Combining slow-release fertilizer and plastic film mulching reduced the carbon footprint and enhanced maize yield on the Loess Plateau.

Agricultural practices significantly contribute to greenhouse gas (GHG) emissions, necessitating cleaner production technologies to reduce environmental pressure and achieve sustainable maize production. Plastic film mulching is commonly used in the Loess Plateau region. Incorporating slow-release fertilizers as a replacement for urea within this practice can reduce nitrogen losses and enhance crop productivity. Combining these techniques represents a novel agricultural approach in semi-arid areas. However, the impact of this integration on soil carbon storage (SOCS), carbon footprint (CF), and economic benefits has received limited research attention. Therefore, we conducted an eight-year study (2015-2022) in the semi-arid northwestern region to quantify the effects of four treatments [urea supplied without plastic film mulching (CK-U), slow-release fertilizer supplied without plastic film mulching (CK-S), urea supplied with plastic film mulching (PM-U), and slow-release fertilizer supplied with plastic film mulching (PM-S)] on soil fertility, economic and environmental benefits. The results revealed that nitrogen fertilizer was the primary contributor to total GHG emissions (≥71.97%). Compared to other treatments, PM-S increased average grain yield by 12.01%-37.89%, water use efficiency by 9.19%-23.33%, nitrogen accumulation by 27.07%-66.19%, and net return by 6.21%-29.57%. Furthermore, PM-S decreased CF by 12.87%-44.31% and CF per net return by 14.25%-41.16%. After eight years, PM-S increased SOCS (0-40 cm) by 2.46%, while PM-U decreased it by 7.09%. These findings highlight the positive effects of PM-S on surface soil fertility, economic gains, and environmental benefits in spring maize production on the Loess Plateau, underscoring its potential for widespread adoption and application.

Structured Deep Neural Network-Based Backstepping Trajectory Tracking Control for Lagrangian Systems.

Deep neural networks (DNNs) are increasingly being used to learn controllers due to their excellent approximation capabilities. However, their black-box nature poses significant challenges to closed-loop stability guarantees and performance analysis. In this brief, we introduce a structured DNN-based controller for the trajectory tracking control of Lagrangian systems using backing techniques. By properly designing neural network structures, the proposed controller can ensure closed-loop stability for any compatible neural network parameters. In addition, improved control performance can be achieved by further optimizing neural network parameters. Besides, we provide explicit upper bounds on tracking errors in terms of controller parameters, which allows us to achieve the desired tracking performance by properly selecting the controller parameters. Furthermore, when system models are unknown, we propose an improved Lagrangian neural network (LNN) structure to learn the system dynamics and design the controller. We show that in the presence of model approximation errors and external disturbances, the closed-loop stability and tracking control performance can still be guaranteed. The effectiveness of the proposed approach is demonstrated through simulations.

A rapid and validated GC-MS/MS method for simultaneous quantification of serum Myo- and D-chiro-inositol isomers.

BACKGROUND: Myo-inositol (MI) and D-chiro-inositol (DCI) are two paramount isomers of inositol, both vital in glucose and steroid metabolism. Deficits in MI, DCI or MI/DCI ratio are expressly concerned with several pathological process, whereas MI and DCI lack practical measurement for human specimen. METHODS: To quantify MI and DCI in serum samples simultaneously, a gas chromatography tandem mass spectrometry (GC-MS/MS) method was established. The process flow was optimized in ion source, derivative agent volume and reaction time. The performance characteristics were verified by commercial standards and clinical serums. RESULTS: This method was confirmed to be sensitive (LOD ≤ 30 ng/mL of MI, ≤3 ng/mL of DCI) and reproducible (RSD < 6 % for repeated analyses). Quantitative determinations performed good linearity within the measurement range of 0.500-10.00 and 0.005-0.500 µg/mL for MI and DCI respectively (R2 > 0.999). The recoveries of MI and DCI were 97.11-99.35 % and 107.82-113.09 %, respectively. This method was successfully applied to 114 clinical specimens. No significant matrix effect was observed in serum samples under current conditions.

Cost-effectiveness of pembrolizumab plus chemotherapy vs. chemotherapy as first-line treatment for advanced biliary tract cancer in China and the US.

Background: Pembrolizumab is a potentially valuable treatment. However, patients, doctors, and healthcare decision-makers are uncertain about its cost-effectiveness and an appropriate pricing for this new therapy. This study aims to appraise the cost-effectiveness of pembrolizumab as a first-line treatment for advanced biliary tract cancer (BTC) patients in China and the United States (US). Methods: A Markov model was constructed from the perspectives of healthcare systems in both China and the US for pharmacoeconomic evaluation. Patient baseline characteristics and key clinical data were sourced from the KEYNOTE-966 trial (ClinicalTrials.gov, NCT04003636). Costs and utilities were collected from drug cost websites and published literature. Cumulative costs (in USD), life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured and compared. Price simulations were conducted under given willingness-to-pay (WTP) thresholds to provide pricing scheme references. The model's robustness was analyzed through one-way sensitivity analysis and probabilistic sensitivity analysis. Results: Basic data analysis illustrates that pembrolizumab ($2662.41/100 mg) in combination with chemotherapy regimen was not cost-effective relative to chemotherapy regimens at the WTP threshold of $38,201.19 in China, and the additional cost relative to chemotherapy regimens was $77,114.94 (ICER $556,689.47/QALY) while increasing 0.14 QALYs. Pembrolizumab ($54.71/1 mg) also increased efficacy by 0.14 QALYs in the US, but remained also not cost-effective at the US WTP threshold of $229,044, and the total cost increased by $160,425.24 (ICER $1,109,462.92/QALY). Conclusion: Compared with chemotherapy, pembrolizumab plus chemotherapy reduces the disease of burden. However, at its current price, it may not be a cost-effective treatment for advanced BTC in both China and the US. This study can aid decision-makers in making optimal choices.

Encryption-decryption-based distributed fault-tolerant consensus tracking control for multi-agent systems.

This study investigates fault-tolerant consensus tracking for discrete-time multi-agent systems (MASs) subject to external eavesdropping threats and additive actuator faults. First, actuator faults are modeled by difference equations, and decentralized observers are constructed to estimate actuator faults as well as system states. To offset fault-induced effects, ensure secure communication, and alleviate communication congestion, neighboring encrypted state information based on the encryption-decryption strategy (EDS) and estimated fault are integrated into a distributed active fault-tolerant consensus tracking control (FCTC) protocol. Through the properties of compatible norms, criteria for the controller, observer, and dynamic encryption key in EDS are derived to achieve leader-following consensus (LFC) of MASs with bias and drift actuator faults. Simulation results confirm the validity of the encryption-decryption-based distributed FCTC strategy.

PLEKv2: predicting lncRNAs and mRNAs based on intrinsic sequence features and the coding-net model.

BACKGROUND: Long non-coding RNAs (lncRNAs) are RNA transcripts of more than 200 nucleotides that do not encode canonical proteins. Their biological structure is similar to messenger RNAs (mRNAs). To distinguish between lncRNA and mRNA transcripts quickly and accurately, we upgraded the PLEK alignment-free tool to its next version, PLEKv2, and constructed models tailored for both animals and plants. RESULTS: PLEKv2 can achieve 98.7% prediction accuracy for human datasets. Compared with classical tools and deep learning-based models, this is 8.1%, 3.7%, 16.6%, 1.4%, 4.9%, and 48.9% higher than CPC2, CNCI, Wen et al.'s CNN, LncADeep, PLEK, and NcResNet, respectively. The accuracy of PLEKv2 was > 90% for cross-species prediction. PLEKv2 is more effective and robust than CPC2, CNCI, LncADeep, PLEK, and NcResNet for primate datasets (including chimpanzees, macaques, and gorillas). Moreover, PLEKv2 is not only suitable for non-human primates that are closely related to humans, but can also predict the coding ability of RNA sequences in plants such as Arabidopsis. CONCLUSIONS: The experimental results illustrate that the model constructed by PLEKv2 can distinguish lncRNAs and mRNAs better than PLEK. The PLEKv2 software is freely available at https://sourceforge.net/projects/plek2/ .

TIMP-1 Promotes Expression of MCP-1 and Macrophage Migration by Inducing Fli-1 in Experimental Liver Fibrosis.

Background and Aims: Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a role in the excessive generation of extracellular matrix in liver fibrosis. This study aimed to explore the pathways through which TIMP-1 controls monocyte chemoattractant protein-1 (MCP-1) expression and promotes hepatic macrophage recruitment. Methods: Liver fibrosis was triggered through carbon tetrachloride, and an adeno-associated virus containing small interfering RNA targeting TIMP-1 (siRNA-TIMP-1) was administered to both rats and mice. We assessed the extent of fibrosis and macrophage recruitment. The molecular mechanisms regulating macrophage recruitment by TIMP-1 were investigated through transwell migration assays, luciferase reporter assays, the use of pharmacological modulators, and an analysis of extracellular vesicles (EVs). Results: siRNA-TIMP-1 alleviated carbon tetrachloride-induced liver fibrosis, reducing macrophage migration and MCP-1 expression. Co-culturing macrophages with hepatic stellate cells (HSCs) post-TIMP-1 downregulation inhibited macrophage migration. In siRNA-TIMP-1-treated HSCs, microRNA-145 (miRNA-145) expression increased, while the expression of Friend leukemia virus integration-1 (Fli-1) and MCP-1 was inhibited. Downregulation of Fli-1 led to decreased MCP-1 expression, whereas Fli-1 overexpression increased MCP-1 expression within HSCs. Transfection with miRNA-145 mimics reduced the expression of both Fli-1 and MCP-1, while miRNA-145 inhibitors elevated the expression of both Fli-1 and MCP-1 in HSCs. miRNA-145 bound directly to the 3'-UTR of Fli-1, and miRNA-145-enriched EVs secreted by HSCs after TIMP-1 downregulation influenced macrophage recruitment. Conclusions: TIMP-1 induces Fli-1 expression through miRNA-145, subsequently increasing MCP-1 expression and macrophage recruitment. MiRNA-145-enriched EVs from HSCs can transmit biological information and magnify the function of TIMP-1.

Early changes in corneal densitometry after FS-LASIK combined with accelerated corneal cross-linking for correction of high myopia.

AIM: To observe the effects of femtosecond laser-assisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking (FS-LASIK Xtra) on corneal densitometry after correcting for high myopia. METHODS: In this prospectively study, 130 patients underwent FS-LASIK or FS-LASIK Xtra for high myopia. Their right eyes were selected for inclusion in the study, of which 65 cases of 65 eyes in the FS-LASIK group, 65 patients with 65 eyes in the FS-LASIK Xtra group. Patients were evaluated for corneal densitometry at 1, 3, and 6mo postoperatively using Pentacam Scheimpflug imaging. RESULTS: Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant (P>0.05). Layer-by-layer analysis revealed statistically significant differences in the anterior (120 µm), central, and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively (all P<0.05), the FS-LASIK Xtra group is higher than that of the FS-LASIK group. Analysis of different diameter ranges showed statistically significant differences between the FS-LASIK group and the FS-LASIK Xtra group at 1mo postoperatively in the ranges of 0-2, 2-6, and 6-10 mm (both P<0.05); At 3mo postoperatively, the FS-LASIK Xtra group is higher than that of the FS-LASIK group in the ranges of 0-2 and 2-6 mm (P<0.05). At 6mo postoperatively, there were no statistically significant differences in corneal densitometry between the FS-LASIK group and the FS-LASIK Xtra group in different diameter ranges (all P>0.05). CONCLUSION: There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high myopia. However, the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery, with the most significant changes observed in the superficial central zone.

Photoelectrochemical Fe/Ni cocatalyzed C-C functionalization of alcohols.

The simultaneous activation of reactants on the anode and cathode via paired electrocatalysis has not been extensively demonstrated. This report presents a paired oxidative and reductive catalysis based on earth-abundant iron/nickel cocatalyzed C-C functionalization of ubiquitous alcohols. A variety of alcohols (i.e., primary, secondary, tertiary, or unstrained cyclic alcohols) can be activated at very low oxidation potential of (~0.30 V vs. Ag/AgCl) via photoelectrocatalysis coupled with versatile electrophiles. This reactivity yields a wide range of structurally diverse molecules with broad functional group compatibility (more than 50 examples).

The amino acid sensor methionyl-tRNA synthetase is required for methionine-induced milk protein synthesis in a domestic pigeon model.

This study was conducted to investigate whether methionyl-tRNA synthetase (MetRS) is a mediator of methionine (Met)-induced crop milk protein synthesis via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signalling pathway in breeding pigeons. In Experiment 1, a total of 216 pairs of breeding pigeons were divided into three groups (control, Met-deficient, and Met-rescue groups). In Experiments 2 and 3, forty pairs of breeding pigeons from each experiment were allocated into four groups. The second experiment included a control group and three MetRS inhibitor (REP8839) groups. The third experiment included a Met-deficient group, Met-sufficient group, REP8839 + Met-deficient group and REP8839 + Met-sufficient group. Experiment 1 showed that Met supplementation increased crop development, crop milk protein synthesis, the protein expression of MetRS and JAK2/STAT5 signalling pathway, and improved squab growth. Experiment 2 showed that crop development, crop milk protein synthesis and the protein expression of MetRS and the JAK2/STAT5 signalling pathway were decreased, and squab growth was inhibited by the injection of 1·0 mg/kg body weight REP8839, which was the selected dose for the third experiment. Experiment 3 showed that Met supplementation increased crop development, crop milk protein synthesis and the expression of MetRS and JAK2/STAT5 signalling pathway and rescued squab growth after the injection of REP8839. Moreover, the co-immunoprecipitation results showed that there was an interaction between MetRS and JAK2. Taken together, these findings indicate that MetRS mediates Met-induced crop milk protein synthesis via the JAK2/STAT5 signalling pathway, resulting in improved squab growth in breeding pigeons.

Tartaric acid ameliorates experimental non-alcoholic fatty liver disease by activating the AMP-activated protein kinase signaling pathway.

Tartaric acid (TA) has been shown beneficial effects on blood pressure and lipid levels. However, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. This study aimed to investigate the role of TA in experimental NAFLD. Mice were fed a Western diet for 8 weeks, followed by administration of TA or a vehicle for an additional 12 weeks while continuing on the Western diet. Blood biochemistry including transaminases and glucose tolerance test and liver tissue RNA sequencing (RNA-seq), lipid content, and histology were investigated. The HepG2 cell line was used to explore the mechanism by which TA regulates lipid metabolism. We found that TA significantly improved weight gain, insulin resistance, hepatic steatosis, inflammation and fibrosis in Western diet-fed mice. By comparing gene expression differences, we found that TA affects pathways related to lipid metabolism, inflammatory response, and fibrosis. Furthermore, TA effectively reduced oleic acid-induced lipid accumulation in HepG2 cells and downregulated the genes associated with fatty acid synthesis, which were enriched in the AMP-activated protein kinase (AMPK) signaling pathway. TA also enhanced the phosphorylation of AMPK which could be reverted by the AMPK inhibitor Compound C in HepG2 cells. Our study suggests that TA improves experimental NAFLD by activating the AMPK signaling pathway. These findings indicate that TA may serve as a potential therapy for the human NAFLD.

Lysine Distinctively Manipulates Myogenic Regulatory Factors and Wnt/Ca2+ Pathway in Slow and Fast Muscles, and Their Satellite Cells of Postnatal Piglets.

Muscle regeneration, representing an essential homeostatic process, relies mainly on the myogenic progress of resident satellite cells, and it is modulated by multiple physical and nutritional factors. Here, we investigated how myogenic differentiation-related factors and pathways respond to the first limiting amino acid lysine (Lys) in the fast and slow muscles, and their satellite cells (SCs), of swine. Thirty 28-day-old weaned piglets with similar body weights were subjected to three diet regimens: control group (d 0-28: 1.31% Lys, n = 12), Lys-deficient group (d 0-28: 0.83% Lys, n = 12), and Lys rescue group (d 0-14: 0.83% Lys; d 15-28: 1.31% Lys, n = 6). Pigs on d 15 and 29 were selectively slaughtered for muscular parameters evaluation. Satellite cells isolated from fast (semimembranosus) and slow (semitendinosus) muscles were also selected to investigate differentiation ability variations. We found Lys deficiency significantly hindered muscle development in both fast and slow muscles via the distinct manipulation of myogenic regulatory factors and the Wnt/Ca2+ pathway. In the SC model, Lys deficiency suppressed the Wnt/Ca2+ pathways and myosin heavy chain, myogenin, and myogenic regulatory factor 4 in slow muscle SCs but stimulated them in fast muscle SCs. When sufficient Lys was attained, the fast muscle-derived SCs Wnt/Ca2+ pathway (protein kinase C, calcineurin, calcium/calmodulin-dependent protein kinase II, and nuclear factor of activated T cells 1) was repressed, while the Wnt/Ca2+ pathway of its counterpart was stimulated to further the myogenic differentiation. Lys potentially manipulates the differentiation of porcine slow and fast muscle myofibers via the Wnt/Ca2+ pathway in opposite trends.

Mulberry Leaf-Derived Morin Activates ß-Catenin by Binding to Frizzled7 to Promote Intestinal Stem Cell Expansion upon Heat-Stable Enterotoxin b Injury.

Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by Escherichia coli remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice. Furthermore, morin supplementation reinstated the impaired small-intestinal epithelial structure and barrier function by stimulating ISC proliferation and differentiation as well as supporting intestinal organoid expansion ex vivo. Importantly, the Wnt/ß-catenin pathway, an ISC fate commitment signal, was reactivated by morin to restore the jejunal crypt-villus architecture in response to STb stimulation. Mechanically, the extracellular morin-initiated ß-catenin axis is dependent or partially dependent on the Wnt membrane receptor Frizzled7 (FZD7). Our data reveal an unexpected role of leaf-derived morin, which represents molecular signaling targeting the FZD7 platform instrumental for controlling ISC regeneration upon STb injury.

Response of Extremely Small Populations to Climate Change-A Case of Trachycarpus nanus in Yunnan, China.

Climate change affects the geographical distribution of plant species. Rare Trachycarpus nanus with a narrow distribution range, high medicinal value and extremely small population is facing increasing extinction risks under global climate change. In this study, 96 recorded occurrences and 23 environmental factors are used to predict the potential suitable area of T. nanus based on the optimized MaxEnt (3.4.4) model and ArcGIS (10.7) software. The results show that when the parameters are FC = LQ and RM = 1, the MaxEnt model is optimal and AUC = 0.946. The distribution patterns were predicted in the past, present, and four future phases, i.e., 2021-2040 (2030), 2041-2060 (2050), 2061-2080 (2070), and 2081-2100 (2090). The main factors are the annual precipitation (bio12), mean temperature of the coldest quarter (bio11), temperature seasonality (bio4), precipitation of the wettest quarter (bio16), and isothermality (bio3). The potential distribution of T. nanus is primarily concentrated in central Chuxiong, encompassing a total potential suitable area of 5.65 × 104 km2. In historical periods, the total habitat area is smaller than that in the present. In the future, the potential suitable area is generally increased. The centroid analysis shows that T. nanus will move to a high-altitude area and to the southeast. But its dispersal capacity may not keep up with the climate change rate. Therefore, additional protection sites for this species should be appropriately established and the habitat connectivity should be enhanced.

Ethylene controls three-dimensional growth involving reduced auxin levels in the moss Physcomitrium patens.

The conquest of land by plants was concomitant with, and possibly enabled by, the evolution of three-dimensional (3D) growth. The moss Physcomitrium patens provides a model system for elucidating molecular mechanisms in the initiation of 3D growth. Here, we investigate whether the phytohormone ethylene, which is believed to have been a signal before land plant emergence, plays a role in 3D growth regulation in P. patens. We report ethylene controls 3D gametophore formation, based on results from exogenously applied ethylene and genetic manipulation of PpEIN2, which is a central component in the ethylene signaling pathway. Overexpression (OE) of PpEIN2 activates ethylene responses and leads to earlier formation of gametophores with fewer gametophores produced thereafter, phenocopying ethylene-treated wild-type. Conversely, Ppein2 knockout mutants, which are ethylene insensitive, show initially delayed gametophore formation with more gametophores produced later. Furthermore, pharmacological and biochemical analyses reveal auxin levels are decreased in the OE lines but increased in the knockout mutants. Our results suggest that evolutionarily, ethylene and auxin molecular networks were recruited to build the plant body plan in ancestral land plants. This might have played a role in enabling ancient plants to acclimate to the continental surfaces of the planet.

2D Memory Selectors with Giant Nonlinearity Enabled by Van der Waals Heterostructures.

The integration of one-selector-one-resistor crossbar arrays requires the selectors featured with high nonlinearity and bipolarity to prevent leakage currents and any crosstalk among distinct cells. However, a selector with sufficient nonlinearity especially in the frame of device miniaturization remains scarce, restricting the advance of high-density storage devices. Herein, a high-performance memory selector is reported by constructing a graphene/hBN/WSe2 heterostructure. Within the temperature range of 300-80 K, the nonlinearity of this selector varies from ≈103 - ≈104 under forward bias, and increases from ≈300 - ≈105 under reverse bias, the highest reported nonlinearity among 2D selectors. This improvement is ascribed to direct tunneling at low bias and Fowler-Nordheim tunneling at high bias. The tunneling current versus voltage curves exhibit excellent bipolarity behavior because of the comparable hole and electron tunneling barriers, and the charge transport polarity can be effectively tuned from N-type or P-type to bipolar by simply changing source-drain bias. In addition, the conceptual memory selector exhibits no sign of deterioration after 70 000 switching cycles, paving the way for assembling 2D selectors into modern memory devices.

A Dilated Convolutional Neural Network for Cross-Layers of Contextual Information for Congested Crowd Counting.

Crowd counting is an important task that serves as a preprocessing step in many applications. Despite obvious improvement reported by various convolutional-neural-network-based approaches, they only focus on the role of deep feature maps while neglecting the importance of shallow features for crowd counting. In order to surmount this issue, a dilated convolutional-neural-network-based cross-level contextual information extraction network is proposed in this work, which is abbreviated as CL-DCNN. Specifically, a dilated contextual module (DCM) is constructed by importing cross-level connection between different feature maps. It can effectively integrate contextual information while conserving the local details of crowd scenes. Extensive experiments show that the proposed approach outperforms state-of-the-art approaches using five public datasets, i.e., ShanghaiTech part A, ShanghaiTech part B, Mall, UCF_CC_50 and UCF-QNRF, achieving MAE 52.6, 8.1, 1.55, 181.8, and 96.4, respectively.

Pathogenesis or a response to lithium? A novel perspective for mitochondrial mass fluctuation of naïve T cells in patients with bipolar disorder.

BACKGROUND: Immune imbalances are associated with the pathogenesis and pharmacological efficacy of bipolar disorder (BD). The underlying mechanisms remain largely obscure but may involve immunometabolic dysfunctions of T-lymphocytes. METHODS: We investigated if inflammatory cytokines and the immunometabolic function of T-lymphocytes, including frequencies of subsets, mitochondrial mass (MM), and low mitochondrial membrane potential (MMPLow) differed between BD patients (n = 47) and healthy controls (HC, n = 43). During lithium treatment of hospitalized patients (n = 33), the association between weekly T-lymphocyte immune metabolism and clinical symptoms was analyzed, and preliminary explorations on possible mechanisms were conducted. RESULTS: In comparison to HC, BD patients predominantly showed a trend toward CD4+ naïve T (Tn) activation and exhibited mitochondrial metabolic disturbances such as decreased MM and increased MMPLow. Lower CD4+ Tn-MM correlated with elevated IL-6, IL-8, and decreased IL-17 A in BD patients. With lithium treatment effective, MM of CD4+ T/Tn was negatively correlated with depression score HAMD. When lithium intolerance was present, MM of CD4+ T/Tn was positively correlated with depression score HAMD and mania score BRMS. Lithium does not mediate through the inositol depletion hypothesis, but the mRNA level of IMPA2 in peripheral blood is associated with mitochondrial function in CD8+ T cells. LIMITATIONS: The cross-sectional design and short-term follow-up meant that we could not directly examine the causality of BD and immune dysregulation. CONCLUSION: The altered metabolism of CD4+ Tn was strongly associated with remodeling of the inflammatory landscape in BD patients and can also be used to reflect the short-term therapeutic effects of lithium.

Matrine reduced intestinal stem cell damage in eimeria necatrix-infected chicks via blocking hyperactivation of Wnt signaling.

BACKGROUND: Coccidiosis is a rapidly spreading and acute parasitic disease that seriously threatening the intestinal health of poultry. Matrine from leguminous plants has anthelmintic and anti-inflammatory properties. PURPOSE: This assay was conducted to explore the protective effects of Matrine and the AntiC (a Matrine compound) on Eimeria necatrix (EN)-infected chick small intestines and to provide a nutritional intervention strategy for EN injury. STUDY DESIGN: The in vivo (chick) experiment: A total of 392 one-day-old yellow-feathered broilers were randomly assigned to six groups in a 21-day study: control group, 350 mg/kg Matrine group, 500 mg/kg AntiC group, EN group, and EN + 350 mg/kg Matrine group, EN + 500 mg/kg AntiC group. The in vitro (chick intestinal organoids, IOs): The IOs were treated with PBS, Matrine, AntiC, 3 µM CHIR99021, EN (15,000 EN sporozoites), EN + Matrine, EN + AntiC, EN + Matrine + CHIR99021, EN + AntiC + CHIR99021. METHODS: The structural integrity of chicks jejunal crypt-villus axis was evaluated by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). And the activity of intestinal stem cells (ISCs) located in crypts was assessed by in vitro expansion advantages of a primary in IOs model. Then, the changes of Wnt/ß-catenin signaling in jejunal tissues and IOs were detected by Real-Time qPCR,Western blotting and immunohistochemistry. RESULTS: The results showed that dietary supplementation with Matrine or AntiC rescued the jejunal injury caused by EN, as indicated by increased villus height, reduced crypt hyperplasia, and enhanced expression of tight junction proteins. Moreover, there was less budding efficiency of the IOs expanded from jejunal crypts of chicks in the EN group than that in the Matrine and AntiC group, respectively. Further investigation showed that AntiC and Matrine inhibited EN-stimulated Wnt/ß-catenin signaling. The fact that Wnt/ß-catenin activation via CHIR99021 led to the failure of Matrine and AntiC to rescue damaged ISCs confirmed the dominance of this signaling. CONCLUSION: Our results suggest that Matrine and AntiC inhibit ISC proliferation and promote ISC differentiation into absorptive cells by preventing the hyperactivation of Wnt/ß-catenin signaling, thereby standardizing the function of ISC proliferation and differentiation, which provides new insights into mitigating EN injury by Matrine and AntiC.