STellaris: a web server for accurate spatial mapping of single cells based on spatial transcriptomics data.

Single-cell RNA sequencing (scRNA-seq) provides insights into gene expression heterogeneities in diverse cell types underlying homeostasis, development and pathological states. However, the loss of spatial information hinders its applications in deciphering spatially related features, such as cell-cell interactions in a spatial context. Here, we present STellaris (https://spatial.rhesusbase.com), a web server aimed to rapidly assign spatial information to scRNA-seq data based on their transcriptomic similarity with public spatial transcriptomics (ST) data. STellaris is founded on 101 manually curated ST datasets comprising 823 sections across different organs, developmental stages and pathological states from humans and mice. STellaris accepts raw count matrix and cell type annotation of scRNA-seq data as the input, and maps single cells to spatial locations in the tissue architecture of properly matched ST section. Spatially resolved information for intercellular communications, such as spatial distance and ligand-receptor interactions (LRIs), are further characterized between annotated cell types. Moreover, we also expanded the application of STellaris in spatial annotation of multiple regulatory levels with single-cell multiomics data, using the transcriptome as a bridge. STellaris was applied to several case studies to showcase its utility of adding value to the ever-growing scRNA-seq data from a spatial perspective.

Interferon-α induces differentiation of cancer stem cells and immunosuppression in hepatocellular carcinoma by upregulating CXCL8 secretion.

Interferon-alpha (IFN-α) is widely used in the clinical treatment of patients with chronic hepatitis B and hepatocellular carcinoma (HCC). However, high levels of CXCL8 are associated with resistance to IFN-α therapy and poorer prognosis in advanced cancers. In this study, we investigated whether IFN-α could directly induce the production of CXCL8 in HCC cells and whether CXCL8 could antagonize the antitumor activity of IFN-α. We found that IFN-α not only upregulated the expression of the inducible genes CXCL9, CXCL10, CXCL11 and PD-L1, but also significantly stimulated CXCL8 secretion in HCC cells. Mechanically, IFN-α induces CXCL8 expression by activating the AKT and JNK pathways. In addition, our results demonstrate that IFN-α exposure significantly increases the differentiation of HCC stem cells, but this effect is reversed by the addition of the CXCL8 receptor CXCR1/2 inhibitor Reparixin and STAT3 inhibitor Stattic. Besides, our study reveals that the cytokine CXCL8 secreted by IFN-α-induced HCC cells inhibits T-cell function. Conversely, inhibition of CXCL8 promotes TNF-α and IFN-γ secretion by T cells. Finally, liver cancer patients who received anti-PD-1/PD-L1 immunotherapy with high CXCL8 expression had a lower immunotherapy efficacy. Overall, our findings clarify that IFN-α triggers immunosuppression and cancer stem cell differentiation in hepatocellular carcinoma by upregulating CXCL8 secretion. This discovery provides a novel approach to enhance the effectiveness of HCC treatment in the future.

Extraction, Modification and Biomedical Application of Agarose Hydrogels: A Review.

Numerous compounds present in the ocean are contributing to the development of the biomedical field. Agarose, a polysaccharide derived from marine red algae, plays a vital role in biomedical applications because of its reversible temperature-sensitive gelling behavior, excellent mechanical properties, and high biological activity. Natural agarose hydrogel has a single structural composition that prevents it from adapting to complex biological environments. Therefore, agarose can be developed into different forms through physical, biological, and chemical modifications, enabling it to perform optimally in different environments. Agarose biomaterials are being increasingly used for isolation, purification, drug delivery, and tissue engineering, but most are still far from clinical approval. This review classifies and discusses the preparation, modification, and biomedical applications of agarose, focusing on its applications in isolation and purification, wound dressings, drug delivery, tissue engineering, and 3D printing. In addition, it attempts to address the opportunities and challenges associated with the future development of agarose-based biomaterials in the biomedical field. It should help to rationalize the selection of the most suitable functionalized agarose hydrogels for specific applications in the biomedical industry.

A reappraisal of the phylogeny and historical biogeography of Sparganium (Typhaceae) using complete chloroplast genomes.

BACKGROUND: Sparganium (Typhaceae) is a widespread temperate genus of ecologically important aquatic plants. Previous reconstructions of the phylogenetic relationships among Sparganium species are incompletely resolved partly because they were based on molecular markers comprising < 7,000 bp. Here, we sequenced and assembled the complete chloroplast genomes from 19 Sparganium samples representing 15 putative species and three putative subspecies in order to explore chloroplast genome evolution in this genus, clarify taxonomic lineages, estimate the divergence times of Sparganium species, and reconstruct aspects of the biogeographic history of the genus. RESULTS: The 19 chloroplast genomes shared a conserved genome structure, gene content, and gene order. Our phylogenomic analysis presented a well-resolved phylogeny with robust support for most clades. Non-monophyly was revealed in three species: S. erectum, S. eurycarpum, and S. stoloniferum. Divergence time estimates suggest that the two subgenera of Sparganium split from each other ca. 30.67 Ma in the middle Oligocene. The subgenus Xanthosparganium diversified in the late Oligocene and Miocene, while the subgenus Sparganium diversified in the late Pliocene and Pleistocene. Ancestral area reconstruction suggested that the two subgenera may have originated in East Eurasia and North America. CONCLUSION: The non-monophyletic nature of three putative species underscores the necessity of taxonomic revision for Sparganium: S. stoloniferum subsp. choui may be more appropriately identified as S. choui, and subspecies of S. erectum may be in fact distinct species. The estimated diversification times of the two subgenera correspond to their species and nucleotide diversities. The likely ancestral area for most of subgenus Xanthosparganium was East Eurasia and North America from where it dispersed into West Eurasia and Australia. Most of subgenus Sparganium likely originated in North America and then dispersed into Eurasia. Our study demonstrates some of the ways in which complete chloroplast genome sequences can provide new insights into the evolution, phylogeny, and biogeography of the genus Sparganium.

Intelligent and Multifunctional Graphene Nanomesh Electronic Skin with High Comfort.

As the aging population increases in many countries, electronic skin (e-skin) for health monitoring has been attracting much attention. However, to realize the industrialization of e-skin, two factors must be optimized. The first is to achieve high comfort, which can significantly improve the user experience. The second is to make the e-skin intelligent, so it can detect and analyze physiological signals at the same time. In this article, intelligent and multifunctional e-skin consisting of laser-scribed graphene and polyurethane (PU) nanomesh is realized with high comfort. The e-skin can be used as a strain sensor with large measurement range (>60%), good sensitivity (GF≈40), high linearity range (60%), and excellent stability (>1000 cycles). By analyzing the morphology of e-skin, a parallel networks model is proposed to express the mechanism of the strain sensor. In addition, laser scribing is also applied to etch the insulating PU, which greatly decreases the impedance in detecting electrophysiology signals. Finally, the e-skin is applied to monitor the electrocardiogram, electroencephalogram (EEG), and electrooculogram signals. A time- and frequency-domain concatenated convolution neural network is built to analyze the EEG signal detected using the e-skin on the forehead and classify the attention level of testers.

hucMSC-Derived Exosomes Alleviate the Deterioration of Colitis via the miR-146a/SUMO1 Axis.

Human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Ex) plays an important role in tissue repair and immunomodulation, leading to the mitigation of inflammatory bowel disease. However, the preventive function of hucMSC-Ex in the onset and progression of colitis-associated colon cancer (CAC) is poorly understood. In the current study, dextran sodium sulfate/azoxymethane-induced colitis mouse model was established, and the mice disease activity index, body weight, colon length, tumor counts, survival curve, tissue H&E/immunohistochemistry, and cytokines expression were analyzed to evaluate the effects of hucMSC-Ex on CAC. In addition, miR-146a mimics were transfected into colonic epithelial cells (fetal human cells) to evaluate their role in the hucMSC-Ex-mediated regulation of SUMO1. The results showed that hucMSC-Ex inhibits the expression of SUMO1 to reduce the process of CAC progression. Further analysis indicated that miR-146a targets and inhibits SUMO1 expression and its binding to ß-catenin. In conclusion, our findings showed that hucMSC-Ex is effective in alleviating the deterioration of colitis via the miR-146a-mediated inhibition of SUMO1, which is crucial in this disease process.

Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease.

BACKGROUND: Recent studies reporting the intricate crosstalk between cellular and molecular mediators and the lymphatic endothelium in the development of inflammatory bowel diseases (IBD) suggest altered inflammatory cell drainage and lymphatic vasculature, implicating the lymphatic system as a player in the occurrence, development, and recurrence of intestinal diseases. This article aims to review recent data on the modulatory functions of cellular and molecular components of the IBD microenvironment on the lymphatic system, particularly lymphangiogenesis. It serves as a promising therapeutic target for IBD management and treatment. The interaction with gut microbiota is also explored. MAIN TEXT: Evidence shows that cells of the innate and adaptive immune system and certain non-immune cells participate in the complex processes of inflammatory-induced lymphangiogenesis through the secretion of a wide spectrum of molecular factors, which vary greatly among the various cells. Lymphangiogenesis enhances lymphatic fluid drainage, hence reduced infiltration of immunomodulatory cells and associated-inflammatory cytokines. Interestingly, some of the cellular mediators, including mast cells, neutrophils, basophils, monocytes, and lymphatic endothelial cells (LECs), are a source of lymphangiogenic molecules, and a target as they express specific receptors for lymphangiogenic factors. CONCLUSION: The effective target of lymphangiogenesis is expected to provide novel therapeutic interventions for intestinal inflammatory conditions, including IBD, through both immune and non-immune cells and based on cellular and molecular mechanisms of lymphangiogenesis that facilitate inflammation resolution.

Dexamethasone Suppresses Radicular Pain Through Targeting the L-PGDS/PI3K/Akt Pathway in Rats With Lumbar Disc Herniation.

PURPOSE: Lumbar disc herniation (LDH) is a frequently occurring disease with unknown etiology, which makes treatment a challenge. The aim of this study was to analyze the effects of dexamethasone on LDH and elucidate the underlying mechanisms. GENERAL METHODS: An LDH rat model was established by nucleus pulposus implantation. The activity of the lipocalin type prostaglandin D synthase (L-PGDS)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) axis was evaluated by Western blotting. Paw withdrawal threshold and paw withdrawal latency were assessed by the Von Frey hairs method and the thermal dolorimeter of Hargreaves, respectively. The 21-point Basso-Beattie-Bresnahan scale was used to assess the locomotor function of rats. Pathological changes in the affected region were analyzed by hematoxylin-eosin staining. Immunofluorescence was used to measure the expression of microtubule-associated protein (MAP-2). FINDINGS: Lumbar disc herniation markedly increased thermo-mechanical allodynia and induced dorsal root ganglion (DRG) degeneration by inactivating the L-PGS/PI3K/Akt pathway. Dexamethasone restored the L-PGDS/PI3K/Akt pathway and relieved LDH-induced thermo-mechanical allodynia. Furthermore, overexpression and knockdown of L-PGDS respectively attenuated and worsened LDH-triggered thermo-mechanical allodynia and tissue degeneration by modulating the PI3K/Akt pathway. Pretreatment with dexamethasone partially abrogated the effect of L-PGDS knockdown through PI3K/Akt activation. CONCLUSIONS: Dexamethasone relieves LDH-mediated radicular pain by exerting anti-inflammatory effects and reducing the suppression of L-PGDS induced by LDH. Meanwhile, the activity of the PI3K/Akt pathway was decreased, possibly due to the attenuated inflammation induced by dexamethasone. Our results revealed the underlying mechanism of dexamethasone, which might be helpful in reducing the side effects of dexamethasone and provide more focused therapy in LDH.

Influence of environmental factors on the genetic variation of the aquatic macrophyte Ranunculus subrigidus on the Qinghai-Tibetan Plateau.

BACKGROUND: Due to the environmental heterogeneity along elevation gradients, alpine ecosystems are ideal study objects for investigating how ecological variables shape the genetic patterns of natural species. The highest region in the world, the Qinghai-Tibetan Plateau, is a hotspot for the studies of evolutionary processes in plants. Many large rivers spring from the plateau, providing abundant habitats for aquatic and amphibious organisms. In the present study, we examined the genetic diversity of 13 Ranunculus subrigidus populations distributed throughout the plateau in order to elucidate the relative contribution of geographic distance and environmental dissimilarity to the spatial genetic pattern. RESULTS: A relatively low level of genetic diversity within populations was found. No spatial genetic structure was suggested by the analyses of molecular variance, Bayesian clustering analysis and Mantel tests. Partial Mantel tests and multiple matrix regression analysis showed a significant influence of the environment on the genetic divergence of the species. Both climatic and water quality variables contribute to the habitat heterogeneity of R. subrigidus populations. CONCLUSIONS: Our results suggest that historical processes involving long-distance dispersal and local adaptation may account for the genetic patterns of R. subrigidus and current environmental factors play an important role in the genetic differentiation and local adaptation of aquatic plants in alpine landscapes.

Zafirlukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Reduces the Effect of Advanced Glycation End-Products in Rat Renal Mesangial Cells In Vitro.

BACKGROUND Zafirlukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1). Advanced glycation end-products (AGEs) are formed by the glycation of lipids and proteins in hyperglycemia, including diabetes mellitus. Zafirlukast has not previously been studied in diabetic nephropathy. This study aimed to investigate the effects of zafirlukast on rat renal mesangial cells cultured with AGEs in vitro. MATERIAL AND METHODS Mesangial cells were cultured in AGEs (0, 20, 50, 100 µg/ml), and with AGEs (100 µg/ml) and zafirlukast (2.5 µm, 5 µm, and 100 µm). An enzyme-linked immunoassay (ELISA) was used to measure the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1). Reactive oxygen species (ROS) were assessed by intracellular fluorescence measurement of 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and detection kits were used to measure malondialdehyde (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD). Cell apoptosis was assessed by flow cytometry, and Western blot was used to measure protein levels. RESULTS In mesangial cells cultured with AGEs, markers of inflammation, oxidative stress, and apoptosis and levels of CysLTR1 increased, and these effects were reduced by zafirlukast in a dose-dependent manner. The effects of zafirlukast as a CysLTR1 antagonist protected mesangial cells from the effects of AGE in vitro. CONCLUSIONS Zafirlukast, a CysLTR1 antagonist, reduced the levels of inflammatory cytokines, markers of oxidative stress, and cell apoptosis induced by AGE in mesangial cells in a dose-dependent way. Future in vivo studies are needed to investigate the potential role for zafirlukast in models of diabetic nephropathy.

Transcriptome profiling of the floating-leaved aquatic plant Nymphoides peltata in response to flooding stress.

BACKGROUND: Waterlogging or flooding is one of the most challenging abiotic stresses experienced by plants. Unlike many flooding-tolerant plants, floating-leaved aquatic plants respond actively to flooding stress by fast growth and elongation of its petioles to make leaves re-floating. However, the molecular mechanisms of this plant group responding to flood have not been investigated before. Here, we investigated the genetic basis of this adaptive response by characterizing the petiole transcriptomes of a floating-leaved species Nymphoides peltata under normal and flooding conditions. RESULTS: Clean reads under normal and flooding conditions with pooled sampling strategy were assembled into 124,302 unigenes. A total of 8883 unigenes were revealed to be differentially expressed between normal and flooding conditions. Among them, top ranked differentially expressed genes were mainly involved in antioxidant process, photosynthesis process and carbohydrate metabolism, including the glycolysis and a modified tricarboxylic acid cycle - alanine metabolism. Eight selected unigenes with significantly differentiated expression changes between normal and flooding conditions were validated by qRT-PCR. CONCLUSIONS: Among these processes, antioxidant process and glycolysis are commonly induced by waterlogging or flooding environment in plants, whereas photosynthesis and alanine metabolism are rarely occurred in other flooding-tolerant plants, suggesting the significant contributions of the two processes in the active response of N. peltata to flooding stress. Our results provide a valuable genomic resource for future studies on N. peltata and deepen our understanding of the genetic basis underlying the response to flooding stress in aquatic plants.

Genetic and geographical structure of boreal plants in their southern range: phylogeography of Hippuris vulgaris in China.

BACKGROUND: Our current understanding of the evolutionary history of boreal and arctic-alpine plants in their southern range in Asia remains relatively poor. Using three cpDNA non-coding regions and nine nuclear microsatellite (nSSR) loci, we examine the phylogeographic pattern in a broad geographic sampling of the boreal plant Hippuris vulgaris to infer its dispersal and diversification in China. In addition, the species distributions at the Last Glacial Maximum (LGM) and at present were predicted using ecological niche modeling (ENM). RESULTS: The cpDNA results revealed two distinct lineages, A and B. A is restricted to Northeast China; B is distributed in Northwest China, the Qinghai-Tibet Plateau (QTP) and North and Northeast (NNE) China; and A and B diverged ca. 1.36 Ma. The nSSR data revealed two genetic clusters corresponding to the two cpDNA lineages and nonreciprocal hybridization with lineage A as the maternal lineage in Northeast China. Cluster B further divided into three subclusters: I, mainly in NNE China and the northeastern border of the QTP; II, in Northwest China and the QTP; and III, on the QTP. ENM predicted a marked range shift on the QTP at the LGM, retreating from the platform to the northeast and southeast edges. CONCLUSIONS: Hippuris vulgaris probably diverged into lineages A and B in high latitudes and then immigrated into Northeast China and Northwest China, respectively. Lineage A persisted and diversified in Northeast China. Lineage B reached the QTP during the mid-Pleistocene, diversified in that region due to the influence of climatic oscillations, migrated into Northeast China and subsequently hybridized with lineage A. Our findings give empirical evidence that boreal plants display complex evolutionary history in their southern range in Asia and provide new insights into the evolution of boreal and arctic-alpine plants.

The phylogeographic structure of Hydrilla verticillata (Hydrocharitaceae) in China and its implications for the biogeographic history of this worldwide-distributed submerged macrophyte.

BACKGROUND: Aquatic vascular plants are a distinctive group, differing from terrestrial plants in their growth forms and habitats. Among the various aquatic plant life forms, the evolutionary processes of freshwater submerged species are most likely distinct due to their exclusive occurrence in the discrete and patchy aquatic habitats. Using the chloroplast trnL-F region sequence data, we investigated the phylogeographic structure of a submerged macrophyte, Hydrilla verticillata, the single species in the genus Hydrilla, throughout China, in addition to combined sample data from other countries to reveal the colonisation and diversification processes of this species throughout the world. RESULTS: We sequenced 681 individuals from 123 sampling locations throughout China and identified a significant phylogeographic structure (NST > GST, p < 0.01), in which four distinct lineages occurred in different areas. A high level of genetic differentiation among populations (global FST = 0.820) was detected. The divergence of Hydrilla was estimated to have occurred in the late Miocene, and the diversification of various clades was dated to the Pleistocene epoch. Biogeographic analyses suggested an East Asian origin of Hydrilla and its subsequent dispersal throughout the world. CONCLUSIONS: The presence of all four clades in China indicates that China is most likely the centre of Hydrilla genetic diversity. The worldwide distribution of Hydrilla is due to recent vicariance and dispersal events that occurred in different clades during the Pleistocene. Our findings also provide useful information for the management of invasive Hydrilla in North America.

Comparative phylogeography of the wild-rice genus Zizania (Poaceae) in eastern Asia and North America.

PREMISE OF THE STUDY: Comparative phylogeography of intercontinental disjunct taxa allowed us not only to elucidate their diversification and evolution following geographic isolation, but also to understand the effect of climatic and geological histories on the evolutionary processes of closely related species. A phylogeographic analysis was conducted on the eastern Asian-North American disjunct genus Zizania to compare intracontinental phylogeographic patterns between different continents. METHODS: Surveys were conducted of 514 individuals using three chloroplast DNA fragments and three nuclear microsatellite loci. These individuals included 246 from 45 populations of Zizania latifolia in eastern Asia, and the following from North America: 154 individuals from 26 populations of Z. aquatica, 84 individuals from 14 populations of Z. palustris, and 30 individuals from one population of Z. texana. KEY RESULTS: The genetic diversity of North American Zizania was significantly higher than that of eastern Asian Zizania. High levels of genetic differentiation among populations and no signal of population expansion were detected in three widespread species. No phylogeographic structure was observed in Z. latifolia, and discordant patterns of cpDNA and microsatellite markers were observed in North American Zizania. CONCLUSIONS: Reduced variation in Zizania latifolia likely reflects its perennial life history, the North American origin of Zizania, and the relative homogeneity of aquatic environments. High levels of genetic differentiation suggest limited dispersal among populations in all Zizania species. The more complex patterns of diversification and evolution in North American Zizania may be driven by the greater impact of glaciation in North America relative to eastern Asia.

Progress in Research on the Role of the Thioredoxin System in Chemical Nerve Injury.

(1) Background: Various factors, such as oxidative stress, mitochondrial dysfunction, tumors, inflammation, trauma, immune disorders, and neuronal toxicity, can cause nerve damage. Chemical nerve injury, which results from exposure to toxic chemicals, has garnered increasing research attention. The thioredoxin (Trx) system, comprising Trx, Trx reductase, nicotinamide adenine dinucleotide phosphate, and Trx-interacting protein (TXNIP; endogenous Trx inhibitor), helps maintain redox homeostasis in the central nervous system. The dysregulation of this system can cause dementia, cognitive impairment, nerve conduction disorders, movement disorders, and other neurological disorders. Thus, maintaining Trx system homeostasis is crucial for preventing or treating nerve damage. (2) Objective: In this review study, we explored factors influencing the homeostasis of the Trx system and the involvement of its homeostatic imbalance in chemical nerve injury. In addition, we investigated the therapeutic potential of the Trx system-targeting active substances against chemical nerve injury. (3) Conclusions: Chemicals such as morphine, metals, and methylglyoxal interfere with the activity of TXNIP, Trx, and Trx reductase, disrupting Trx system homeostasis by affecting the phosphatidylinositol-3-kinase/protein kinase B, extracellular signal-regulated kinase, and apoptotic signaling-regulated kinase 1/p38 mitogen-activated protein kinase pathways, thereby leading to neurological disorders. Active substances such as resveratrol and lysergic acid sulfide mitigate the symptoms of chemical nerve injury by regulating the Ras/Raf1/extracellular signal-regulated kinase pathway and the miR-146a-5p/TXNIP axis. This study may guide the development of Trx-targeting modulators for treating neurological disorders and chemical nerve injuries.

Dibromoacetonitrile induced autophagy by mediating the PERK signalling pathway and ROS interaction in HT22 cell.

Dibromoacetonitrile (DBAN) is a high-risk haloacetonitrile (HAN) generated as a byproduct of chloramine disinfection in drinking water. DBAN-induced neurotoxicity in mouse hippocampal neuronal cells (HT22) and mammals was observed to be related to reactive oxygen species (ROS). ROS, endoplasmic reticulum stress (ERS) and autophagy play crucial roles in regulating a variety of cellular processes. However, whether ERS and autophagy are associated with HAN-responsive apoptosis remains unclear. This study indicated that DBAN (10 µM, 24 h) activated the ERS protein kinase like endoplasmic reticulum kinase (PERK) signaling pathway. The ERS inhibitor 4-phenylbutyric acid (4-PBA) reversed DBAN-inhibited cell viability and alleviated DBAN-induced apoptosis in HT22 cell, indicating that activation of the ERS PERK pathway mediates DBAN induced cytotoxicity. Moreover, DBAN activated autophagy. The autophagy inhibitor 3-methyladenine(3-MA) reversed DBAN-inhibited cell viability and alleviated DBAN-induced apoptosis in HT22 cell, suggesting that autophagy activation mediates DBAN-induced cell toxicity. Notably, the results showed that 4-PBA inhibited DBAN-activated autophagy, demonstrating that ERS-PERK promotes DBAN-induced cellular autophagy. Pretreatment with antioxidant N-acetylcysteine (NAC) inhibited the increase in ROS production and the activation of ERS, and protected cells from toxicity. Furthermore, 4-PBA pretreatment reduced the increase in ROS production, indicating that the ROS and PERK promote each other and form a positive feedback loop. ROS also promoted DBAN-induced autophagy. In summary, our findings indicate that DBAN induced autophagy by mediating the PERK signalling pathway and ROS interaction, leading to HT22 cell damage. Accordingly, targeting these pathogenic mechanisms may provide a potential target and theoretical basis for preventing and improving HAN-induced neurotoxicity.

Fabrication, structure, characterization and emulsion application of citrate agar.

In this study, citric acid successfully reacted with agar through the dry heat method, and citrate agar (CA) gel was used to stabilize O/W emulsions. The mechanisms of the CA structure and emulsion pH that affected emulsion stabilization were analyzed, and the application of CA gel emulsion (CAGE) was explored. Compared with native agar (NA), CA showed lower gel strength, higher transparency, and higher water contact angle. These changes indicate that a cross-linking reaction occurred, and it was demonstrated via FTIR and NMR. The emulsion properties were evaluated using particle size, ζ-potential, and the emulsification activity index. Results showed that CAGEs had a smaller particle size and lower ζ-potential than the native agar gel emulsion (NAGE). Meanwhile, confocal laser scanning microscopy confirmed that the CA gels stabilized the emulsions by forming a protective film around the oil droplets. Stability experiments revealed that CAGE (prepared with CA gel [DS = 0.145]) exhibited better stability than NAGE in the pH range of 3-11, and the rheological results further confirmed that the stability of the emulsions was influenced by the network structure and oil droplet interaction forces. Afterward, the application prospect of CAGE was evaluated by encapsulating vitamin D3 and curcumin.

Origin of functional de novo genes in humans from "hopeful monsters".

For a long time, it was believed that new genes arise only from modifications of preexisting genes, but the discovery of de novo protein-coding genes that originated from noncoding DNA regions demonstrates the existence of a "motherless" origination process for new genes. However, the features, distributions, expression profiles, and origin modes of these genes in humans seem to support the notion that their origin is not a purely "motherless" process; rather, these genes arise preferentially from genomic regions encoding preexisting precursors with gene-like features. In such a case, the gene loci are typically not brand new. In this short review, we will summarize the definition and features of human de novo genes and clarify their process of origination from ancestral non-coding genomic regions. In addition, we define the favored precursors, or "hopeful monsters," for the origin of de novo genes and present a discussion of the functional significance of these young genes in brain development and tumorigenesis in humans. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.

Structure, characterization, and application of a novel thermoreversible emulsion gel fabricated by citrate agar.

A novel thermoreversible emulsion gel was successfully prepared with citrate agar (CA) as the sole emulsifier. Compared with native agar gel emulsion, CA gel emulsion (CAGE) formed a stable emulsion gel when the CA concentration was increased to 1.25 % (w/w). Results of time-temperature scanning experiments showed that the emulsion gel rapidly transformed into liquid emulsion when heated to 40-50 °C and then solidified into emulsion gel after cooling to the critical temperature of solidification. The emulsion gel had stable sol-gel transformation ability after seven cycles repeated heating-cooling treatment (HCT) at 85 °C and 4 °C. However, the stability of emulsion gels gradually decreased because of the large-droplet formation during heating, which affected the CA molecular-reconfiguration network structure in cooling. The conjunction analysis of microstructure and properties of the emulsion gel indicated that its stability depended primarily on the spatial repulsion and electrostatic repulsion provided by CA gel, and the main factor driving thermal reversibility was the temperature-responsive gelation performance of CA. The retention of quercetin was >90.23 % after seven HCTs because CAGEG enhanced the homogeneity and stability of the droplets.

Benchmarking four large language models' performance of addressing Chinese patients' inquiries about dry eye disease: A two-phase study.

Purpose: To evaluate the performance of four large language models (LLMs)-GPT-4, PaLM 2, Qwen, and Baichuan 2-in generating responses to inquiries from Chinese patients about dry eye disease (DED). Design: Two-phase study, including a cross-sectional test in the first phase and a real-world clinical assessment in the second phase. Subjects: Eight board-certified ophthalmologists and 46 patients with DED. Methods: The chatbots' responses to Chinese patients' inquiries about DED were assessed by the evaluation. In the first phase, six senior ophthalmologists subjectively rated the chatbots' responses using a 5-point Likert scale across five domains: correctness, completeness, readability, helpfulness, and safety. Objective readability analysis was performed using a Chinese readability analysis platform. In the second phase, 46 representative patients with DED asked the two language models (GPT-4 and Baichuan 2) that performed best in the in the first phase questions and then rated the answers for satisfaction and readability. Two senior ophthalmologists then assessed the responses across the five domains. Main outcome measures: Subjective scores for the five domains and objective readability scores in the first phase. The patient satisfaction, readability scores, and subjective scores for the five-domains in the second phase. Results: In the first phase, GPT-4 exhibited superior performance across the five domains (correctness: 4.47; completeness: 4.39; readability: 4.47; helpfulness: 4.49; safety: 4.47, p < 0.05). However, the readability analysis revealed that GPT-4's responses were highly complex, with an average score of 12.86 (p < 0.05) compared to scores of 10.87, 11.53, and 11.26 for Qwen, Baichuan 2, and PaLM 2, respectively. In the second phase, as shown by the scores for the five domains, both GPT-4 and Baichuan 2 were adept in answering questions posed by patients with DED. However, the completeness of Baichuan 2's responses was relatively poor (4.04 vs. 4.48 for GPT-4, p < 0.05). Nevertheless, Baichuan 2's recommendations more comprehensible than those of GPT-4 (patient readability: 3.91 vs. 4.61, p < 0.05; ophthalmologist readability: 2.67 vs. 4.33). Conclusions: The findings underscore the potential of LLMs, particularly that of GPT-4 and Baichuan 2, in delivering accurate and comprehensive responses to questions from Chinese patients about DED.