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Abstract The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals. Graphical Abstract

Abstract Upwelling along oceanic eastern boundaries has attracted significant attention due to its profound effects on ocean productivity and associated biological and socioeconomic implications. However, uncertainty persists regarding the evolution of coastal upwelling with climate change, particularly its impact on future biological production. Here, using a series of state-of-the-art climate models, we identify a significant seasonal advancement and prolonged duration of upwelling in major upwelling systems. Nevertheless, the upwelling intensity (total volume of upwelled water) exhibits complex changes in the future. In the North Pacific, the upwelling is expected to attenuate, albeit with a minor magnitude. Conversely, in other basins, coastal upwelling diminishes significantly in equatorward regions but displays a slight decline or even an enhancement at higher latitudes. The climate simulations also reveal a robust connection between changes in upwelling intensity and net primary production, highlighting the crucial impact of future coastal upwelling alterations on marine ecosystems.

Buckwheat sprouts are rich in pectic polysaccharides, which possess numerous health-improving benefits. However, the precise structure–activity relationship of pectic polysaccharides from Tartary buckwheat sprouts (TP) is still scant, which ultimately restricts their applications in the food industry. Hence, both ultrasound-assisted Fenton treatment (UAFT) and mild alkali treatment (MATT) were utilized for the modification of TP, and then the effects of physicochemical characteristics of original and modified TPs on their bioactivities were assessed. Our findings reveled that the UAFT treatment could precisely reduce TP’s molecular weight, with the levels decreased from 8.191 × 104 Da to 0.957 × 104 Da. Meanwhile, the MATT treatment could precisely reduce TP’s esterification degree, with the values decreased from 28.04 % to 4.72 %. Nevertheless, both UAFT and MATT treatments had limited effects on the backbone and branched chain of TP. Moreover, our findings unveiled that the UAFT treatment could notably promote TP’s antioxidant, antiglycation, and immunostimulatory effects, while remarkedly reduce TP’s anti-hyperlipidemic effect, which were probably owing to that the UAFT treatment obviously reduced TP’s molecular weight. Additionally, the MATT treatment could also promote TP’s immunostimulatory effect, which was probably attributed to that the MATT treatment significantly decreased TP’s esterification degree. Interestingly, the MATT treatment could regulate TP’s antioxidant and antiglycation effects, which was probably attributed to that the MATT treatment simultaneously reduced its esterification degree and bound phenolics. Our findings are conducive to understanding TP’s structure–activity relationship, and can afford a scientific theoretical basis for the development of functional or healthy products based on TPs. Besides, the UAFT treatment can be a promising approach for the modification of TP to improve its biological functions.

ABSTRACT The existing literature addresses the importance of food system disruptions and the risk of the global food crisis. However, there is insufficient understanding of response strategies and their effectiveness evaluations. This study offers a comprehensive introduction to China's food security policies and evaluates their effectiveness in enhancing the nation's risk resistance capability. Utilizing the Entropy Weight Method (EWM) and the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), we evaluated China's provincial food security resilience (FSR) from 2003 to 2020 and adopted the ArcGIS platform to map spatiotemporal trends. Our findings reveal significant improvements in FSR nationwide, with a notable average annual growth rate of 1%–5%. However, regional disparities persist, with higher resilience observed in eastern provinces compared to the west. The study emphasizes the effectiveness of China's food security policies, which have synergistically enhanced grain production, agricultural mechanization, and farmers’ economic conditions. The article offers policy recommendations aimed at bolstering China's FSR and challenges with global implications. Our study contributes to the broader discourse on global food security by offering a nuanced understanding of the effectiveness of policy interventions in a major agricultural economy.

Abstract Large-scale marine heatwaves in the Northeast Pacific (NEP), identified here and previously as ‘warm blobs’, have devastating impacts on regional ecosystems. An anomalous atmospheric ridge over the NEP is known to be crucial for maintaining these warm blobs, also causing abnormally cold temperatures over North America during the cold season. Previous studies linked this ridge to teleconnections from tropical sea surface temperature anomalies. However, it was unclear whether teleconnections from the extratropics could also contribute to the ridge. Here we show that planetary wave trains, triggered by increased rainfall and latent heat release over the Mediterranean Sea accompanied by decreased rainfall over the North Atlantic, can transport wave energy to the NEP, guided by the westerly jet, and induce a quasi-barotropic ridge there. Our findings provide insights into extratropical teleconnections sustaining the NEP ridge, offering a source of potential predictability for the warm blobs and temperature fluctuations over North America.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized for its global prevalence and potential progression to more severe liver diseases such as non-alcoholic steatohepatitis (NASH). The primary treatment for NASH is modifying lifestyle through dietary or exercise interventions. The aim of the current study is to investigate the roles of Fufang Zhenzhu Tiaozhi polysaccharides (FTZPs) in mice with NASH. FTZPs were concurrently administered to high-fat diet (HFD)-induced 24-week NASH model mice. FTZPs treatment effectively improved liver lipid metabolism, reduced inflammation and fibrosis, improved the integrity of the intestinal mucosal barrier, and modulated the structure of the intestinal microbiota. FTZPs treatment significantly reduced the abundance of Gammaproteobacteria, Clostridium, and Coprococcus while as induced the abundance of Dehalobacteraceae and Dehalobacterium. Furthermore, sixteen differential metabolites were screened by metabolomics, and the change of asparagine was the most significant. In addition, the correlation analysis showed that there was a significant correlation between asparagine and the aforementioned differential bacteria. The present study demonstrated that FTZPs, as the fundamental pharmacological elements of FTZ (Fufang Zhenzhu Tiaozhi), protect against NASH by improving intestinal barrier damage and regulating intestinal flora with the increase in asparagine.

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) leaf has abundant rhamnogalacturonan-I enriched pectic polysaccharides, which exert various health-promoting effects. Nevertheless, the potential relationship between the chemical structure and the biological function of pectic polysaccharides from Tartary buckwheat leaves (TBP) remains unclear. Therefore, to bridge the gap between the chemical structure and the biological function of TBP, the impacts of ultrasound-assisted Fenton degradation (UFD) and mild alkaline de-esterification (MAD) on structural properties and biological effects of TBP were systematically studied. Compared with the native TBP (molecular mass, 9.537 × 104 Da), the molecular masses of degraded TBPs (TBP-MMW, 4.811 × 104 Da; TBP-LMW, 2.101 × 104 Da) were significantly reduced by the UFD modification, while their primary chemical structures were overall stable. Besides, compared with the native TBP (esterification degree, 22.73 %), the esterification degrees of de-esterified TBPs (TBP-MDE, 14.27 %; TBP-LDE, 6.59 %) were notably reduced by the MAD modification, while their primary chemical structures were also overall stable. Furthermore, the results revealed that both UFD and MAD modifications could significantly improve the antioxidant, antiglycation, and immunostimulatory effects of TBP. Indeed, TBP’s biological effects were negatively correlated to its molecular mass and esterification degree, while positively linked to its free uronic acids. The findings demonstrate that both UFD and MAD modifications are promising techniques for the structural modification of TBP, which can remarkedly promote its biological effects. Besides, the present results are conducive to better understanding TBP’s structure-bioactivity relationship.

Abstract Background The increasing prevalence of neurocognitive disorders (NCDs) in the aging population worldwide has become a significant concern due to subjectivity of evaluations and the lack of precise diagnostic methods and specific indicators. Developing personalized diagnostic strategies for NCDs has therefore become a priority. Results Multimodal electroencephalography (EEG) data of a matched cohort of normal aging (NA) and NCDs seniors were recorded, and their faecal samples and urine exosomes were collected to identify multi-omics signatures and metabolic pathways in NCDs by integrating metagenomics, proteomics, and metabolomics analysis. Additionally, experimental verification of multi-omics signatures was carried out in aged mice using faecal microbiota transplantation (FMT). We found that NCDs seniors had low EEG power spectral density and identified specific microbiota, including Ruminococcus gnavus, Enterocloster bolteae, Lachnoclostridium sp. YL 32, and metabolites, including L-tryptophan, L-glutamic acid, gamma-aminobutyric acid (GABA), and fatty acid esters of hydroxy fatty acids (FAHFAs), as well as disturbed biosynthesis of aromatic amino acids and TCA cycle dysfunction, validated in aged mice. Finally, we employed a support vector machine (SVM) algorithm to construct a machine learning model to classify NA and NCDs groups based on the fusion of EEG data and multi-omics profiles and the model demonstrated 92.69% accuracy in classifying NA and NCDs groups. Conclusions Our study highlights the potential of multi-omics profiling and EEG data fusion in personalized diagnosis of NCDs, with the potential to improve diagnostic precision and provide insights into the underlying mechanisms of NCDs. Video Abstract

In this study, multi-objective optimal dispatching of demand response-enabled microgrid considering uncertainty in renewable energy generations is designed to obtain optimal energy point sets of microgrid. The proposed dispatching model contains upper-level model and lower-level model. The economic and environmental benefits of the microgrid are adopted as the optimization objectives in the upper-level model and the economic benefits under incentive-based demand response is taken as the optimization objective in the lower-level load demand. In the upper-level model, sequence operation theory is designed to deal with the uncertainty in renewable energy generations, and virtual real-time tariffs and electricity credibility of power consumption are utilized to make demand response by shifting load in the lower-level model. To optimally solve the proposed model, improved enhanced multi-objective optimization sparrow search algorithm (EMOSSA) based on sinusoidal search strategy, diversity variant processing by Cauchy variation and external archive updating mechanism is developed to optimize the objective functions of the upper-level model and mixed integer linear programming CPLEX is employed to determine the load demand for the lower-level model. After that, the power demand plan of the lower-level model and the real-time prices of the upper-level model are updated iteratively to obtain the optimal dispatching solutions using the real-time pricing mechanism. Eventually, experimental results of several operation scenarios illustrate the proposed optimal dispatching method can deal with the uncertainty of renewable energy generations and the randomness of load, thus, achieving a well supply and demand balance between microgrid and users.

Abstract Plant-derived nanovesicles (NVs) and extracellular vesicles (EVs) are the next generation of nanocarrier platforms for biotherapeutics and drug delivery. EVs exist not only in the extracellular space, but also within the cell wall. Due to the limitations of existing isolation methods, the EVs extraction efficiency is low, and a large amount of plant material is wasted, which is of concern for rare and expensive medicinal plants. We proposed and validated a novel method for isolation of plant EVs by enzyme degradation of the plant cell wall to release the EVs. The released EVs can easily be collected. The new method was used for extraction of EVs from the roots of Morinda officinalis (MOEVs). For comparison, nanoparticles from the roots (MONVs) were extracted using the grinding method. The new method yielded a greater amount of MOEVs, and the vesicles had a smaller diameter compared to MONVs. Both MOEVs and MONVs were readily absorbed by endothelial cells without cytotoxic effect and promoted the expression of miR-155. The promotion of miR-155 by MOEVs was dose-dependent. More importantly, we found that MOEVs and MONVs were enriched toward bone tissue. These results support our hypothesis that EVs in plants could be efficiently extracted by enzymatic cell wall digestion and confirm the potential of MOEVs as therapeutic agents and drug carriers.

As a ligand-dependent transcription factor, retinoid-associated orphan receptor γt (RORγt) that controls T helper (Th) 17 cell differentiation and interleukin (IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions. An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production. Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric- or allosteric-binding sites in the ligand-binding domain. Some of small-molecule inhibitors have entered clinical evaluations. Therefore, in current review, the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted. Notably, the recently developed RORγt inhibitors were summarized, with an emphasis on their optimization from lead compounds, efficacy, toxicity, mechanisms of action, and clinical trials. The limitations of current development in this area were also discussed to facilitate future research.

Ulcerative colitis (UC) is an idiopathic, chronic, and progressive inflammatory set of conditions that affects the colonic mucosa. Natural polyphenols are well documented for their excellent antioxidant properties and have obvious advantages in the strategy of anti-oxidation treatment of UC. However, the poor water solubility, low bioavailability, and unstable nature have hindered their clinical application. Therefore, we efficiently encapsulated bioactive polyphenol epigallocatechin gallate (EGCG) with poly(N-vinylpyrrolidone) (PVP) via reliable intermolecular hydrogen-bonded interactions, and conjugated polysaccharide chondroitin sulfate (CS) with excellent gastrointestinal stability and CD44 active targeting capability onto the surface to achieve targeted delivery (EPC). The obtained EPC system showed an average diameter of 54 nm, monodisperse size distribution, and negatively charged surface. In vitro studies demonstrated the obvious reactive oxygen species (ROS)-scavenging and anti-inflammatory abilities of the EPC system. After oral administration, EPC system localized in the inflamed colon and effectively alleviated the symptoms in dextran sulfate sodium salt (DSS)-induced UC mice. Specifically, the EPC system down-regulated the expression of inflammatory cytokines, up-regulated the expression of tight junction-associated proteins to restore intestinal barrier, and modulated the gut microbiota. This oral drug delivery system with a simple self-assembling process may pave new strategy for polyphenol-based therapy in UC.

The process of rapid urbanization has exerted immense pressure on the ecological environment of cities. Consequently, achieving green development during urbanization has emerged as the new focal point. Based on 2011–2020 panel data of 110 cities at the prefecture level and above in the Yangtze River Economic Belt (YREB), this study aims to investigate the impact of urbanization on urban green development. Specifically, this study analyzes the spatial and temporal evolution patterns of urbanization and urban green development, and examines the spatial disparities and influencing mechanisms of urbanization on urban green development with the help of panel econometric model and mediation model. The results verify that the urbanization and urban green development levels in the YREB have generally improved, but there are significant differences across cities in terms of their aggregate level and growth rate. The relationship between urbanization and urban green development in the YREB follows a “U” shaped curve, where urbanization initially hinders green development but later facilitates it. Spatially, cities located in the middle and lower reaches, as well as urban agglomerations, benefit from location and organization advantages that amplify the effect of urbanization on urban green development. Conversely, cities in the upper reaches and non-urban agglomerations, with their advantages in late development, have the great potential to promote urban green development at a lower threshold. Moreover, Urbanization influences urban green development through non-linear mediating effects. As the level of urbanization increases, green life consumption (GLC) and green technology innovation (GTI) gradually replace infrastructure construction (IC) as the primary mechanisms driving urban green development in the YREB.

Fresh leaves of Echa 1 were fixed by roller, steam/hot air and light-wave, and the effects of the three fixation methods on the chemical characteristics of straight-shaped green teas (GTs) were studied by widely targeted metabolomic analysis. 1001 non-volatile substances was identified, from which 97 differential metabolites were selected by the criteria of variable importance in projection (VIP) > 1, p 1. Correlation analysis indicated that 14 taste-active metabolites were the major contributors to the taste differences between differently processed GTs. High-temperature fixation induces protein oxidation or degradation, γ-glutamyl peptide transpeptidation, degradation of flavonoid glycosides and epimerization of cis-catechins, resulting in the accumulation of amino acids, peptides, flavonoids and trans-catechins, which have flavor characteristics such as umami, sweetness, kokumi, bitterness and astringency, thereby affecting the overall taste of GTs. These findings provided a scientific basis for the directional processing technology of high-quality green tea.

Abstract Agaricus bisporus (A. bisporus) is a rich source of polysaccharides with medical and nutraceutical interests; however, the complex structure of A. bisporus polysaccharides (ABPs) poses a challenge to its quality control. This study aims to investigate the immunomodulatory fractions of ABPs and further establish a quality control system for the detection and characterization of bioactive ABPs. Two fractions of ABPs were obtained using gradient alcohol precipitation combined ultrafiltration, followed by characterization of molecular weight, monosaccharide composition, chemical structure, and evaluation of immunomodulatory activity. Results showed that the two isolated fractions with different molecular weight, 8.95 × 106 Da (ABP17‐1) and 1.73 × 104 Da (ABP17‐2), were more homogeneous and exerted stronger immunomodulatory activity than that of ABPs. Furthermore, an integrated fingerprint technique including HPSEC‐MALL‐RID and HPLC was applied for the fingerprint analysis of ABPs from 17 batches of A. bisporus, which showed high similarity. Besides, two polysaccharide fractions, two monosaccharides (glucose and galactose), and the main cellulose hydrolysate glucose were identified as potential quality control markers of ABPs. Overall, this study could help better understand the structure–activity relationship of ABPs and serve as a guidance for the quality control of active ABPs and their related products.

The biologically productive eastern boundary upwelling systems (EBUSs) are regarded as thermal refugia in a warming climate. However, the authors here show that Southern Hemisphere EBUSs are likely to become hotspots of future marine heatwaves.

Melanoma is a highly aggressive cancer that can metastasize at early stage. The aim of this study is to clarify the role of Piezo1 and its potential mechanism in regulating the malignant phenotypes of melanoma. In the present study, we first showed that Piezo1 was abnormally expressed in melanoma, which accelerated the malignant progression by activating AKT/mTOR signaling. Firstly, we found that Piezo1 was upregulated in melanoma and associated with poor survival. Additionally, Piezo1 knockdown significantly weakened intracellular calcium signal and viability of melanoma cells. Furthermore, Piezo1 knockdown inhibited the transendothelial migration and invasion in vitro, as well as metastasis in vivo. Mechanistically, we found that Piezo1 activated AKT/mTOR signaling to maintain malignant phenotypes of melanoma. Therefore, Piezo1 acts as an oncogene in melanoma cells and provides a novel candidate for melanoma diagnosis and treatment.

Rabdosia serra (R. serra), an important component of Chinese herbal tea, has traditionally been used to treat hepatitis, jaundice, cholecystitis, and colitis. However, the chemical composition of R. serra and its effect against colitis remain unclear. In this study, the chemical composition of the water extract of R. serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer (UPLC-LTQ-Orbitrap-MS). A total of 46 compounds, comprising ent-kaurane diterpenoids, flavonoids, phenolic acids, and steroids, were identified in the water extract of R. serra, and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length, upregulating anti-inflammatory factors, downregulating proinflammatory factors, and restoring the balance of T helper 17/T regulatory cells. R. serra also preserved intestinal barrier function by increasing the level of tight junction proteins (zonula occludens 1 and occludin) in mouse colonic tissue. In addition, R. serra modulated the gut microbiota composition by increasing bacterial richness and diversity, increasing the abundance of beneficial bacteria (Muribaculaceae, Bacteroides, Lactobacillus, and Prevotellaceae_UCG-001), and decreasing the abundance of pathogenic bacteria (Turicibacter, Eubacterium_fissicatena_group, and Eubacterium_xylanophilum_group). Gut microbiota depletion by antibiotics further confirmed that R. serra alleviated colitis in a microbiota-dependent manner. Overall, our findings provide chemical and biological evidence for the potential application of R. serra in the management of colitis.

Under global warming, increased variability in El Niño sea surface temperature was projected to be detectable by about 2070. Here the authors show that the increased variability of a type of more impactful El Niño events is likely detectable by 2030.

Abstract Background Infectious diseases have caused huge economic loss and food security issues in fish aquaculture. Current management and breeding strategies heavily rely on the knowledge of regulative mechanisms underlying disease resistance. Though the intestinal microbial community was linked with disease infection, there is little knowledge about the roles of intestinal microbes in fish disease resistance. Cynoglossus semilaevis is an economically important and widely cultivated flatfish species in China. However, it suffers from outbreaks of vibriosis, which results in huge mortalities and economic loss. Results Here, we used C. semilaevis as a research model to investigate the host-microbiome interactions in regulating vibriosis resistance. The resistance to vibriosis was reflected in intestinal microbiome on both taxonomic and functional levels. Such differences also influenced the host gene expressions in the resistant family. Moreover, the intestinal microbiome might control the host immunological homeostasis and inflammation to enhance vibriosis resistance through the microbe-intestine-immunity axis. For example, Phaeobacter regulated its hdhA gene and host cyp27a1 gene up-expressed in bile acid biosynthesis pathways, but regulated its trxA gene and host akt gene down-expressed in proinflammatory cytokines biosynthesis pathways, to reduce inflammation and resist disease infection in the resistant family. Furthermore, the combination of intestinal microbes and host genes as biomarkers could accurately differentiate resistant family from susceptible family. Conclusion Our study uncovered the regulatory patterns of the microbe-intestine-immunity axis that may contribute to vibriosis resistance in C. semilaevis. These findings could facilitate the disease control and selective breeding of superior germplasm with high disease resistance in fish aquaculture. Video Abstract

Introduction: Ulcerative colitis (UC) is a chronic recurrent idiopathic disease characterized by damage to the colonic epithelial barrier and disruption of inflammatory homeostasis. At present, there is no curative therapy for UC, and the development of effective and low-cost therapies is strongly advocated. Objectives: Multiple lines of evidence support that tannic acid (TA) and berberine (BBR), two active ingredients derived from Chinese herb pair (Rhei Radix et Rhizoma and Coptidis Rhizoma), have promising therapeutic effects on colonic inflammation. This study aims to develop a targeted delivery system based on BBR/TA-based self-assemblies for the treatment of UC. Methods: TA and BBR self-assemblies were optimized, and hyaluronic acid (HA) was coated to achieve targeted colon delivery via HA-cluster of differentiation 44 (CD44) interactions. The system was systematically characterized and dextran sodium sulfate (DSS)-induced mouse colitis model was further used to investigate the biodistribution behavior, effect and mechanism of the natural system. Results: TA and BBR could self-assemble into stable particles (TB) and HA-coated TB (HTB) further increased cellular uptake and accumulation in inflamed colon lesions. Treatment of HTB inhibited pro-inflammatory cytokine levels, restored expression of tight junction-associated proteins and recovered gut microbiome alteration, thereby exerting anti-inflammatory effects against DSS-induced acute colitis. Conclusion: Our targeted strategy may provide a convenient and powerful platform for UC and reveal new modes of application of herbal combinations.

Abstract The response of upwelling in the eastern boundary upwelling systems (EBUSs) to anthropogenic climate change has attracted much scientific attention due to its core role in nourishing marine ecosystems. A decade‐old hypothesis suggests that greenhouse warming may intensify upwelling‐favorable winds and subsequently the upwelling in EBUSs, but the impact of greenhouse warming on the seasonal cycle of upwelling remains unknown. Using the recent generation of global climate simulations under a high carbon emission scenario, we show a universal weakening of the upwelling seasonal cycle in the major EBUSs. This is mainly ascribed to the projected weakened seasonal cycle of the upwelling‐favorable winds. In addition, long‐term changes in geostrophic transport exert a nonnegligible contribution to the changes in the upwelling seasonal cycle. Our study suggests that the upwelling in the EBUSs is likely to have a more complicated response to greenhouse warming than previously thought.

In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations.

In order to explore the correlation between mineral elements content and quality ingredients of flat green tea, ten representative flat green tea samples from five production areas (Dawu County, Hubei Province, Pan'an County, Zhejiang Province, She County, Anhui Province, Meitan County, Guizhou Province and Emeishan City, Sichuan Province) were collected. The content of nine mineral elements (Mg, K, Ca, P, Al, Mn, Fe, Zn, B) and five quality ingredients (water extracts, tea polyphenols, free amino acids, total soluble sugars, caffeine) were determined. Results showed that the mineral elements influenced each other and existed with synergistic or antagonistic effects. The water extracts content was significantly negatively correlated with the B content (P

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Abstract Placenta plays essential role in successful pregnancy, as the most important organ connecting and interplaying between mother and fetus. However, the cellular characteristics and molecular interaction of cell populations within the fetomaternal interface is still poorly understood. Here, we surveyed the single-cell transcriptomic landscape of human full-term placenta and revealed the heterogeneity of cytotrophoblast cell (CTB) and stromal cell (STR) with the fetal/maternal origin consecutively localized from fetal section (FS), middle section (Mid_S) to maternal section (Mat_S) of maternal–fetal interface. Then, we highlighted a subpopulation of CTB, named trophoblast progenitor-like cells (TPLCs) existed in the full-term placenta and mainly distributed in Mid_S, with high expression of a pool of putative cell surface markers. Further, we revealed the putative key transcription factor PRDM6 that might promote the differentiation of endovascular extravillous trophoblast cells (enEVT) by inhibiting cell proliferation, and down-regulation of PRDM6 might lead to an abnormal enEVT differentiation process in PE. Together, our study offers important resources for better understanding of human placenta and stem cell-based therapy, and provides new insights on the study of tissue heterogeneity, the clinical prevention and control of PE as well as the maternal–fetal interface.

Abstract Background Rheum tanguticum is utilized as one of the well known traditional Chinese medicine for the treatment of gastrointestinal diseases. Recently, R. tanguticum polysaccharides (RP) have received increasing attention due to their diversely pharmacological activities. Usually, the pharmacological activities of polysaccharides are closely correlated to their metabolic properties from the stomach to the intestine. However, the digestive behavior and fecal fermentation characteristics of RP are unknown, which need to be fully investigated. Methods In this study, an in vitro simulated gastrointestinal model was carried out for the investigation of the digestive behavior and fecal fermentation characteristics of RP. The possible changes in physicochemical properties of RP, such as molecular weight, monosaccharide composition, reducing sugar released, chemical composition, pH value, and short chain fatty acids, were determined during in vitro simulated digestion and human fecal fermentation, and its effect on the modulation of gut microbial composition was also evaluated. Results The results revealed that RP was indigestible under the in vitro simulated digestion conditions according to its stabilities in physicochemical properties. Conversely, the indigestible RP (RPI) could be notably utilized by colonic microbiota in human feces after the in vitro fermentation, especially, at the initial fermentation stage (0–6 h). The fecal fermentation characteristics of RPI were revealed. Results showed that the content of reducing sugars obviously increased from 0.177 to 0.778 mg/mL at the initial stage of fermentation, and its molecular weight notably declined from 2.588 × 105 to 0.828 × 105 Da at the end stage of fermentation. Notably, the utilization of arabinose and galactose in RPI by colonic bacteria was faster than that of galacturonic acid. Besides, RPI could obviously modulate gut microbial composition via promoting the relative abundances of several beneficial bacteria, such as genera Bacteroides, Bifidobacterium, and Megamonas, resulting in the promoted production of several short-chain fatty acids, such as acetic, propionic, and butyric acids. Conclusions Results from this study showed that RP was indigestible in the human upper gastrointestinal tract in vitro, but could be easily utilized by colonic microbiota in human feces at the initial stage of fermentation. RP could be used as potential prebiotics for the improvement of intestinal health.

A core-shell structure UiO-66-(OH)2@UiO-66-NH2 (MOF@MOF) nanoparticle was synthesized through a simple hydrothermal method and employed as an adsorbent and laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) matrix for the quantitative analysis of rhubarb anthraquinones (RAs). The properties of the materials were characterized by field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, and Brunauer-Emmett-Teller. The results indicate that MOF@MOF is regular octahedral structure with a size distribution of about 100 nm, having large BET specific surface area (920 m2/g). Using the MOF@MOF as a matrix shows lower background interference, higher sensitivity, and better storage stability than that of traditional matrices. The MOF@MOF matrix exhibits excellent salt tolerance even under a NaCl concentration of 150 mM. Then, the enrichment conditions were optimized, and the adsorption time of 10 min, adsorption temperature of 40 °C and adsorbent amount of 100 μg were selected. In addition, the possible mechanism of MOF@MOF as an adsorbent and matrix was discussed. Finally, the MOF@MOF nanoparticle was employed as a matrix for the sensitive MALDI-TOF-MS analysis of RAs in spiked rabbit plasma, and the recoveries are in the range of 88.3–101.5% with RSD ≤9.9%. In short, the novel MOF@MOF matrix has demonstrated its potential in the analysis of small-molecule compounds in biological samples.

This study aimed to evaluate the effects of dietary bile acids on growth performance, feed utilization, body composition, digestive enzyme activity, and related gene expression in juvenile leopard coral grouper (Plectropomus leopardus). Five diets with varying levels of dietary bile acids (0, 0.15, 0.3, 0.45 and 0.6%) were formulated and each diet was fed to triplicate groups of 15 fish (13.14 ± 0.14 g) for ten weeks. Results showed that the significant enhancement in weight gain (WG) and specific growth rate (SGR) was observed in fish fed 0.3% bile acids (P < 0.05). Additionally, feed conversion ratio (FCR) was significantly improved with bile acids inclusion (P < 0.05). Higher feed intake was also recorded in bile acids inclusion groups, and significantly up-regulated gene expression of hypothalamus neuropeptide Y (NPY) was found in 0.3% group compared with the control group (P < 0.05). Dietary bile acids (0.3%) significantly decreased lipid deposition in the whole-body (P < 0.05), and lower hepatosomatic index (HSI) and viscerosomatic index (VSI) were also found in this group. Moreover, intestinal trypsin and lipase activities were significantly increased in 0.3% group (P < 0.05) to promote feed digestion. In addition, the relative expression levels of intestinal fatty acid binding protein 2 (FABP2) significantly up-regulated with inclusion of dietary bile acids, suggesting an enhancement of fatty acid transport (P < 0.05). In contrast, cholesterol transport related genes NPC1 like intracellular cholesterol transporter 1 (NPC1L1) and CD36 were notably down-regulated as bile acids inclusion (P < 0.05). This study provides valuable information for the formulation of diets for juvenile coral trout and indicates that dietary bile acids could potentially be used to improve growth performance and feed utilization.

Abstract El Niño/Southern Oscillation (ENSO) exhibits evident amplitude asymmetry with stronger El Niño than La Niña events. Equatorial submesoscale eddies act as an important damper of ENSO via their induced upward heat flux (Qeddy,vsub) from the subsurface to the surface ocean. Yet their effect on ENSO amplitude asymmetry remains unexplored. Using a high‐resolution global climate simulation, we found that strengthening of Qeddy,vsub in the Niño3.4 region during La Niña is more evident than weakening of Qeddy,vsub during El Niño, resulting in stronger damping of La Niña than El Niño events. This asymmetric response of Qeddy,vsub to ENSO is primarily ascribed to that of the temperature fronts associated with larger‐scale processes. Using a recharge oscillator model modified to include the effects of Qeddy,vsub, we show that the asymmetric damping of ENSO by Qeddy,vsub contributes importantly to the ENSO amplitude asymmetry.

In order to analyze the changes in the microbial community structure during the pile fermentation of Qingzhuan tea and their correlation with the formation of quality compounds in Qingzhuan tea, this study carried out metagenomic and metabolomic analyses of tea samples during the fermentation process of Qingzhuan tea. The changes in the expression and abundance of microorganisms during the pile fermentation were investigated through metagenomic assays. During the processing of Qingzhuan tea, there is a transition from a bacterial dominated ecosystem to an ecosystem enriched with fungi. The correlation analyses of metagenomics and metabolomics showed that amino acids and polyphenol metabolites with relatively simple structures exhibited a significant negative correlation with target microorganisms, while the structurally complicated B-ring dihydroxy puerin, B-ring trihydroxy galloyl puerlin, and other compounds showed a significant positive correlation with target microorganisms. Aspergillus niger, Aspergillus glaucus, Penicillium in the Aspergillaceae family, and Talaromyces and Rasamsonia emersonii in Trichocomaceae were the key microorganisms involved in the formation of the characteristic qualities of Qingzhuan tea.

In this study, near-infrared spectroscopy (NIRS) combined with a variety of chemometrics methods was used to establish a fast and non-destructive prediction model for the purchase price of fresh tea leaves. Firstly, a paired t-test was conducted on the quality index (QI) of seven quality grade fresh tea samples, all of which showed statistical significance (p < 0.05). Further, there was a good linear relationship between the QI, quality grades, and purchase price of fresh tea samples, with the determination coefficient being greater than 0.99. Then, the original near-infrared spectra of fresh tea samples were obtained and preprocessed, with the combination (standard normal variable (SNV) + second derivative (SD)) as the optimal preprocessing method. Four spectral intervals closely related to fresh tea prices were screened using the synergy interval partial least squares (si-PLS), namely 4377.62 cm−1–4751.74 cm−1, 4755.63 cm−1–5129.75 cm−1, 6262.70 cm−1–6633.93 cm−1, and 7386 cm−1–7756.32 cm−1, respectively. The genetic algorithm (GA) was applied to accurately extract 70 and 33 feature spectral data points from the whole denoised spectral data (DSD) and the four characteristic spectral intervals data (FSD), respectively. Principal component analysis (PCA) was applied, respectively, on the data points selected, and the cumulative contribution rates of the first three PCs were 99.856% and 99.852%. Finally, the back propagation artificial neural (BP-ANN) model with a 3-5-1 structure was calibrated with the first three PCs. When the transfer function was logistic, the best results were obtained (Rp2 = 0.985, RMSEP = 6.732 RMB/kg) by 33 feature spectral data points. The detection effect of the best BP-ANN model by 14 external samples were R2 = 0.987 and RMSEP = 6.670 RMB/kg. The results of this study have achieved real-time, non-destructive, and accurate evaluation and digital display of purchase prices of fresh tea samples by using NIRS technology.

Ginseng is an international herb that has been used for thousands of years. Two species most commonly applied and investigated in the ginseng family are Asian ginseng and American ginseng. The number of randomized controlled clinical trials (RCTs) has conspicuously increased, driven by the rapid development of ginseng. However, the reporting of RCT items of ginseng is deficient because of different trial designs and reporting formats, which is a challenge for researchers who are looking for the data with high quality and reliability. Thus, this study focused on providing an extensive analysis of these two species and examined the quality of the RCTs, based on the Consolidated Standards of Reporting Trials (CONSORT) guideline. Ninety-one RCTs conducted from 1980 to 2019 that were related to Asian ginseng and American ginseng used singly met our inclusion criteria. We found that the reporting quality of the two species has improved during the past 40 years. Publication date and sample size were significantly associated with the reporting quality. Rigorous RCTs designed for the species of ginseng are warranted, which can shed light on product research and development of ginseng in the future.

Abstract Background Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigated the pharmacological mechanisms. Methods The main components of QWS aqueous extract were analyzed by LC–MS, and potential pathways of QWS targeting OU were predicted by network pharmacology. The db/db mice were administered with the decoction of dried Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the model mice were treated with QWS, and OU wound healing status were recorded. The pathological changes of gastric tissue and oral mucosa were evaluated using hematoxylin–eosin staining, and the morphology of collagen fibers in oral mucosa was assessed by Masson staining. The levels of thromboxane B2 (TXB2), 6-Keto-prostaglandin F1α (6-keto-PGF1α), interleukin-1 β (IL-1β), IL-2, IL-6, tumor necrosis factor-α (TNF-α), β-endorphin (β-EP) and 5-Hydroxytryptamine (5-HT) were determined by ELISA assay. The protein expressions of Toll-like receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα and nuclear factor kappa-B (NF-κB) p65 were measured by Western Blotting. Results A total of 183 compounds in QWS were identified by LC–MS, and identified 79 bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose treatment significantly reduced the level of TXB2 and the ratio of TXB2/6-keto-PGF1α. Meanwhile, it improved mucosal pathological morphology, and reduced the area of OU and local edema. Simultaneously, the levels of TNF-α, IL-1β, IL-6, IL-2 and 5-HT, and the expressions of TLR4, TRAF6, MyD88, p-IκΒα and NF-κB p65 were decreased. Conclusion QWS treatment facilitates the healing of OU, ameliorates pathological morphologies of gastric and oral mucosa and decreases the levels of pro-inflammatory cytokines in db/db mice subjected to stomach heat syndrome, whose mechanism may be associated with the inhibition of TLR4/MyD88/NF-κB signaling pathway to exert anti-inflammatory effects.

This study sought to examine the role of bile acids in the regulation of glucose and lipid metabolism, intestinal flora, and growth in high-fat diet-fed common carp (Cyprinus carpio L.). Fish (6.34±0.07 g) were fed for 56 days with three different diets, the control diet (CO, 5.4% lipid), high-fat diet (HF, 11% lipid), and high-fat diet with 60 mg/kg bile acids (BAs, 11% lipid). The results showed that high-fat diets resulted in poor growth performance and increased triglyceride (TG) in serum and the liver. The addition of bile acids significantly alleviated the adverse effects of a high-fat diet. The mRNA expression results indicated that bile acids may improve lipid metabolism through the enhancement of the peroxisome proliferator-activated receptor (PPARa). The expression of gluconeogenesis-related phosphoenolpyruvate carboxykinase (PEPCK) mRNA was inhibited, while fibroblast growth factor 19 (FGF19) was significantly higher. Bile acids reshaped the intestinal microflora community, with the level of Bacteroidetes increasing. The correlation analysis indicated that Patescibacteria, Dependentiae, Myxococcota, and Planctomycetota in the gut are associated with genes involved in glucose and lipid metabolism. These results indicated that bile acids could ameliorate the negative effects of high-fat diets on common carp.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

Digital rural development has become an emerging dynamic force for high-quality rural development in China. This paper constructs the “environmental-economic-social” analysis framework for digital rural development, analyzes the spatial variation of the digital rural development level (DRDL) in Chinese counties in 2020, and conducts the factor detection and interaction detection of its influencing factors. It is found that: (1) digital rural development has its own unique spatial differentiation mechanism, which can be analyzed from three dimensions: environmental system, economic system, and social system, which play a fundamental role, decisive role, and a magnifying effect on digital rural development, respectively. (2) The DRDL in China’s counties has significant spatial distribution, spatial correlation, and spatial clustering characteristics. The DRDL in general shows a decreasing distribution trend from coastal to inland regions, and the overall differences in DRDL mainly come from intra-regional differences rather than inter-regional differences. The rural infrastructure digitalization dimension has stronger spatial correlation while the spatial correlation of the rural governance digitalization dimension is weaker. There are obvious hotspot and coldspot areas in the DRDL, with large differences between the coldspot and hotspot areas of different sub-dimensions. (3) The spatial divergence of the DRDL is closely related to geographical elements and is the result of the combined effect of several geographical factors. The factor detection results show that the dominant factors within the four regions are significant different. The interaction detection results show that the driving force of the two-factor interaction is stronger than that of the single-factor interaction and that the interaction among the factors further deepens the spatial differentiation of the DRDL.

A biomimetic mineralization method was used in the facile and rapid preparation of nanoflowers for immobilizing alcohol dehydrogenase (ADH). The method mainly uses ADH as an organic component and zinc phosphate as an inorganic component to prepare flower-like ADH/Zn3(PO4)2 organic-inorganic hybrid nanoflowers (HNFs) with the high specific surface area through a self-assembly process. The synthesis conditions of the ADH HNFs were optimized and its morphology was characterized. Under the optimum enzymatic reaction conditions, the Michaelis-Menten constant (Km) of ADH HNFs (β-NAD+ as substrate) was measured to be 3.54 mM, and the half-maximal inhibitory concentration (IC50) of the positive control ranitidine (0.2–0.8 mM) was determined to be 0.49 mM. Subsequently, the inhibitory activity of natural medicine Penthorum chinense Pursh and nine small-molecule compounds on ADH was evaluated using ADH HNFs. The inhibition percentage of the aqueous extract of P. chinense is 57.9%. The vanillic acid, protocatechuic acid, gallic acid, and naringenin have obvious inhibitory effects on ADH, and their percentages of inhibition are 55.1%, 68.3%, 61.9%, and 75.5%, respectively. Moreover, molecular docking analysis was applied to explore the binding modes and sites of the four most active small-molecule compounds to ADH. The results of this study can broaden the application of immobilized enzymes through biomimetic mineralization, and provide a reference for the discovery of ADH inhibitors from natural products.

Abstract The desire to extend the wisdom of traditional health systems has motivated the trade of many phytomedicine on a global scale for centuries, especially some dietary herbs, making a great overlap exits between western and eastern phytomedicine. Despite the communication since ancient times, a key disconnect still exists in the dialog among western and eastern herbal researchers. There is very little systematic effort to tap into the friction and fusion of eastern and western wisdom in utilizing phytomedicine. In this review, we analyzed the similarities and differences of three representative phytomedicine, namely Rhodiola, seabuckthorn, and fenugreek, aiming to open up new horizons in developing novel health products by integrating the wisdom of the east and the west.

Skeletal muscle stem cells (MuSCs), also called satellite cells, are instrumental for postnatal muscle growth and skeletal muscle regeneration. Numerous signaling cascades regulate the fate of MuSCs during muscle regeneration but the molecular mechanism by which MuSCs sense mechanical stimuli remain unclear. Here, we describe that Piezo1, a mechanosensitive ion channel, keeps MuSCs in a quiescent state and prevents senescence. Absence of Piezo1 induces precocious activation of MuSCs, attenuates proliferation, and impairs differentiation, essentially abolishing efficient skeletal muscle regeneration and replenishment of the MuSC pool. Furthermore, we discovered that inactivation of Piezo1 results in compensatory up-regulation of T-type voltage-gated Ca2+ channels, leading to increased Ca2+ influx, which strongly induces NOX4 expression via cPKC. Elevated NOX4 expression in Piezo1-deficient MuSCs increases ROS levels and DNA damage, causing P53-dependent cellular senescence and cell death. The importance of the P53/P21-axis for mediating Piezo1-dependent cellular defects was confirmed by pharmacological inhibition of P53 in Piezo1-deficient mice, which abrogates increased senescence of muscle cells and normalizes muscle regeneration. Our findings uncover an essential role of Piezo1-mediated mechano-signaling in MuSCs for maintaining quiescence and preventing senescence. Reduced mechano-signaling due to decreased physical activity during aging may contribute to the increase of senescent cells and the decline of MuSC numbers in geriatric mice and humans.

Steamed green tea has unique characteristics that differ from other green teas. However, the alteration patterns of non-volatile metabolites during steamed green tea processing are not fully understood. In this study, a widely targeted metabolomic method was employed to explore the changes in non-volatile metabolites during steamed green tea processing. A total of 735 non-volatile compounds were identified, covering 14 subclasses. Of these, 256 compounds showed significant changes in at least one processing step. Most amino acids, main catechins, caffeine, and main sugars were excluded from the analysis. The most significant alterations were observed during steaming, followed by shaping and drying. Steaming resulted in significant increases in the levels of most amino acids and their peptides, most phenolic acids, most organic acids, and most nucleotides and their derivates, as well as some flavonoids. Steaming also resulted in significant decreases in the levels of most lipids and some flavonoids. Shaping and drying caused significant increases in the levels of some flavonoids, phenolic acids, and lipids, and significant decreases in the levels of some amino acids and their peptides, some flavonoids, and some other compounds. Our study provides a comprehensive characterization of the dynamic alterations in non-volatile metabolites during steamed green tea manufacturing.

Abstract Background Shikonin (SKO) is a natural naphthoquinone derived from Chinese herbal medicine Arnebiae Radix with high development potentials due to its anti-inflammatory and anti-tumor activities. Overwhelming evidences have indicated that SKO can induce both necrosis and apoptosis in cancer cells, while the mechanisms for triple negative breast cancer cells is still need to be disclosed. Methods In this study, kinds of molecular biological technologies, including flow-cytometry, Western blot, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA) as well as real-time quantitative PCR (RT-qPCR), were applied for investigation on the underlying mechanisms of SKO induced necrosis and apoptosis for MDA-MB-231 cells. Inhibitors were also used for validation ofthe key signaling pathways involved in SKO triggered necrosis and apoptosis. Results We found that SKO significantly triggered necrosis and apoptosis of MDA-MB-231 cells in both a concentration- and time-dependent manner. Mechanism studies demonstrated that SKO significantly promoted the autoubiquitination levels and facilitated the proteasome dependent degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and cIAP2 in MDA-MB-231 cells. Autoubiquitination and degradation of cIAP1 and cIAP2 induced by SKO further led to significant decreased ubiquitination and inactivation of RIP1, which played an important role in inhibition of pro-survival and accelerating of necrosis of MDA-MB-231 cells. Treatment with proteasome inhibitor lactacystin significantly rescued the cell viability induced by treatment of SKO. Conclusions Our results demonstrate that SKO promotes the autoubiquitination and degradation of cIAP1 and cIAP2, which further induces the decrease of the ubiquitination of RIP1 to inhibit the activation of pro-survival signaling pathways and accelerate the necrosis of MDA-MB-231 cells. The disclosed mechanisms of SKO induced necrosis and apoptosis in our study is firstly reported, and it is believed that SKO could be considered as a potential candidate and further developed for the treatment of triple negative breast cancer.

A 10-week feeding trial was conducted to investigate the beneficial effects of bile acids (BAs) on hepatic health status in tongue sole (Cynoglossus semilaevis). Three experimental diets were prepared with different levels of BA inclusion in the commercial basal diet: control group (CT: 0 mg/kg basal diet), low-level group (BA1: 300 mg/kg basal diet), and high-level group (900 mg/kg basal diet). At the end of the feeding trial, growth performance and survival rate were measured, as well as numerous physiological and biochemical parameters of the liver, including four hepatic function indices, five antioxidant indices, five lipid metabolism parameters, and three digestive enzyme activities. Moreover, the mRNA expression levels of three growth-related genes and three immune-related genes in the liver were assayed. Results showed that growth performance and survival were substantially improved in both low- and high-level BA inclusive groups. Further, the tested liver physiological and biochemical parameters combined with the quantitative real-time PCR results revealed enhanced antioxidant capacity, energy metabolism, digestive ability, and immune response. Finally, these findings provide a wider spectrum of the beneficial effects of dietary BAs on liver health in tongue sole.

Mesenchymal stem/stromal cells derived from placenta (PMSCs) are an attractive source for regenerative medicine because of their multidifferentiation potential and immunomodulatory capabilities. However, the cellular and molecular heterogeneity of PMSCs has not been fully characterized. Here, we applied single-cell RNA sequencing (scRNA-seq) and assay for transposase-accessible chromatin sequencing (scATAC-seq) techniques to cultured PMSCs from human full-term placenta. Based on the inferred characteristics of cell clusters, we identify several distinct subsets of PMSCs with specific characteristics, including immunomodulatory-potential and highly proliferative cell states. Furthermore, integrative analysis of gene expression and chromatin accessibility showed a clearer chromatin accessibility signature than those at the transcriptional level on immunomodulatory-related genes. Cell cycle gene-related heterogeneity can be more easily distinguished at the transcriptional than the chromatin accessibility level in PMSCs. We further reveal putative subset-specific cis-regulatory elements regulating the expression of immunomodulatory- and proliferation-related genes in the immunomodulatory-potential and proliferative subpopulations, respectively. Moreover, we infer a novel transcription factor PRDM1, which might play a crucial role in maintaining immunomodulatory capability by activating PRDM1-regulon loop. Collectively, our study first provides a comprehensive and integrative view of the transcriptomic and epigenomic features of PMSCs, which paves the way for a deeper understanding of cellular heterogeneity and offers fundamental biological insight of PMSC subset-based cell therapy.

The expansion of the white adipose tissue during obesity is accompanied by increased cellular stress, but factors that protect adipocytes from cell death are not well known. Here the authors report that the transcriptional co-activators YAP and TAZ are activated in adipocytes during obesity, which increases adipocyte survival through the proapoptotic factor BIM.

Abstract Coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly around the globe. By the establishment of an integrative system combining both traditional Chinese medicine (TCM) and western medicine, China has achieved good clinical efficacy in the prevention and control of the pandemic. The advantages of TCM in the treatment of COVID-19 include effective relief of symptoms, retarding the development from mild and moderate to severe, improvement of cure rate, reducing death rates, and promotion of rehabilitation. Besides, according to the different severity levels of individual cases, the National Health Commission of the People’s Republic of China issued treatment guidelines that provide corresponding prescriptions for patients. From the perspective of TCM, this review aims to analyze the role of a variety of TCM prescriptions in the treatment of COVID-19, focusing on the analysis of the “Three TCM prescriptions and three medicines” recommended by the Chinese authorities during the pandemic. We expect that this review will provide insights into the prevention and treatment of COVID-19 with TCM.

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years’ development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.