luciferase reporter assays. GNAS-AS1 and CXCL12 expression were upregulated and miR-196a-5p expression was downregulated in clinical tissues from patients with keloids. GNAS-AS1 knockdown inhibited proliferation, migration, and extracellular matrix (ECM) accumulation of HKFs, all of which were reversed by miR-196a-5p downregulation. Signal transducer and activator of transcription 3 (STAT3) induced GNAS-AS1 transcription through GNAS-AS1 promoter interaction, and niclosamide, a STAT3 inhibitor, decreased GNAS-AS1 expression. GNAS-AS1 positively regulated CXCL12 by sponging miR-196-5p. Furthermore, CXCL12 knockdown restrained STAT3 phosphorylation in HKFs. Our findings revealed a feedback loop of STAT3/GNAS-AS1/miR-196a-5p/CXCL12/STAT3 that promoted HKF proliferation, migration and ECM accumulation and affected keloid progression.

Determinants of macaques' space use: A test for the ecological constraints model using GPS collars.

As a central topic in Behavioral Ecology, animal space use involves dynamic responses to social and ecological factors. We collared 22 rhesus macaques (Macaca mulatta) from six groups on Neilingding Island, China, and collected 80,625 hourly fixes over a year. Using this high-resolution location data set, we quantified the macaques' space use at the individual level and tested the ecological constraints model while considering various environmental and human interfering factors. As predicted by the ecological constraints model, macaques in larger groups had longer daily path lengths (DPLs) and larger home ranges. We found an inverted U-shape relationship between mean daily temperatures and DPLs, indicating that macaques traveled farther on mild temperature days, while they decreased DPLs when temperatures were too high or too low. Anthropogenic food subsidies were positively correlated to DPLs, while the effect of rainfall was negative. Macaques decreased their DPLs and core areas when more flowers and less leaves were available, suggesting that macaques shifted their space use patterns to adapt to the seasonal differences in food resources. By applying GPS collars on a large number of individuals living on a small island, we gained valuable insights into within-group exploitation competition in wild rhesus macaques.

Social risk to infant: The role of kin for maternal visual monitoring in Tibetan macaques.

Maternal monitoring of conspecifics is a crucial anti-predator strategy that also protects infants against risks within the social group. This study examines how maternal characteristics, infant characteristics, mother-infant distance, and the social environment affect maternal monitoring behaviors in free-ranging Tibetan macaques (Macaca thibetana). We observed 12 females with infants and analyzed their visual monitoring patterns. Our findings indicate that maternal rank significantly influences the time allocated to maternal visual monitoring, higher-ranking mothers spending less time than lower-ranking mothers. Maternal experience also played a role in monitoring strategies. Differences in monitoring strategies were observed based on maternal experience: first-time mothers (primiparity) engaged in longer but less frequent monitoring sessions compared to experienced mothers (multiparity). The time and frequency of maternal monitoring decreased as infants aged, and mothers with male infants showed higher levels of monitoring than those with female infants. The distance between mother and infant also affected visual monitoring behavior, with mothers increasing their monitoring levels when infants were nearby (1-5 m), rather than within reach (0-1 m) or beyond nearby (>5 m). Additionally, the presence of kin and non-kin influenced monitoring: as the number of nearby kin increased, monitoring levels decreased, while the presence of more non-kin males led to an increase in monitoring time, and higher-ranking non-kin neighbors increased the frequency of monitoring. These results suggest that Tibetan macaque mothers can adapt their visual monitoring to the social risks faced by their infants, adjusting their strategies to their status and the needs of their offspring.

Policy choices for China to reduce carbon emissions in coping with extreme weather: Applying a dynamic two-stage undesirable non-radial directional distance function.

China is the world's largest carbon emitter and also one of many countries most affected by extreme weather. Although its government has set carbon reduction targets, the public has not established a connection between carbon reduction and coping with extreme weather. This study aims to help establish the above connection and applies a dynamic two-stage undesirable non-radial directional distance function to evaluate energy performance in the first stage while establishing CO2 emissions as a link to evaluate coping with extreme weather performance in the second stage. From empirical results, the average efficiency of 30 provinces in China in coping with extreme weather from 2011 to 2020 is only 0.484, or far lower than the energy efficiency value of 0.709. Based on the differences in performance between the two stages and the changing trends in the room for improvement of CO2 emissions, this study proposes policy options to promote the participation of the entire society in the emission reduction process.

Exploring the environmental risks and seasonal variations of potentially toxic elements (PTEs) in fine road dust in resource-based cities based on Monte Carlo simulation, geo-detector and random forest model.

The environmental pollution caused by mineral exploitation and energy consumption poses a serious threat to ecological security and human health, particularly in resource-based cities. To address this issue, a comprehensive investigation was conducted on potentially toxic elements (PTEs) in road dust from different seasons to assess the environmental risks and influencing factors faced by Datong City. Multivariate statistical analysis and absolute principal component score were employed for source identification and quantitative allocation. The geo-accumulation index and improved Nemerow index were utilized to evaluate the pollution levels of PTEs. Monte Carlo simulation was employed to assess the ecological-health risks associated with PTEs content and source orientation. Furthermore, geo-detector and random forest analysis were conducted to examine the key environmental variables and driving factors contributing to the spatiotemporal variation in PTEs content. In all PTEs, Cd, Hg, and Zn exhibited higher levels of content, with an average content/background value of 3.65 to 4.91, 2.53 to 3.34, and 2.15 to 2.89 times, respectively. Seasonal disparities were evident in PTEs contents, with average levels generally showing a pattern of spring (winter) > summer (autumn). PTEs in fine road dust (FRD) were primarily influenced by traffic, natural factors, coal-related industrial activities, and metallurgical activities, contributing 14.9-33.9 %, 41.4-47.5 %, 4.4-8.3 %, and 14.2-29.4 % to the total contents, respectively. The overall pollution and ecological risk of PTEs were categorized as moderate and high, respectively, with the winter season exhibiting the most severe conditions, primarily driven by Hg emissions from coal-related industries. Non-carcinogenic risk of PTEs for adults was within the safe limit, yet children still faced a probability of 4.1 %-16.4 % of unacceptable risks, particularly in summer. Carcinogenic risks were evident across all demographics, with children at the highest risk, mainly due to Cr and smelting industrial sources. Geo-detector and random forest model indicated that spatial disparities in prioritized control elements (Cr and Hg) were primarily influenced by particulate matter (PM10) and anthropogenic activities (industrial and socio-economic factors); variations in particulate matter (PM10 and PM2.5) and meteorological factors (wind speed and precipitation) were the primary controllers of seasonal disparities of Cr and Hg.

Genomic variation, environmental adaptation, and feralization in ramie, an ancient fiber crop.

Feralization is an important evolutionary process, but the mechanisms behind it remain poorly understood. Here, we use the ancient fiber crop ramie (Boehmeria nivea (L.) Gaudich.) as a model to investigate genomic changes associated with both domestication and feralization. We first produced a chromosome-scale de novo genome assembly of feral ramie and investigated structural variations between feral and domesticated ramie genomes. Next, we gathered 915 accessions from 23 countries, comprising cultivars, major landraces, feral populations, and the wild progenitor. Based on whole-genome resequencing of these accessions, we constructed the most comprehensive ramie genomic variation map to date. Phylogenetic, demographic, and admixture signal detection analyses indicated that feral ramie is of exoferal or exo-endo origin, i.e., descended from hybridization between domesticated ramie and the wild progenitor or ancient landraces. Feral ramie has higher genetic diversity than wild or domesticated ramie, and genomic regions affected by natural selection during feralization differ from those under selection during domestication. Ecological analyses showed that feral and domesticated ramie have similar ecological niches that differ substantially from the niche of the wild progenitor, and three environmental variables are associated with habitat-specific adaptation in feral ramie. These findings advance our understanding of feralization, providing a scientific basis for the excavation of new crop germplasm resources and offering novel insights into the evolution of feralization in nature.

Feeding adaptation of François' langurs (Trachypithecus francoisi) to the fragmented limestone habitats in Southwest China.

Limestone forests are an unusual habitat for primates, especially fragmented limestone habitats. However, while some research has been conducted on François' langurs (Trachypithecus francois) in these habitats, there is still a need to improve the understanding of their behavioral adaptations to the fragmented limestone habitat. We collected data on the diet of François' langurs in a fragmented limestone habitat in Encheng National Nature Reserve, southwestern Guangxi, China using instantaneous scanning sampling, and their feeding adaptations to the fragmented forest were examined. The results indicated that a total of 101 species of plants were consumed by the langurs. They also fed on two non-plant components, including cliff minerals and at least one species of insect. The langurs ate a higher number of food species in Encheng when compared with the other geographic populations, and they maintained a high level of food diversity and ate more vines. Moreover, they were highly selective in their use of vegetation in their home range, and fewer plants provided a high-quality food source. During the season when food resources were scarce, the consumption of fruits and young leaves decreased as their availability decreased. This led to the use of other food components, such as mature leaves and seeds. The findings support that François' langurs adjust their feeding behavior to cope with seasonal and micro-variations in their dietary requirements and to adapt to their particular environment.

Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming.

Esophageal squamous cell carcinoma (ESCC), a highly aggressive subtype of esophageal cancer, is characterized by late-stage diagnosis and limited treatment options. Recent advancements in transcriptome sequencing technologies have illuminated the molecular intricacies of ESCC tumors, revealing metabolic reprogramming as a prominent feature. Specifically, the Warburg effect, marked by enhanced glycolysis, has emerged as a hallmark of cancer, offering potential therapeutic targets. In this study, we comprehensively analyzed bulk RNA-seq data from ESCC patients, uncovering elevated SRA1 expression in ESCC development and a poorer prognosis. Silencing of SRA1 led to a modulation of glycolysis-related products and a shift in PKM2 expression. Our findings shed light on the intricate molecular landscape of ESCC, highlighting SRA1 as a potential therapeutic target to disrupt glycolysis-dependent energy production. This metabolic reprogramming may hold the key to innovative treatment strategies for ESCC, ultimately improving patient outcomes.

Recent advances in the application of clay-containing hydrogels for hemostasis and wound healing.

INTRODUCTION: Immediate control of bleeding and anti-infection play important roles in wound management. Multiple organ dysfunction syndrome and death may occur if persistent bleeding, hemodynamic instability, and hypoxemia are not addressed. The combination of clay and hydrogel provides a new outlet for wound hemostasis. In this review, the current research progress of hydrogel/clay composite hemostatic agents was reviewed. AREAS COVERED: This paper summarizes the characteristics of several kinds of clay including kaolinite, montmorillonite, laponite, sepiolite, and palygorskite. The advantages and disadvantages of its application in hemostasis were also summarized. Future directions for the application of hydrogel/clay composite hemostatic agents are presented. EXPERT OPINION: Clay can activate the endogenous hemostatic pathway by increasing blood cell concentration and promoting plasma absorption to accelerate the hemostasis. Clay is antimicrobial due to the slow release of metal ions and has a rich surface charge with a high affinity for proteins and cells to promote tissue repair. Hydrogels have some properties such as good biocompatibility, strong adhesion, high stretchability, and good self-healing. Despite promising advances, hydrogel/clay composite hemostasis remains a limitation. Therefore, more evidence is needed to further elucidate the risk factors and therapeutic effects of hydrogel/clay in hemostasis and wound healing.

Precise large-fragment deletions in mammalian cells and mice generated by dCas9-controlled CRISPR/Cas3.

Currently, the Cas9 and Cas12a systems are widely used for genome editing, but their ability to precisely generate large chromosome fragment deletions is limited. Type I-E CRISPR mediates broad and unidirectional DNA degradation, but controlling the size of Cas3-mediated DNA deletions has proven elusive thus far. Here, we demonstrate that the endonuclease deactivation of Cas9 (dCas9) can precisely control Cas3-mediated large-fragment deletions in mammalian cells. In addition, we report the elimination of the Y chromosome and precise retention of the Sry gene in mice using CRISPR/Cas3 and dCas9-controlled CRISPR/Cas3, respectively. In conclusion, dCas9-controlled CRISPR/Cas3-mediated precise large-fragment deletion provides an approach for establishing animal models by chromosome elimination. This method also holds promise as a potential therapeutic strategy for treating fragment mutations or human aneuploidy diseases that involve additional chromosomes.

Programmable RNA 5-methylcytosine (m5C) modification of cellular RNAs by dCasRx conjugated methyltransferase and demethylase.

5-Methylcytosine (m5C), an abundant RNA modification, plays a crucial role in regulating RNA fate and gene expression. While recent progress has been made in understanding the biological roles of m5C, the inability to introduce m5C at specific sites within transcripts has hindered efforts to elucidate direct links between specific m5C and phenotypic outcomes. Here, we developed a CRISPR-Cas13d-based tool, named reengineered m5C modification system (termed 'RCMS'), for targeted m5C methylation and demethylation in specific transcripts. The RCMS editors consist of a nuclear-localized dCasRx conjugated to either a methyltransferase, NSUN2/NSUN6, or a demethylase, the catalytic domain of mouse Tet2 (ten-eleven translocation 2), enabling the manipulation of methylation events at precise m5C sites. We demonstrate that the RCMS editors can direct site-specific m5C incorporation and demethylation. Furthermore, we confirm their effectiveness in modulating m5C levels within transfer RNAs and their ability to induce changes in transcript abundance and cell proliferation through m5C-mediated mechanisms. These findings collectively establish RCMS editors as a focused epitranscriptome engineering tool, facilitating the identification of individual m5C alterations and their consequential effects.

Eco-evolutionary dynamics of gut phageome in wild gibbons (Hoolock tianxing) with seasonal diet variations.

It has been extensively studied that the gut microbiome provides animals flexibility to adapt to food variability. Yet, how gut phageome responds to diet variation of wild animals remains unexplored. Here, we analyze the eco-evolutionary dynamics of gut phageome in six wild gibbons (Hoolock tianxing) by collecting individually-resolved fresh fecal samples and parallel feeding behavior data for 15 consecutive months. Application of complementary viral and microbial metagenomics recovers 39,198 virulent and temperate phage genomes from the feces. Hierarchical cluster analyses show remarkable seasonal diet variations in gibbons. From high-fruit to high-leaf feeding period, the abundances of phage populations are seasonally fluctuated, especially driven by the increased abundance of virulent phages that kill the Lachnospiraceae hosts, and a decreased abundance of temperate phages that piggyback the Bacteroidaceae hosts. Functional profiling reveals an enrichment through horizontal gene transfers of toxin-antitoxin genes on temperate phage genomes in high-leaf season, potentially conferring benefits to their prokaryotic hosts. The phage-host ecological dynamics are driven by the coevolutionary processes which select for tail fiber and DNA primase genes on virulent and temperate phage genomes, respectively. Our results highlight complex phageome-microbiome interactions as a key feature of the gibbon gut microbial ecosystem responding to the seasonal diet.

Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease.

BACKGROUND: An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD. OBJECTIVE: To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications. METHODS: We performed secondary analyses of heart rate and blood pressure data from the Study in Parkinson's Disease of Exercise (SPARX). RESULTS: 128 individuals were enrolled into SPARX (63.7±9.3 years; 57.0% male, 0.4 years since diagnosis [median]). 103 individuals were not taking chronotropic medications, of which 90 had a normal maximal heart rate response to exercise testing (155.3±14.0 bpm; PDnon-chrono) and 13 showed evidence of chronotropic incompetence (121.3±11.3 bpm; PDchrono, p < 0.05). PDchrono had decreased VO2peak compared to PDnon-chrono (19.7±4.5 mL/kg/min and 24.3±5.8 mL/kg/min, respectively, p = 0.027). There was a positive correlation between peak heart rate during exercise and the change in systolic blood pressure from supine to standing (r = 0.365, p < 0.001). CONCLUSIONS: A subgroup of individuals with early PD not on dopaminergic medication had chronotropic incompetence and decreased VO2peak, which may be related to autonomic dysfunction. Evaluation of both heart rate responses to incremental exercise and orthostatic vital signs may serve as biomarkers of early autonomic impairment and guide treatment. Further studies should investigate whether cardiovascular autonomic dysfunction affects the ability to exercise and whether exercise training improves autonomic dysfunction.

Vocal fingerprinting reveals a substantially smaller global population of the Critically Endangered cao vit gibbon (Nomascus nasutus) than previously thought.

The cao vit gibbon (Nomascus nasutus) is one of the rarest primates on Earth and now only survives in a single forest patch of less than 5000 ha on the Vietnam-China border. Accurate monitoring of the last remaining population is critical to inform ongoing conservation interventions and track conservation success over time. However, traditional methods for monitoring gibbons, involving triangulation of groups from their songs, are inherently subjective and likely subject to considerable measurement errors. To overcome this, we aimed to use 'vocal fingerprinting' to distinguish the different singing males in the population. During the 2021 population survey, we complemented the traditional observations made by survey teams with a concurrent passive acoustic monitoring array. Counts of gibbon group sizes were also assisted with a UAV-mounted thermal camera. After identifying eight family groups in the acoustic data and incorporating long-term data, we estimate that the population was comprised of 74 individuals in 11 family groups, which is 38% smaller than previously thought. We have no evidence that the population has declined-indeed it appears to be growing, with new groups having formed in recent years-and the difference is instead due to double-counting of groups in previous surveys employing the triangulation method. Indeed, using spatially explicit capture-recapture modelling, we uncovered substantial measurement error in the bearings and distances from field teams. We also applied semi- and fully-automatic approaches to clustering the male calls into groups, finding no evidence that we had missed any males with the manual approach. Given the very small size of the population, conservation actions are now even more urgent, in particular habitat restoration to allow the population to expand. Our new population estimate now serves as a more robust basis for informing management actions and tracking conservation success over time.

Targeted mutagenesis in mice via an engineered AsCas12f1 system.

SpCas9 and AsCas12a are widely utilized as genome editing tools in human cells, but their applications are largely limited by their bulky size. Recently, AsCas12f1 protein, with a small size (422 amino acids), has been demonstrated to be capable of cleaving double-stranded DNA protospacer adjacent motif (PAM). However, low editing efficiency and large differences in activity against different genomic loci have been a limitation in its application. Here, we show that engineered AsCas12f1 sgRNA has significantly improved the editing efficiency in human cells and mouse embryos. Moreover, we successfully generated three stable mouse mutant disease models using the engineered CRISPR-AsCas12f1 system in this study. Collectively, our work uncovers the engineered AsCas12f1 system expands mini CRISPR toolbox, providing a remarkable promise for therapeutic applications.

Hybridized local and charge transfer dendrimers with near-unity exciton utilization for enabling high-efficiency solution-processed hyperfluorescent OLEDs.

Achieving both high emission efficiency and exciton utilization efficiency (ηS) in hot exciton materials is still a formidable task. Herein, a proof-of-concept design for improving ηS in hot exciton materials is proposed via elaborate regulation of singlet-triplet energy difference, leading to an additional thermally activated delayed fluorescence (TADF) process. Two novel dendrimers, named D-TTT-H and D-TTT-tBu, were prepared and characterized, in which diphenylamine derivatives were used as a donor moiety and tri(triazolo)triazine (TTT) as an acceptor fragment. Compounds D-TTT-H and D-TTT-tBu showed an intense green color with an emission efficiency of approximately 80% in solution. Impressively, both dendrimers simultaneously exhibited a hot exciton process and TADF characteristic in the solid state, as was demonstrated via theoretical calculation, transient photoluminescence, magneto-electroluminescence and transient electroluminescence measurements, thus achieving almost unity ηS. A solution processable organic light-emitting diode (OLED) employing the dendrimer as a dopant represents the best performance with the highest luminance of 15090 cd m-2 and a maximum external quantum efficiency (EQEmax) of 11.96%. Moreover, using D-TTT-H as a sensitizer, an EQEmax of 30.88%, 24.08% and 14.33% were achieved for green, orange and red solution-processed OLEDs, respectively. This research paves a new avenue to construct a fluorescent molecule with high ηS for efficient and stable OLEDs.

From emerging modalities to advanced applications of hydrogel piezoelectrics based on chitosan, gelatin and related biological macromolecules: A review.

The rapid development of functional materials and manufacturing technologies is fostering advances in piezoelectric materials (PEMs). PEMs can convert mechanical energy into electrical energy. Unlike traditional power sources, which need to be replaced and are inconvenient to carry, PEMs have extensive potential applications in smart wearable and implantable devices. However, the application of conventional PEMs is limited by their poor flexibility, low ductility, and susceptibility to fatigue failure. Incorporating hydrogels, which are flexible, stretchable, and self-healing, providing a way to overcome these limitations of PEMs. Hydrogel-based piezoelectric materials (H-PEMs) not only resolve the shortcomings of traditional PEMs but also provide biocompatibility and more promising application potential. This paper summarizes the working principle of H-PEMs. Recent advances in the use of H-PEMs as sensors and in vitro energy harvesting devices for smart wearable devices are described in detail, with emphasis on application scenarios in human body like fingers, wrists, ankles, and feet. In addition, the recent progress of H-PEMs in implantable medical devices, especially the potential applications in human body parts such as bones, skin, and heart, are also elaborated. In addition, challenges and potential improvements in H-PEMs are discussed.