scCancer2: data-driven in-depth annotations of the tumor microenvironment at single-level resolution.

SUMMARY: Single-cell RNA-seq (scRNA-seq) is a powerful technique for decoding the complex cellular compositions in the tumor microenvironment (TME). As previous studies have defined many meaningful cell subtypes in several tumor types, there is a great need to computationally transfer these labels to new datasets. Also, different studies used different approaches or criteria to define the cell subtypes for the same major cell lineages. The relationships between the cell subtypes defined in different studies should be carefully evaluated. In this updated package scCancer2, designed for integrative tumor scRNA-seq data analysis, we developed a supervised machine learning framework to annotate TME cells with annotated cell subtypes from 15 scRNA-seq datasets with 594 samples in total. Based on the trained classifiers, we quantitatively constructed the similarity maps between the cell subtypes defined in different references by testing on all the 15 datasets. Secondly, to improve the identification of malignant cells, we designed a classifier by integrating large-scale pan-cancer TCGA bulk gene expression datasets and scRNA-seq datasets (10 cancer types, 175 samples, 663 857 cells). This classifier shows robust performances when no internal confidential reference cells are available. Thirdly, scCancer2 integrated a module to process the spatial transcriptomic data and analyze the spatial features of TME. AVAILABILITY AND IMPLEMENTATION: The package and user documentation are available at http://lifeome.net/software/sccancer2/ and https://doi.org/10.5281/zenodo.10477296.

Single-cell and spatially resolved transcriptomics for liver biology.

Single-cell transcriptomics enables the identification of rare cell types and the inference of state transitions, whereas spatially resolved transcriptomics allows the quantification of cells and genes in the context of tissues. The recent progress in these new technologies is improving our understanding of the cell landscape and its roles in diseases. Here, we review key biological insights into liver homeostasis, development, regeneration, chronic liver disease, and cancer obtained from single-cell and spatially resolved transcriptomics. We highlight recent progress in the liver cell atlas that characterizes the comprehensive cellular composition; diversity and function; the spatial architecture such as liver zonation, cell communication, and proximity; the cell identity conversion and cell-specific alterations that are associated with liver pathology; and new therapeutic targets. We further discuss outstanding challenges, advanced experimental technologies, and computational methods that help to address these challenges.

Analysis of extreme ultraviolet radiation and hydrodynamics simulation at the core of laser-produced nickel plasmas.

The non-uniformity and transient nature of laser-produced plasma are critical factors that affect the analysis of the extreme ultraviolet spectra of highly charged ions and the diagnosis of plasma states. This paper systematically investigates the characteristics of extreme ultraviolet radiation and the hydrodynamic evolution of laser-produced nickel plasmas from two perspectives: high-spatio-temporal-resolution extreme-ultraviolet spectroscopic measurement and radiation hydrodynamics simulation. The consistency between the four-band experimental spectra and their theoretically simulated spectra confirms the accuracy of the atomic structure parameters and plasma state parameters. We also analyze the significant contribution of the 3d-4f double-excited state radiation to the spectral profile and discuss the influence of the self-absorption caused by plasma opacity on the characteristics of extreme ultraviolet radiation. The findings are crucial for accurately understanding the characteristics of extreme ultraviolet radiation, the hydrodynamic evolution, and the application of medium- and high-Z laser-produced plasma as a pulsed short-wavelength light source.

Reconstruction and analysis of transient evolution images of laser-produced plasma plumes.

We introduce a method for the analysis and simulation of transient images of laser-produced plasma (LPP) plumes. This method comprises three steps: (i) calculating the two-dimensional distribution of plasma parameters using a radiation hydrodynamics model, (ii) constructing radiation paths through ray tracing, and (iii) solving the radiation transport equation along these paths. In our simulations, we have meticulously considered factors that could influence the imaging results, including the quantum efficiency to different radiation wavelengths, the imaging lens' transmittance, the target surface's reflectivity, and the absorption, emission, and scattering quantum effect of the detector processes occurring in the plasma. We applied this method to analyze and simulate the transient images of aluminum plasma plumes in a background air environment at a pressure of 2000 Pa. The results demonstrate that our method not only produces simulated images that align with experimental results but also provides a reliable distribution of plasma state parameters and clearly identifies the ion species radiating in different bands. Given its capability in transient image reconstruction and its adaptability as a tool for spectral simulation and analysis of LPPs, we believe this method holds significant potential for spectral diagnostics in fields such as laser-induced breakdown spectroscopy, extreme ultraviolet lithography sources, and high-energy-density physics, among others.

miR-21-5p-loaded bone mesenchymal stem cell-derived exosomes repair ovarian function in autoimmune premature ovarian insufficiency by targeting MSX1.

RESEARCH QUESTION: What is the effect of micro-RNA (miR)-21-5p-loaded bone marrow mesenchymal stem cell-derived exosomes (miR-21-Exo) on autoimmune premature ovarian insufficiency (POI)? DESIGN: The Cell Counting Kit 8 (CCK8) assay, fluorescence-activated cell sorting, western blotting, quantitative reverse transcriptase (qRT)-PCR and enzyme-linked immunosorbent assay (ELISA) verified the effect of miR-21-Exo on interferon-γ (IFN-γ)-induced KGN cells. qRT-PCR, western blotting and dual-luciferase reporter gene assays verified that miR-21-Exo mediated Msh homeobox 1 (MSX1) regulation of the Notch signalling pathway and that miR-21 interacted directly with MSX1. The effects of miR-21-Exo on the ovaries were verified by monitoring of the oestrous cycle, haematoxylin and eosin staining, follicle counts, ELISA, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL), western blotting and qRT-PCR. RESULTS: The results showed that miR-21-Exo promoted IFN-γ-induced KGN cell proliferation and hormone synthesis, and inhibited apoptosis. Using dual-luciferase reporter gene assays, miR-21 and MSX1 were shown to have direct interactions. Moreover, the findings elucidated that miR-21-Exo inhibited cell apoptosis and promoted hormone synthesis by mediating MSX1 to regulate the Notch signalling pathway. miR-21-Exo restored the ovarian structure in a mouse model of autoimmune POI, promoted endocrine function and proliferation, and inhibited apoptosis and inflammation in vivo. CONCLUSIONS: This study demonstrates that miR-21-Exo regulates the MSX1-mediated Notch signalling pathway to inhibit granulosa cell apoptosis and improve hormone synthesis function, providing insight into a potential mechanism of molecular therapy for the treatment of autoimmune POI.

Diverse amdoparvoviruses infection of farmed Asian badgers (Meles meles).

Amdoparvoviruses infect various carnivores, including mustelids, canids, skunks, and felids. Aleutian mink disease virus (AMDV) belongs to the prototypical species Amdoparvovirus carnivoran1. Here, we identified a novel amdoparvovirus in farmed Asian badgers (Meles meles), and we named this virus "Meles meles amdoparvovirus" (MMADV). A total of 146 clinical samples were collected from 134 individual badgers, and 30.6% (41/134) of the sampled badgers tested positive for amdoparvovirus by PCR. Viral DNA was detected in feces, blood, spleen, liver, lung, and adipose tissue from these animals. Viral sequences from eight samples were determined, five of which represented nearly full-length genome sequences (4,237-4,265 nt). Six serum samples tested positive by PCR, CIEP, and IAT, four of which had high antibody titers (> 512) against AMDV-G. Twenty-six of the 41 amdoparvovirus-positive badgers showed signs of illness, and necropsy revealed lesions in their organs. Sequence comparisons and phylogenetic analysis of the viral NS1 and VP2 genes of these badger amdoparvoviruses showed that their NS1 proteins shared 62.6%-88.8% sequence identity with known amdoparvoviruses, and they clustered phylogenetically into two related clades. The VP2 proteins shared 76.6%-97.2% identity and clustered into two clades, one of which included raccoon dog and arctic fox amdoparvovirus (RFAV), and the other of which did not include other known amdoparvoviruses. According to the NS1-protein-based criterion for parvovirus species demarcation, the MMADV isolate from farm YS should be classified as a member of a new species of the genus Amdoparvovirus. In summary, we have discovered a novel MMADV and other badger amdoparvoviruses that naturally infect Asian badgers and are possibly pathogenic in badgers.

Occurrence and fate of current-use pesticides in Chinese forest soils.

Pesticides play a crucial role in securing global food production to meet increasing demands. However, because of their pervasive use, they are now ubiquitous environmental pollutants that have adverse effects on both ecosystems and human health. In this study, the environmental occurrence and fate of 16 current-use pesticides (CUPs) were investigated in 93 forest soil samples obtained from 11 distinct mountains in China. The concentrations of the target pesticides ranged from 0.36 to 55 ng/g dry weight. Cypermethrin, dicofol, chlorpyrifos, chlorothalonil, and trifluralin were the most frequently detected CUPs. The CUP concentrations were generally higher in the O-horizon than in the A-horizon. Chlorpyrifos, chlorothalonil, and dicofol were detected in most deep layers in soil profiles from three mountains selected to represent distinct climate zones. No clear altitudinal trend in organic carbon-normalized concentrations of CUPs was observed in the O- or A-horizons within individual mountains. A negative correlation was noted between the CUP concentrations and the altitudes across all sampling sites. This indicated that proximity to emission sources was a key factor affecting the spatial distribution of CUPs in mountain forest soil on a national scale. The ecological risk assessment showed that dicofol and cypermethrin pose potential risks to earthworms. This study emphasizes the importance of source control when setting management strategies for CUPs.

Warming-induced shifts in alpine soil microbiome: An ecosystem-scale study with environmental context-dependent insights.

Climate warming is a pressing global issue with substantial impacts on soil health and function. However, the influence of environmental context on the responses of soil microorganisms to warming remains largely elusive, particularly in alpine ecosystems. This study examined the responses of the soil microbiome to in situ experimental warming across three elevations (3850 m, 4100 m, and 4250 m) in the meadow of Gongga Mountain, eastern Tibetan Plateau. Our findings demonstrate that soil microbial diversity is highly resilient to warming, with significant impacts observed only at specific elevations. Furthermore, the influence of warming on the composition of the soil microbial community is also elevation-dependent, underscoring the importance of local environmental context in shaping microbial evolution in alpine soils under climate warming. Notably, we identified soil moisture at 3850 m and carbon-to-nitrogen ratio at 4250 m as indirect predictors regulating the responses of microbial diversity to warming at specific elevations. These findings underscore the paramount importance of considering pre-existing environmental conditions in predicting the response of alpine soil microbiomes to climate warming. Our study provides novel insights into the intricate interactions between climate warming, soil microbiome, and environmental context in alpine ecosystems, illuminating the complex mechanisms governing soil microbial ecology in these fragile and sensitive environments.

Comparison of pregnancy outcomes among patients of different ages who underwent frozen-thawed high-quality single blastocyst transfer.

OBJECTIVE: To investigate the feasibility of performing frozen-thawed high-quality single blastocyst transfer in women of different ages. METHODS: A total of 1,279 women were divided into four groups: a 38-40-year-old group (n = 147), 35-37-year-old group (n = 164), 30-34-year-old group (n = 483), and < 30-year-old group (n = 485). Intergroup comparisons of baseline characteristics and pregnancy and neonatal outcomes were made. RESULTS: The clinical pregnancy rate (47.6%), and live birth rate (34.0%) in the 38-40-year-old group were significantly lower than those in the 30-34-year-old group (64.4%, 50.9%, respectively; all P < 0.001) and < 30-year-old group (62.9%, 50.7%, respectively; all P < 0.001). However, the 35-37-year-old group did not differ from the other three groups in these two dimensions (all P > 0.05). Moreover, there were no differences in the rates of biochemical pregnancy, miscarriage, or obstetric or neonatal complications among the four groups (all P > 0.05). According to the multivariate logistic regression analysis, the 35-37-year-old group was not associated with non-live birth outcomes, adverse pregnancy outcomes, or obstetric or neonatal complications. However, being 38-40 years of age was a risk factor for non-live birth (OR = 2.121, 95% CI: 1.233-3.647) and adverse pregnancy outcomes (OR = 1.630, 95% CI: 1.010-2.633). Post hoc power analysis showed that the study was sufficiently powered to detect meaningful differences. CONCLUSION: Frozen-thawed high-quality single blastocyst transfer produces the same satisfactory pregnancy outcomes for women aged 35-37 years as younger patients. Future prospective randomized controlled studies with larger populations are needed to verify the feasibility and safety of this method.

Ultrasonic Evaluation of the Asian Nasal Soft Tissue Envelope.

OBJECTIVE: The thickness of the nasal soft tissue envelope (STE) plays a crucial role in the final rhinoplasty results. The Asian nasal contour is typically characterized by a thicker STE and broader nasal tip, but objective data are lacking. The purpose of this study was to objectively measure nasal dermal thickness and overall STE thickness and to determine any demographic differences. METHODS: From July to September 2023, 110 patients presenting for consultation underwent ultrasound evaluation of their nasal STE. STE thickness was measured at predetermined subsites and compared with published data on white patients. RESULTS: The thickness of the STE in Asian patients was greater than that in white patients. The STE was thickest at the supratip (mean [SD]), (4.88 [0.74] mm) rather than at the nasion and thinnest at the rhinion (2.25 [0.51] mm). The nasal tip (4.07 [0.72] mm) showed comparable STE thickness with the nasion (4.13 [0.72] mm) but had a significantly thicker dermis than the nasion (2.35 ± 0.49 mm vs. 1.35 ± 0.35 mm, P < 0.05). Male sex and higher BMI tended to be correlated with a thicker nasal STE, but age did not show any relationship. A thicker nasal tip STE showed significantly greater nasal tip width and nasal alar thickness. CONCLUSION: STE thickness at different nasal subsites varies and affects external nasal contour and rhinoplasty outcomes. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Microbial nutrient limitation and carbon use efficiency changes under different degrees of litter decomposition.

Alpine ecosystems are important terrestrial carbon (C) pools, and microbial decomposers play a key role in litter decomposition. Microbial metabolic limitations in these ecosystems, however, remain unclear. The objectives of this study aim to elucidate the characteristics of microbial nutrient limitation and their C use efficiency (CUE), and to evaluate their response to environmental factors. Five ecological indicators were utilized to assess and compare the degree of microbial elemental homeostasis and the nutrient limitations of the microbial communities among varying stages of litter decomposition (L, F, and H horizon) along an altitudinal gradient (2800, 3000, 3250, and 3500 m) under uniform vegetation (Abies fabri) on Gongga Mountain, eastern Tibetan Plateau. In this study, microorganisms in the litter reached a strictly homeostatic of C content exclusively during the middle stage of litter decomposition (F horizon). Based on the stoichiometry of soil enzymes, we observed that microbial N- and P-limitation increased during litter degradation, but that P-limitation was stronger than N-limitation at the late stages of degradation (H horizon). Furthermore, an increase in microbial CUE corresponded with a reduction in microbial C-limitation. Additionally, redundancy analysis (RDA) based on forward selection further showed that microbial biomass C (MBC) is closely associated with the enzyme activities and their ratios, and MBC was also an important factor in characterizing changes in microbial nutrient limitation and CUE. Our findings suggest that variations in MBC, rather than N- and P-related components, predominantly influence microbial metabolic processes during litter decomposition on Gongga Mountain, eastern Tibetan Plateau.

Pollution and mobility of heavy metals in the soils of a typical agricultural zone in eastern China.

The pollution of heavy metals (HMs) in agricultural soils profoundly threatens national food safety, and the mobility and environmental behaviors of HMs are closely implicated in crop safety. Here, we assessed the pollution level and mobility of ten HMs and explored their environmental behaviors in the soils of three different land uses from a main crop production zone in eastern China. The concentrations of HMs in the soils were higher in the farmland than the woodland and wasteland, and Cd showed a relatively higher pollution and ecological risk levels compared to other metals. Cadmium was dominated by the reducible (41%) and exchangeable (23%) fractions, and the rest of HMs were mainly in the residual fraction (> 60%). The significant correlation between the exchangeable and DGT-labile Cd indicates relatively higher mobility of Cd in the soils. Soil pH, organic matters and mineral elements had significant correlation with the exchangeable and reducible fractions of most of the HMs (e.g., Cd, Co, Mn, Ni, Pb and V; p < 0.05), indicating their good predictors of the HMs mobility. However, this was not the case for the DGT-labile fraction, which suggests a marked difference in the controlling mechanisms of the mobility versus potential bioavailability of HMs in the soils. The results of this study indicate that both the chemically extracted fractions and the bioavailable fractions of HMs need be considered when effectively assessing the safety of agricultural soils.

Clinical efficacy of blood derivatives on wound healing: A systematic review and network meta-analysis.

This study aims to evaluate the clinical effects of different blood derivatives on wound healing using network meta-analysis. PubMed, Embase, OVID, Web of Science, SCOPUS and Cochrane Central were searched to obtain studies about blood derivatives on wound healing until October 2023. R 4.2.0 and Stata 15.0 softwares were used for data analysis. Forty-four studies comprising 5164 patients were included. The results of network meta-analysis showed that the healing area from high to low was GF + ORCCB, ORCCB, GF, PRF, Unnas paste dressing, APG, PRP injection, PRP, PRP + thrombin gel, PPP, HPL, CT. The healing time from low to high was PRP + thrombin gel, GF, PRP, PC + K, PC, APG, PRF, CT, Silver sulfadiazine ointment. The number of patients cured from high to low was APG, PRP injection, PRP, Aurix, PRF, Leucopatch, HPL, Antimicrobial Ointment Dressing, CT, 60 µg/cm2 repifermin, 120 µg/cm2 repifermin, AFG, PPP. The order of analgesic effect from high to low was AFG, Aminogam gel, PRF, PRP, Oxidised oil, APG, GF, CT. The order of the number of wound infection cases from low to high is APG, 20 µg/cm2 repifermin, 60 µg/cm2 repifermin, PRP, LeucoPatch, CT, PPP, Antiseptic ointment dressing. Healing area: GF + ORCCB had the best effect; Healing time: PRP + thrombin gel took the shortest time. The number of cured patients and the reduction of wound infection: APG has the best effect. Analgesic effect: AFG has the best effect. More studies with large sample sizes are needed to confirm the above findings.

Effect the accumulation of bioactive constituents of a medicinal plant (Salvia Miltiorrhiza Bge.) by arbuscular mycorrhizal fungi community.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with various terrestrial plants and have attracted considerable interest as biofertilizers for improving the quality and yield of medicinal plants. Despite the widespread distribution of AMFs in Salvia miltiorrhiza Bunge's roots, research on the impact of multiple AMFs on biomass and active ingredient accumulations has not been conducted. In this study, the effects of five native AMFs (Glomus formosanum, Septoglomus constrictum, Rhizophagus manihotis, Acaulospora laevis, and Ambispora gerdemannii) and twenty-six communities on the root biomass and active ingredient concentrations of S. miltiorrhiza were assessed using the total factor design method. RESULTS: Thirty-one treatment groups formed symbiotic relationships with S. miltiorrhiza based on the pot culture results, and the colonization rate ranged from 54.83% to 89.97%. AMF communities had higher colonization rates and total phenolic acid concentration than single AMF, and communities also appeared to have higher root fresh weight, dry weight, and total phenolic acid concentration than single inoculations. As AMF richness increased, there was a rising trend in root biomass and total tanshinone accumulations (ATTS), while total phenolic acid accumulations (ATP) showed a decreasing trend. This suggests that plant productivity was influenced by the AMF richness, with higher inoculation benefits observed when the communities contained three or four AMFs. Additionally, the affinities of AMF members were also connected to plant productivity. The inoculation effect of closely related AMFs within the same family, such as G. formosanum, S. constrictum, and R. manihotis, consistently yielded lower than that of mono-inoculation when any combinations were applied. The co-inoculation of S. miltiorrhiza with nearby or distant AMFs from two families, such as G. formosanum, R. manihotis, and Ac. laevis or Am. gerdemannii resulted in an increase of ATP and ATTS by more than 50%. AMF communities appear to be more beneficial to the yield of bioactive constituents than the single AMF, but overall community inoculation effects are related to the composition of AMFs and the relationship between members. CONCLUSION: This study reveals that the AMF community has great potential to improve the productivity and the accumulation of bioactive constituents in S. miltiorrhiza, indicating that it is an effective way to achieve sustainable agricultural development through using the AMF community.

Real optical imaging simulation of laser-produced aluminum plasmas.

We developed a post-processing optical imaging model based on two-dimensional axisymmetric radiation hydrodynamics. Simulation and program benchmarks were performed using laser-produced Al plasma optical images obtained via transient imaging. The emission profiles of a laser-produced Al plasma plume in air at atmospheric pressure were reproduced, and the influence of plasma state parameters on radiation characteristics were clarified. In this model, the radiation transport equation is solved on the real optical path, which is mainly used to study the radiation of luminescent particles during plasma expansion. The model outputs consist of the electron temperature, particle density, charge distribution, absorption coefficient, and corresponding spatio-temporal evolution of the optical radiation profile. The model helps with understanding element detection and quantitative analysis of laser-induced breakdown spectroscopy.

Structure of the full-length glucagon class B G-protein-coupled receptor.

The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled receptor family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 Å crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation. The two domains are connected by a 12-residue segment termed the stalk, which adopts a ß-strand conformation, instead of forming an α-helix as observed in the previously solved structure of the GCGR transmembrane domain. The first extracellular loop exhibits a ß-hairpin conformation and interacts with the stalk to form a compact ß-sheet structure. Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics studies suggest that the stalk and the first extracellular loop have critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding of the signalling mechanisms of class B G-protein-coupled receptors.

Soil covering measure mitigates vanadium loss during short-term simulated rainfall in the vanadium titano-magnetite tailings reservoir.

Soil covering is an operative measure to decline pollutant release in tailings reservoirs and promote vegetation restoration, yet urgent research still needs to probe into pollutant leaching and migration in the artifact technology under extreme precipitation. Here, a soil column leaching experiment was designed to explore the migration and behaviors of vanadium (V) in the system of vanadium titano-magnetite tailings (VTMTs) covered by soils with different depths (5 cm, 10 cm, and 15 cm). Chemical fractions of V in the VTMTs and covered soils were analyzed to decipher the mechanisms underlying the V migration. We found a limited V leaching (0.26-0.52 µg/L, <0.01% of total V) in the columns during the experiments, and V in the VTMTs was not apt to be leached or migrate upward to the overlying soils. The soil volumes overlaid had nonsignificant effect on the V behaviors in the VTMTs (P > 0.05), because of the dominant and stable residual V (96.4% of total V) in the tailings. Although acid soluble V might be transformed to oxidizable V, it was resupplied by the fractions of weak-bound V in the solid phases during the leaching experiments. The mineral metal (hydr)oxides (e.g., aluminum, iron) determined the V behaviors in the VTMTs via absorption effect, and the high affinity of V to organic matters probably prevented its migration throughout the overlying soils. The results indicate that soil covering measure in the VTMTs reservoirs effectively reduces V migration or release from the tailings through leaching or upward migration, which provides a significant guidance for vegetation restoration in V-rich tailings reservoirs.

Protective Role of lncRNA TTN-AS1 in Sepsis-Induced Myocardial Injury Via miR-29a/E2F2 Axis.

OBJECTIVE: Approximately 50% of patients with sepsis encounter myocardial injury. The mortality of septic patients with cardiac dysfunction (approx. 70%) is much higher than that of patients with sepsis only (20%). A large number of studies have suggested that lncRNA TTN-AS1 promotes cell proliferation in a variety of diseases. This study delves into the function and mechanism of TTN-AS1 in sepsis-induced myocardial injury in vitro and in vivo. METHODS: LPS was used to induce sepsis in rats and H9c2 cells. Cardiac function of rats was assessed by an ultrasound system. Myocardial injury was revealed by hematoxylin-eosin (H&E) staining. Gain and loss of function of TTN-AS1, miR-29a, and E2F2 was achieved in H9c2 cells before LPS treatment. The expression levels of inflammatory cytokines and cTnT were monitored by ELISA. The expression levels of cardiac enzymes as well as reactive oxygen species (ROS) activity and mitochondrial membrane potential (MMP) were measured using the colorimetric method. The expression levels of TTN-AS1, miR-29a, E2F2, and apoptosis-related proteins were measured by RT-qPCR and/or western blotting. The proliferation and apoptosis of H9c2 cells were separately detected by CCK-8 and flow cytometry. Luciferase reporter assay was used to verify the targeting relationships among TTN-AS1, miR-29a and E2F2, and RIP assay was further used to confirm the binding between miR-29a and E2F2. RESULTS: TTN-AS1 was lowly expressed, while miR-29a was overexpressed in the cell and animal models of sepsis. Overexpression of TTN-AS1 or silencing of miR-29a reduced the expression levels of CK, CK-MB, LDH, TNF-B, IL-1B, and IL-6 in the supernatant of LPS-induced H9c2 cells, attenuated mitochondrial ROS activity, and enhanced MMP. Consistent results were observed in septic rats injected with OE-TTN-AS1. Knockdown of TTN-AS1 or overexpression of miR-29a increased LPS-induced inflammation and injury in H9c2 cells. TTN-AS1 regulated the expression of E2F2 by targeting miR-29a. Overexpression of miR-29a or inhibition of E2F2 abrogated the suppressive effect of TTN-AS1 overexpression on myocardial injury. CONCLUSION: This study indicates TTN-AS1 attenuates sepsis-induced myocardial injury by regulating the miR-29a/E2F2 axis and sheds light on lncRNA-based treatment of sepsis-induced cardiomyopathy.

The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation.

Sepsis-induced acute kidney injury (AKI) is a common and life-threatening complication in hospitalized and critically ill patients and has unacceptable morbidity and mortality rates. However, effective approaches for the diagnosis and treatment of septic AKI are still lacking. Here, we demonstrated significant increases in the miR-26a-5p levels in renal tubular cells of LPS-induced septic AKI models both in vivo and in vitro. Mechanistically, we provided evidence of the involvement of NF-κB in miR-26a-5p induction. LPS treatment of renal tubular cells led to the activation of NF-κB, and inhibition of NF-κB by TPCA-1 prevented the induction of miR-26a-5p. These results indicated that NF-κB was a key upstream factor for the induction of miR-26a-5p in septic AKI. Anti-miR-26a-5p enhanced the expression of IL-6 at both the protein and mRNA levels following LPS treatment. Furthermore, our luciferase microRNA target reporter assay verified that IL-6 is a direct target of miR-26a-5p. Blocking miR-26a-5p promoted renal inflammation and worsened kidney injury. Thus, our study indicated that the miR-26a-5p/IL-6 axis can alleviate sepsis-induced acute kidney injury by inhibiting renal inflammation. This mechanism may represent a therapeutic target for septic AKI.

Novel ecological ditch system for nutrient removal from farmland drainage in plain area: Performance and mechanism.

The loading of nitrogen (N) and phosphorus (P) from agricultural drainage as the non-point sources is a worldwide environmental issue for aquatic ecosystem. However, how to remove these nutrients effectively from agricultural drainage remains a big challenge with increasing cemented ditches for better management. Here, we designed a novel ecological ditch system which integrated an earth ditch and a cemented ditch with iron-loaded biochar in the Chengdu Plain to reduce the loss of N and P from farmland. After a two-year monitoring, the removal efficiency of total N and total P reached 24.9% and 36.1% by the earth ditch and 30.7% and 57.8% by the integrated ditch system, respectively. The water quality was evidently improved after passing through the ditch system with the marked decrease in the concentrations of N and P. Dissolved organic N, nitrate, and particulate P became the dominant fractions of N and P loss. Rainfall soon after fertilization increased the concentrations of N and P in the ditch system and markedly affected their removal efficiency. The iron-loaded biochar effectively removed N and P from the drainage, especially at the high concentrations, which was mainly attributed to its high adsorption of the dissolved N and P fractions and the interception of the particulate nutrients. Our results indicate that the designed ecological ditch system has a high potential for alleviating agricultural non-point source pollution in the plain area and can be extended to other lowland agricultural ecosystems.