Sciadonic acid attenuates high-fat diet-induced bone metabolism disorders in mice.

High-fat diet (HFD) has been associated with certain negative bone-related outcomes, such as bone metabolism disruption and bone loss. Sciadonic acid (SC), one of the main nutritional and functional components of Torreya grandis seed oil, is a unique Δ5-unsaturated-polymethylene-interrupted fatty acid (Δ5-UPIFA) that has been claimed to counteract such disorders owing to some of its physiological effects. However, the role of SC in ameliorating bone metabolism disorders due to HFD remains unclear. In the present investigation, we observed that SC modulates the OPG/RANKL/RANK signaling pathway by modifying the lipid metabolic state and decreasing inflammation in mice. In turn, it could balance bone resorption and formation as well as calcium and phosphorus levels, enhance bone strength and bone mineral density (BMD), and improve its microstructure. In addition, SC could inhibit fat vacuoles in bone, reverse the phenomenon of reduced numbers and poor continuity of bone trabeculae, and promote orderly arrangement of collagen fibers and cartilage repair. This study provides some theoretical basis for SC as a dietary intervention agent to enhance bone nutrition.

Feasibility of tracheal reconstruction using silicone-stented aortic allografts.

OBJECTIVES: Tracheal reconstruction post-extensive resection remains an unresolved challenge in thoracic surgery. This study evaluates the use of aortic allografts (AAs) for tracheal replacement and reconstruction in a rat model, aiming to elucidate the underlying mechanisms of tracheal regeneration. METHODS: AAs from female rats were employed for tracheal reconstruction in 36 male rats, with the replacement exceeding half of the tracheal length. To avert collapse, silicone stents were inserted into the AA lumens. No immunosuppressive therapy was administered. The rats were euthanized biweekly, and the AAs were examined for neovascularization, cartilage formation, respiratory epithelial ingrowth, submucosal gland regeneration and the presence of the Sex-determining region of Y-chromosome (SRY) gene. RESULTS: All procedures were successfully completed without severe complications. The AA segments were effectively integrated into the tracheal framework, with seamless distinction at suture lines. Histological analysis indicated an initial inflammatory response, followed by the development of squamous and mucociliary epithelia, new cartilage ring formation and gland regeneration. In situ hybridization identified the presence of the SRY gene in newly formed cartilage rings, confirming that regeneration was driven by recipient cells. CONCLUSIONS: This study demonstrates the feasibility of AAs transforming into functional tracheal conduits, replicating the main structural and functional characteristics of the native trachea. The findings indicate that this approach offers a novel pathway for tissue regeneration and holds potential for treating extensive tracheal injuries.

Brucella-driven host N-glycome remodeling controls infection.

Many powerful methods have been employed to elucidate the global transcriptomic, proteomic, or metabolic responses to pathogen-infected host cells. However, the host glycome responses to bacterial infection remain largely unexplored, and hence, our understanding of the molecular mechanisms by which bacterial pathogens manipulate the host glycome to favor infection remains incomplete. Here, we address this gap by performing a systematic analysis of the host glycome during infection by the bacterial pathogen Brucella spp. that cause brucellosis. We discover, surprisingly, that a Brucella effector protein (EP) Rhg1 induces global reprogramming of the host cell N-glycome by interacting with components of the oligosaccharide transferase complex that controls N-linked protein glycosylation, and Rhg1 regulates Brucella replication and tissue colonization in a mouse model of brucellosis, demonstrating that Brucella exploits the EP Rhg1 to reprogram the host N-glycome and promote bacterial intracellular parasitism, thereby providing a paradigm for bacterial control of host cell infection.

Analyzing river disruption factors and ecological flow in China's Liu River Basin amid environmental changes.

Water resources variability and availability in a basin affect river flows and sustain river ecosystems. Climate change and human activities disrupt runoff sequences, causing water environmental issues like river channel interruptions. Therefore, determining ecological flow in changing environments is challenging in hydrological research. Based on an analysis of long-term changes in hydrological and meteorological variables and interruption conditions in the semi-arid Liu River Basin (LRB), this study summarizes the controlling factors of river interruption at different temporal and spatial scales and proposes a framework to determine ecological flow under changing environments. Hydrological model and the monthly optimal probability distribution were used to determine the optimal ecological runoff of LRB. The results showed that from 1956 to 2017, precipitation and potential evapotranspiration in the basin showed no significant decreasing trend, but the streamflow significantly decreased, and the downstream interruption worsened, with an average annual interruption duration of 194 days at Xinmin Station from 1988 to 2017. The controlling factors of river interruption are as follows: (1) soil and water conservation measures in the upstream significantly reduce the runoff capacity; (2) the operation mode of the controlling reservoir in the middle reaches changes from "all-year discharge" to "winter storage and spring release" to "combined storage and supply," severing the hydraulic connection between upstream and downstream; and (3) siltation in the downstream river channel coupled with over-extraction of groundwater increases the seepage capacity of the river. The monthly ecological flow of Naodehai Reservoir was determined by considering the monthly seepage losses after reconstructing the natural runoff using the SWAT model and determining the optimal probability distribution function for monthly runoff. The findings are important for downstream LRB ecological restoration and for determining the ecological flow of other river basins in changing environments.

Preparation and characterisation of baicalin magnesium and its protective effect in ulcerative colitis via gut microbiota-bile acid axis modulation.

BACKGROUND: Scutellaria baicalensis Georgi is a well-known herb in traditional Chinese medicine that is frequently prescribed for various gastrointestinal conditions, including ulcerative colitis (UC). Its primary active constituent, baicalin, has poorly water solubility that reduces its efficacy. PURPOSE: To enhance the aqueous solubility of baicalin by optimising its extraction process. We compared the modulatory effects of isolated water-soluble baicalin and water-insoluble baicalin on UC, and delved deeper into the potential mechanisms of water-soluble baicalin. METHODS: We successfully extracted a more hydrophilic baicalin directly from an aqueous S. baicalensis Georgi extract through the process of recrystallisation following alcoholic precipitation of the aqueous extract obtained from S. baicalensis Georgi, eliminating the need for acid additives. This specific form of baicalin was conclusively identified by UV, IR, atomic absorption spectroscopy, elemental analysis, 1H NMR, 13C NMR, and ESI-HRMS. We subsequently compared the regulatory effects of baicalin on UC before and after optimisation, employing 16S rDNA sequencing, bile acid-targeted metabolomics, and transcriptome analysis to elucidate the potential mechanism of water-soluble baicalin; and the key genes and proteins implicated in this mechanism were verified through RT-PCR and western blotting. RESULTS: A new form of baicalin present in the aqueous solution of S. baicalensis Georgi was isolated, and its structural characterisation showed that it was bound to magnesium ions (baicalin magnesium) and exhibited favorable water solubility. Baicalin magnesium offers enhanced therapeutic benefits over baicalin for UC treatment, which alleviated the inflammatory response and oxidative stress levels while improving intestinal mucosal damage. Further investigation of the mechanism revealed that baicalin magnesium could effectively regulate bile acid metabolism and maintain intestinal microecological balance in UC mice, and suppress the activation of the nuclear factor-kappa B and peroxisome proliferator-activated receptor α signalling pathways, thereby playing a therapeutic role. CONCLUSIONS: Baicalin magnesium has good water solubility, which solves the bottleneck problem of water insolubility in the practical applications of baicalin. Moreover, baicalin magnesium exhibits therapeutic potential for UC significantly better than baicalin.

Depression promotes breast cancer progression by regulating amino acid neurotransmitter metabolism and gut microbial disturbance.

INTRODUCTION: Breast cancer (BC) is the most prevalent type of cancer and has the highest mortality among women worldwide. BC patients have a high risk of depression, which has been recognized as an independent factor in the progression of BC. However, the potential mechanism has not been clearly demonstrated. METHODS: To explore the correlation and mechanism between depression and BC progression, we induced depression and tumor in BC mouse models. Depression was induced via chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS). Amino acid (AA) neurotransmitter-targeted metabonomics and gut microbiota 16S rDNA gene sequencing were employed in the mouse model after evaluation with behavioral tests and pathological analysis. RESULTS: The tumors in cancer-depression (CD) mice grew faster than those in cancer (CA) mice, and lung metastasis was observed in CD mice. Metabonomics revealed that the neurotransmitters and plasma AAs in CD mice were dysregulated, namely the tyrosine and tryptophan pathways and monoamine neurotransmitters in the brain. Gut microbiota analysis displayed an increased ratio of Firmicutes/Bacteroides. In detail, the abundance of f_Lachnospiraceae and s_Lachnospiraceae increased, whereas the abundance of o_Bacteroidales and s_Bacteroides_caecimuris decreased. Moreover, the gut microbiota was more closely associated with AA neurotransmitters than with plasma AA. CONCLUSION: Depression promoted the progression of BC by modulating the abundance of s_Lachnospiraceae and s_Bacteroides_caecimuris, which affected the metabolism of monoamine neurotransmitters in the brain and AA in the blood.

Sciadonic acid ameliorates cyclophosphamide-induced immunosuppression by modulating the immune response and altering the gut microbiota.

BACKGROUND: Cyclophosphamide (Cy) is a frequently used chemotherapeutic drug, but long-term Cy treatment can cause immunosuppression and intestinal mucosal damage. The intestinal mucosal barrier and gut flora play important roles in regulating host metabolism, maintaining physiological functions and protecting immune homeostasis. Dysbiosis of the intestinal flora affects the development of the intestinal microenvironment, as well as the development of various external systemic diseases and metabolic syndrome. RESULTS: The present study investigated the influence of sciadonic acid (SA) on Cy-induced immunosuppression in mice. The results showed that SA gavage significantly alleviated Cy-induced immune damage by improving the immune system organ index, immune response and oxidative stress. Moreover, SA restored intestinal morphology, improved villus integrity and activated the nuclear factor κB signaling pathway, stimulated cytokine production, and reduced serum lipopolysaccharide (LPS) levels. Furthermore, gut microbiota analysis indicated that SA increased t beneficial bacteria (Alistipes, Lachnospiraceae_NK4A136_group, Rikenella and Odoribacter) and decreased pathogenic bacteria (norank-f-Oscillospiraceae, Ruminococcus and Desulfovibrio) to maintain intestinal homeostasis. CONCLUSION: The present study provided new insights into the SA regulation of intestinal flora to enhance immune responses. © 2024 Society of Chemical Industry.

Immunosuppressive enzyme-responsive nanoparticles for enhanced accumulation in liver allograft to overcome acute rejection.

Acute rejection is a life-threatening complication after liver transplantation. Immunosuppressants such as tacrolimus are used to inhibit acute rejection of liver grafts in clinic. However, inefficient intragraft accumulation may reduce the therapeutic outcomes of tacrolimus. Here, an enzyme-responsive nanoparticle is developed to selectively enhance the accumulation of tacrolimus in liver allograft through enzyme-induced aggregation to refine immunotherapeutic efficacy of tacrolimus. The nanoparticles are composed of amphiphilic tacrolimus prodrugs synthesized by covalently conjugating tacrolimus and matrix metalloproteinase 9 (MMP9)-cleavable peptide-containing methoxy poly (ethylene glycol) to poly (l-glutamic acid). Upon exposure to MMP9, which is overexpressed in rejected liver allografts, the nanoparticles undergo a morphological transition from spherical micellar nanoparticles to microscale aggregate-like scaffolds. Intravenous administration of MMP9-responsive nanoparticles into a rat model of acute liver graft rejection results in enhanced nanoparticle accumulation in allograft as compared to nonresponsive nanoparticles. Consequently, the MMP9-responsive nanoparticles significantly inhibit intragraft inflammatory cell infiltration and proliferation, maintain intragraft immunosuppressive environment, alleviate graft damage, improve liver allograft function, abate weight loss and prolong recipient survival. This work proves that morphology-switchable enzyme-responsive nanoparticles represent an innovative strategy for selectively enhancing intragraft accumulation of immunosuppressive agents to improve treatment of liver allograft rejection.

Partially Ion-Paired Solvation Structure Design for Lithium-Sulfur Batteries under Extreme Operating Conditions.

Achieving increased energy density under extreme operating conditions remains a major challenge in rechargeable batteries. Herein, we demonstrate an all-fluorinated ester-based electrolyte comprising partially fluorinated carboxylate and carbonate esters. This electrolyte exhibits temperature-resilient physicochemical properties and moderate ion-paired solvation, leading to a half solvent-separated and half contact-ion pair in a sole electrolyte. As a result, facile desolvation and preferential reduction of anions/fluorinated co-solvents for LiF-dominated interphases are achieved without compromising ionic conductivity (>1 mS cm-1 even at -40 °C). These advantageous features were found to apply to both lithium metal and sulfur-based electrodes even under extreme operating conditions, allowing stable cycling of Li || sulfurized polyacrylonitrile (SPAN) full cells with high SPAN loading (>3.5 mAh cm-2 ) and thin Li anode (50 µm) at -40, 23 and 50 °C. This work offers a promising path for designing temperature-resilient electrolytes to support high energy density Li metal batteries operating in extreme conditions.

Exploring the effects of epigallocatechin gallate on lipid metabolism in the rat steatotic liver during normothermic machine perfusion: Insights from lipidomics and RNA sequencing.

BACKGROUND: Hepatic steatosis is the leading cause of discarded liver grafts. Defatting steatotic liver grafts using drug combinations during ex vivo normothermic machine perfusion (NMP) has been reported. However, the effectiveness of NMP in reducing fat content using epigallocatechin gallate (EGCG) as a single defatting agent and its effect on lipid metabolism are poorly investigated. METHODS: In this study, an NMP system was set up to perfuse a steatotic liver from a rat model with 10 mM EGCG. Livers without EGCG served as NMP controls, whereas static cold-preserved livers in the University of Wisconsin medium were used as static cold storage controls. Liver enzyme, reactive oxygen species (ROS), histology, and lipid content assessments were conducted post-perfusion, complemented by lipidomics, RNA sequencing, and western blotting to determine the lipid metabolism changes. RESULTS: EGCG during NMP reduced hepatocellular injury markers and defatted steatotic liver grafts. Additionally, we observed a significant increase in triglyceride (TG) content in the perfusate post-NMP in the NMP + EGCG group, suggesting TG output from the liver. Furthermore, lipidomics analysis revealed that EGCG primarily affected metabolites involved in glycerophospholipid (GP) and glycerolipid (GL) metabolism. Further, the RNA sequencing indicated the modulation of these metabolic pathways via ECGC, which was associated with the downregulated Lpin1 and Gpat3 expression. CONCLUSIONS: EGCG defats steatotic livers as a single defatting agent during NMP by promoting GL and GP metabolism via decreasing Lpin1 and Agpat9 levels.

The curvature effect on the distribution behavior of nonpolar atoms in nano-confined space.

The chemical and physical properties of nonpolar atoms are obviously affected by confinement. A curvature-based theoretical model for helium particles distributed in carbon nanotubes is proposed by considering the L-J pair potential and the Boltzmann distribution. The potential gap formed by the non-bonded interaction between a helium atom and a carbon nanotube surface leads to a layered structure distribution with high density near the surface. By assuming adsorption as a competition between the potential gap and the thermal energy, the desorption critical temperature is discussed for helium adsorbed on the layer, which is confirmed to be a monotonic decreasing function of nanotube diameter. The helium atom distribution relations between the nanotube diameter, temperature and the potential gap obtained from molecular dynamics simulations are consistent with the curvature-based model predictions. The adsorption ratio is defined by the numbers of particles adsorbed on the near surface layered structure over total particle numbers, which decreases with the increase of temperature and carbon nanotube diameter. The curvature-based model is further confirmed by studying krypton and argon atoms in the appendix. This work provides a simple model to predict the distribution behavior and reveals the curvature effect on the distribution and adsorption of non-polar atoms confined in nano-space, which could be important for a better understanding of the chemical and physical properties of gas storage in the nano-confined space.

Toward a quantitative interfacial description of solvation for Li metal battery operation under extreme conditions.

The future application of Li metal batteries (LMBs) at scale demands electrolytes that endow improved performance under fast-charging and low-temperature operating conditions. Recent works indicate that desolvation kinetics of Li+ plays a crucial role in enabling such behavior. However, the modulation of this process has typically been achieved through inducing qualitative degrees of ion pairing into the system. In this work, we find that a more quantitative control of the ion pairing is crucial to minimizing the desolvation penalty at the electrified interface and thus the reversibility of the Li metal anode under kinetic strain. This effect is demonstrated in localized electrolytes based on strongly and weakly bound ether solvents that allow for the deconvolution of solvation chemistry and structure. Unexpectedly, we find that maximum degrees of ion pairing are suboptimal for ultralow temperature and high-rate operation and that reversibility is substantially improved via slight local dilution away from the saturation point. Further, we find that at the optimum degree of ion pairing for each system, weakly bound solvents still produce superior behavior. The impact of these structure and chemistry effects on charge transfer are then explicitly resolved via experimental and computational analyses. Lastly, we demonstrate that the locally optimized diethyl ether-based localized-high-concentration electrolytes supports kinetic strained operating conditions, including cycling down to -60 °C and 20-min fast charging in LMB full cells. This work demonstrates that explicit, quantitative optimization of the Li+ solvation state is necessary for developing LMB electrolytes capable of low-temperature and high-rate operation.

Dendritic cells in liver transplantation immune response.

Dendritic cells (DCs) are the most powerful antigen presenting cells (APCs), they are considered one of the key regulatory factors in the liver immune system. There is currently much interest in modulating DC function to improve transplant immune response. In liver transplantation, DCs participate in both the promotion and inhibition of the alloreponse by adopting different phenotypes and function. Thus, in this review, we discussed the origin, maturation, migration and pathological effects of several DC subsets, including the conventional DC (cDC), plasmacytoid DC (pDC) and monocyte-derived DC (Mo-DC) in liver transplantation, and we summarized the roles of these DC subsets in liver transplant rejection and tolerance. In addition, we also outlined the latest progress in DC-based related treatment regimens. Overall, our discussion provides a beneficial resource for better understanding the biology of DCs and their manipulation to improve the immune adaptability of patients in transplant status.

Effect of Electrolyte Chemistry and Sulfur Content in Li||Sulfurized Polyacrylonitrile (SPAN) Batteries.

Sulfurized polyacrylonitrile (SPAN) is considered as a high-value cathode material, which leverages the high energy of S redox while mitigating the negative externalities that limit elemental S cycling. As such, the sulfur content in Li-SPAN batteries plays a critical role. In this work, we demonstrate that high-S loading SPAN cathodes, where the PAN backbone approaches the saturation point without signs of elemental S, are highly dependent on the electrolyte chemistry for long-term reversibility. Specifically, we find that a localized-high-concentration electrolyte (LHCE) further enhances the reversible capacity and cycling stability of SPAN cathode with optimized S content relative to a carbonate control, largely due to the formation of a compatible interphase. With this LHCE as the electrolyte and 43% sulfur ratio of SPAN as the cathode, a full cell applying N/P ratio = 1.82, a cathode loading of 6 mAh cm-2 (9.2 mg cm-2), and an electrolyte loading of 7 µL mg-1 SPAN can be cycled for 100 cycles with 433 mAh g-1 retained capacity and retains much of this reversibility even at 60 °C. This work reveals the molecular origin of optimized sulfur ratio in SPAN cathodes while providing guidance in electrolyte design for Li||SPAN cells with high capacity and cyclability.

LncRNA CYP4A22-AS1 promotes the progression of lung adenocarcinoma through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes.

OBJECTIVES: Lung adenocarcinoma (LUAD) exhibits a higher fatality rate among all cancer types worldwide, yet the precise mechanisms underlying its initiation and progression remain unknown. Mounting evidence suggests that long non-coding RNAs (lncRNAs) exert significant regulatory roles in cancer development and progression. Nevertheless, the precise involvement of lncRNA CYP4A22-AS1 in LUAD remains incompletely comprehended. METHODS: Bioinformatics analyses evaluated the expression level of CYP4A22-AS1 in lung adenocarcinoma and paracancer. The LUAD cell line with a high expression of CYP4A22-AS1 was constructed to evaluate the role of CYP4A22-AS1 in the proliferation and metastasis of LUAD by CCK8, scratch healing, transwell assays, and animal experiments. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. Luciferase reporter gene analyses, west-blotting, and qRT-PCR were carried out to reveal the interaction between CYP4A22-AS1, miR-205-5p/EREG, and miR-34c-5p/BCL-2 axes. RESULTS: CYP4A22-AS1 expression was significantly higher in LUAD tissues than in the adjacent tissues. Furthermore, we constructed a LUAD cell line with a high expression of CYP4A22-AS1 and noted that the high expression of CYP4A22-AS1 significantly enhanced the proliferation and metastasis of LUAD. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. CYP4A22-AS1 increased the expression of EREG and BCL-2 by reducing the expression of miR-205-5p and miR-34-5p and activating the downstream signaling pathway of EGFR and the anti-apoptotic signaling pathway of BCL-2, thereby triggering the proliferation and metastasis of LUAD. The transfection of miR-205-5p and miR-34-5p mimics inhibited the role of CYP4A22-AS1 in enhancing tumor progression. CONCLUSION: This study elucidates the molecular mechanism whereby CYP4A22-AS1 overexpression promotes LUAD progression through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes.

Surface engineering of Al2O3 nanotubes by ureasolysis method for activating persulfate degradation of antibiotics.

Though ecofriendly, pure Al2O3 has never been used for activation of peroxodisulfate (PDS) to degrade pollutants. We report the fabrication of Al2O3 nanotubes by ureasolysis method for efficient activating PDS degradation of antibiotics. The fast ureasolysis in aqueous AlCl3 solution produces NH4Al(OH)2CO3 nanotubes, which are calcined to porous Al2O3 nanotubes, and the release of ammonia and carbon dioxide engineers the surface features of large surface area, numerous acidic-basic sites and suitable Zeta potentials. The synergy of these features facilitates the adsorption of the typical antibiotics ciprofloxacin and PDS activation, which is proved by experiment results and density functional theory simulation. The proposed Al2O3 nanotubes can catalyze 92-96% degradation of 10 ppm ciprofloxacin within 40 min, with chemical oxygen demand removal of 65-66% in aqueous, and 40-47% in whole including aqueous and catalysts. Ciprofloxacin at high concentration, other fluoroquinolones and tetracycline can also be effectively degraded. These data demonstrate the Al2O3 nanotubes prepared by the nature-inspired ureasolysis method has unique features and great potentials for antibiotics degradation.

Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of ß-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the ß-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Immature and activated phenotype of blood NK cells is associated with acute rejection in adult liver transplant.

Natural killer (NK) cells contribute to liver transplant (LTx) rejection. However, the blood-circulating NK-cell dynamics of patients who experience acute rejection (AR) are unclear. Herein, we longitudinally profiled the total NK cells and their subsets, along with the expression of activating and inhibitory receptors in sequential peripheral blood mononuclear cell samples, spanning from before LTx to the first year after LTx of 32 patients with AR and 30 patients under a steady immune status. Before transplantation, patients with AR (rejectors) contained a significantly higher proportion of the immature CD56 bright CD16 - subset and a lower cytolytic CD56 dim CD16 + in the total blood-circulating NK cells than patients with steady immunity. Both subsets contained a high NKp30-positive population, and CD56 dim CD16 + additionally exhibited a high NKp46-positive ratio. The NKp30-positive ratio in CD56 dim CD16 + subset showed the most prominent AR predictive ability before LTx and was an independent risk factor of LTx AR. After transplantation, the blood-circulating NK cells in rejectors maintained a higher CD56 bright CD16 - and lower CD56 dim CD16 + composition than the controls throughout the first year after LTx. Moreover, both subsets maintained a high NKp30-positive ratio, and CD56 dim CD16 + retained a high NKp46-positive ratio. The blood-circulating NK cell subset composition was consistent during AR, while the expressions of NKp30 and NKp46 were augmented. Collectively, a more immature CD56 bright CD16 - subset composition and an activated phenotype of high NKp30 expression were the general properties of blood-circulating NK cells in rejected LTx recipients, and the NKp30-positive ratio in CD56 dim CD16 + NK subset before LTx possessed AR predictive potential.

Quantifying the impact of climate variability and human activities on streamflow variation in Taoer River Basin, China.

Climate variability and human activity are the two driving forces that alter the hydrological cycle and spatiotemporal distribution of water resources. Using the Taoer River Basin (TRB) as an example, this study analyzed the impacts of climate variability and human activities on streamflow discharge in various periods and the resulting hydrological alterations. First, historical streamflow data were divided into four periods (baseline period and altered periods 1, 2, and 3). Based on the proposed basic identification framework, four assessment methods (the hydrological sensitivity method, distributed hydrological model, linear regression model, and runoff restoring computation) are used and provided relatively consistent estimates of streamflow attribution. Climate variability is the driving factor for streamflow changes, and the relative contributions in altered periods 1, 2, and 3 are 81% (+ 50.34 mm), 68% (+ 13.37 mm), and 53% (-19.23 mm), respectively. In addition, climate variability and reservoir construction have different impacts on the hydrological regime at different periods, and reservoir regulation's effect on the hydrological regime depends on climatic conditions. Combined with this case study, we further discuss the necessity of breakpoint selection and period subdivision in the attribution of streamflow changes, and analyze the applicability of different methods with current ideas for improvement. This study not only has practical significance for water resource planning and adaptive policy formulation in the TRB but also provides a useful reference for similar studies.

Sciadonic acid attenuates high-fat diet-induced obesity in mice with alterations in the gut microbiota.

Obesity has been reported to be associated with dysbiosis of gut microbiota. Sciadonic acid (SC) is one of the main functional components of Torreya grandis "Merrillii" seed oil. However, the effect of SC on high-fat diet (HFD)-induced obesity has not been elucidated. In this study, we evaluated the effects of SC on lipid metabolism and the gut flora in mice fed with a high-fat diet. The results revealed that SC activates the PPARα/SREBP-1C/FAS signaling pathway and reduces the levels of total cholesterol (TC), triacylglycerols (TG), and low-density lipoprotein cholesterol (LDL-C), but increases the level of high-density lipoprotein cholesterol (HDL-C) and inhibits weight gain. Among them, high-dose SC was the most effective; the TC, TG and LDL-C levels were reduced by 20.03%, 28.40% and 22.07%, respectively; the HDL-C level was increased by 8.55%. In addition, SC significantly increased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels by 98.21% and 35.17%, respectively, decreased oxidative stress, and ameliorated the pathological damage to the liver caused by a high-fat diet. Furthermore, SC treatment altered the composition of the intestinal flora, promoting the relative abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, while simultaneously decreasing the relative abundance of potentially harmful bacteria such as Faecalibaculum, norank_f_Desulfovibrionaceae, and Romboutsia. Spearman's correlation analysis indicated that the gut microbiota was associated with SCFAs and biochemical indicators. In summary, our results suggested that SC can improve lipid metabolism disorders and regulate the gut microbial structure.