Radiating diversification and niche conservatism jointly shape the inverse latitudinal diversity gradient of Potentilla L. (Rosaceae).

BACKGROUND: The latitudinal diversity gradient (LDG), characterized by an increase in species richness from the poles to the equator, is one of the most pervasive biological patterns. However, inverse LDGs, in which species richness peaks in extratropical regions, are also found in some lineages and their causes remain unclear. Here, we test the roles of evolutionary time, diversification rates, and niche conservatism in explaining the inverse LDG of Potentilla (ca. 500 species). We compiled the global distributions of ~ 90% of Potentilla species, and reconstructed a robust phylogenetic framework based on whole-plastome sequences. Next, we analyzed the divergence time, ancestral area, diversification rate, and ancestral niche to investigate the macroevolutionary history of Potentilla. RESULTS: The genus originated in the Qinghai-Tibet Plateau during the late Eocene and gradually spread to other regions of the Northern Hemisphere posterior to the late Miocene. Rapid cooling after the late Pliocene promoted the radiating diversification of Potentilla. The polyploidization, as well as some cold-adaptive morphological innovations, enhanced the adaptation of Potentilla species to the cold environment. Ancestral niche reconstruction suggests that Potentilla likely originated in a relatively cool environment. The species richness peaks at approximately 45 °N, a region characterized by high diversification rates, and the environmental conditions are similar to the ancestral climate niche. Evolutionary time was not significantly correlated with species richness in the latitudinal gradient. CONCLUSIONS: Our results suggest that the elevated diversification rates in middle latitude regions and the conservatism in thermal niches jointly determined the inverse LDG in Potentilla. This study highlights the importance of integrating evolutionary and ecological approaches to explain the diversity pattern of biological groups on a global scale.

Scalable Preparation of Polyimide Sandwiched Separator for Durable High-Rate Lithium-Metal Battery.

The ever-growing demands for efficient energy storage accelerate the development of high-rate lithium-metal battery (LMB) with desirable energy density, power density, and cycling stability. Nevertheless, the practical application of LMB is critically impeded by internal temperature rise and lithium dendrite growth, especially at high charge/discharge rates. It is highly desired but remains challenging to develop high-performance thermotolerant separators that can provide favorable channels to enable fast Li+ transport for high-rate operation and simultaneously homogenize the lithium deposition for dendrite inhibition. Polyimide-based separators with superior thermal properties are promising candidate alternatives to the commercial polyolefin-based separators, but previous strategies of designing either nanoporous or microporous channels in polyimide-based separators often meet a dilemma. Here, a facile and scalable approach is reported to develop a polyimide fiber/aerogel (denoted as PIFA) separator with the microporous polyimide fiber membrane sandwiched between two nanoporous polyimide aerogel layers, which can enable LMBs with remarkable capacity retention of 97.2% after 1500 cycles at 10 C. The experimental and theoretical studies unravel that the sandwiched structure of PIFA can appreciably enhance the electrolyte adsorption and ionic conductivity; while, the aerogel coating can effectively inhibit dendrite growth to realize durable high-rate LMBs.

Phylogenomic conflict analyses of the plastid and mitochondrial genomes via deep genome skimming highlight their independent evolutionary histories: A case study in the cinquefoil genus Potentilla sensu lato (Potentilleae, Rosaceae).

Phylogenomic conflicts are widespread among genomic data, with most previous studies primarily focusing on nuclear datasets instead of organellar genomes. In this study, we investigate phylogenetic conflict analyses within and between plastid and mitochondrial genomes using Potentilla as a case study. We generated three plastid datasets (coding, noncoding, and all-region) and one mitochondrial dataset (coding regions) to infer phylogenies based on concatenated and multispecies coalescent (MSC) methods. Conflict analyses were then performed using PhyParts and Quartet Sampling (QS). Both plastid and mitochondrial genomes divided the Potentilla into eight highly supported clades, two of which were newly identified in this study. While most organellar loci were uninformative for the majority of nodes (bootstrap value < 70%), PhyParts and QS detected conflicting signals within the two organellar genomes. Regression analyses revealed that conflict signals mainly occurred among shorter loci, whereas longer loci tended to be more concordant with the species tree. In addition, two significant disagreements between the two organellar genomes were detected, likely attributed to hybridization and/or incomplete lineage sorting. Our results demonstrate that mitochondrial genes can fully resolve the phylogenetic relationships among eight major clades of Potentilla and are not always linked with plastome in evolutionary history. Stochastic inferences appear to be the primary source of observed conflicts among the gene trees. We recommend that the loci with short sequence length or containing limited informative sites should be used cautiously in MSC analysis, and suggest the joint application of concatenated and MSC methods for phylogenetic inference using organellar genomes.

Single-atom catalysts for electrocatalytic nitrate reduction into ammonia.

Ammonia (NH3) is a versatile and important compound with a wide range of uses, which is currently produced through the demanding Haber-Bosch process. Electrocatalytic nitrate reduction into ammonia (NRA) has recently emerged as a sustainable approach for NH3synthesis under ambient conditions. However, the NRA catalysis is a complex multistep electrochemical process with competitive hydrogen evolution reaction that usually results in poor selectivity and low yield rate for NH3synthesis. With maximum atom utilization and well-defined catalytic sites, single atom catalysts (SACs) display high activity, selectivity and stability toward various catalytic reactions. Very recently, a number of SACs have been developed as promising NRA electrocatalysts, but systematical discussion about the key factors that affect their NRA performance is not yet to be summarized to date. This review focuses on the latest breakthroughs of SACs toward NRA catalysis, including catalyst preparation, catalyst characterization and theoretical insights. Moreover, the challenges and opportunities for improving the NRA performance of SACs are discussed, with an aim to achieve further advancement in developing high-performance SACs for efficient NH3synthesis.

Relationship between uric acid to high-density cholesterol ratio (UHR) and circulating α-klotho: evidence from NHANES 2007-2016.

OBJECTIVE: To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and circulating α-klotho levels in U.S. adults. METHODS: A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Circulating α-klotho was defined as the dependent variable and UHR was defined as the independent variable. Multivariable linear regression was performed to assess the relationship between the independent and dependent variables. The nonlinear relationship and effect size between UHR and α-klotho were evaluated using smooth curve fitting and threshold effect analysis. Subgroup analysis and sensitivity analysis were conducted to determine the stability of the results. The diagnostic performance of UHR and α-klotho in common elderly diseases was compared using ROC (Receiver Operating Characteristic) analysis. RESULTS: Among 12,849 participants, there was a negative relationship between the UHR and circulating α-klotho. In the fully adjusted overall model, each unit increase in UHR was associated with a decrease of 4.1 pg/mL in α-klotho. The threshold effect analysis showed that before the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 15.0 pg/mL in α-klotho; beyond the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 2.8 pg/mL in α-klotho. Subgroup analyses and sensitivity analysis indicated that the relationship between UHR and α-klotho remained stable across most populations. The ROC diagnostic test indicated that the evaluative efficacy of UHR in diagnosing age-related diseases was comparable to that of α-klotho. CONCLUSION: This study revealed that the UHR was associated with the circulating α-klotho concentration, with a negative association observed in most cases. This finding suggested that the UHR might be a promising indicator for evaluating circulating α-klotho levels.

Past climate cooling and orogenesis of the Hengduan Mountains have influenced the evolution of Impatiens sect. Impatiens (Balsaminaceae) in the Northern Hemisphere.

BACKGROUND: Impatiens sect. Impatiens is distributed across the Northern Hemisphere and has diversified considerably, particularly within the Hengduan Mountains (HDM) in southwest China. Yet, the infra-sectional phylogenetic relationships are not well resolved, largely due to limited taxon sampling and an insufficient number of molecular markers. The evolutionary history of its diversification is also poorly understood. In this study, plastome data and the most complete sampling to date were used to reconstruct a robust phylogenetic framework for this section. The phylogeny was then used to investigate its biogeographical history and diversification patterns, specifically with the aim of understanding the role played by the HDM and past climatic changes in its diversification. RESULTS: A stable phylogeny was reconstructed that strongly supported both the monophyly of the section and its division into seven major clades (Clades I-VII). Molecular dating and ancestral area reconstruction suggest that sect. Impatiens originated in the HDM and Southeast China around 11.76 Ma, after which different lineages dispersed to Northwest China, temperate Eurasia, and North America, mainly during the Pliocene and Pleistocene. An intercontinental dispersal event from East Asia to western North America may have occurred via the Bering Land Bridge or Aleutian Islands. The diversification rate was high during its early history, especially with the HDM, but gradually decreased over time both within and outside the HDM. Multiple linear regression analysis showed that the distribution pattern of species richness was strongly associated with elevation range, elevation, and mean annual temperature. Finally, ancestral niche analysis indicated that sect. Impatiens originated in a relatively cool, middle-elevation area. CONCLUSIONS: We inferred the evolutionary history of sect. Impatiens based on a solid phylogenetic framework. The HDM was the primary source or pump of its diversity in the Northern Hemisphere. Orogeny and climate change may have also shaped its diversification rates, as a steady decrease in the diversification rate coincided with the uplift of the HDM and climate cooling. These findings provide insights into the distribution pattern of sect. Impatiens and other plants in the Northern Hemisphere.

Phylogenomics and historical biogeography of Hydrangeeae (Hydrangeaceae) elucidate the effects of geologic and climatic dynamics on diversification.

Demonstrating the process of transregional biogeography and mechanisms underlying evolutionary radiations is crucial to understanding biological evolution. Here, we use Hydrangeeae (Hydrangeaceae), a tribe with a unique disjunct distribution and complex trait variations, using a solid phylogenetic framework, to investigate how geographical and climatic factors interact with functional traits to trigger plant evolutionary radiations. We constructed the first highly supported and dated phylogenetic framework using 79 protein-coding genes obtained from 81 plastomes, representing 63 species and all major clades, and found that most extant species originated from asynchronous diversification of two lineages undergoing repeated expansion and retraction, at middle and high latitudes of the Northern Hemisphere between East Asia and North America, during the Eocene to Pleistocene (driven by geologic and climatic dynamics). In accordance with these drivers, interactions of flora between central-eastern China and Japan occurred frequently after the Late Tertiary. We found that resource limitation and range fragmentation probably accelerated the diversification of Hydrangeeae, which supports the resource-use hypothesis. Our study sheds light on the evolutionary radiation and assembly of flora within East Asia, and the East Asian-North American disjunction, through integration of phylogenomic and biogeographic data with functional trait and ecological data.

Prognostic value of triglyceride-glucose index in patients with chronic coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a reliable surrogate marker of insulin resistance and an independent predictor of major adverse cardiovascular events (MACEs). Several recent studies have shown the relationship between the TyG index and cardiovascular outcomes; however, the role of the TyG index in chronic coronary syndrome (CCS) progression has not been extensively assessed especially in population after revascularization. This study aimed to investigate the prognostic value of the TyG index in predicting MACEs in CCS patients undergoing percutaneous coronary intervention (PCI). METHODS: The data for the study were taken from the Hospital Information System database in China-Japan Friendship Hospital over the period 2019-2021. Eligible participants were divided into groups according to the TyG index tertiles. The Boruta algorithm was performed for feature selection. Multivariate Cox proportional hazards models and restricted cubic spline (RCS) analysis were applied to examine the dose-response relationship between the TyG index and endpoint, and the results were expressed with hazard ratio (HR) and 95% confidence interval (CI) values. The area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), and clinical impact curve (CIC) were plotted to comprehensively evaluate the predictive accuracy and clinical value of the model. The goodness-of-fit of models was evaluated using the calibration curve and χ2 likelihood ratio test. RESULTS: After applying inclusion and exclusion criteria, 1353 patients with CCS undergoing PCI were enrolled in the study. After adjusting for all confounders, we found that those with the highest TyG index had a 59.5% increased risk of MACEs over the 1-year follow-up (HR 1.595, 95% CI 1.370 ~ 1.855). Using the lowest TyG index tertile as the reference (T1), the fully adjusted HRs (95% CIs) for endpoints was 1.343 (1.054 ~ 1.711) in the middle (T2) and 2.297 (1.842 ~ 2.864) in highest tertile (T3) (P for trend < 0.001). The TyG index had an excellent predictive performance according to the results of AUC 0.810 (0.786, 0.834) and χ2 likelihood ratio test (χ2 = 7.474, P = 0.486). DCA and CIC analysis also suggested a good overall net benefit and clinical impact of the multivariate model. The results in the subgroup analysis were consistent with the main analyses. RCS model demonstrated that the TyG index was nonlinearly associated with the risk of MACEs within one year (P for nonlinear < 0.001). CONCLUSION: The elevated TyG index is associated with an increased risk of cardiovascular events and predicts future MACEs in patients with CCS undergoing PCI independently of known cardiovascular risk factors, indicating that the TyG index may be a potential marker for risk stratification and prognosis in CCS patients undergoing PCI.

Developing long-term conservation priority planning for medicinal plants in China by combining conservation status with diversity hotspot analyses and climate change prediction.

BACKGROUND: Medicinal plants have always played an important role in the history of human health. However, the populations and sustainable use of medicinal plants have been severely affected by human activities and climate change. Little is known about the current conservation status and distribution pattern of medicinal plants. In this study, based on accurate geographical distribution information of 9756 medicinal plants, we identified diversity hotspots and conservation gaps, evaluated conservation effectiveness of nature reserves, and predicted suitable habitat areas for medicinal plants in China to provide scientific guidance for their long-term conservation and sustainable use. RESULTS: A total of 150 diversity hotspot grid cells, mainly concentrated in central and southern China, were identified. These only accounted for 5% of the total distribution area but contained 96% of the medicinal plants of the country. The hotspot grid cells included all traditional hotspot areas, but we also detected three new hotspots, namely Mufu-Lushan Mountains, Tianshan-Altai Mountains, and Changbai Mountains. The current national and provincial nature reserves protect 125 hotspot grid cells, which harbor 94% of all medicinal plants. However, 25 hotspot grid cells, distributed in the Tianshan-Altai Mountains and Hengduan Mountains, are located outside the national and provincial nature reserves. An analysis of the predicted effects of climate change indicated that the suitable habitat areas will shift from southern to northern China, and that southern China will face a considerable loss of suitable habitat areas, while the east and west parts of China will encompass remarkably more suitable habitat areas in the future. CONCLUSIONS: The current conservation networks have achieved high conservation effectiveness with regard to medicinal plants; however, the conservation gaps we identified should not be neglected, and conservation planning needs to take into account the predicted shifts of some hotspots of medicinal plants due to climate change.

Label-free detection of biomarker alpha fetoprotein in serum by ssDNA aptamer functionalized magnetic nanoparticles.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the clinic, with the characteristics of occult onset, rapid progression, and high degree of malignancy. Alpha fetoprotein (AFP) is the most important biomarker of HCC, which is widely used in early screening, diagnosis, and prognosis observation. A series of immunoassays have been developed and frequently used in the detection of AFP based on antibodies. Unfortunately, the shortcomings of antibodies, such as thermal unstable and fluctuant activity by batches, lead to the inaccuracy in the detection of AFP. In this study, aptamers instead of antibodies were adopted as the specific recognition element for AFP, aiming to seek an alternative strategy to immunoassays. An AFP-specific ssDNA aptamer was grafted to magnetic nanoparticles (Fe3O4@SiO2) via avidin-biotin interaction, and the resultant aptamer functionalized magnetic nanoparticles (Ap-MNPs) were adequately characterized and tested. The Ap-MNPs in solution exhibited a fast response to the outer magnetic field, and can be completely separated in several minutes. It was found that Ap-MNPs have good specificity to the target AFP, as the recovery of AFP (87.0%) was much higher than the competitive proteins IgG (38.9%), HSA (18.5%), and FIB (11.4%). A convenient and efficient label-free detection method of AFP in serum was developed based on Ap-MNPs in combination with high-performance liquid chromatography. The linearity of this method was over a range of 1-50 µg ml-1 with a correlation coefficient of 0.9999, and the limit of detection was 0.27 µg ml-1. This study indicated that aptamers are an ideal tool for the recognition and detection of biomarkers, and thus will find wide applications in clinical practice.

Graphene oxide-based magnetic nanocomposites for the delivery of melittin to cervical cancer HeLa cells.

Melittin (MEL), the primary active component of bee venom, has recently emerged as a promising cancer chemotherapeutic agent. However, the instability and rapid degradation of MEL is a significant challenge in practical therapeutic applications. In the present study, graphene oxide (GO)-based magnetic nanocomposites (PEG-GO-Fe3O4) were prepared and adopted as the drug delivery vehicles of MEL, and the anticancer effects of PEG-GO-Fe3O4/MEL complexes on human cervical cancer HeLa cells were studied. PEG-GO-Fe3O4 exhibited a series of unique physical and chemical properties resulting in multiple interactions with MEL, and ultimately the release of MEL. In vitro experiments showed that PEG-GO-Fe3O4/MEL not only distinctly enhanced the inhibition effect on HeLa cells, but also induced pore formation in the cell membrane that ultimately led to cell lysis. In this newly developed drug delivery system, PEGylated GO plays the role of a MEL protector while Fe3O4 nanoparticles act as magnetic responders; therefore active MEL can be released over a long period of time (up to 72 h) and maintain its inhibition effect on HeLa cells.

Dissociative adsorption of O2 on strained Pt(111).

The adsorption and dissociation of O2 and the adsorption of O* adatoms over strained Pt(111) surfaces have been systematically studied using density functional theory calculations. When the applied bilateral strain ranges from compressive (-5%) to tensile (5%), the adsorption strengths of O and O2 at various sites can be varied substantially by 0.3 to 0.9 eV. Moreover, the preferred adsorption site of O2 also changes from tbt to tfb when tensile strain is larger than 3%. The activation barrier of O2 dissociation can be significantly varied by nearly 0.4 eV from -3% to 3% strain. Meanwhile, the combination of O* adatoms and the applied strain can pull the Pt atom out of the surface and result in dramatic surface buckling. The z direction shift of a Pt atom sandwiched by two fcc O* adatoms is over 0.45 Å when compressive strain goes beyond -2%. The abnormal non-linear responses of O adsorption strength and the lateral O-O interaction to strain all arise from the up-buckled Pt atom. We show that strain is a very powerful tool for tuning the thermodynamic and kinetic properties of oxygen adsorption, dissociation and surface bucking of metal surfaces, which are crucial for understanding the catalytic properties and initial oxidation of transition metal based catalysts.

Association between cardiometabolic index and testosterone levels in adult men: NHANES 2011-2016.

OBJECTIVE: Exploring the relationship between the cardiometabolic index (CMI) and serum testosterone levels as well as testosterone deficiency in American adult males. Additionally, comparing the diagnostic value of the CMI with several common obesity and metabolism indices for identifying testosterone deficiency. METHODS: This cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. Serum testosterone levels and testosterone deficiency were used as dependent variables, with the cardiometabolic index as the independent variable. Multivariable regression was used to assess the relationship between the independent and dependent variables, while subgroup analyses were performed to ensure the stability of the results. Smooth curve fitting was utilized to evaluate the nonlinear relationship between the CMI and testosterone levels. Receiver operating characteristic curves (ROC) were plotted for several obesity and metabolism prediction indices and the area under the curve was calculated to compare the specificity and sensitivity of each diagnostic index in the diagnosis of testosterone deficiency. RESULTS: Among 3541 adult male participants, CMI is negatively associated with serum testosterone levels and positively associated with testosterone deficiency. In the fully adjusted model, for every unit increase in CMI, serum testosterone decreased by 14.89 ng/dl. Comparing the highest quartile to the lowest quartile of CMI, each unit increase in CMI, serum testosterone decreased by 98.58 ng/dl. Furthermore, each unit increase in CMI was associated with a 16% increase in incidence of testosterone deficiency. By plotting the ROC curves, we found that the AUCs for Lipid Accumulation Product (LAP), Body Mass Index (BMI), Weight Adjusted Waist Index (WWI), CMI, Visceral Adiposity Index (VAI) and Triglyceride glucose index (TyG) were 0.73, 0.72, 0.71, 0.69, 0.66, and 0.66 respectively. CONCLUSION: Elevated levels of CMI are associated with lower testosterone levels and an increased risk of testosterone deficiency. The predictive value of the LAP was superior to that of CMI, while the predictive value of CMI was higher than VAI and TyG.

Comparative efficacy of eight oral Chinese patent medicines for dilated cardiomyopathy with heart failure: a Bayesian network meta-analysis.

BACKGROUND: Chinese patent medicines (CPMs) are widely used in China as an adjuvant treatment in dilated cardiomyopathy with heart failure (DCM-HF). However, comprehensive and systematic evidence supporting the beneficial effects of CPMs combined with current complementary and alternative medicine (CAM) treatments against DCM-HF was limited. This network meta-analysis (NMA) aimed to assess and rank the relative efficacy of eight different CPMs for DCM-HF. METHODS: To retrieve randomized controlled trials (RCTs) focusing on the use of CPMs combined with CAM for DCM-HF, the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, ProQuest, China National Knowledge Infrastructure (CNKI), China Science Periodical Database (CSPD), Chinese Citation Database (CCD), Chinese Biomedical Literature Database (CBM), and ClinicalTrials.gov were comprehensively searched from their inception to 29 February 2024. The quality of the included RCTs was examined using the Cochrane Risk of Bias assessment tool, version 2.0 (RoB 2). Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the relative efficacy. Bayesian network meta-analysis was designed to assess the efficacy of different CPMs. RESULTS: After applying the inclusion and exclusion criteria, a total of 77 eligible RCTs involving 6980 patients were enrolled. The outcomes assessed included clinical effectiveness rate (CER), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), 6-min walk test (6MWT), brain natriuretic peptide (BNP), and cardiac output (CO). The results of the NMA indicated that Qili Qiangxin capsule (QLQX), Wenxin granule (WX), Tongxinluo capsule (TXL), Qishen Yiqi dropping pill (QSYQ), Shexiang Baoxin pill (SXBX), Yangxinshi tablet (YXST), Yixinshu capsule (YXSC), and Getong Tongluo capsule (GTTL) combined with CAM significantly improved performance compared with CAM alone in treating DCM-HF. YXST + CAM (MD = - 9.93, 95% CI - 12.83 to - 7.03) had the highest probability of being the best treatment on account of the enhancement of LVEF. WX + CAM had the highest likelihood of being the best treatment considering the improvement in LVEDD (MD = - 11.7, 95% CI - 15.70 to - 7.79) and 6MWT (MD = - 51.58, 95% CI - 73.40 to - 29.76). QLQX + CAM (MD = - 158.59, 95% CI - 267.70 to - 49.49) had the highest likelihood of being the best intervention for the reduction in BNP. TXL + CAM (MD = - 0.93, 95% CI - 1.46 to - 0.40) might be the optimal choice for increasing CO levels in DCM-HF patients. No serious treatment-emergent adverse events were observed. CONCLUSION: This NMA suggested that adding CPMs to the current CAM treatment exerted a more positive effect on DCM-HF. Thereinto, QLQX + CAM, TXL + CAM, WX + CAM, and YXST + CAM showed a preferable improvement in patients with DCM-HF when unified considering the clinical effectiveness rate and other outcomes. Furthermore, due to the lack of information on CPMs against DCM-HF and the uneven distribution of included studies among interventions, more high-quality studies are needed to provide more robust evidence to support our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42023482669).

Framework nucleic Acid-MicroRNA mediated hepatic differentiation and functional hepatic spheroid development for treating acute liver failure.

The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.

3D Printing of a Vascularized Mini-Liver Based on the Size-Dependent Functional Enhancements of Cell Spheroids for Rescue of Liver Failure.

The emerging stem cell-derived hepatocyte-like cells (HLCs) are the alternative cell sources of hepatocytes for treatment of highly lethal acute liver failure (ALF). However, the hostile local environment and the immature cell differentiation may compromise their therapeutic efficacy. To this end, human adipose-derived mesenchymal stromal/stem cells (hASCs) are engineered into different-sized multicellular spheroids and co-cultured with 3D coaxially and hexagonally patterned human umbilical vein endothelial cells (HUVECs) in a liver lobule-like manner to enhance their hepatic differentiation efficiency. It is found that small-sized hASC spheroids, with a diameter of ≈50 µm, show superior pro-angiogenic effects and hepatic differentiation compared to the other counterparts. The size-dependent functional enhancements are mediated by the Wnt signaling pathway. Meanwhile, co-culture of hASCs with HUVECs, at a HUVECs/hASCs seeding density ratio of 2:1, distinctly promotes hepatic differentiation and vascularization both in vitro and in vivo, especially when endothelial cells are patterned into hollow hexagons. After subcutaneous implantation, the mini-liver, consisting of HLC spheroids and 3D-printed interconnected vasculatures, can effectively improve liver regeneration in two ALF animal models through amelioration of local oxidative stress and inflammation, reduction of liver necrosis, as well as increase of cell proliferation, thereby showing great promise for clinical translation.

Medicinal plants used by minority ethnic groups in China: Taxonomic diversity and conservation needs.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous communities have long relied on medicinal plants (MPs) for primary healthcare. The ethnomedicinal knowledge are different among ethnic groups since the local flora and people's health beliefs generally vary among biocultural backgrounds. China with its diverse biocultural environment is rich in culturally important plant species including MPs. They are also essential in the context of conservation of plant resources and the related traditional medical knowledge, requiring an integrated perspective on these MPs. AIM OF THE STUDY: Focusing on the MPs used by the minority ethnic groups, this study assesses the diversity of MPs in China used in local indigenous traditions, as well as their conservation needs. MATERIALS AND METHODS: The MPs used by the 18 selected minority ethnic groups were extracted from an ethnic MP dictionary. After standardizing, the names then were compiled as an inventory. Next, following statistics were computed: the number of species in each order and family, species used by each ethnic group, species documented in the national herbal resource dataset, species adopted in drug standards, and species at different levels of conservation lists. The overall similarity of the MPs used by the ethnic groups included was achieved using a cluster and principal component analysis. RESULTS: In total 5886 vascular plant species are reported as medicines in the 18 ethnic groups, which belong to 1657 genera and 243 families. It is found that 3195 species are used exclusively by one ethnic group, indicating their cultural salience and potential restrictedness in ecological terms. Moreover, 1159 species are included in national/regional drug standards, indicating their importance in the national medical flora. However, only 3541 species of them are documented in the national herbal resource dataset, and 761 species are at different levels of threatened status, highlighting the conservation needs of Chinese MPs and the related traditional medical knowledge. CONCLUSIONS: Using a quantitative approach, for the first time the present study reveals the high level of taxonomic diversity of MPs used by minority ethnic groups of China. However, of these species, 40% are still not inventoried in the national herbal resource dataset, and more than half are used exclusively by one ethnic group, and around 13% are included in the conservation lists of different levels. These together urge the conservation of MP resources and related traditional medical knowledge. Additionally, we recommend fostering the cross-cultural communication the regional ethnomedicinal knowledge, for the purpose of maximizing the benefits of regional plants to human.

Smart Microneedle Arrays Integrating Cell-Free Therapy and Nanocatalysis to Treat Liver Fibrosis.

Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome-based cell-free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell-free and platinum-based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70-90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.

Mechanically Strong and Thermally Insulating Polyimide Aerogel Fibers Reinforced by Prefabricated Long Polyimide Fibers.

Aerogel fibers inherit the merits of aerogel and fibrous materials, such as high porosity and satisfactory knittability, demonstrating great potential as thermal protective materials applied in harsh environments. Nevertheless, the inferior mechanical property resulting from the porous structure immensely hampers the practical application of aerogel fibers. Herein, we develop robust and thermally insulating long polyimide fiber-reinforced polyimide composite aerogel fibers (LPF-PAFs). The porous crosslinked polyimide aerogel as the sheath endows LPF-PAFs with good thermal insulation performance, while the long polyimide fibers as the core provide LPF-PAFs with superior mechanical strength. Due to the introduction of the high-strength long polyimide fibers to undertake significant stress, LPF-PAFs display outstanding strength surpassing 150 MPa without obvious mechanical performance degeneration in a wide range of temperatures from -100 to 300 °C. Moreover, the textile woven by LPF-PAFs exhibits a superior thermal insulation ability and stability to cotton textile at 200 and -100 °C, indicating its potential application in thermal protective clothing under extreme environments.

MicroRNA-122-functionalized DNA tetrahedron stimulate hepatic differentiation of human mesenchymal stem cells for acute liver failure therapy.

As the most abundant liver-specific microRNA, microRNA-122 (miR122) played a crucial role in the differentiation of stem cells into hepatocytes. However, highly efficient miR122 delivery still confronts challenges including poor cellular uptake and easy biodegradation. Herein, we for the first time demonstrated that the tetrahedral DNA (TDN) nanoplatform had great potential in inducing the differentiation of human mesenchymal stem cells (hMSCs) into functional hepatocyte-like cells (HLCs) by transferring the liver-specific miR122 to hMSCs efficiently without any extrinsic factors. As compared with miR122, miR122-functionalized TDN (TDN-miR122) could significantly up-regulate the protein expression levels of mature hepatocyte markers and hepatocyte-specific marker genes in hMSCs, indicating that TDN-miR122 could particularly activate the hepatocyte-specific properties of hMSCs for developing cell-based therapies in vitro. The transcriptomic analysis further indicated the potential mechanism that TDN-miR122 assisted hMSCs differentiated into functional HLCs. The TDN-miR122-hMSCs exhibited hepatic cell morphology phenotype, significantly up-regulated specific hepatocyte genes and hepatic biofunctions in comparison with the undifferentiated MSCs. Preclinical in vivo transplantation appeared that TDN-miR122-hMSCs in combination with or without TDN could efficiently rescue acute liver failure injury through hepatocyte function supplement, anti-apoptosis, cellular proliferation promotion, and anti-inflammatory. Collectively, our findings may provide a new and facile approach for hepatic differentiation of hMSCs for acute liver failure therapy. Further large animal model explorations are needed to study their potential in clinical translation in the future.