Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.

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.

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.

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.

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.

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.

DLL1 orchestrates CD8+ T cells to induce long-term vascular normalization and tumor regression.

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.

Nanoscale Manipulation of Wrinkle-Pinned Vortices in Iron-Based Superconductors.

The controlled manipulation of Abrikosov vortices is essential for both fundamental science and logical applications. However, achieving nanoscale manipulation of vortices while simultaneously measuring the local density of states within them remains challenging. Here, we demonstrate the manipulation of Abrikosov vortices by moving the pinning center, namely one-dimensional wrinkles, on the terminal layers of Fe(Te,Se) and LiFeAs, by utilizing low-temperature scanning tunneling microscopy/spectroscopy (STM/S). The wrinkles trap the Abrikosov vortices induced by the external magnetic field. In some of the wrinkle-pinned vortices, robust zero-bias conductance peaks are observed. We tailor the wrinkle into short pieces and manipulate the wrinkles by using an STM tip. Strikingly, we demonstrate that the pinned vortices move together with these wrinkles even at high magnetic field up to 6 T. Our results provide a universal and effective routine for manipulating wrinkle-pinned vortices and simultaneously measuring the local density of states on the iron-based superconductor surfaces.

Genetic imprints of grafting in wild iron walnut populations in southwestern China.

BACKGROUND: Anthropogenic activities are causing unprecedented loss of genetic diversity in many species. However, the effects on genetic diversity from large-scale grafting onto wild plants of crop species are largely undetermined. Iron walnut (Juglans sigillata Dode) is a deciduous nut tree crop endemic to southwestern China with a long history of cultivation. Due to the rapid expansion of the walnut industry, many natural populations are now being replaced by cultivars grafted onto wild rootstocks. However, little is known about the potential genetic consequences of such action on natural populations. RESULTS: We sampled the scion and the rootstock from each of 149 grafted individuals within nine wild populations of J. sigillata from Yunnan Province which is the center of walnut diversity and cultivation in China, and examined their genetic diversity and population structure using 31 microsatellite loci. Scions had lower genetic diversity than rootstocks, and this pattern was repeated in seven of the nine examined populations. Among those seven populations, AMOVA and clustering analyses showed a clear genetic separation between all rootstocks and all scions. However, the two remaining populations, both from northern Yunnan, showed genetic similarity between scions and rootstocks, possibly indicating that wild populations here are derived from feralized local cultivars. Moreover, our data indicated probable crop-to-wild gene flow between scions and rootstocks, across all populations. CONCLUSIONS: Our results indicate that large-scale grafting has been causing genetic diversity erosion and genetic structure breakdown in the wild material of J. sigillata within Yunnan. To mitigate these effects, we caution against the overuse of grafting in wild populations of iron walnut and other crop species and recommend the preservation of natural genotypes through in situ  and ex situ conservation.

RIS-aided dynamically adaptive wide field-of-view receiver for visible light communication in industrial internet of things.

In the current visible light communication (VLC) system, a condenser lens is generally used in the front of receiver to achieve a higher data rate, making an extremely narrow field-of-view for the receiver. With the spread of Industrial Internet of Things (IIoT), the communication between mobile terminals is urgently required. A wide-range detecting method for VLC system in IIoT scenario is asked. In this paper, a novel self-adaptive wide-FoV receiver involving reconfigurable intelligent surfaces (RIS) is proposed. The effective detecting range of the receiver can be expanded by dynamically adjusting the incident light directions with the assistance of RIS. Based on the maximum arrived flux criterion, the mathematical model is established and the optimized RIS parameter tuning algorithm is presented. The feasibility and validity of the method are verified by simulation. The results show that the tolerable transceiver offset can be increased to 2∼4 times as the conventional receiver.

A novel AGK splicing mutation in a patient with Sengers syndrome and left ventricular non-compaction cardiomyopathy.

BACKGROUND: Sengers syndrome characterized by hypertrophic cardiomyopathy is an extremely rare genetic disorder. Sengers syndrome associated with left ventricular non-compaction (LVNC) has not been described. METHODS: Genetic testing was used to identify candidate AGK variants in the proband. The predicted molecular structures were constructed by protein modeling. Exon skipping caused by the identified splicing mutations was verified by in silico analyses and in vitro assays. The genotypic and phenotypic features of patients with AGK splicing mutations were extracted by a systematic review. RESULTS: The proband was characterized by Sengers syndrome and LVNC and caused by a novel compound heterozygous AGK splicing mutation. This compound mutation simultaneously perturbed the protein sequences and spatial conformation of the acylglycerol kinase protein. In silico and in vitro analyses demonstrated skipping of exons 7 and 8 and premature truncation as a result of exon 8 skipping. The systematic review indicated that patients with an AGK splicing mutation may have milder phenotypes of Sengers syndrome. CONCLUSIONS: The genotypic and phenotypic spectrums of Sengers syndrome have been expanded, which will provide essential information for genetic counseling. The molecular mechanism in AGK mutations can offer insights into the potential targets for treatment. IMPACT: First description of a child with Sengers syndrome and left ventricular non-compaction cardiomyopathy. A novel pathogenic compound heterozygous splicing mutation in AGK for Sengers syndrome was identified. The identified mutations led to exons skipping by in silico analyses and in vitro assays.

Effects of climate and land-cover change on the conservation status of gibbons.

Species shift their distribution in response to climate and land-cover change, which may result in a spatial mismatch between currently protected areas (PAs) and priority conservation areas (PCAs). We examined the effects of climate and land-cover change on potential range of gibbons and sought to identify PCAs that would conserve them effectively. We collected global gibbon occurrence points and modeled (ecological niche model) their current and potential 2050s ranges under climate-change and different land-cover-change scenarios. We examined change in range and PA coverage between the current and future ranges of each gibbon species. We applied spatial conservation prioritization to identify the top 30% PCAs for each species. We then determined how much of the PCAs are conserved in each country within the global range of gibbons. On average, 31% (SD 22) of each species' current range was covered in PAs. PA coverage of the current range of 9 species was <30%. Nine species lost on average 46% (SD 29) of their potential range due to climate change. Under climate-change with an optimistic land-cover-change scenario (B1), 12 species lost 39% (SD 28) of their range. In a pessimistic land-cover-change scenario (A2), 15 species lost 36% (SD 28) of their range. Five species lost significantly more range under the A2 scenario than the B1 scenario (p = 0.01, SD 0.01), suggesting that gibbons will benefit from effective management of land cover. PA coverage of future range was <30% for 11 species. On average, 32% (SD 25) of PCAs were covered by PAs. Indonesia contained more species and PCAs and thus has the greatest responsibility for gibbon conservation. Indonesia, India, and Myanmar need to expand their PAs to fulfill their responsibility to gibbon conservation. Our results provide a baseline for global gibbon conservation, particularly for countries lacking gibbon research capacity.

Las especies modifican su distribución como respuesta a los cambios en el clima y el uso de suelo, lo que puede derivar en una disparidad espacial entre las áreas protegidas (AP) y las áreas de conservación prioritarias (ACP). Analizamos los efectos del cambio en el clima y el uso de suelo sobre la distribución potencial de los gibones para identificar las ACP que lograrían su conservación exitosa. Recopilamos puntos globales de presencia de gibones y modelamos (modelo de nicho ecológico) su distribución actual y potencial para la década de 2050 bajo diferentes escenarios de cambio climático y de uso de suelo. Después exploramos los cambios en la distribución y la cobertura de las AP entre la distribución actual y a futuro de cada especie de gibón y aplicamos la priorización de la conservación espacial para identificar el mejor 30% de ACP para cada especie. Posteriormente determinamos la extensión conservada de las ACP en cada país dentro de la distribución mundial de gibones. En promedio, el 31% (DS 22) de la distribución actual de cada especie está cubierta en las AP. La distribución actual de nueve especies tiene una cobertura de áreas protegidas menor al 30%. Como promedio, nueve especies perdieron el 46% (DS 29) de su rango potencial debido al cambio climático. Bajo un escenario de cambio climático con un cambio de suelo optimista (B1), doce especies perdieron el 39% (DS 28) de su distribución. Con un escenario pesimista (A2), 15 especies perdieron el 36% (DS 28) de su distribución. Cinco especies perdieron considerablemente más distribución bajo el escenario A2 en relación con el B1 (p = 0.01, SD 0.01), lo que sugiere que los gibones se beneficiarán con la gestión efectiva de la cobertura terrestre. La cobertura dentro de las AP de la distribución futura fue < 30% para once especies. En promedio, el 32% (DS 25) de las ACP estuvo cubierto dentro de las AP. Indonesia albergó más especies y más ACP, por lo que tuvo la mayor responsabilidad en la conservación de los gibones. Indonesia, India y Myanmar necesitan expandir sus AP para cumplir con su responsabilidad en la conservación de los gibones. Nuestros resultados proporcionan una línea base para la conservación mundial de los gibones, particularmente para aquellos países que carecen de los recursos para investigarlos.

Dexmedetomidine provides type-specific tumour suppression without tumour-enhancing effects in syngeneic murine models.

BACKGROUND: Dexmedetomidine is a widely used anaesthetic adjuvant for cancer resection surgeries. However, recent reports suggest that it may promote tumour growth or metastasis, so it is essential to clarify its tumour-related effects. METHODS: Seven syngeneic murine tumour models were used to assess the impact of dexmedetomidine on primary tumour growth, spontaneous tumour metastasis, and surgical resection-associated metastasis. Cancer cell proliferation and apoptosis experiments, terminal deoxynucleotidyl transferase dUTP nick-end labelling assays, immune cell analysis, specific T-cell depletion experiments, and gene transcription analysis were conducted to identify the underlying mechanisms. RESULTS: Dexmedetomidine did not affect growth of EO771 or 4T1 breast tumours, LAP0297 or LLC lung tumours, MCA205 fibrosarcoma, or their spontaneous lung metastases. It did not promote lung metastasis after breast cancer resection. Dexmedetomidine significantly suppressed MCA38 and CT26 colorectal tumour growth (P<0.01) and promoted apoptosis in MCA38 tumour tissues (P<0.05) without affecting proliferation and apoptosis of MCA38 tumour cells in vitro, suggesting indirect anti-tumour effects. Dexmedetomidine increased the proportions of intratumour CD4+ T (P<0.01), CD8+ T (P<0.001), and natural killer cells (P<0.01), and it upregulated transcription of the cytotoxicity-related genes Infg, Tnfa, and Cxcl9 (P<0.05) in MCA38 tumours. Either CD8+ or CD4+ T-cell depletion reversed the anti-tumour effects of dexmedetomidine on MCA38 tumours (P<0.05). CONCLUSIONS: Dexmedetomidine conferred colorectal tumour-type specific suppression by modulation of tumour CD4+ and CD8+ T cells without tumour-enhancing effects.

Childhood-Onset Refractory Hypertension Results from Neurofibromatosis Type 1 Caused by a Splicing NF1 Mutation.

INTRODUCTION: Neurofibromatosis type 1 (NF-1) is caused by mutations in the NF1 gene that encodes neurofibromin, a negative regulator of RAS proto-oncogene. Approximately one-third of the reported pathogenic mutations in NF1 are splicing mutations, but most consequences are unclear. The objective of this study was to identify the pathogenicity of splicing mutation in a Chinese family with NF-1 and determine the effects of the pre-mRNA splicing mutation by in vitro functional analysis. METHODS: Next-generation sequencing was used to screen candidate mutations. We performed a minigene splicing assay to determine the effect of the splicing mutation on NF1 expression, and three-dimensional structure models of neurofibromin were generated using SWISS-MODEL and PROCHECK methods, respectively. RESULTS: A pathogenic splicing mutation c.479+1G>C in NF1 was found in the proband characterized by childhood-onset refractory hypertension. In vitro analysis demonstrated that c.479+1G>C mutation caused the skipping of exon 4, leading to a glutamine-to-valine substitution at position 97 in neurofibromin and an open reading frame shift terminating at codon 108. Protein modeling showed that several major domains were missing in the truncated neurofibromin protein. CONCLUSION: The splicing mutation c.479+1G>C identified in a Chinese patient with NF-1 and childhood-onset refractory hypertension caused the skipping of exon 4 and a truncated protein. Our findings offer new evidence for the molecular diagnosis of NF-1.

Gut microbiota of skywalker hoolock gibbons (Hoolock tianxing) from different habitats and in captivity: Implications for gibbon health.

The gut microbiota plays an integral role in the metabolism and immunity of animal hosts, and provides insights into the health and habitat assessment of threatened animals. The skywalker hoolock gibbon (Hoolock tianxing) is a newly described gibbon species, and is considered an endangered species. Here, we used 16S rRNA amplicon sequencing to describe the fecal bacterial community of skywalker hoolock gibbons from different habitats and in captivity. Fecal samples (n = 5) from two captive gibbons were compared with wild populations (N = 6 gibbons, n = 33 samples). At the phylum level, Spirochetes, Proteobacteria, Firmicutes, Bacteroidetes dominated in captive gibbons, while Firmicutes, Bacteroidetes, and Tenericutes dominated in wild gibbons. At the genus level, captive gibbons were dominated by Treponema-2, followed by Succinivibrio and Cerasicoccus, while wild gibbons were dominated by Anaeroplasma, Prevotellaceae UCG-001, and Erysipelotrichaceae UCG-004. Captive rearing was significantly associated with lower taxonomic alpha-diversity, and different relative abundance of some dominant bacteria compared to wild gibbons. Predicted Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that captive gibbons have significantly lower total pathway diversity and higher relative abundance of bacterial functions involved in "drug resistance: antimicrobial" and "carbohydrate metabolism" than wild gibbons. This study reveals the potential influence of captivity and habitat on the gut bacterial community of gibbons and provides a basis for guiding the conservation management of captive populations.

TCF-Trans: Temporal Context Fusion Transformer for Anomaly Detection in Time Series.

Anomaly detection tasks involving time-series signal processing have been important research topics for decades. In many real-world anomaly detection applications, no specific distributions fit the data, and the characteristics of anomalies are different. Under these circumstances, the detection algorithm requires excellent learning ability of the data features. Transformers, which apply the self-attention mechanism, have shown outstanding performances in modelling long-range dependencies. Although Transformer based models have good prediction performance, they may be influenced by noise and ignore some unusual details, which are significant for anomaly detection. In this paper, a novel temporal context fusion framework: Temporal Context Fusion Transformer (TCF-Trans), is proposed for anomaly detection tasks with applications to time series. The original feature transmitting structure in the decoder of Informer is replaced with the proposed feature fusion decoder to fully utilise the features extracted from shallow and deep decoder layers. This strategy prevents the decoder from missing unusual anomaly details while maintaining robustness from noises inside the data. Besides, we propose the temporal context fusion module to adaptively fuse the generated auxiliary predictions. Extensive experiments on public and collected transportation datasets validate that the proposed framework is effective for anomaly detection in time series. Additionally, the ablation study and a series of parameter sensitivity experiments show that the proposed method maintains high performance under various experimental settings.

A Wide Energy Range and 4π-View Gamma Camera with Interspaced Position-Sensitive Scintillator Array and Embedded Heavy Metal Bars.

(1) Background: Gamma cameras have wide applications in industry, including nuclear power plant monitoring, emergency response, and homeland security. The desirable properties of a gamma camera include small weight, good resolution, large field of view (FOV), and wide imageable source energy range. Compton cameras can have a 4π FOV but have limited sensitivity at low energy. Coded-aperture gamma cameras are operatable at a wide photon energy range but typically have a limited FOV and increased weight due to the thick heavy metal collimators and shielding. In our lab, we previously proposed a 4π-view gamma imaging approach with a 3D position-sensitive detector, with which each detector element acts as the collimator for other detector elements. We presented promising imaging performance for 99mTc, 18F, and 137Cs sources. However, the imaging performance for middle- and high-energy sources requires further improvement. (2) Methods: In this study, we present a new gamma camera design to achieve satisfactory imaging performance in a wide gamma energy range. The proposed gamma camera consists of interspaced bar-shaped GAGG (Ce) crystals and tungsten absorbers. The metal bars enhance collimation for high-energy gamma photons without sacrificing the FOV. We assembled a gamma camera prototype and conducted experiments to evaluate the gamma camera's performance for imaging 57Co, 137Cs, and 60Co point sources. (3) Results: Results show that the proposed gamma camera achieves a positioning accuracy of <3° for all gamma energies. It can clearly resolve two 137Cs point sources with 10° separation, two 57Co and two 60Co point sources with 20° separation, as well as a 2 × 3 137Cs point-source array with 20° separation. (4) Conclusions: We conclude that the proposed gamma camera design has comprehensive merits, including portability, 4π-view FOV, and good angular resolution across a wide energy range. The presented approach has promising potential in nuclear security applications.

Source-specific probabilistic risk evaluation of potentially toxic metal(loid)s in fine dust of college campuses based on positive matrix factorization and Monte Carlo simulation.

Contamination, hazard level and source of 10 widely concerned potentially toxic metal(loid)s (PTMs) Co, As, Pb, Cr, Cu, Zn, Ni, Mn, Ba, and V in fine dust with particle size below 63 µm (FD63) were investigated to assess the environmental quality of college campuses and influencing factors. PTMs sources were qualitatively analyzed using statistical methods and quantitatively apportioned using positive matrix factorization. Probabilistic contamination degrees of PTMs were evaluated using enrichment factor and Nemerow integrated enrichment factor. Eco-health risk levels of content-oriented and source-oriented for PTMs were evaluated using Monte Carlo simulation. Mean levels of Zn (643.8 mg kg-1), Pb (146.0 mg kg-1), Cr (145.9 mg kg-1), Cu (95.5 mg kg-1), and Ba (804.2 mg kg-1) in FD63 were significantly larger than soil background values. The possible sources of the concerned PTMs in FD63 were traffic non-exhaust emissions, natural source, mixed source (auto repair waste, paints and pigments) and traffic exhaust emissions, which accounted for 45.7%, 25.4%, 14.5% and 14.4% of total PTMs contents, respectively. Comprehensive contamination levels of PTMs were very high, mainly caused by Zn pollution and non-exhaust emissions. Combined ecological risk levels of PTMs were low and moderate, chiefly caused by Pb and traffic exhaust emissions. The non-cancer risks of the PTMs in FD63 to college students fell within safety level, while the carcinogenic PTMs in FD63 had a certain cancer risks to college students. The results of source-specific health risk assessment indicated that Cr and As were the priority PTMs, and the mixed source was the priority pollution source of PTMs in FD63 from college campuses, which should be paid attention to by the local government.

Preparation of Biocompatible Manganese Selenium-Based Nanoparticles with Antioxidant and Catalytic Functions.

The specificity of the tumor microenvironment (TME) severely limits the effectiveness of tumor treatment. In this study, we prepared a composite nanoparticle of manganese dioxide and selenite by a one-step redox method, and their stability under physiological conditions was improved with a bovine serum protein modification to obtain MnO2/Se-BSA nanoparticles (SMB NPs). In the SMB NPs, manganese dioxide and selenite endowed the SMB NPs with acid-responsive and catalytic, and antioxidant properties, respectively. The weak acid response, catalytic activity, and antioxidant properties of composite nanoparticles were verified experimentally. Moreover, in an in vitro hemolysis assay, different concentrations of nanoparticles were incubated with mouse erythrocytes, and the hemolysis ratio was less than 5%. In the cell safety assay, the cell survival ratio was as high as 95.97% after the co-culture with L929 cells at different concentrations for 24 h. In addition, the good biosafety of composite nanoparticles was verified at the animal level. Thus, this study helps to design high-performance and comprehensive therapeutic reagents that are responsive to the hypoxia, weak acidity, hydrogen peroxide overexpression nature of TME and overcome the limitations of TME.

Chitosan-Based Hemostatic Hydrogels: The Concept, Mechanism, Application, and Prospects.

The design of new hemostatic materials to mitigate uncontrolled bleeding in emergencies is challenging. Chitosan-based hemostatic hydrogels have frequently been used for hemostasis due to their unique biocompatibility, tunable mechanical properties, injectability, and ease of handling. Moreover, chitosan (CS) absorbs red blood cells and activates platelets to promote hemostasis. Benefiting from these desired properties, the hemostatic application of CS hydrogels is attracting ever-increasing research attention. This paper reviews the recent research progress of CS-based hemostatic hydrogels and their advantageous characteristics compared to traditional hemostatic materials. The effects of the hemostatic mechanism, effects of deacetylation degree, relative molecular mass, and chemical modification on the hemostatic performance of CS hydrogels are summarized. Meanwhile, some typical applications of CS hydrogels are introduced to provide references for the preparation of efficient hemostatic hydrogels. Finally, the future perspectives of CS-based hemostatic hydrogels are presented.